Sample records for prestroke oral anticoagulation

  1. Oral Anticoagulant Therapy

    PubMed Central

    Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero

    2012-01-01

    Background: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. Methods: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban Results: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. Conclusions: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID:22315269

  2. New horizons in anticoagulation: Direct oral anticoagulants and their implications in oral surgery

    PubMed Central

    Ripollés-de Ramón, Jorge; Collado-Yurrita, Luis; Vaello-Checa, Iris; Colmenero-Ruiz, Constantino; Helm, Alexandra; Ciudad-Cabañas, Maria-José; Serrano-Cuenca, Victoriano

    2017-01-01

    Background Thrombotic disorders remain a leading cause of death in the Western World. For decades, vitamin K antagonists used in the prevention of this pathology, such as warfarin or sintrom, were the only oral agents available for long-term anticoagulation, in spite of their disadvantages. Material and Methods An electronic database search was carried out on MedLine and The Cochrane Library Plus, without restrictions on the type of study nor dates, in English and Spanish. Abstracts were reviewed, and complete articles if necessary, considering all articles that included recommendations on DOACs and oral surgery. Results In recent years, the so-called “new oral anticoagulants” have been introduced in clinical practice to treat those patients whose medical conditions require long-term anticoagulant treatment, replacing traditional oral anticoagulants. Conclusions The new oral anticoagulants represent new therapeutic options, with a number of advantages such as poor interaction with food, minor drug interactions, and do not require periodic dose adjustments or routine controls. The purpose of this review is to establish an update on the new oral anticoagulants: Dabigatran, Rivarozaban, Apixaban and Edoxaban. Key words:Novel oral anticoagulants, Dabigatran, Rivaroxaban, Apixaban, Edoxaban, bleeding management, oral surgery, Anti-IIa, Anti Xa. PMID:28809374

  3. Direct oral anticoagulants: An update.

    PubMed

    Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

    2017-12-30

    Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  4. The role of oral anticoagulants in epistaxis.

    PubMed

    Buchberger, A M S; Baumann, A; Johnson, F; Peters, N; Piontek, G; Storck, K; Pickhard, A

    2018-06-23

    The purpose of this retrospective study was to identify the impact of oral anticoagulants on epistaxis with the focus on new oral anticoagulants. The study was conducted at the Department  for Ear- Nose- and Throat (ENT), Head and Neck Surgery, Technical University Munich, Germany. All patients presenting in 2014 with the diagnosis of epistaxis to a specialized ENT accident and emergency department were identified and analyzed in clinical data and medication. 600 adult cases, with a median age of 66.6 years were identified with active bleeding. 66.8% of all cases were anticoagulated. Classic oral anticoagulants (COAC) were three times more common in patients than new-generation oral anticoagulants (NOAC). Recurrent bleeding was significantly associated with oral anticoagulants (OAC) (p = 0.014) and bleeding location was most often anterior (p = 0.006). In contrast, severe cases, which required surgery or embolization were significantly more likely in non-anticoagulated middle-aged patients with posterior bleedings (p < 0.05). In our epistaxis cohort, OAC were highly overrepresented (40%) when compared to the general German population (1%) but COAC as well as NOAC played only a minor role in severe courses of epistaxis. Oral anticoagulation, especially with new-generation drugs, is not associated with more complicated and severe courses of epistaxis, but rather with recurrent bleeding. One should keep this information in mind when triaging the patient in the emergency room and when planning further procedures.

  5. [Cataract surgery under topical anesthesia with oral anticoagulants].

    PubMed

    Wirbelauer, C; Weller, A; Häberle, H; Pham, D T

    2004-09-01

    Approximately 14 % of cataract surgery patients receive blood-thinning agents. In a prospective study, the influence of oral anticoagulants on intraoperative and postoperative hemorrhages in patients undergoing cataract surgery in topical anesthesia was investigated. 128 patients presenting for cataract surgery under oral anticoagulation were included. The mean preoperative prothrombin time was 39 +/- 18 %. Most patients (81 %) continued their oral anticoagulation (prothrombin time 34 +/- 13 %). All surgeries were performed in topical anesthesia. In 9 patients (7 %) an ocular hemorrhagic event was observed. These were not sight-threatening and resorbed spontaneously within a few days. Only one patient (0.8 %) had a slight hemorrhage in the anterior chamber. There were no differences (P > 0.05) between patients with or without hemorrhagic complications in the postoperative visual acuity, the intraocular pressure, the prothrombin time or the discontinuation of oral anticoagulants. Cataract surgery in topical anesthesia under oral anticoagulation did not increase the risk of sight-threatening hemorrhages. The continuation of oral anticoagulation seems particularly indicated for ambulatory cataract surgery.

  6. Influence of novel oral anticoagulants on anticoagulation care management.

    PubMed

    Janzic, Andrej; Kos, Mitja

    2017-09-01

    Anticoagulation treatment was recently improved by the introduction of novel oral anticoagulants (NOACs). Using a combination of qualitative and quantitative methods, this study explores the effects of the introduction of NOACs on anticoagulation care in Slovenia. Face-to-face interviews with key stakeholders revealed evolvement and challenges of anticoagulation care from different perspectives. Obtained information was further explored through the analysis of nationwide data of drug prescriptions and realization of health care services. Simplified management of anticoagulation treatment with NOACs and their high penetration expanded the capacity of anticoagulation clinics, and consequentially the treated population increased by more than 50 % in the last 5 years. The main challenge concerned the expenditures for medicines, which increased approximately 10 times in just a few years. At the same time, the anticoagulation clinics and their core organisation were not affected, which is not expected to change, since they are vital in delivering high-quality care.

  7. [New oral anticoagulant drugs].

    PubMed

    Berkovits, Alejandro; Aizman, Andrés; Zúñiga, Pamela; Pereira, Jaime; Mezzano, Diego

    2011-10-01

    Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin K antagonists, whose anticoagulant effect is exerted inhibiting vitamin K epoxide reductase. Warfarin and acenocoumarol are the most commonly used. In the last five years several new drugs for long term anticoagulation have been developed, which can inhibit single clotting factors with the purpose of improving drug therapeutic range and, ideally, minimizing bleeding risks. This review addresses the state of the art on the clinical use of inhibitors of activated factor X and thrombin.

  8. Novel oral anticoagulants for atrial fibrillation.

    PubMed

    How, Choon How

    2015-12-01

    Anticoagulation therapy is effective in preventing primary and secondary thromboembolic events due to atrial fibrillation. Warfarin, which was approved by the United States in 1954, was the only long-term oral anticoagulation therapy till the approval of dabigatran in 2010, and of rivaroxaban and other direct factor Xa inhibitors from 2011, forming a group known as novel oral anticoagulants (NOAC). NOAC have fewer food and drug interactions compared to warfarin; hence, the patient will require fewer clinic visits. However, the short half-life of NOAC means that twice-a-day dosing is needed and there is higher risk of a prothrombotic state when doses are missed. Other disadvantages are the lack of long-term data on NOAC, their high cost and the current lack of locally available antidotes.

  9. Novel oral anticoagulants for atrial fibrillation

    PubMed Central

    How, Choon How

    2015-01-01

    Anticoagulation therapy is effective in preventing primary and secondary thromboembolic events due to atrial fibrillation. Warfarin, which was approved by the United States in 1954, was the only long-term oral anticoagulation therapy till the approval of dabigatran in 2010, and of rivaroxaban and other direct factor Xa inhibitors from 2011, forming a group known as novel oral anticoagulants (NOAC). NOAC have fewer food and drug interactions compared to warfarin; hence, the patient will require fewer clinic visits. However, the short half-life of NOAC means that twice-a-day dosing is needed and there is higher risk of a prothrombotic state when doses are missed. Other disadvantages are the lack of long-term data on NOAC, their high cost and the current lack of locally available antidotes. PMID:26702159

  10. Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance.

    PubMed

    Martin, Karlyn A; Lee, Craig R; Farrell, Timothy M; Moll, Stephan

    2017-05-01

    Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Satisfaction with oral anticoagulants in patients with atrial fibrillation

    PubMed Central

    Suárez Fernández, Carmen; Castilla-Guerra, Luis; Cantero Hinojosa, Jesus; Suriñach, Josep Maria; Acosta de Bilbao, Fernando; Tamarit, Juan José; Diaz Diaz, José Luis; Hernandez, Jose Luis; Pose, Antonio; Montero-Pérez-Barquero, Manuel; Roquer, Jaume; Gállego, Jaime; Vivancos, José; Mostaza, Jose María

    2018-01-01

    Background Although, by itself, atrial fibrillation is associated with an impairment of quality of life antithrombotic therapy may play a role. Objective To evaluate the satisfaction with anticoagulant treatment in patients with nonvalvular atrial fibrillation who attended internal medicine departments in Spain. Methods Patients from two different cross-sectional studies were combined. To measure the satisfaction with anticoagulant treatment, the Anti-Clot-Treatment Scale (ACTS) questionnaire was completed by every patient. A multivariate analysis was performed to determine the variables associated with satisfaction of patients receiving oral anticoagulants. Results A total of 1,309 patients (mean age 78.5±8.4 years; 49.3% men; CHA2DS2VASC 4.9±1.5; HAS-BLED 2.0±0.9) were included in the study, of whom 902 (68.9%) were taking vitamin K antagonists (VKA) and 407 (31.1%) direct oral anticoagulants (DOACs). Overall, satisfaction with oral anticoagulation was high (ACTS Burdens scale 49.69±9.45; ACTS Benefits scale 11.35±2.61). The perceived burdens with anticoagulant treatment were lower in men, as well as in patients with no dependency, normal renal function, who were not polymedicated, or who had moderate bleeding risk. Among patients taking VKA, those subjects with a lower number of International Normalized Ratio (INR) determinations in the last 6 months or with an optimal time in the therapeutic range exhibited a lower perceived burden. Patients taking DOACs (vs VKA) showed a lower perceived burden with anticoagulation. Benefits with anti-coagulation were higher in men, younger patients, those with no dependency, or low bleeding risk. Perceived benefits were higher in patients taking DOACs (vs VKA). Conclusion Satisfaction with oral anticoagulation was high in patients with nonvalvular atrial fibrillation, who were attending internal medicine departments daily in Spain. Among patients taking VKA, those subjects with a lower number of INR determinations in the

  12. Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study

    PubMed Central

    Hogg, Kerstin; Bahl, Bharat; Latrous, Meriem; Scaffidi Argentina, Sarina; Thompson, Jesse; Chatha, Aasil Ayyaz; Castellucci, Lana; Stiell, Ian G.

    2015-01-01

    Background: Over the past 5 years, dabigatran, rivaroxaban and apixaban were approved for stroke prevention. Phase III studies have shown a lower risk of intracranial bleeding with these direct oral anticoagulants than with warfarin; however, there is a lack of real-life data to validate this. We analyzed time trends in atraumatic intracranial bleeding from 2009 to 2013 among patients prescribed oral anticoagulants and those not prescribed oral anticoagulants. Methods: We used ICD-10-CA (enhanced Canadian version of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) codes to identify all patients with atraumatic intracranial bleeding who presented to our neurosurgical centre (serving a population of more than 1.2 million). Trained researchers extracted data on anticoagulant medications used in the week before diagnosis of the intracranial bleed. Provincial prescription data for oral anticoagulants were obtained from IMS Brogan CompuScript Market Dynamics. The primary outcome was the time trend in incident intracranial bleeds associated with oral anticoagulation during the period 2009-2013. The secondary outcomes were the time trend in intracranial bleeds not associated with oral anticoagulation and the provincial prescribing patterns for oral anticoagulants during the same period. Results: A total of 2050 patients presented with atraumatic intracranial bleeds during the study period. Of the 371 (18%) prescribed an anticoagulant in the week before presentation, 335 were prescribed an oral anticoagulant. There was an increasing time trend in intracranial bleeding associated with oral anticoagulants (p = 0.009; 6 additional events per year) and in intracranial bleeding not associated with oral anticoagulation (p = 0.06). During 2013, prescriptions for warfarin decreased to 70% of all oral anticoagulant prescriptions in the province, whereas those for dabigatran and rivaroxaban increased to 17% and 12

  13. Acute management of bleeding in patients on novel oral anticoagulants.

    PubMed

    Siegal, Deborah M; Crowther, Mark A

    2013-02-01

    Novel oral anticoagulants that directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are currently available for prevention of venous thromboembolism (VTE) after orthopaedic surgery, treatment of acute VTE, and prevention of arterial thromboembolism in non-valvular atrial fibrillation. These agents offer advantages over VKAs, including rapid onset, shorter half-lives, fewer drug interactions, and lack of need for routine monitoring. However, there are no established agents to reverse their anticoagulant effect. We review the risk of bleeding with the novel oral anticoagulants and the limitations of conventional coagulation assays for measuring anticoagulant effect. We provide an approach to the management of patients with bleeding complications with evidence for various interventions for reversal, where available.

  14. Oral Anticoagulation in Chronic Kidney Disease and Atrial Fibrillation.

    PubMed

    Heine, Gunnar H; Brandenburg, Vincent; Schirmer, Stephan H

    2018-04-27

    Cardiological societies recommend, in their guidelines, that patients with atrial fibrillation and an intermediate (or higher) risk of stroke and systemic embolization should be treated with oral anticoagulant drugs. For patients who do not have mitral valve stenosis or a mechanical valve prosthesis, non-vitamin-K dependent oral anticoagulants (NOAC) are preferred over vitamin K antagonists (VKA) for this purpose. It is unclear, however, whether patients with chronic kidney disease and atrial fibrillation benefit from oral anticoagulation to the same extent as those with normal kidney function. It is also unclear which of the two types of anti - coagulant drug is preferable for patients with chronic kidney disease; NOAC are, in part, renally eliminated. This review is based on pertinent publications retrieved by a selective literature search, and on international guidelines. Current evidence suggests that patients with atrial fibrillation who have chronic kidney disease with a glomerular filtration rate (GFR) above 15 mL/ min/1.73 m² should be treated with an oral anticoagulant drug if they have an at least intermediate risk of embolization, as assessed with the CHA2DS2-VASc score. For patients with advanced chronic kidney disease (GFR from 15 to 29 mL/ min/1.73 m²), however, this recommendation is based only on registry studies. For dialysis patients with atrial fibrillation, decisions whether to give oral anticoagulant drugs should be taken on an individual basis, in view of the elevated risk of hemorrhage and the unclear efficacy of such drugs in these patients. The subgroup analyses of the NOAC approval studies show that, for patients with atrial fibrillation and chronic kidney disease with a creatinine clearance of >25-30 mL/min, NOAC should be given in preference to VKA, as long as the patient does not have mitral valve stenosis or a mechanical valve prosthesis. For those whose creatinine clearance is less than 25 mL/min, the relative merits of NOAC versus

  15. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis.

    PubMed

    van Walraven, Carl; Hart, Robert G; Singer, Daniel E; Laupacis, Andreas; Connolly, Stuart; Petersen, Palle; Koudstaal, Peter J; Chang, Yuchiao; Hellemons, Beppie

    2002-11-20

    Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke and other vascular events. To compare the risk of vascular and bleeding events in patients with nonvalvular AF treated with vitamin K -inhibiting oral anticoagulants or acetylsalicylic acid (aspirin). Pooled analysis of patient-level data from 6 published, randomized clinical trials. A total of 4052 patients with AF randomly assigned to receive therapeutic doses of oral anticoagulant or aspirin with or without low-dose oral anticoagulants. Ischemic and hemorrhagic stroke, other cardiovascular events, all-cause death, and major bleeding events. Person-year incidence rates were calculated to provide crude comparisons. Relative efficacy was assessed using proportional hazards modeling stratified by study. The variation of the oral anticoagulant's relative effect by pertinent patient factors was explored with interaction terms. All analyses were conducted using the intention-to-treat principle. Patients receiving oral anticoagulant and aspirin were balanced for important prognostic factors. There was no significant heterogeneity between trials in the relative efficacy of oral anticoagulant vs aspirin for any outcome. Patients receiving oral anticoagulant were significantly less likely to experience any stroke (2.4 vs 4.5 events per 100 patient-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71), ischemic stroke (HR, 0.48; 95% CI, 0.37-0.63), or cardiovascular events (HR, 0.71; 95% CI, 0.59-0.85) but were more likely to experience major bleeding (2.2 vs 1.3 events per 100 patient-years; HR, 1.71; 95% CI, 1.21-2.41). The reduction in ischemic stroke risk was similar in patients with paroxysmal AF (1.5 vs 4.7 events per 100 patient-years; HR, 0.32; 95% CI, 0.16-0.61; P<.001). Treating 1000 patients with AF for 1 year with oral anticoagulant rather than aspirin would prevent 23 ischemic strokes while causing 9 additional major bleeds. Overall all-cause survival did not

  16. POST-NOAC: Portuguese observational study of intracranial hemorrhage on non-vitamin K antagonist oral anticoagulants.

    PubMed

    Marques-Matos, Cláudia; Alves, José Nuno; Marto, João Pedro; Ribeiro, Joana Afonso; Monteiro, Ana; Araújo, José; Silva, Fernando; Grenho, Fátima; Viana-Baptista, Miguel; Sargento-Freitas, João; Pinho, João; Azevedo, Elsa

    2017-08-01

    Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA 2 DS 2 VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39-1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55-2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants

  17. Clinical considerations on the posology of direct oral anticoagulants.

    PubMed

    Sáez-Peñataro, J; Avendaño-Solá, C; González-Juanatey, J R

    2016-10-01

    The efficacy of dicoumarin anticoagulants has been shown in patients with nonvalvular atrial fibrillation. However, they have drawbacks such as the need to adjust the dosage and the interaction with drugs and food. Direct oral anticoagulants are an effective and safe alternative and have a less complicated clinical management. There is considerable debate on the selection criteria for the posology regimens of direct oral anticoagulants. The differences among them and their administration regimens have raised questions about the clinical, pharmacokinetic and pharmacodynamic selection criteria that support the posology. This review critically analyses the available evidence and its impact on the final selection of the dosage regimen. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  18. Considerations for long-term anticoagulant therapy in patients with venous thromboembolism in the novel oral anticoagulant era.

    PubMed

    Toth, Peter P

    2016-01-01

    Patients who have had a venous thromboembolic event are generally advised to receive anticoagulant treatment for 3 months or longer to prevent a recurrent episode. Current guidelines recommend initial heparin and an oral vitamin K antagonist (VKA) for long-term anticoagulation. However, because of the well-described disadvantages of VKAs, including extensive food and drug interactions and the need for regular anticoagulation monitoring, novel oral anticoagulants (NOACs) have become an attractive option in recent years. These agents are given at fixed doses and do not require routine coagulation-time monitoring. The NOACs are discussed in this review with regard to the needs of patients on long-term anticoagulation. Current guidelines from Europe and North America that refer to the treatment of deep vein thrombosis and/or pulmonary embolism are included, as well as published randomized Phase III clinical trials of NOACs. PubMed searches were used for sourcing case studies of long-term anticoagulant treatment, and results were filtered for human application and screened for relevance. NOAC-based therapy showed a similar efficacy and safety profile to heparins/VKAs but without the need for regular anticoagulation monitoring or dietary adjustments, and can be taken as a fixed-dose regimen once or twice daily. This represents a significant step forward in facilitating the management of long-term anticoagulation therapy. Furthermore, in the EINSTEIN studies, improved patient satisfaction was documented with the NOAC rivaroxaban, which may result in better adherence to therapy and an overall reduction in the incidence of recurrent venous thromboembolism.

  19. Dietary vitamin K guidance: an effective strategy for stable control of oral anticoagulation?

    USDA-ARS?s Scientific Manuscript database

    Numerous factors have been identified as risk factors for instability of oral anticoagulation, including variability in vitamin K intake. However few studies have directly tested the feasibility of manipulating dietary vitamin K to achieve stable oral anticoagulation. Recent findings from a rando...

  20. Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

    PubMed

    Fonseca, Roberto J C; Sucupira, Isabela D; Oliveira, Stephan Nicollas M C G; Santos, Gustavo R C; Mourão, Paulo A S

    2017-04-03

    Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

  1. New oral anticoagulants--a review.

    PubMed

    Ghanima, Waleed; Atar, Dan; Sandset, Per Morten

    2013-10-01

    Dabigatran, rivaroxaban and apixaban are three new oral anticoagulants that have recently been approved in Norway. The aim of this article is to provide an overview of the mechanisms of action, the most important indications and practical advice on the use of these drugs. The review is based on published phase 3 studies, a literature search in PubMed and the authors' clinical experience. Indications for use of the new anticoagulants include thromboprophylaxis after total hip and knee replacement surgery (all three), prevention of stroke and systemic embolism in non-valvular atrial fibrillation (all three), treatment of acute venous thrombosis and secondary prophylaxis after venous thrombosis (currently only rivaroxaban). For the aforementioned indications, these drugs have proven to be non-inferior to standard established anticoagulation therapy. For atrial fibrillation, all three drugs have also shown a lower incidence of intracranial bleeding compared with standard treatment. It is important to limit the use of these drugs to approved indications, to select patients who show good compliance, to rule out contraindications and to identify drug interactions. Monitoring of coagulation is not required, but patients should be followed up regularly to detect conditions that may lead to changes in the expected efficacy or safety.

  2. Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kumar, Pradesh, E-mail: pradeshkumar@doctors.org.uk; Ravi, Rajeev, E-mail: rajeev.ravi@aintree.nhs.uk; Sundar, Gaurav, E-mail: gaurav.sundar@aintree.nhs.uk

    The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address themore » strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.« less

  3. Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: The SAMURAI‐NVAF Study

    PubMed Central

    Arihiro, Shoji; Todo, Kenichi; Yamagami, Hiroshi; Kimura, Kazumi; Furui, Eisuke; Terasaki, Tadashi; Shiokawa, Yoshiaki; Kamiyama, Kenji; Takizawa, Shunya; Okuda, Satoshi; Okada, Yasushi; Kameda, Tomoaki; Nagakane, Yoshinari; Hasegawa, Yasuhiro; Mochizuki, Hiroshi; Ito, Yasuhiro; Nakashima, Takahiro; Takamatsu, Kazuhiro; Nishiyama, Kazutoshi; Kario, Kazuomi; Sato, Shoichiro; Koga, Masatoshi; Nagatsuka, K; Minematsu, K; Nakagawara, J; Akiyama, H; Shibazaki, K; Maeda, K; Shibuya, S; Yoshimura, S; Endo, K; Miyagi, T; Osaki, M; Kobayashi, J; Okata, T; Tanaka, E; Sakamoto, Y; Takizawa, H; Takasugi, J; Tokunaga, K; Homma, K; Kinoshita, N; Matsuki, T; Higashida, K; Shiozawa, M; Kanai, H; Uehara, S

    2015-01-01

    Background Large clinical trials are lack of data on non‐vitamin K antagonist oral anticoagulants for acute stroke patients. Aim To evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk‐factor Assessment and Improvement‐NVAF registry (ClinicalTrials.gov NCT01581502). Method The study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23‐day stay) was assessed. Results Warfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10‐month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS 2, CHA 2 DS 2‐VASc, and HAS‐BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four‐days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20‐day or

  4. Anticoagulated patient's perception of their illness, their beliefs about the anticoagulant therapy prescribed and the relationship with adherence: impact of novel oral anticoagulant therapy - study protocol for The Switching Study: a prospective cohort study.

    PubMed

    Auyeung, Vivian; Patel, Jignesh P; Abdou, John K; Vadher, Bipin; Bonner, Lynda; Brown, Alison; Roberts, Lara N; Patel, Raj K; Arya, Roopen

    2016-01-01

    Anticoagulant therapy is prescribed for millions of patients worldwide for the prevention and treatment of both arterial and venous thrombosis. Historically, only vitamin K antagonists have been available for clinicians to prescribe. The anticoagulation landscape is changing. The recent availability of the novel oral anticoagulants overcome many of the disadvantages associated with vitamin K antagonists. However the lack of formal monitoring and clinic follow-up is a concern for clinicians, as medication adherence is being assumed, which is known to decline in patients prescribed medications for chronic conditions. The switching study is a programme of work investigating the association between medication adherence and patient's beliefs about anticoagulation therapy (warfarin and subsequently novel oral anticoagulants), together with beliefs about their illness and anticoagulation related quality of life. The anticoagulation database at King's College Hospital will be interrogated and two groups of patients will be identified; those with a time in therapeutic range on warfarin of ≥75 % and those <50 %. These groups of patients will have their illness perceptions, anticoagulation specific quality of life and beliefs about medications compared. Those patients in the time in therapeutic range <50 % group, will be then be invited to switch to a novel oral anticoagulant, as per local guidance. Those patients, who do switch, will then be followed longitudinally and have their adherence, illness perceptions, anticoagulation specific quality of life and beliefs about medications, re-evaluated on the novel agent. The results from these sub-studies, will inform a clinical pathway to support patients on these novel agents, which will be evaluated in an independent group of patients. The results from the switching study will be used to develop a clinical pathway to support patient's prescribed novel oral anticoagulant therapy long-term.

  5. Abnormal uterine bleeding in women receiving direct oral anticoagulants for the treatment of venous thromboembolism.

    PubMed

    Godin, Richard; Marcoux, Violaine; Tagalakis, Vicky

    2017-08-01

    Abnormal uterine bleeding (AUB) is a common complication of anticoagulant therapy in premenopausal women affected with acute venous thromboembolism. AUB impacts quality of life, and can lead to premature cessation of anticoagulation. There is increasing data to suggest that the direct oral anticoagulants when used for the treatment of venous thromboembolism differ in their menstrual bleeding profile. This article aims to review the existing literature regarding the association between AUB and the direct oral anticoagulants and make practical recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. A surgeon's guide to anticoagulant and antiplatelet medications part one: warfarin and new direct oral anticoagulant medications

    PubMed Central

    McBeth, Paul B; Weinberg, Jordan A; Sarani, Babak; Yeung, Louise Y Y; May, Addison K

    2016-01-01

    An increasing number of potent antiplatelet and anticoagulant medications are being used for the long-term management of cardiac, cerebrovascular, and peripheral vascular conditions. Management of these medications in the perioperative and peri-injury settings can be challenging for surgeons, mandating an understanding of these agents and the risks and benefits of various management strategies. In this two-part review, agents commonly encounter by surgeons in the perioperative and peri-injury settings are discussed and management strategies for patients on long-term antiplatelet and anticoagulant therapy reviewed. In part I, we review warfarin and the new direct oral anticoagulants. In part II, we review antiplatelet agents and assessment of platelet function and the perioperative management of long-term anticoagulant and antiplatelet therapy. PMID:29767647

  7. [Factors influencing activity of oral anticoagulants. Interactions with drugs and food].

    PubMed

    Sawicka-Powierza, Jolanta; Rogowska-Szadkowska, Dorota; Ołtarzewska, Alicja Małgorzata; Chlabicz, Sławomir

    2008-05-01

    Oral anticoagulants (OAC) are commonly used as a life-long therapy in prevention of systemic embolism in patients with atrial fibrillation, valvular heart disease and prosthetic hart valves and in the primary and secondary prevention of venous thromboembolism. They are also used for the prevention of thromboembolic events in patients with acute myocardial infarction and with angina pectoris, in patients with biological hart valves and after some types of orthopaedics surgery. The International Normalized Ratio (INR) is used to evaluate the efficacy of anti-coagulant therapy. The risk of thromboembolic and haemorrhagic complications increases when the INR is out of the therapeutic range. The aim of this study was to present information about the factors influencing activity of oral anticoagulants and interactions between oral anticoagulants and drugs or food. The effect of oral anticoagulants is influenced by genetic and environmental factors such as: medicines, food, diseases and pre-existing conditions. A common mutation in the gene coding for the cytochrome P450 (CYP2C9), with one or more combinations of its polymorphisms, is responsible for the reduced warfarin requirements or for the resistance to warfarin. A mutation in the factor IX is responsible for the risk of bleeding during OAC therapy without excessive prolongation of the prothrombin time (PT). Drugs, herbs and multivitamin supplements can alter the absorption, pharmacokinetics or pharmakodynamics of OAC. Nonsteroid anti-inflammatory drugs and paracetamol in combination with OAC seem to be the most dangerous because they are available without prescription and are used without medical consultation. Patients on OAC therapy are sensitive to changing dietary intake of vitamin K, which is supplied from phylloquinones in plants or from vitamin K-containing medicines. The effect of OAC can be influenced by other existing factors like: fever, diarrhoea, alcohol abuse or physical hyperactivity. Some malignancies

  8. [Use of non-vitamin K antagonist oral anticoagulants in Primary Care: ACTUA study].

    PubMed

    Barrios, V; Escobar, C; Lobos, J M; Polo, J; Vargas, D

    2017-10-01

    Approximately 40% of patients with non-valvular auricular fibrillation (NVAF) who receive vitamin K antagonists (VKA) in Primary Care in Spain have poor anticoagulation control. The objective of the study Actuación en antiCoagulación, Tratamiento y Uso de anticoagulantes orales de acción directa (ACOD) en Atención primaria (ACTUA) (Action in Coagulation, Treatment and Use of direct oral anticoagulants [DOACs]) in Primary Care) was to analyse the current situation regarding the use of VKA and non-vitamin K antagonist oral anticoagulants (NOACs) in patients with NVAF in Primary Care in Spain and the possible issues arising from it. An online survey was created covering various aspects of the use of oral anticoagulants in NAFV. A two-round modified Delphi approach was used. Results were compiled as a set of practical guidelines. Forty-four experts responded to the survey. Consensus was reached in 62% (37/60) of the items. Experts concluded that a considerable number of patients with NVAF who receive VKA do not have a well-controlled INR and that a substantial group of patients who could benefit from being treated with NOACs do not receive them. The use of NOACs increases the probability of having good anticoagulation control and decreases the risk of severe and intracranial haemorrhage. Current limitations to the use of NOACs include administrative barriers, insufficient knowledge about the benefits and risks of NOACs, limited experience of doctors in using them, and their price. Renal insufficiency influences the choice of a particular anticoagulant. The ACTUA study highlights the existing controversies about the use of oral anticoagulants for the treatment of NVAF in Primary Care in Spain, and provides consensus recommendations that may help to improve the use of these medications. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Trends in oral anticoagulant use in Qatar: a 5-year experience.

    PubMed

    Elewa, Hazem; Alhaddad, Amani; Al-Rawi, Safa; Nounou, Amir; Mahmoud, Hesham; Singh, Rajvir

    2017-04-01

    In Qatar, dabigatran was introduced in 2011 followed by rivaroxaban in 2014. In this study, we aim to explore the trends in oral anticoagulant use in Qatar over the past 5 years and to what extent did DOACs replace warfarin. We also explored the extent of switching between different anticoagulants (from warfarin to DOACs and vice versa). We collected all anticoagulant prescriptions dispensed as in- or out-patient from 2011 to 2015 in all Hamad Medical Corporation (HMC) hospitals. Overall number of patients using warfarin, dabigatran and rivaroxaban over the last 5 years collectively was calculated. Per each calendar year, we calculated the number of all 3 OAC used (warfarin, dabigatran and rivaroxaban), frequency of use of each one of the OAC prescribed and compared the change in proportion of DOACs to warfarin prescriptions over the years. Overall, 6961 patients were using OAC over the past 5 years among which 5849 (84%) used warfarin, 496 (7.1%) used dabigatran and 616 (8.8%) used rivaroxaban. Oral anticoagulants use increased gradually from 2091 in 2011 to 3688 in 2015. Number of patients receiving DOACs increased significantly compared to warfarin [11 (0.5%) in 2011 vs. 849 (23%) in 2015 (p < 0.0001)]. Since its introduction in 2014, number of rivaroxaban users increased significantly compared to dabigatran [212 (40.9%) in 2014 vs. 544 (64.1%) in 2015]. DOACs have been gradually replacing warfarin in Qatar and the trend of their use is similar to that reported in other countries. Warfarin remains the most commonly used oral anticoagulant.

  10. Direct oral anticoagulants and its implications in dentistry. A review of literature.

    PubMed

    Lanau, Neus; Mareque, Javier; Giner, Lluis; Zabalza, Michel

    2017-11-01

    Four novel direct oral anticoagulants (DOACs) named dabigatran, rivaroxaban, edoxaban and apixaban have been recently introduced to overcome some of the drawbacks of existing anticoagulants. They have less interactions and do not require routine monitoring. However, there is not enough scientific data about the protocol to apply in these patients on DOACs undergoing dental treatment. Thus is necessary to evaluate the potential bleeding risk of these drugs, the possibility of thromboembolic events occurring if they are withdrawn or the need to change to heparin previously. A comprehensive search of the PubMed, Scopus and ISI Web of Science databases was conducted to identify studies that evaluated the relationship between direct oral anticoagulants and dental procedures. The quality of the reported information was assessed following the PRISMA statement. Eleven studies that met the inclusion criteria were included in the review: 2 randomized clinical trials, 3 prospective studies, 3 retrospective studies, 2 case series and 1 case report. DOACs are safe drugs in terms of bleeding. The possible postoperative bleeding complications are manageable with conventional haemostasis measurements. The bridging approach with heparin does not seem to be recommended. Consensus among the professionals involved in the management of the patient is fundamental in invasive dental treatments and in complex patients. Key words: Oral anticoagulants, DOAC, NOAC, dabigatran, rivaroxaban, apixaban, edoxaban, bleeding, oral surgery.

  11. Economic evaluation of prescribing conventional and newer oral anticoagulants in older adults.

    PubMed

    Hasan, Syed Shahzad; Kow, Chia Siang; Curley, Louise E; Baines, Darrin L; Babar, Zaheer-Ud-Din

    2018-05-09

    Anticoagulants refer to a variety of agents that inhibit one or more steps in the coagulation cascade. Generally, clinical conditions that require the prescribing of an oral anticoagulant increase in frequency with age. However, a major challenge of anticoagulation use among older patients is that this group of patients also experience the highest bleeding risk. To date, economic evaluation of prescribing of anticoagulants that includes the novel or newer oral anticoagulants (NOACs) in older adults has not been conducted and is warranted. Areas covered: A review of articles that evaluated the cost of prescribing conventional (e.g. vitamin K antagonists) and NOACs (e.g. direct thrombin inhibitors and direct factor Xa inhibitors) in older adults. Expert commentary: While the use of NOACs significantly increases the cost of the initial treatment for thromboembolic disorders, they are still considered cost-effective relative to warfarin since they offer reduced risk of intracranial haemorrhagic events. The optimum anticoagulation with warfarin can be achieved by providing specialised care; clinics managed by pharmacists have been shown to be cost-effective relative to usual care. There are suggestions that genotyping the CYP2C9 and VKORC1 genes is useful for determining a more appropriate initial dose and thereby increasing the effectiveness and safety of warfarin.

  12. New developments in pediatric venous thromboembolism and anticoagulation, including the target-specific oral anticoagulants.

    PubMed

    Lyle, Courtney A; Sidonio, Robert F; Goldenberg, Neil A

    2015-02-01

    Pediatric venous thromboembolism (VTE) can affect children of all ages, requiring considerable pharmacologic intervention and is often associated with significant morbidity. Current research efforts are directed toward the development of risk-stratified VTE prevention strategies employing pharmacologic thromboprophylaxis, the optimization of conventional anticoagulation, and the investigation of the safety and efficacy of target-specific oral anticoagulants (TSOACs) in children. Recent research has considerably improved the understanding of risk factors of hospital-acquired VTE and how these factors may be employed in risk-stratified paradigms for VTE prevention in children. Additional insight has been gained in the optimization of conventional anticoagulants in special populations such as neonates and children with inflammatory conditions, and in improving the overall safety and compliance with periprocedural anticoagulation and the use of home International Normalized Ratio monitoring. Furthermore, the use of TSOACs has been described in children and is the focus of numerous ongoing clinical trials that are evaluating the safety and efficacy of these agents in children with VTE. Identification of hospital-acquired VTE risk factors may inform pediatric VTE prevention strategies. Although initial use of TSOACs may be promising, investigation of safety and efficacy in children is still underway.

  13. [Management of new oral anticoagulants in gastrointestinal bleeding and endoscopy].

    PubMed

    del Molino, Fátima; Gonzalez, Isabel; Saperas, Esteve

    2015-10-01

    New oral direct anticoagulants agents are alternatives to warfarin for long-term anticoagulation in a growing number of patients that require long-term anticoagulation for atrial fibrillation, deep venous thrombosis and pulmonary embolism. These new agents with predictable pharmacokinetic and pharmacodynamics profiles offer a favorable global safety profile, but increased gastrointestinal bleeding compared to the vitamin K antagonists. Many gastroenterologists are unfamiliar and may be wary of these newer drugs, since Clinical experience is limited and no specific antidote is available to reverse their anticoagulant effect. In this article the risk of these new agents and, how to manage these agents in both the presence of acute gastrointestinal bleeding and in patients undergoing endoscopic procedures is reviewed. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  14. Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

    PubMed

    Samuelson, Bethany T; Cuker, Adam; Siegal, Deborah M; Crowther, Mark; Garcia, David A

    2017-01-01

    Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r 2  = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r 2  = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available. Copyright © 2016 American College of Chest Physicians. Published by Elsevier

  15. Evaluation of bleeding in patients receiving direct oral anticoagulants

    PubMed Central

    Hellenbart, Erika L; Faulkenberg, Kathleen D; Finks, Shannon W

    2017-01-01

    Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major and other bleeding results have varied among the agents compared to vitamin K antagonists. We have reviewed the bleeding incidence and severity from randomized and real-world data in patients receiving DOACs in an effort to provide the clinician with a critical review of bleeding and offer practical considerations for avoiding adverse events with these anticoagulants. PMID:28860793

  16. Oral anticoagulation management in patients with atrial fibrillation undergoing cardiac implantable electronic device implantation.

    PubMed

    Black-Maier, Eric; Kim, Sunghee; Steinberg, Benjamin A; Fonarow, Gregg C; Freeman, James V; Kowey, Peter R; Ansell, Jack; Gersh, Bernard J; Mahaffey, Kenneth W; Naccarelli, Gerald; Hylek, Elaine M; Go, Alan S; Peterson, Eric D; Piccini, Jonathan P

    2017-09-01

    Oral anticoagulation (OAC) therapy is associated with increased periprocedural risks after cardiac implantable electronic device (CIED) implantation. Patterns of anticoagulation management involving non-vitamin K antagonist oral anticoagulants (NOACs) have not been characterized. Anticoagulation strategies and outcomes differ by anticoagulant type in patients undergoing CIED implantation. Using the nationwide Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we assessed how atrial fibrillation (AF) patients undergoing CIED implantation were cared for and their subsequent outcomes. Outcomes were compared by oral anticoagulant therapy (none, warfarin, or NOAC) as well as by anticoagulation interruption status. Among 9129 AF patients, 416 (5%) underwent CIED implantation during a median follow-up of 30 months (interquartile range, 24-36). Of these, 60 (14%) had implantation on a NOAC. Relative to warfarin therapy, those on a NOAC were younger (70.5 years [range, 65-77.5 years] vs 77 years [range, 70-82 years]), had less valvular heart disease (15.0% vs 31.3%), higher creatinine clearance (67.3 [range, 59.7-99.0] vs 65.8 [range, 50.0-91.6]), were more likely to have persistent AF (26.7% vs 22.9%), and use concomitant aspirin (51.7% vs 35.2%). OAC therapy was commonly interrupted for CIED in 64% (n = 183 of 284) of warfarin patients and 65% (n = 39 of 60) of NOAC patients. Many interrupted patients received intravenous bridging anticoagulation: 33/183 (18%) interrupted warfarin and 4/39 (10%) interrupted NOAC patients. Thirty-day periprocedure bleeding and stroke adverse events were infrequent. Management of anticoagulation among AF patients undergoing CIED implantation is highly variable, with OAC being interrupted in more than half of both warfarin- and NOAC-treated patients. Bleeding and stroke events were infrequent in both warfarin and NOAC-treated patients. © 2017 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.

  17. Drug Interactions of Direct-Acting Oral Anticoagulants.

    PubMed

    Fitzgerald, John Leonard; Howes, Laurence Guy

    2016-09-01

    In recent years, new direct-acting oral anticoagulants (DOACs) have been introduced into clinical practice that specifically inhibit either factor Ia or Xa. These drugs have, to a large extent, replaced warfarin for the treatment of venous thrombosis, pulmonary embolism, and non-valvular atrial fibrillation. They have potential advantages over warfarin in providing more stable anticoagulation and the lack of a need for regular venesection to monitor activity. They also have the promise of less drug and food interactions. All of these drugs are substrates for the permeability glycoprotein (P-gp) excretion system, and several are metabolised, in part, by cytochrome P450 (CYP) 3A4. This current article assesses the interactions that do or may occur with the DOACs, particularly with respect to the P-gp and CYP3A4 systems.

  18. Suspected adverse drug reaction reports with oral anticoagulants in Portugal: a pharmacovigilance study.

    PubMed

    Caldeira, Daniel; Rodrigues, Raquel; Abreu, Daisy; Anes, Ana Marta; Rosa, Mário M; Ferreira, Joaquim J

    2018-04-01

    In this pharmacovigilance study, we aimed to determine the incidence of spontaneously reported suspected adverse drug reactions (ADRs) related to oral anticoagulants: non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban, rivaroxaban) and vitamin K antagonists (VKA) Research design and methods: In this retrospective observational study, we extracted all the individual case safety reports related to oral anticoagulants recorded in the Portuguese Pharmacovigilance Database (January 2010 to April 2015). The annual incidence of suspected ADRs was estimated using drug exposure data. Disproportionality of reporting ADR was addressed through reporting odds ratio (ROR) and 99% confidence intervals. We appraised 794 suspected ADR (78% related to NOACs). The annual number of ADRs increased overtime with 9 ADRs/million Defined Daily Dose (DDD) at the end of 2014. The incidence of NOACs ADRs decreased from 2012 onwards. VKA showed a disproportion in 'Investigation' (ROR 0.10, 99%CI 0.05-0.22) and 'Injury, poisoning and procedural complications' (ROR 0.36, 99%CI 0.19-0.69) ADRs compared with NOACs. NOACs had a higher significant disproportion of 'Nervous system disorders' related ADRs (ROR 3.98, 99%CI 1.50-10.53). Reporting of ADRs associated with oral anticoagulants (mainly NOACs), is increasing. Exploratory disproportion analyses showed an increase of reports of nervous system ADRs with NOACs, and INR-related ADRs with VKA.

  19. Dependence in prestroke mobility predicts adverse outcomes among patients with acute ischemic stroke.

    PubMed

    Dallas, Mary I; Rone-Adams, Shari; Echternach, John L; Brass, Lawrence M; Bravata, Dawn M

    2008-08-01

    Stroke survivors are commonly dependent in activities of daily living; however, the relation between prestroke mobility impairment and poststroke outcomes is poorly understood. The primary objective of this study was to evaluate the association between prestroke mobility impairment and 4 poststroke outcomes. The secondary objective was to evaluate the association between prestroke mobility impairment and a plan for physical therapy. This was a secondary analysis of the National Stroke Project data, a retrospective cohort of Medicare beneficiaries who were hospitalized with an acute ischemic stroke (1998 to 2001). Logistic-regression modeling was used to examine the adjusted association between prestroke mobility impairment with patient outcomes and a plan for physical therapy. Among the 67,445 patients hospitalized with an ischemic stroke, 6% were dependent in prestroke mobility. Prestroke mobility dependence was independently associated with an increased odds of poststroke mobility impairment (odds ratio [OR]=9.9; 95% CI, 9.0 to 10.8); in-hospital mortality (OR=2.4; 95% CI, 2.2 to 2.7); discharge to a skilled nursing facility (OR=3.5; 95% CI, 3.2 to 3.8); and the combination of in-hospital death or discharge to a skilled nursing facility (OR=3.5; 95% CI, 3.3 to 3.8). Prestroke mobility dependence was independently associated with a decreased odds of having a plan for physical therapy (OR=0.79; 95% CI, 0.73 to 0.85). These data, obtained from a large, geographically diverse cohort from the United States, demonstrate a strong association between dependence in prestroke mobility and adverse outcomes among elderly stroke patients. Clinicians should screen patients for prestroke mobility impairment to identify patients at greatest risk for adverse events.

  20. Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs direct oral anticoagulants.

    PubMed

    Yanagisawa, Naohiro; Nagata, Naoyoshi; Watanabe, Kazuhiro; Iida, Tatsuhiro; Hamada, Mariko; Kobayashi, Sakurako; Shimbo, Takuro; Akiyama, Junichi; Uemura, Naomi

    2018-04-14

    To verify the validity of the endoscopy guidelines for patients taking warfarin or direct oral anticoagulants (DOAC). We collected data from 218 patients receiving oral anticoagulants (73 DOAC users, 145 warfarin users) and 218 patients not receiving any antithrombotics (age- and sex-matched controls) who underwent polypectomy. (1) We evaluated post-polypectomy bleeding (PPB) risk in patients receiving warfarin or DOAC compared with controls; (2) we assessed the risks of PPB and thromboembolism between three AC management methods: Discontinuing AC with heparin bridge (HPB) (endoscopy guideline recommendation), continuing AC, and discontinuing AC without HPB. PPB rate was significantly higher in warfarin users and DOAC users compared with controls (13.7% and 13.7% vs 0.9%, P < 0.001), but was not significantly different between rivaroxaban (13.2%), dabigatran (11.1%), and apixaban (13.3%) users. Two thromboembolic events occurred in warfarin users, but none in DOAC users. Compared with the continuing anticoagulant group, the discontinuing anticoagulant with HPB group (guideline recommendation) had a higher PPB rate (10.8% vs 19.6%, P = 0.087). These findings were significantly evident in warfarin but not DOAC users. One thrombotic event occurred in the discontinuing anticoagulant with HPB group and the discontinuing anticoagulant without HPB group; none occurred in the continuing anticoagulant group. PPB risk was similar between patients taking warfarin and DOAC. Thromboembolism was observed in warfarin users only. The guideline recommendations for HPB should be re-considered.

  1. Risk of gastrointestinal bleeding with direct oral anticoagulants: a systematic review and network meta-analysis.

    PubMed

    Burr, Nick; Lummis, Katie; Sood, Ruchit; Kane, John Samuel; Corp, Aaron; Subramanian, Venkataraman

    2017-02-01

    Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin. For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs). We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47-1·08]; warfarin vs dabigatran 0·88 [0·59-1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42-2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20-1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07-0.76]) or dabigatran (0.24 [0.07-0.77]). Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with

  2. Oral anticoagulant dosing, administration, and storage: a cross-sectional survey of Canadian health care providers.

    PubMed

    Piran, Siavash; Schulman, Sam; Panju, Mohamed; Pai, Menaka

    2018-01-01

    Direct oral anticoagulant (DOAC) use is increasing worldwide. However, if not taken or prescribed correctly, DOACs have serious side effects. It is crucial that healthcare providers (HCPs) offer patients accurate information and counselling around DOACs, to optimize safe and effective use. To assess knowledge around oral anticoagulant indication, dosing, storage, and administration, an electronic survey was distributed to HCPs across Canada from June to August 2017, with 18 questions on the practical use of oral anticoagulants. A total of 191 responses were received: 100 from nurse practitioners, 42 from pharmacists, 27 from Hematologists, 5 from Thrombosis specialists, 4 from internists, 9 from residents and fellows, and 2 each from family physicians and registered nurses. Only 51 (26.7%) of the respondents correctly identified all the approved indications for warfarin and 4 DOACs. Only 101 (52.9%) correctly identified that DOACs are not approved for treatment of heparin-induced thrombocytopenia, cerebral sinus venous thrombosis, or mechanical prosthetic valves. 112 (58.6%) felt comfortable or very comfortable prescribing oral anticoagulants. Half of the respondents knew that dabigatran should not be crushed, however only 85 (44.5%) knew that it should not be exposed to moisture. 94 (49%) knew that higher dose rivaroxaban should be taken with food. The results of our study demonstrate that there are important knowledge gaps around HCPs' practical understanding of oral anticoagulants. Future research should focus on educational interventions to improve HCPs' knowledge around indications, dosing, storage, and administration, with the goal of enhancing patient safety.

  3. Novel oral anticoagulants for stroke prevention in patients with atrial fibrillation: dawn of a new era.

    PubMed

    Contractor, Tahmeed; Levin, Vadim; Martinez, Matthew W; Marchlinski, Francis E

    2013-01-01

    Atrial fibrillation (AF) is an important cause of ischemic stroke and is the underlying cause of > 20% of all strokes, with increasing age being a risk factor. Until recently, warfarin was the only available oral anticoagulant used to decrease this risk in patients with AF. However, there are several disadvantages of warfarin use, such as the requirement for monitoring the international normalized ratio, its wide range of drug-food interactions, and its narrow therapeutic index. Thus, there has been a strong impetus for the development of newer oral anticoagulants with predictable pharmacokinetics that obviate the need for monitoring the international normalized ratio. The US Food and Drug Administration has approved a direct thrombin inhibitor (dabigatran) and 2 factor Xa inhibitors (rivaroxaban and apixaban) for stroke prevention in patients with nonvalvular AF. There are several other new oral anticoagulant agents on the horizon, including the factor Xa inhibitor edoxaban. This review article discusses the pharmacological properties, clinical trial data, and practical issues associated with the use of these novel oral anticoagulants.

  4. Oral Anticoagulation in Patients With Liver Disease.

    PubMed

    Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

    2018-05-15

    Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Effects of novel oral anticoagulants on left atrial and left atrial appendage thrombi: an appraisal.

    PubMed

    Marsico, Fabio; Cecere, Milena; Parente, Antonio; Paolillo, Stefania; de Martino, Fabiana; Dellegrottaglie, Santo; Trimarco, Bruno; Perrone Filardi, Pasquale

    2017-02-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and predisposes to an increased risk of thromboembolic events. Patients affected by AF exhibit an increased risk of stroke compared with those in sinus rhythm, with the most common location of thrombi in the left atrial appendage. Until 2009, warfarin and other vitamin K antagonists were the only class of oral anticoagulants available. More recently, dabigatran, rivaroxaban, apixaban, and edoxaban have been approved by regulatory authorities for prevention of stroke in patients with non-valvular AF. Few data are available about the efficacy of novel oral anticoagulants for the treatment of left atrial and left atrial appendage thrombosis. Aim of this review is to summarize available evidence regarding the effectiveness of novel oral anticoagulants on left atrial appendage thrombosis.

  6. Anterior mediastinal haematoma and left haemothorax on well-controlled oral anticoagulant therapy.

    PubMed Central

    Abaskaron, M.; Peterson, G.; Huang, T. Y.

    1983-01-01

    An anterior mediastinal haematoma and left haemothorax developed in a hypertensive diabetic patient on oral anticoagulant therapy. This occurred in spite of well-controlled anticoagulation and the absence of other evidence of systemic bleeding. Angiography and daily chest X-ray follow-up were not only sufficient to confirm the diagnosis, but also avoided hazardous interventional procedures. Images Fig. 1a Fig. 1b PMID:6844193

  7. Cross-cultural Adaptation of the Oral Anticoagulation Knowledge Test to the Brazilian Portuguese.

    PubMed

    Praxedes, Marcus Fernando da Silva; Abreu, Mauro Henrique Nogueira Guimarães; Ribeiro, Daniel Dias; Marcolino, Milena Soriano; Paiva, Saul Martins de; Martins, Maria Auxiliadora Parreiras

    2017-05-01

    Patients' knowledge about oral anticoagulant therapy may favor the achievement of therapeutic results and the prevention of adverse pharmacotherapy-related events. Brazil lacks validated instruments for assessing the patient's knowledge about treatment with warfarin. This study aimed to perform the cross-cultural adaptation of the Oral Anticoagulation Knowledge (OAK) Test instrument from English into Portuguese. This is a methodological study developed in an anticoagulation clinic of a public university hospital. The study included initial translation, synthesis of translations, back-translation, review by the experts committee and pre-testing with 30 individuals. We obtained semantic equivalence through the analysis of the referential and general meaning of each item. The conceptual equivalence of the items sought to demonstrate the relevance and acceptability of the instrument. The process of cross-cultural adaptation produced the final version of the OAK Test in Brazilian Portuguese entitled "Teste de Conhecimento sobre Anticoagulação Oral". There was a suitable semantic and conceptual equivalence between the adapted version and the original version, as well as an excellent acceptability of this instrument.

  8. Impact of prestroke selective serotonin reuptake inhibitor treatment on stroke severity and mortality.

    PubMed

    Mortensen, Janne Kaergaard; Larsson, Heidi; Johnsen, Søren Paaske; Andersen, Grethe

    2014-07-01

    Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of bleeding but also a possible neuroprotective effect in stroke. We aimed to examine the implications of prestroke SSRI use in hemorrhagic and ischemic stroke. We conducted a registry-based propensity score-matched follow-up study among first-ever patients with hemorrhage and ischemic stroke in Denmark (2003-2012). Multiple conditional logistic regression was used to compute adjusted odds ratios of severe stroke and death within 30 days. Among 1252 hemorrhagic strokes (626 prestroke SSRI users and 626 propensity score-matched nonusers), prestroke SSRI use was associated with an increased risk of the strokes being severe (adjusted propensity score-matched odds ratios, 1.41; confidence interval, 1.08-1.84) and an increased risk of death within 30 days (adjusted propensity score-matched odds ratios, 1.60; confidence interval, 1.17-2.18). Among 8956 patients with ischemic stroke (4478 prestroke SSRI users and 4478 propensity score-matched nonusers), prestroke SSRI use was not associated with the risk of severe stroke or death within 30 days. Prestroke SSRI use is associated with increased stroke severity and mortality in patients with hemorrhagic stroke. Although prestroke depression in itself may increase stroke severity and mortality, this was not found in SSRI users with ischemic stroke. © 2014 American Heart Association, Inc.

  9. Adherence to Guidelines for Oral Anticoagulation after Venous Thrombosis and Pulmonary Embolism

    PubMed Central

    Ganz, David A; Glynn, Robert J; Mogun, Helen; Knight, Eric L; Bohn, Rhonda L; Avorn, Jerry

    2000-01-01

    OBJECTIVE Guidelines for oral anticoagulation after deep venous thrombosis (DVT) or pulmonary embolism (PE) have recommended that patients be anticoagulated for at least 3 months after hospital discharge. We sought to determine whether this recommendation was being followed and what patient characteristics predict a shorter than recommended duration of therapy. DESIGN Retrospective cohort study using linked health care claims data. SETTING Routine clinical practice. PATIENTS Five hundred seventy-three members of New Jersey's Medicaid or Pharmacy Assistance for the Aged and Disabled programs aged 65 years and older who were hospitalized for DVT or PE between January 1, 1991 and June 30, 1994. RESULTS Of the 573 patients, 129 (23%) filled prescriptions covering less than 90 days of oral anticoagulant therapy. In multivariate models, African-American race was associated with an increased risk of a shorter than recommended duration of therapy (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.14 to 3.08), but age and gender were not. Patients who used anticoagulants in the year prior to admission were less likely to have a short duration of therapy (OR, 0.30; 95% CI, 0.12 to 0.78), than were patients with PE (OR, 0.58; 95% CI, 0.38 to 0.88). CONCLUSIONS Nearly a quarter of those anticoagulated following DVT or PE received therapy for less than the recommended length of time after hospital discharge, with African Americans more likely to have a shorter than recommended course of treatment. Further research is needed to evaluate the causes of shorter than recommended duration of therapy and racial disparities in anticoagulant use. PMID:11119169

  10. Evaluation of Oral Anticoagulant-Associated Intracranial Parenchymal Hematomas Using CT Findings.

    PubMed

    Gökçe, E; Beyhan, M; Acu, B

    2015-06-01

    Intracranial hemorrhage (ICH) is one of the most serious and lethal complications of anticoagulants with a reported incidence of 5-18.5 %. Computed tomographic (CT) findings, should be carefully studied because early diagnosis and treatment of oral anticoagulant use-associated hematomas are vitally important. In the present study, CT findings of intraparenchymal hematomas associated with anticoagulant and antihypertensive use are presented. This study included 45 patients (25 men, 20 women) under anticoagulant (21 patients) or antihypertensive (24 patients) treatment who had brain CT examinations due to complaints and findings suggesting cerebrovascular disease during July 2010-October 2013 period. CT examinations were performed to determine hematoma volumes and presence of swirl sign, hematocrit effect, mid-line shift effect, and intraventricular extension. The patients were 40-89 years of age. In four cases, a total of 51 intraparenchymal hematomas (42 cerebral, 7 cerebellar and 2 brain stem) were detected in multiple foci. Hematoma volumes varied from 0.09 to 284.00 ml. Swirl sign was observed in 87.5 and 63.0 % of OAC-associated ICHs and non-OAC-associated ICHs, respectively. In addition, hematocrit effect was observed in 41.6 % of OAC-associated and in 3.7 % of non-OAC-associated ICHs. Volume increases were observed in all 19 hematomas where swirl sign was detected, and follow-up CT scanning was conducted. Mortality of OAC-associated ICHs was correlated with initial volumes of hematoma, mid-line shift amount, and intraventricular extension. Detection of hematocrit effect by CT scanning of intracranial hematomas should be cautionary in oral anticoagulant use, while detection of swirl sign should be suggestive of active hemorrhage.

  11. The Reversal of Direct Oral Anticoagulants in Animal Models

    PubMed Central

    Honickel, Markus; Akman, Necib; Grottke, Oliver

    2017-01-01

    ABSTRACT Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. The optimal strategy for DOAC reversal is being refined, and may include use of hemostatic agents such as prothrombin complex concentrates (PCCs; a source of concentrated clotting factors), or DOAC-specific antidotes (which bind their target DOAC to abrogate its activity). Though promising, most specific antidotes are still in development. Preclinical animal research is the key to establishing the efficacy and safety of potential reversal agents. Here, we summarize published preclinical animal studies on reversal of DOAC anticoagulation. These studies (n = 26) were identified via a PubMed search, and used rodent, rabbit, pig, and non-human primate models. The larger of these animals have the advantages of similar blood volume/hemodynamics to humans, and can be used to model polytrauma. We find that in addition to varied species being used, there is variability in the models and assays used between studies; we suggest that blood loss (bleeding volume) is the most clinically relevant measure of DOAC anticoagulation-related bleeding and its reversal. The studies covered indicate that both PCCs and specific reversal agents have the potential to be used as part of a clinical strategy for DOAC reversal. For the future, we advocate the development and use of standardized, clinically, and pharmacologically relevant animal models to study novel DOAC reversal strategies. PMID:28471371

  12. The future prospects of pharmacogenetics in oral anticoagulation therapy

    PubMed Central

    Kamali, Farhad; Pirmohamed, Munir

    2006-01-01

    Coumarins are the mainstay of oral anticoagulation for the treatment and prophylaxis of thromboembolic disorders. They have a narrow therapeutic index and regular monitoring is therefore required to avoid serious adverse effects. There is wide interindividual variability in dosage requirements, which makes anticoagulation response unpredictable. Current dosing titrations are haphazard and inconvenient and poor initial control leads to morbidity, and occasional mortality, because of bleeding and further thromboembolism. Recent discoveries have helped to characterize the factors that contribute to the interindividual variability in responses to coumarins. Patient and environmental factors that affect anticoagulation response to coumarins include age, body size, dietary vitamin K status, concurrent disease and drug interactions. More recently, single nucleotide polymorphisms in the 2C9 isoform of cytochrome P450 (CYP2C9) and vitamin K epoxide reductase (VKOR) have been shown to make significant contributions to the variability in coumarin dosage requirements. Polymorphisms in other genes that mediate the actions of coumarins may also contribute to this variability. Racial and cultural differences influence dosage requirements, which can be explained, at least in part, by genetic and dietary factors. Incorporation of genetic and environmental factors could help in the prediction of more individualized loading and maintenance doses for safer anticoagulation therapy. PMID:16722840

  13. Risk of stroke and oral anticoagulant use in atrial fibrillation: a cross-sectional survey

    PubMed Central

    Holt, Tim A; Hunter, Tina D; Gunnarsson, Candace; Khan, Nada; Cload, Paul; Lip, Gregory YH

    2012-01-01

    Background Oral anticoagulants substantially reduce the risk of stroke in atrial fibrillation but are underutilised in current practice. Aim To measure the distribution of stroke risk in patients with atrial fibrillation (using the CHADS2 and CHA2DS2-VASc scores) and changes in oral anticoagulant use during 2007–2010. Design and setting Longitudinal series of cross-sectional survey in 583 UK practices linked to the QResearch® database providing 99 351 anonymised electronic records from people with atrial fibrillation. Method The proportion of patients in each CHADS2 and CHA2DS2-VASc risk band in 2010 was calculated; for each of the years 2007–2010, the proportions with risk scores ≥2 that were using anticoagulants or antiplatelet agents were estimated. The proportions identified at high risk were re-estimated using alternative definitions of hypertension based on coded data. Finally, the prevalence of comorbid conditions in treated and untreated high-risk (CHADS2 ≥2) groups was derived. Results The proportion at high risk of stroke in 2010 was 56.9% according to the CHADS2 ≥2 threshold, and 84.5% according to CHA2DS2-VASc ≥2 threshold. The proportions of these groups receiving anticoagulants were 53.0% and 50.7% respectively and increased during 2007–2010. The means of identifying the population of individuals with hypertension significantly influenced the estimated proportion at high risk. Comorbid conditions associated with avoidance of anticoagulants included history of falls, use of nonsteroidal anti-inflammatory drugs, and dementia. Conclusion Oral anticoagulant use in atrial fibrillation has increased in UK practice since 2007, but remains suboptimal. Improved coding of hypertension is required to support systematic identification of individuals at high risk of stroke and could be assisted by practice-based software. PMID:23265231

  14. Target specific oral anticoagulants in the management of thromboembolic disease in the elderly.

    PubMed

    Maddula, Surekha; Ansell, Jack

    2013-08-01

    The elderly population represents a population at highest risk of thromboembolism, but also the most vulnerable to hemorrhage. In the community setting there is a general tendency to under- treat this patient group. Specific consideration must be taken with elderly patients because they have reduced renal function, co-morbidities and risk of falls, altered pharmacodynamics, and challenges with adherence. Vitamin K antagonists, most often warfarin, have been the first line choice of therapy for long-term anticoagulation and enjoyed an unopposed position in the market for the last 70 years. Recently several new oral anticoagulants have been developed and found to be equally effective as warfarin in phase III studies and may provide an optimal treatment option in the elderly population. In this review we explore the target-specific oral anticoagulants and the pharmacological differences between them with a focus on the elderly population in whom these new drugs would constitute a possible alternative to warfarin therapy.

  15. Role of Pharmacogenomics in the Management of Traditional and Novel Oral Anticoagulants

    PubMed Central

    Cavallari, Larisa H.; Shin, Jaekyu; Perera, Minoli A.

    2013-01-01

    Warfarin is the most commonly prescribed oral anticoagulant. However, it remains a difficult drug to manage mostly because of its narrow therapeutic index and wide interpatient variability in anticoagulant effects. Over the past decade, there has been substantial progress in our understanding of genetic contributions to variable warfarin response, particularly with regard to warfarin dose requirements. The genes encoding for cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are the major genetic determinants of warfarin pharmacokinetics and pharmacodynamics, respectively. Numerous studies have demonstrated significant contributions of these genes to warfarin dose requirements. The CYP2C9 gene has also been associated with bleeding risk with warfarin. The CYP4F2 gene influences vitamin K availability and makes minor contributions to warfarin dose requirements. Less is known about genes influencing warfarin response in African-American patients compared with other racial groups, but this is the focus of ongoing research. Several warfarin pharmacogenetic dosing algorithms and United States Food and Drug Administration–cleared genotyping tests are available for clinical use. Clinical trials are ongoing to determine the clinical utility and cost-effectiveness of genotype-guided warfarin dosing. Results from these trials will likely influence clinical uptake and third party payer reimbursement for genotype-guided warfarin therapy. There is still a lack of pharmacogenetic data for the newly approved oral anticoagulants, dabigatran and rivaroxaban, and with other oral anticoagulants in the research and development pipeline. These data, once known, could be of great importance as routine monitoring parameters for these agents are not available. PMID:22122181

  16. Switching, Adverse Effects and Use of Over-the-Counter Analgesics among Users of Oral Anticoagulants: A Pharmacy-based Survey.

    PubMed

    Hellfritzsch, Maja; Hyllested, Lea Maria Rønneberg; Meegaard, Line; Wiberg-Hansen, Alexander; Grove, Erik Lerkevang; Pottegård, Anton

    2017-07-01

    Oral anticoagulants are widely used but information on important aspects in that respect is not available from medical registers or clinical databases. Therefore, we conducted a survey including patients filling a prescription for oral anticoagulants at two large Danish community pharmacies. We collected information concerning the patients' knowledge of their anticoagulant treatment including prior drug switching. Further, patients were asked about use of over-the-counter analgesics, adverse effects and how the treatment affected their everyday life. Among 335 eligible patients, 301 (90%) agreed to participate. Atrial fibrillation was the most common indication (65%), and most patients filled a prescription for a non-vitamin K antagonist oral anticoagulant (NOAC) (58%). Among the 12% (n = 35) of participants who had switched oral anticoagulant treatment, 69% had switched from a vitamin K antagonist (VKA) to a NOAC. Switching was most frequently caused by inconvenience (34%) and adverse effects (23%). Although half of all patients had recently bought over-the-counter analgesics, purchase of ibuprofen and aspirin was rare (6%). More VKA users than NOAC users felt limited in their everyday life because of anticoagulant treatment (18% versus 9%). Among non-incident NOAC users, 21% had experienced adverse effects during their current treatment. Based on first-hand information from a large sample of anticoagulant users, we conclude that the main drug-related issues leading to anticoagulant switching and perceived limitations in everyday life were inconvenience and adverse effects. This varied between drug groups. Further, use of NSAIDs obtained over the counter was rare. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  17. Atrial Fibrillation, Type 2 Diabetes, and Non-Vitamin K Antagonist Oral Anticoagulants: A Review.

    PubMed

    Plitt, Anna; McGuire, Darren K; Giugliano, Robert P

    2017-04-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a 5-fold increase in the risk for stroke. Type 2 diabetes is an independent risk factor for both stroke and atrial fibrillation, and in the setting of AF, type 2 diabetes is independently associated with a 2% to 3.5% increase in absolute stroke rate per year. The overlap in the pathophysiologies of AF and type 2 diabetes are not well understood, and current practice guidelines provide few recommendations regarding patients with both conditions. In this article, we review the epidemiology and pathophysiology of the nexus of AF and type 2 diabetes. Furthermore, we analyze the subgroup of patients with type 2 diabetes enrolled in phase 3 clinical trials of non-vitamin K antagonist oral anticoagulants in prevention of arterial thromboembolism in AF, highlighting the greater absolute benefit of non-vitamin K oral anticoagulants in patients with type 2 diabetes. Finally, we offer recommendations on risk stratification and therapy for patients with concomitant AF and type 2 diabetes. We highlight the increased thromboembolic risk with coexisting AF and type 2 diabetes. We recommend that further studies be done to evaluate the potential benefits of anticoagulation for all patients who have both and the potential for non-vitamin K oral anticoagulants to have greater benefits than risks over vitamin K antagonists.

  18. Assessment of psychometric properties of the Brazilian version of the oral anticoagulation knowledge test.

    PubMed

    Praxedes, Marcus Fernando da Silva; de Abreu, Mauro Henrique Nogueira Guimarães; Paiva, Saul Martins; Mambrini, Juliana Vaz de Melo; Marcolino, Milena Soriano; Martins, Maria Auxiliadora Parreiras

    2016-06-24

    The aim of this study was to evaluate the psychometric properties of the Brazilian version of the Oral Anticoagulation Knowledge (OAK) Test. This study, conducted in an anticoagulation clinic, included 201 Brazilian participants aged over 18 years, who had been using warfarin for more than two months. The reliability of the instrument was evaluated by assessing internal consistency (Kuder-Richardson coefficient) and reproducibility (test-retest reliability). The validity was evaluated by hypothesizing that there would be a positive correlation of moderate to strong intensity between the correctness levels of the OAK Test and time within therapeutic range (TTR) values, which is a measure used to evaluate the quality of oral anticoagulation. The instrument exhibited good psychometric properties. The total a Kuder-Richardson coefficient value was 0.818 and intraclass correlation coefficient was 0.967. The validity revealed a strong positive correlation between the values of the level of knowledge, as measured by the OAK Test and the TTR values (rs = 0.780). The instrument proved to be a reliable and valid tool for evaluating the knowledge of Brazilian patients on oral anticoagulation therapy with warfarin. This instrument may be incorporated into the practice of health care for substantiating the structuring of educational activities to ensure the improvement of knowledge about the use of warfarin, thereby increasing the effectiveness and safety of treatment.

  19. [Prevention and treatment of venous thromboembolism: the place of new oral anticoagulants].

    PubMed

    Reis, Abílio

    2012-04-01

    Venous thromboembolism (VTE) is still an important problem of Public Health, due to its impact in terms of morbidity, mortality, resource allocation and associated costs. In the prevention and treatment of VTE, pharmacological therapy is well defined and efficacious but has some inconveniences that leave space for improvement. Several new oral anticoagulants are being developed and tested for the prevention and treatment of VTE. The better studied are the selective Factor Xa inhibitors apixaban, rivaroxaban and edoxaban, and the thrombin antagonist dabigatran. They all are orally administrated, don't have important interactions with food or other drugs, have a convenient fixed-dose regimen and a predictable action, and dispense routine monitoring of their anticoagulant effect. The major part of them has phase III studies concluded and published. Some of them are already approved by de European Medicines Agency (EMA) and the Food and Drug Administration (FDA) and recommended by the international guidelines. Rivaroxaban is approved by the EMA for the treatment of deep venous thrombosis (DVT) and for the prevention of recurrences of DVT and pulmonary embolism. In this article the available evidences are reviewed, the place of the new oral anticoagulants is discussed and future perspectives regarding the prevention and treatment of VTE are outlined. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  20. Risk of long-term anticoagulation under sustained severe arterial hypertension: A translational study comparing warfarin and the new oral anticoagulant apixaban

    PubMed Central

    Pfeilschifter, Waltraud; Steinstraesser, Thurid; Paulus, Patrick; Zeiner, Pia Susan; Bohmann, Ferdinand; Theisen, Alf; Lindhoff-Last, Edelgard; Penski, Cornelia; Wagner, Marlies; Mittelbronn, Michel

    2016-01-01

    New oral anticoagulants for the prevention of stroke and systemic embolism in patients with atrial fibrillation have recently been introduced. In this translational study, we explored the risk of long-term anticoagulation on intracerebral hemorrhage under sustained severe arterial hypertension. We initiated anticoagulation with warfarin or apixaban in spontaneously hypertensive rats prone to develop severe hypertension and subsequent intracerebral bleeding complications. A non-anticoagulated group served as control. During an 11-week-study period, blood pressure, anticoagulation parameters, and clinical status were determined regularly. The incidence of histopathologically proven intracerebral hemorrhage was defined as the primary endpoint. Both warfarin and apixaban anticoagulation was fairly stable during the study period, and all rats developed severe hypertension. Intracerebral hemorrhage was determined in 29% (4/14) of warfarin rats and in 10% (1/10) of apixaban rats. Controls did not show cerebral bleeding complications (chi-square not significant). Mortality rate at study termination was 33% (2/6) in controls, 43% (6/14) in the warfarin group, and 60% (6/10) in the apixaban group. Animals died from extracerebral complications in most cases. Our study describes an experimental intracerebral hemorrhage model in the context of sustained hypertension and long-term anticoagulation. Extracerebral bleeding complications occurred more often in warfarin-treated animals compared with apixaban and control rats. PMID:27189904

  1. Stroke prevention with oral anticoagulation in older people with atrial fibrillation - a pragmatic approach.

    PubMed

    Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

    2012-08-01

    With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians' fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients' views.

  2. Stroke Prevention with Oral Anticoagulation in Older People with Atrial Fibrillation - A Pragmatic Approach

    PubMed Central

    Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

    2012-01-01

    With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians’ fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients’ views. PMID:23185715

  3. Managing direct oral anticoagulants in patients undergoing dentoalveolar surgery.

    PubMed

    Patel, J P; Woolcombe, S A; Patel, R K; Obisesan, O; Roberts, L N; Bryant, C; Arya, R

    2017-02-24

    Our objective was to describe our experience of managing a cohort of adult patients prescribed direct oral anticoagulants (DOACs) undergoing dentoalveolar procedures between November 2012 and May 2016. Prior to conducting a procedure a formal assessment was made of each patient's anticoagulation treatment. A specific plan was then formulated, balancing the risk of bleeding with the risk of thrombosis. Patients received a telephone consultation one week following treatment to assess any post-operative bleeding. Eighty-two patients underwent 111 oral surgical procedures, the majority of which were dental extractions. In the case of 35 (32%) procedures, advice was given to omit the DOAC, either before or after treatment. There was no bleeding following the majority of procedures. Persistent bleeding followed 15 (13.5%) procedures, of which 7 (6.3%) procedures required specific intervention. The majority of patients prescribed DOACs can undergo dentoalveolar procedures safely. Important considerations when planning treatment are: (i) when the patient usually takes their dose of DOAC, (ii) the time the procedure is performed and, (iii) when the DOAC is taken post-procedure. In our experience, if these factors are considered carefully, omission of DOAC doses is unlikely to be required for most patients.

  4. Dental Procedures in Patients with Atrial Fibrillation and New Oral Anticoagulants

    PubMed Central

    2014-01-01

    This review discusses the basic pharmacology of new oral anticoagulants that are used for prevention of thromboembolism in patients with atrial fibrillation. It presents available evidence, and provides recommendations for the management of patients requiring invasive procedures in dental practice. PMID:26835072

  5. Sex and Gender Differences in Thromboprophylactic Treatment of Patients With Atrial Fibrillation After the Introduction of Non-Vitamin K Oral Anticoagulants.

    PubMed

    Loikas, Desirée; Forslund, Tomas; Wettermark, Björn; Schenck-Gustafsson, Karin; Hjemdahl, Paul; von Euler, Mia

    2017-10-15

    To examine sex differences in thromboprophylaxis in patients with atrial fibrillation before and after the introduction of non-vitamin K oral anticoagulants, we performed a cross-sectional registry study based on anonymized individual-level patient data of all individuals with a diagnosis of nonvalvular atrial fibrillation (International Classification of Diseases, Tenth Revision code I48) in the region of Stockholm, Sweden (2.2 million inhabitants), in 2011 and 2015, respectively. Thromboprophylaxis improved considerably during the period. During 2007 to 2011, 23,198 men and 18,504 women had an atrial fibrillation diagnosis. In 2011, more men than women (53% men vs 48% women) received oral anticoagulants (almost exclusively warfarin) and more women received aspirin only (35% women vs 30% men), whereas there was no sex difference for no thromboprophylaxis (17%). During 2011 to 2015, 27,237 men and 20,461 women had a diagnosis of atrial fibrillation. Compared with the earlier time period, a higher proportion used oral anticoagulants (71% women vs 70% men), but fewer women ≥80 years received anticoagulants (67% women vs 72% men), more women received aspirin (15% women vs 13% men), and fewer women had no thromboprophylaxis (15% women vs 17% men). Patients with co-morbidities potentially complicating oral anticoagulant use used more oral anticoagulant in 2015 compared with 2011. The sex differences observed in 2011 with fewer women using oral anticoagulants had disappeared in 2015 except in women 80 years and older and in patients with complicated co-morbidity. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Percutaneous left atrial appendage occlusion in atrial fibrillation patients with a contraindication to oral anticoagulation: a focused review.

    PubMed

    Nishimura, Marin; Sab, Shiv; Reeves, Ryan R; Hsu, Jonathan C

    2017-12-08

    Stroke is the most feared complication of atrial fibrillation (AF). Although oral anticoagulation with non-vitamin K antagonist and non-vitamin K antagonist oral anticoagulants (NOACs) have been established to significantly reduce risk of stroke, real-world use of these agents are often suboptimal due to concerns for adverse events including bleeding from both patients and clinicians. Particularly in patients with previous serious bleeding, oral anticoagulation may be contraindicated. Left atrial appendage occlusion (LAAO), mechanically targeting the source of most of the thrombi in AF, holds an immense potential as an alternative to OAC in management of stroke prophylaxis. In this focused review, we describe the available evidence of various LAAO devices, detailing data regarding their use in patients with a contraindication for oral anticoagulation. Although some questions of safety and appropriate use of these new devices in patients who cannot tolerate anticoagulation remain, LAAO devices offer a significant step forward in the management of patients with AF, including those patients who may not be able to be prescribed OAC at all. Future studies involving patients fully contraindicated to OAC are warranted in the era of LAAO devices for stroke risk reduction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  7. [Anticoagulation in polypathological patients with atrial fibrillation].

    PubMed

    Díez-Manglano, Jesús; Bernabeu-Wittel, Máximo; Barón-Franco, Bosco; Murcia-Zaragoza, José; Fuertes Martín, Aurelio; Alemán, Antonio; Ollero-Baturone, Manuel

    2013-02-02

    To determine the use of oral anticoagulants in polypathological patients with atrial fibrillation and its influence on mortality and loss of functionality. Patients with polypathological patient criteria and atrial fibrillation were included in an observational, prospective and multicenter study. Data on demographic, clinical, functional and sociofamilial characteristics, CHADS2 score, levels of hemoglobin, albumin and creatinine, use of oral anticoagulants and survival and functional status at one year were collected. Five hundred and thirty-two (32.6%) of 1,632 polypathological patients had atrial fibrillation. The stroke risk was high in 505 (94.9%), moderate in 24 (4.5%) and low in 3 (0.6%) patients. Oral anticoagulants were used in 61% of patients with CHADS2 score≥2 and in 37.5% with CHADS2 score=1. Oral anticoagulants were less used in older patients, with more functional and cognitive impairment. Heart failure was associated with more use of oral anticoagulants. There was no difference by the presence of hypertension, diabetes, anemia, renal insufficiency or stroke. In multivariate analysis the use of oral anticoagulants was independently associated with lower age, lower cognitive impairment, absence of hepatic disease and with higher stroke risk. The prescription of oral anticoagulants was independently associated with more survival at one year with no influence on functional status. Oral anticoagulants are underused in polypathological patients with atrial fibrillation despite being associated with more survival. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  8. Cost-Effectiveness of Oral Anticoagulants for Ischemic Stroke Prophylaxis Among Nonvalvular Atrial Fibrillation Patients.

    PubMed

    Shah, Anuj; Shewale, Anand; Hayes, Corey J; Martin, Bradley C

    2016-06-01

    The objective of the study is to compare the cost-effectiveness of oral anticoagulants among atrial fibrillation patients at an increased stroke risk. A Markov model was constructed to project the lifetime costs and quality-adjusted survival (QALYs) of oral anticoagulants using a private payer's perspective. The distribution of stroke risk (CHADS2 score: congestive heart failure, hypertension, advanced age, diabetes mellitus, stroke) and age of the modeled population was derived from a cohort of commercially insured patients with new-onset atrial fibrillation. Probabilities of treatment specific events were derived from published clinical trials. Event and downstream costs were determined from the cost of illness studies. Drug costs were obtained from 2015 National Average Drug Acquisition Cost data. In the base case analysis, warfarin was the least costly ($46 241; 95% CI, 44 499-47 874) and apixaban had the highest QALYs (9.38; 95% CI, 9.24-9.48 QALYs). Apixaban was found to be a cost-effective strategy over warfarin (incremental cost-effectiveness ratio=$25 816) and dominated other anticoagulants. Probabilistic sensitivity analysis showed that apixaban had at least a 61% chance of being the most cost-effective strategy at willingness to pay value of $100 000 per QALY. Among patients with CHADS2 ≥3, dabigatran was the dominant strategy. The model was sensitive to efficacy estimates of apixaban, dabigatran, and edoxaban and the cost of these drugs. All the newer oral anticoagulants compared were more effective than adjusted dosed warfarin. Our model showed that apixaban was the most effective anticoagulant in a general atrial fibrillation population and has an incremental cost-effectiveness ratio <$50 000/QALY. For those with higher stroke risk (CHADS2≥3), dabigatran was the most cost-effective treatment option. © 2016 American Heart Association, Inc.

  9. Gastrointestinal bleeding risk of non-vitamin K oral anticoagulants is similar to warfarin - a Japanese retrospective cohort study
.

    PubMed

    Shirai, Tsuguru; Yamamoto, Takatsugu; Kawasugi, Kazuo; Kuyama, Yasushi; Kita, Hiroto

    2016-11-01

    Although several non-vitamin K oral anticoagulants have been developed to prevent cardiogenic thrombosis, the status of hemorrhagic complications in the clinical setting among Asian populations, including Japan, remains unclear. We conducted this retrospective cohort study to clarify the current status of hemorrhagic events during antithrombotic therapy with non-vitamin K oral anticoagulants, with particular focus on gastrointestinal bleeding. Medical charts of 475 patients prescribed dabigatran, rivaroxaban, or apixaban between April 2011 and September 2014 were reviewed to examine whether any hemorrhagic events occurred, compared with 135 patients who received warfarin between April 2009 and March 2011. Incidences of total and actionable hemorrhage in patient taking non-vitamin K oral anticoagulants were 13.8% per year and 4.6% per year, respectively, showing no significant differences from those in warfarin users (9.3% per year and 5.0% per year, respectively). In addition, actionable gastrointestinal hemorrhage occurred at similar rates in non-vitamin K oral anticoagulants users (2.1% per year) and warfarin users (1.5% per year). Most hemorrhages were from the lower gastrointestinal tract, and considerable events involved perianal bleeding. Multiple regression analysis showed that age, concomitant dual antiplatelet therapy, and concomitant nonsteroidal anti-inflammatory drug therapy were significant factors related to actionable gastrointestinal bleeding. Risk of gastrointestinal hemorrhage in patients taking non-vitamin K oral anticoagulants was similar to that in patients taking warfarin. The dominant bleeding site was the lower gastrointestinal tract.
.

  10. Prescription frequency and predictors for the use of novel direct oral anticoagulants for secondary stroke prevention in the first year after their marketing in Europe--a multicentric evaluation.

    PubMed

    Luger, Sebastian; Hohmann, Carina; Kraft, Peter; Halmer, Ramona; Gunreben, Ignaz; Neumann-Haefelin, Tobias; Kleinschnitz, Christoph; Walter, Silke; Haripyan, Veronika; Steinmetz, Helmuth; Foerch, Christian; Pfeilschifter, Waltraud

    2014-07-01

    Direct oral anticoagulants (DOAC) are alternatives to the use of vitamin K antagonists (VKA) as oral anticoagulant therapies to prevent stroke in patients with atrial fibrillation. We assembled a representative secondary prevention cohort from four tertiary care stroke centers to identify factors that independently influence therapeutic decision making 1) not to anticoagulate with either VKA or DOAC and 2) to use DOAC if the patient appears suitable for oral anticoagulant therapy. We identified all patients discharged with the diagnoses 'ischemic stroke' (ICD-10 code I63) or 'transient ischemic attack' (G45) in combination with 'atrial fibrillation' (I48) during 1 year. We performed binary logistic regression analyses to identify factors independently influencing the aforementioned decisions. Our cohort comprised 758 patients. At discharge from the stroke service, 374 patients (49·3%) received oral anticoagulant therapy. Older age, severe stroke, poor recovery in the acute phase, and higher serum creatinine were independent factors to withhold oral anticoagulant therapy, whereas prior oral anticoagulant therapy favored the decision to anticoagulate. Among patients who were anticoagulated, prescription was balanced for VKA (50·3%) and DOAC (49·7%). Renal function and prior oral anticoagulant therapies were the most important factors in this decision. Shortly after their marketing, DOAC are used as frequently as VKA for secondary stroke prevention in patients with atrial fibrillation. The decision between VKA and DOAC is mainly determined by the patient's renal function and the absence or presence of prior oral anticoagulant therapy. © 2014 World Stroke Organization.

  11. Pharmacogenetics of novel oral anticoagulants: a review of identified gene variants & future perspectives.

    PubMed

    Ašić, Adna; Marjanović, Damir; Mirat, Jure; Primorac, Dragan

    2018-05-16

    Novel oral anticoagulants (NOACs) are becoming a therapy of choice in everyday clinical practice after almost 50 years during which warfarin and related coumarin derivatives were used as the main anticoagulants. Advantages of NOACs over standard anticoagulants include their predictable pharmacodynamics and pharmacokinetics, stable plasma concentrations and less drug-drug and food-drug interactions. However, pharmacogenetics has its place in administration of NOACs, as considerable interindividual variations have been detected. In this review, previous findings in pharmacogenetics of dabigatran, rivaroxaban, apixaban and edoxaban are summarized, along with recommendations for studying genes encoding metabolically important enzymes for four selected NOACs. Future directions include identification of clinically relevant SNPs, and change in optimum dosage for patients who are carriers of significant variants.

  12. Response to warfarin and other oral anticoagulants: effects of disease states.

    PubMed

    Demirkan, K; Stephens, M A; Newman, K P; Self, T H

    2000-05-01

    Warfarin is associated with numerous drug and food interactions, and much attention has been appropriately focused on this subject. Because several disease states may also affect response to oral anticoagulants, we present a summary of the literature. We searched MEDLINE for original articles on the effect of disease states on response to warfarin. Liver disease and thyroid dysfunction are well-documented as affecting warfarin response. Further study is needed to establish whether febrile illness, congestive heart failure, and other disease states enhance the effect of warfarin in some patients. Careful monitoring of anticoagulant therapy in patients with diseases that have the potential to affect warfarin response could increase safety and efficacy of this important agent.

  13. Effect of oral anticoagulants on the outcome of faecal immunochemical test

    PubMed Central

    Bujanda, L; Sarasqueta, C; Lanas, Á; Quintero, E; Cubiella, J; Hernandez, V; Morillas, J D; Perez-Fernández, T; Salas, D; Andreu, M; Carballo, F; Bessa, X; Portillo, I; Jover, R; Balaguer, F; Cosme, A; Castells, A

    2014-01-01

    Background: We aimed to evaluate whether oral anticoagulants (OACs) alter faecal immunochemical test (FIT) performance in average-risk colorectal cancer (CRC) screening. Methods: Individuals aged 50–69 years were invited to receive one FIT sample (cutoff 75 ng ml–1) between November 2008 and June 2011. Results: Faecal immunochemical test was positive in 9.3% (21 out of 224) of users of OAC and 6.2% (365 out of 5821) of non-users (P-trend=0.07). The positive predictive value (PPV) for advanced neoplasia (AN) in non-users was 50.4% vs 47.6% in users (odds ratio, 0.70; 95% CI, 0.3–1.8; P=0.5). The PPV for AN in OAC more antiplatelets (aspirin or clopidogrel) was 75% (odds ratio, 2; 95% CI, 0.4–10.8; P=0.4). Conclusions: Oral anticoagulant did not significantly modify the PPV for AN in this population-based colorectal screening program. The detection rate of advanced adenoma was higher in the combination OAC more antiplatelets. PMID:24496455

  14. A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer - A real world experience.

    PubMed

    Phelps, Megan K; Wiczer, Tracy E; Erdeljac, H Paige; Van Deusen, Kelsey R; Porter, Kyle; Philips, Gary; Wang, Tzu-Fei

    2018-01-01

    Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry "lower risk" features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.

  15. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

    PubMed

    Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Hoffman, Elaine B; Deenadayalu, Naveen; Ezekowitz, Michael D; Camm, A John; Weitz, Jeffrey I; Lewis, Basil S; Parkhomenko, Alexander; Yamashita, Takeshi; Antman, Elliott M

    2014-03-15

    Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the

  16. Optimizing the use of oral anticoagulant therapy for atrial fibrilation in primary care: a pharmacist-led intervention.

    PubMed

    Virdee, Mandeep S; Stewart, Derek

    2017-02-01

    Background Updated evidence-based guidelines for the management of atrial fibrillation (AF) necessitate patient review, particularly with respect to oral anticoagulants, to ensure maximum health gain around stroke prophylaxis. Objective To quantify the level of anticoagulation utilisation in patients with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female) according to evidence-based guidelines and to assess the impact of a pharmacist-led intervention to optimise therapy. Setting Fifteen general medical practices in Liverpool, North-West England with a practice population of 99,129. Method GRASP-AF software was employed to interrogate patient electronic medical records to identify and risk stratify AF patients (using CHA 2 DS 2 -VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female). Recommendations were discussed with a general practitioner (GP) and those patients in whom the need for anticoagulation was agreed were invited for a consultation with either the pharmacist or GP and therapy optimised where appropriate. The GPs were responsible for managing those patients referred for diagnosis confirmation or further specialist opinion. Main outcome measure Proportion of patients eligible/not eligible for anticoagulation; proportions in whom anticoagulants initiated, refused, antiplatelets discontinued. Results Five hundred and twenty-three patients (31% of patients identified with AF and a CHA 2 DS 2 -VASc ≥1/≥2 (male/female)) were not receiving an anticoagulant (26 subsequently died or left the practice leaving 497). Three hundred and eighty-two (77%) pharmacist recommendations to a GP were agreed without modification. Following outcomes of diagnostic investigations and specialist referrals, 202 (41%) patients were candidates for anticoagulation, 251 (51%) were not eligible for anticoagulation, 103 (21%) were anticoagulated (56 warfarin, 47 DOAC). Conclusion A pharmacist

  17. Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians

    PubMed Central

    Peacock, W. Frank; Rafique, Zubaid; Singer, Adam J.

    2016-01-01

    Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed. PMID:27293895

  18. Status of oral anticoagulant treatment in patients with nonvalvular atrial fibrillation in Spain. REACT-AF Study.

    PubMed

    de Andrés-Nogales, F; Oyagüez, I; Betegón-Nicolás, L; Canal-Fontcuberta, C; Soto-Álvarez, J

    2015-03-01

    Oral anticoagulant therapy is complex due to the need for control and the hemorrhagic risk the therapy entails. This study aims to determine the standard clinical practice in the treatment for preventing stroke in patients with nonvalvular atrial fibrillation (NVAF) in Spain. The Real Evidence of Anti Coagulation Treatment in AF is a European, multicenter, multinational, observational, retrospectively monitored cohort of patients with NVAF. This study included patients recruited in Spain with at least one visit during the period of inclusion (May 2010/April 2012). The study evaluated the following: a) persistence of oral anticoagulant treatment (time to discontinuation); b) persistence rate (% of patients in treatment) at 6, 12 and 24 months and at 5 years; c) therapeutic compliance (medication possession ratio); d) the correlation between the treatment followed and that recommended by the European Society of Cardiology; and the incidence of stroke and hemorrhagic events. The patients treated with oral anticoagulants (n=7,526) had a median time to discontinuation of treatment of 1.99 years and a persistence rate at 5 years of 26% (discontinuation ≥3 months). The compliance (mean MPR) was 0.54±0.36. The incidence of stroke was 0.3/100 person-years, and the incidence of hemorrhagic events was 2.4/100 person-years. Fifty-eight percent of the patients with NVAF (n=12,514) followed the recommendations of the European Society of Cardiology. Forty-two percent of the patients with NVAF did not follow the recommendations of the European Society of Cardiology. We detected low persistence and treatment compliance rates for oral anticoagulants. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  19. Practical considerations in emergency management of bleeding in the setting of target-specific oral anticoagulants.

    PubMed

    Miller, Michael P; Trujillo, Toby C; Nordenholz, Kristen E

    2014-04-01

    The recent arrival of the target-specific oral anticoagulants (TSOACs) offers potential advantages in the field of anticoagulation. However, there are no rapid and accurate and routinely available laboratory assays to evaluate their contribution to clinical bleeding. With the expanding clinical indications for the TSOACs, and the arrival of newer reversal agents on the market, the emergency clinician will need to be familiar with drug specifics as well as methods for anticoagulation reversal. This review offers a summary of the literature and some practical strategies for the approach to the patient taking TSOACs and the management of bleeding in these cases. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. New Target-Specific Oral Anticoagulants and Intracranial Bleeding: Management and Outcome in a Single-Center Case Series.

    PubMed

    Senger, Sebastian; Keiner, Dörthe; Hendrix, Philipp; Oertel, Joachim

    2016-04-01

    New target-specific anticoagulants such as the direct thrombin inhibitor dabigatran and the factor Xa inhibitor rivaroxaban are used in an increasing number of patients. Several studies comparing these new oral anticoagulants with vitamin K antagonists revealed a lower risk of severe bleeding complications and reduced thromboembolic events. However, the lack of antidotes is a challenging issue in the treatment of traumatic or spontaneous intracranial hemorrhage. A retrospective analysis of patients with intracranial bleeding under new oral anticoagulants was performed; these patients were admitted to our department between January 2011 and November 2014. Treatment, reversal management of blood coagulopathy, and outcome of the patients were analyzed. Seventeen patients were included. The median age was 80.4 years. Seven patients were treated with dabigatran and 10 with rivaroxaban. Eight patients had traumatic intracranial bleeding and 9 patients had spontaneous intracranial hemorrhage. Complex perioperative hematologic treatment followed. In 9 cases, the clinical outcome was devastating with severe neurologic deficits (n = 2), comatose status (n = 4), or death (n = 3). Patients with the indication for acute surgical treatment had a high risk for a critical clinical outcome. Only a few case reports have analyzed the clinical course and the outcome after intracranial bleeding under new target-specific oral anticoagulants. Here, one of the first larger series is presented. Because of the lack of reversibility of the anticoagulative effects and the overall risks with geriatric patients, surgical treatment should be delayed as long as possible and comorbidities have to be considered. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of warfarin anticoagulation control.

    PubMed

    Janzic, Andrej; Kos, Mitja

    2015-04-01

    Vitamin K antagonists, such as warfarin, are standard treatments for stroke prophylaxis in patients with atrial fibrillation. Patient outcomes depend on quality of warfarin management, which includes regular monitoring and dose adjustments. Recently, novel oral anticoagulants (NOACs) that do not require regular monitoring offer an alternative to warfarin. The aim of this study was to evaluate whether cost effectiveness of NOACs for stroke prevention in atrial fibrillation depends on the quality of warfarin control. We developed a Markov decision model to simulate warfarin treatment outcomes in relation to the quality of anticoagulation control, expressed as percentage of time in the therapeutic range (TTR). Standard treatment with adjusted-dose warfarin and improved anticoagulation control by genotype-guided dosing were compared with dabigatran, rivaroxaban, apixaban and edoxaban. The analysis was performed from the Slovenian healthcare payer perspective using 2014 costs. In the base case, the incremental cost-effectiveness ratio for apixaban, dabigatran and edoxaban was below the threshold of €25,000 per quality-adjusted life-years compared with adjusted-dose warfarin with a TTR of 60%. The probability that warfarin was a cost-effective option was around 1%. This percentage rises as the quality of anticoagulation control improves. At a TTR of 70%, warfarin was the preferred treatment in half the iterations. The cost effectiveness of NOACs for stroke prevention in patients with nonvalvular atrial fibrillation who are at increased risk for stroke is highly sensitive to warfarin anticoagulation control. NOACs are more likely to be cost-effective options in settings with poor warfarin management than in settings with better anticoagulation control, where they may not represent good value for money.

  2. Changes in oral anticoagulation for elective cardioversion: results from a European cardioversion registry

    PubMed Central

    Papp, Judit; Zima, Endre; Bover, Ramon; Karaliute, Rasa; Rossi, Andrea; Szymanski, Catherine; Troccoli, Rossella; Schneider, Jonas; Fagerland, Morten Wang; Camm, A John; Atar, Dan

    2017-01-01

    Abstract Aims In patients with atrial fibrillation (AF) pharmacological or electrical cardioversion may be performed to restore sinus rhythm. The procedure is associated with an increased risk of thromboembolic events, which can be significantly reduced by adequate anticoagulation (OAC). Our aim was to create a partly prospective, partly retrospective cardioversion registry, particularly focusing on OAC strategies in different European countries, and on emerging choice of OAC over time. Methods From September 2014 to October 2015, cardioversions due to AF performed in six European city hospitals in five European countries (Hungary: Budapest-1 and -2; Italy: Bari and Pisa; France: Amiens; Spain: Madrid; and Lithuania: Kaunas) were recorded in the registry. Results A total of 1101 patients (retrospective/prospective: 679/422, male/female: 742/359, mean age: 67.3 years ± 11.2) were registered. Most of the cardioversions were electrical (97%). Oral anticoagulants were administered in 87% of the patient, the usage of non-VKA oral anticoagulants (NOACs) vs Vitamin K antagonists (VKA) was 31.5% vs 68.5%, respectively. Seventy seven percent of the patients were given oral anticoagulants more than 3 weeks prior to the procedure, and 86% more than 4 weeks after the procedure. When using VKA, international normalized ratio (INR) at cardioversion was above 2.0 in 76% of the cases. A decline in VKA usage (P = 0.033) in elective cardioversion over approximately 1 year was observed. During the observation period, there was an increase in apixaban (P < 0.001), a slight increase in rivaroxaban (P = 0.028) and no changes in dabigatran (P = 0.34) usage for elective cardioversion. There were differences in use of OAC between the countries: Spain used most VKA (89%), while France used least VKA (39%, P < 0.001). Conclusion According to current AF guidelines, NOACs are adequate alternatives to VKA for thromboembolic prevention in AF patients undergoing elective

  3. Battle of oral anticoagulants in the field of atrial fibrillation scrutinized from a clinical practice (the real world) perspective

    PubMed Central

    2011-01-01

    Warfarin has a long history of benefit and has become the gold standard medication for the prevention of ischemic stroke in patients with atrial fibrillation. Nevertheless, it is far from perfect and there is no doubt that new drugs must be found to replace warfarin. The new oral anticoagulants that are on the market or awaiting approval or under research offer some benefits but not enough to replace warfarin until results of additional studies can show an adequate balance between effectiveness/safety and cost/benefit. There are several issues concerning the new oral anticoagulants. It is essential that the effect of any anticoagulant can be measured in plasma. But to date, there is no test to assess the effect or therapeutic range for the new oral anticoagulants. There is no antidote to neutralize the action of the new drugs in cases of bleeding or when acute surgical intervention is necessary. Dabigatran requires dose adjustment in patients with moderate renal impairment and is contraindicated in patients with severe renal failure. Rivaroxaban should be used with caution in patients with severe renal impairment. Apixaban excretion is also partly dependent on renal function, although the impact of renal insufficiency has not yet been determined. How anticoagulant bridging can be done before surgery has not yet been established. In conclusion, although thousands of patients have been treated in phase III studies, additional data are necessary before conclusions can be drawn on the potential for these new anticoagulant drugs to replace warfarin in patients with atrial fibrillation. PMID:21794130

  4. Impact of self-funding on patient experience of oral anticoagulation self-monitoring: a qualitative study

    PubMed Central

    Tompson, Alice; Heneghan, Carl; Sutton, Stephen; Fitzmaurice, David; Ward, Alison

    2016-01-01

    Objective To explore the impact self-funding has on patient experience of oral anticoagulation therapy self-monitoring. Design Semistructured, qualitative interviews were conducted. Transcripts were analysed thematically using constant comparison. Setting England. Participants Interviewees were participants of the Cohort Study of Anticoagulation Self-Monitoring (CASM). Cohort members were recruited as they bought a monitor from the major manufacturer in the UK. A purposive sample was invited to be interviewed on completion of the 12-month cohort follow-up. Data Patient narratives on their experiences of self-monitoring their oral anticoagulation therapy in non-trial conditions. Results 26 interviews were completed. Interviewees viewed purchasing the monitoring device as a long-term commitment balancing the limitations of clinic-based monitoring against the cost. They were unable to try out the monitor prior to purchase and therefore had to be confident in their own ability to use it. The variable provision of self-monitoring equipment caused resentment, and interviewees were uncomfortable negotiating with healthcare professionals. High test strip usage while learning how to use the monitor caused anxiety that was exacerbated by worries about their cost. However, self-funding did mean that interviewees felt a sense of ownership and were determined to persevere to overcome problems. Conclusions Self-funding has negative implications in terms of equity of access; however, the money invested acts as a barrier to discontinuation. If oral anticoagulation therapy self-monitoring devices and consumables were provided free of charge in routine care, the training and support available in England may need to be reviewed to prevent discontinuation rates rising to those observed in clinical trials. PMID:28011812

  5. Safety of local anaesthesia in dental patients taking oral anticoagulants: is it still controversial?

    PubMed

    Bajkin, Branislav V; Todorovic, Ljubomir M

    2012-01-01

    The aim of this study was to investigate the safety of local infiltration techniques and the inferior alveolar nerve block (IANB) in dental patients taking oral anticoagulants. A total of 352 patients were given a total of 560 injections of local anaesthetic (119 IANB and 441 others). The study group comprised 279 patients with therapeutic international normalised ratios (INRs), and the control group 73 patients who were taking oral anticoagulants but had subtherapeutic INR on the day of operation. Blood was aspirated 7 times (7.3%) during the IANB in the study group. However, there were no clinical signs of prolonged haemorrhage into the medial pterygoid muscle or pterygomandibular space after 96 IANB, including those from whom blood had been aspirated. Only two minor haematomas developed after multiple infiltrations in the lingual sulci. The results suggest that bleeding as a result of the use of local anaesthesia in patients with therapeutic INR is unlikely, provided that the IANB is done correctly. Copyright © 2010 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  6. Risk of Myocardial Infarction in Patients with Long-Term Non-Vitamin K Antagonist Oral Anticoagulant Treatment.

    PubMed

    Tornyos, Adrienn; Kehl, Dániel; D'Ascenzo, Fabrizio; Komócsi, András

    2016-01-01

    The relative cardiovascular (CV) safety of oral anticoagulants continues to be debated, and in particular concerns for risk of myocardial infarction (MI) have been raised. We analyzed the risk of MI in patients treated long term with oral anticoagulants (vitamin K antagonists [VKA], direct thrombin inhibitors or activated X factor antagonist) for atrial fibrillation, deep vein thrombosis or pulmonary embolism using a network meta-analysis (NMA). Randomized, phase 3 trials comparing novel anticoagulants to VKA were searched. Information on study design and clinical outcomes was extracted. The primary end-point of the analysis was the occurrence of MI or acute coronary syndrome. A Bayesian multiple treatment analysis was performed using fixed-effect and random-effects modeling. Twelve trials including 100,524 randomized patients were analyzed. The odds for MI in NMA were worse with dabigatran when compared to VKA, rivaroxaban, apixaban, and edoxaban (OR: 0.66 CI: 0.49-0.87; OR: 0.56 CI: 0.38-0.82, OR: 0.59 CI 0.40-0.88, and OR: 0.71 CI: 0.50-1.0, respectively).The posterior probability of being the first best choice of treatment was 53.5% for rivaroxaban, 33.8% for apixaban, 9.5% for ximelagatran, 2.0% for edoxaban, 1.2% for VKA, and 0.007% for dabigatran. There is a considerable heterogeneity regarding CV safety among oral anticoagulants. Differences in risk of MI may influence the choice of treatment. Multiple treatment NMA found 29%-44% higher odds of MI with dabigatran supporting the concerns regarding its CV safety. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Anticoagulation in pregnant women with mechanical heart valve prostheses

    PubMed Central

    Meschengieser, S; Fondevila, C; Santarelli, M; Lazzari, M

    1999-01-01

    OBJECTIVE—To evaluate the outcome of pregnancy in women with mechanical heart valve prostheses in relation to the anticoagulant treatment used in the first trimester and the incidence of thrombotic and bleeding complications.
METHODS—92 pregnancies in 59 women were followed between 1986 and 1997. In 31 pregnancies, oral anticoagulants were discontinued when pregnancy was diagnosed and subcutaneous heparin was started (12 500 U every 12 hours) adjusted to prolong the adjusted partial thromboplastin time to twice the control level. In the second trimester oral anticoagulants were resumed but changed to heparin again 15 days before the expected delivery date. In 61 pregnancies oral anticoagulants were continued during the first trimester. The same regimen of heparin was used for delivery.
RESULTS—Abortion or fetal losses were similar (p = 0.5717) in women exposed to oral anticoagulants in the first trimester (13/61; 25%) compared with those who received adjusted subcutaneous heparin (6/31; 19%). Embolic episodes were more common (p = 0.0029) in women who received heparin (4.92%) compared with those on oral anticoagulants (0.33%). Embolic episodes were cerebral and transient. No valve thromboses were observed. No malformations appeared in the 71 newborns, except for one case of hydrocephalus. There were no maternal deaths secondary to thrombotic complications. The only death was the result of major bleeding after the delivery of a premature stillborn.
CONCLUSIONS—Oral anticoagulants seem to be safer for the mother than adjusted subcutaneous heparin. Heparin does not offer a clear advantage over oral anticoagulation in the pregnancy outcome.


Keywords: pregnancy; oral anticoagulants; heparin; prosthetic valves PMID:10377303

  8. Estimated Prestroke Peak VO2 Is Related to Circulating IGF-1 Levels During Acute Stroke.

    PubMed

    Mattlage, Anna E; Rippee, Michael A; Abraham, Michael G; Sandt, Janice; Billinger, Sandra A

    2017-01-01

    Background Insulin-like growth factor-1 (IGF-1) is neuroprotective after stroke and is regulated by insulin-like binding protein-3 (IGFBP-3). In healthy individuals, exercise and improved aerobic fitness (peak oxygen uptake; peak VO 2 ) increases IGF-1 in circulation. Understanding the relationship between estimated prestroke aerobic fitness and IGF-1 and IGFBP-3 after stroke may provide insight into the benefits of exercise and aerobic fitness on stroke recovery. Objective The purpose of this study was to determine the relationship of IGF-1 and IGFBP-3 to estimated prestroke peak VO 2 in individuals with acute stroke. We hypothesized that (1) estimated prestroke peak VO 2 would be related to IGF-1 and IGFBP-3 and (2) individuals with higher than median IGF-1 levels will have higher estimated prestroke peak VO 2 compared to those with lower than median levels. Methods Fifteen individuals with acute stroke had blood sampled within 72 hours of hospital admission. Prestroke peak VO 2 was estimated using a nonexercise prediction equation. IGF-1 and IGFBP-3 levels were quantified using enzyme-linked immunoassay. Results Estimated prestroke peak VO 2 was significantly related to circulating IGF-1 levels (r = .60; P = .02) but not IGFBP-3. Individuals with higher than median IGF-1 (117.9 ng/mL) had significantly better estimated aerobic fitness (32.4 ± 6.9 mL kg -1 min -1 ) than those with lower than median IGF-1 (20.7 ± 7.8 mL kg -1 min -1 ; P = .03). Conclusions Improving aerobic fitness prior to stroke may be beneficial by increasing baseline IGF-1 levels. These results set the groundwork for future clinical trials to determine whether high IGF-1 and aerobic fitness are beneficial to stroke recovery by providing neuroprotection and improving function. © The Author(s) 2016.

  9. [Perioperative management of new oral anticoagulants].

    PubMed

    Samama, Charles-Marc; Pernod, Gilles; Albaladejo, Pierre; Sie, Pierre

    2014-06-01

    New oral anticoagulants do represent a major step forward as compared to low molecular weight heparins and vitamin K antagonists. Several issues deserve attention regarding their perioperative management. Three (and very soon four or five) active molecules are available on the market, adding to the major intra- and inter-individual variability, to the high number of drug-drug interactions, and to the interferences of renal function and many other parameters. New tests are available including the diluted thrombin time for dabigatran and a specific anti-Xa test for rivaroxaban and apixaban. No antidote is approved yet. Scheduled surgery: the safest suggestion is to mimic the perioperative management of vitamin K antagonist, with a 5-day interruption and low molecular weight heparin bridging whenever necessary. Emergency procedures: several suggestions issued from the Groupe d'Intérêt en Hémostase Péri-opératoire are proposed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. Evaluation of computerized decision support for oral anticoagulation management based in primary care.

    PubMed

    Fitzmaurice, D A; Hobbs, F D; Murray, E T; Bradley, C P; Holder, R

    1996-09-01

    Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as within the appropriate therapeutic range of International Normalised Ratio (INR). All patients receiving warfarin from two Birmingham inner city general practices were invited to attend a practice-based anticoagulation clinic. In practice A all patients were managed using DSS. In practice B patients were randomized to receive dosing advice either through DSS or through the local hospital laboratory. Clinical outcomes, adverse events and patient acceptability were recorded. Forty-nine patients were seen in total. There were significant improvements in INR control from 23% to 86% (P > 0.001) in the practice where all patients received dosing through DSS. In the practice where patients were randomized to either DSS or hospital dosing, logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients (P < 0.001). Mean recall times were significantly extended in patients who were dosed by the practice DSS through the full 12 months (24 days to 36 days) (P = 0.033). Adverse events were comparable between hospital and practice-dosed patients, although a number of esoteric events occurred. Patient satisfaction with the practice clinics was high. Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control, frequency of review and general acceptability.

  11. Oral anticoagulant use in cardiovascular disorders: a perspective on present and potential indications for rivaroxaban.

    PubMed

    Camm, A John; Fox, Keith A A

    2018-05-21

    Four non-vitamin-K-antagonist oral anticoagulants (NOACs) have been approved for use in various cardiovascular indications. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban and rivaroxaban are now increasingly used in clinical practice. For some of these agents, available data from real-world studies support the efficacy and safety data in phase III clinical trials. This review aims to summarize the current status of trials and observational studies of oral anticoagulant use over the spectrum of cardiovascular disorders (excluding venous thrombosis), provide a reference source beyond stroke prevention for atrial fibrillation (AF) and examine the potential for novel applications in the cardiovascular field. We searched the recent literature for data on completed and upcoming trials of oral anticoagulants with a particular focus on rivaroxaban. Recent data in specific patient subgroups, such as patients with AF undergoing catheter ablation or cardioversion, have led to an extended approval for rivaroxaban, whereas the other NOACs have ongoing or recently completed trials in this setting. However, there are unmet medical needs for several arterial thromboembolic-related conditions, including patients with: AF and acute coronary syndrome, AF and coronary artery disease undergoing elective percutaneous coronary intervention, coronary artery disease and peripheral artery disease, implanted cardiac devices, and embolic stroke of unknown source. NOACs may provide alternative treatment options in areas of unmet need, and numerous studies are underway to assess their benefit-risk profiles in these settings.

  12. Changes in oral anticoagulation for elective cardioversion: results from a European cardioversion registry.

    PubMed

    Papp, Judit; Zima, Endre; Bover, Ramon; Karaliute, Rasa; Rossi, Andrea; Szymanski, Catherine; Troccoli, Rossella; Schneider, Jonas; Fagerland, Morten Wang; Camm, A John; Atar, Dan

    2017-07-01

    In patients with atrial fibrillation (AF) pharmacological or electrical cardioversion may be performed to restore sinus rhythm. The procedure is associated with an increased risk of thromboembolic events, which can be significantly reduced by adequate anticoagulation (OAC). Our aim was to create a partly prospective, partly retrospective cardioversion registry, particularly focusing on OAC strategies in different European countries, and on emerging choice of OAC over time. From September 2014 to October 2015, cardioversions due to AF performed in six European city hospitals in five European countries (Hungary: Budapest-1 and -2; Italy: Bari and Pisa; France: Amiens; Spain: Madrid; and Lithuania: Kaunas) were recorded in the registry. A total of 1101 patients (retrospective/prospective: 679/422, male/female: 742/359, mean age: 67.3 years ± 11.2) were registered. Most of the cardioversions were electrical (97%). Oral anticoagulants were administered in 87% of the patient, the usage of non-VKA oral anticoagulants (NOACs) vs Vitamin K antagonists (VKA) was 31.5% vs 68.5%, respectively. Seventy seven percent of the patients were given oral anticoagulants more than 3 weeks prior to the procedure, and 86% more than 4 weeks after the procedure. When using VKA, international normalized ratio (INR) at cardioversion was above 2.0 in 76% of the cases. A decline in VKA usage (P = 0.033) in elective cardioversion over approximately 1 year was observed. During the observation period, there was an increase in apixaban (P < 0.001), a slight increase in rivaroxaban (P = 0.028) and no changes in dabigatran (P = 0.34) usage for elective cardioversion. There were differences in use of OAC between the countries: Spain used most VKA (89%), while France used least VKA (39%, P < 0.001). According to current AF guidelines, NOACs are adequate alternatives to VKA for thromboembolic prevention in AF patients undergoing elective cardioversion. Our results indicate that

  13. Direct oral anticoagulants compared with warfarin in patients with severe blunt trauma.

    PubMed

    Feeney, James M; Neulander, Matthew; DiFiori, Monica; Kis, Lilla; Shapiro, David S; Jayaraman, Vijay; Marshall, William T; Montgomery, Stephanie C

    2017-01-01

    We queried our Trauma Quality Improvement Program registry for patients who presented between 6/1/2011 and 9/1/2015 with severe (injury severity score (ISS)>15) blunt traumatic injury during anticoagulant use. Patients were then grouped into those prescribed warfarin and patients prescribed any of the available novel Direct Oral Anticoagulants (DOAC) medications. We excluded severe (AIS≧4) head injuries. There were no differences between DOAC and warfarin groups in terms of age, gender mean ISS, median hospital or intensive care unit lengths of stay, complication proportions, numbers of complications per patient, or the proportion of patients requiring transfusion. Finally, excluding patients who died, the observed proportion of discharge to skilled nursing facility was similar. In our sample of trauma patients, DOAC use was associated with significantly lower mortality (DOAC group 8.3% vs. warfarin group 29.5%, p<0.015). The ratio of units transfused per patient was also lower in the DOAC group (2.8±1.8 units/patient in the DOAC group vs. 6.7±6.4 units per patient in the warfarin group; p=0.001). In conclusion, we report an association with decrease in mortality and a decrease in transfused blood products in severely injured trauma patients with likely minimal or no head injury taking novel DOACs over those anticoagulated with warfarin for outpatient anticoagulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Patient Education on Oral Anticoagulation.

    PubMed

    Hawes, Emily M

    2018-04-20

    Given the potential harm associated with anticoagulant use, patient education is often provided as a standard of care and emphasized across healthcare settings. Effective anticoagulation education involves face-to-face interaction with a trained professional who ensures that the patient understands the risks involved, the precautions that should be taken, and the need for regular monitoring. The teaching should be tailored to each patient, accompanied with written resources and utilize the teach-back method. It can be incorporated in a variety of pharmacy practice settings, including in ambulatory care clinics, hospitals, and community pharmacies.

  15. Stroke prevention in the elderly atrial fibrillation patient with comorbid conditions: focus on non-vitamin K antagonist oral anticoagulants

    PubMed Central

    Turagam, Mohit K; Velagapudi, Poonam; Flaker, Greg C

    2015-01-01

    Stroke prevention in elderly atrial fibrillation patients remains a challenge. There is a high risk of stroke and systemic thromboembolism but also a high risk of bleeding if anticoagulants are prescribed. The elderly have increased chronic kidney disease, coronary artery disease, polypharmacy, and overall frailty. For all these reasons, anticoagulant use is underutilized in the elderly. In this manuscript, the benefits of non-vitamin K antagonist oral anticoagulants compared with warfarin in the elderly patient population with multiple comorbid conditions are reviewed. PMID:26366064

  16. A pharmacoeconomic study of traditional anticoagulation versus direct oral anticoagulation for the treatment of venous thromboembolism in the emergency department.

    PubMed

    Law, Stephanie; Ghag, Daljit; Grafstein, Eric; Stenstrom, Robert; Harris, Devin

    2016-09-01

    Patients with venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [PE]) are commonly treated as outpatients. Traditionally, patients are anticoagulated with low-molecular-weight heparin (LMWH) and warfarin, resulting in return visits to the ED. The direct oral anticoagulant (DOAC) medications do not require therapeutic monitoring or repeat visits; however, they are more expensive. This study compared health costs, from the hospital and patient perspectives, between traditional versus DOAC therapy. A chart review of VTE cases at two tertiary, urban hospitals from January 1, 2010 to December 31, 2012 was performed to capture historical practice in VTE management, using LMWH/warfarin. This historical data were compared against data derived from clinical trials, where a DOAC was used. Cost minimization analyses comparing the two modes of anticoagulation were completed from hospital and patient perspectives. Of the 207 cases in the cohort, only 130 (63.2%) were therapeutically anticoagulated (international normalized ratio 2.0-3.0) at emergency department (ED) discharge; patients returned for a mean of 7.18 (range: 1-21) visits. Twenty-one (10%) were admitted to the hospital; 4 (1.9%) were related to VTE or anticoagulation complications. From a hospital perspective, a DOAC (in this case, rivaroxaban) had a total cost avoidance of $1,488.04 per VTE event, per patient. From a patient perspective, it would cost an additional $204.10 to $349.04 over 6 months, assuming no reimbursement. VTE management in the ED has opportunities for improvement. A DOAC is a viable and cost-effective strategy for VTE treatment from a hospital perspective and, depending on patient characteristics and values, may also be an appropriate and cost-effective option from a patient perspective.

  17. The future of anticoagulation clinics.

    PubMed

    Macik, B Gail

    2003-01-01

    Anticoagulation therapy is the foundation of treatment for thromboembolic disorders; and coumarin derivatives (warfarin in the United States) are the only orally administered anticoagulant medications currently available. Due to the expense and relative difficulties associated with this route of administration, parenteral drugs are not used routinely for long-term therapy, leaving warfarin as the anticoagulant of choice in the outpatient setting. The management of warfarin is problematic, however, due the nuances of its pharmacodynamic and pharmacokinetic profile and the requirement for frequent monitoring of blood levels. Although management by anticoagulation clinics is considered the gold standard for warfarin therapy, management by an anticoagulation clinic may not be the optimal option from a clinician's view and, in many cases, may not be an option at all. Anticoagulation clinics may impinge on the doctor-patient relationship. Difficulties of communication and reimbursement are not ameliorated by a specialty clinic. Innovations in warfarin management, including patient self-management and computerized dosing programs, are alternatives for improved care that are available with or without input by an anticoagulation service. New oral drugs on the horizon do not require the same intensity of monitoring and do not present the same pharmacodynamic problems associated with warfarin. Warfarin will become obsolete in the foreseeable future. If anticoagulation clinics continue, they must re-define their role as the major part of the workload, warfarin management, disappears. To adapt, clinics must strengthen and enhance their role as coordinators and educators, and less so, managers of anticoagulation therapy.

  18. [Treatment with inhibitors of new oral direct anticoagulants in patients with severe bleedings or urgent surgical procedures. The new dabigatran antidote: the place of idarucizumab in clinical practice].

    PubMed

    Boda, Zoltán

    2016-03-20

    Only vitamin K antagonists could be applied as oral anticoagulants over the past six decades. Coumarols have narrow therapeutic range, and unpredictable anticoagulant effects are resulted by multiple drug interactions. Therefore, regular routine monitoring of the international normalized ratio is necessary. There are two groups of factor-specific anticoagulants: molecules with anti-FIIa (dabigatran) and anti-FXa (rivaroxaban, apixaban and edoxaban) effect. Author summarizes the most important clinical features of the new oral anticoagulants, their indications and the possibilities of laboratory controls. Bleedings are the most important side effects of anticoagulants. This review summarizes the current published evidences for new oral anticoagulants reversal (non-specific and specific) agents, especially in cases with severe acute bleedings or urgent surgery procedures. It reports on how to use inhibitors, the recommended doses and the most important clinical results. The review focuses on idarucizumab - already approved by the U.S. Food and Drug Administration and the European Medicines Agency - which has a key role as the first specific inhibitor of dabigatran.

  19. Benefit, risk and cost of new oral anticoagulants and warfarin in atrial fibrillation; A multicriteria decision analysis.

    PubMed

    Mendoza-Sanchez, Jose; Silva, Federico; Rangel, Lady; Jaramillo, Linda; Mendoza, Leidy; Garzon, Jenny; Quiroga, Andrea

    2018-01-01

    Warfarin and new oral anticoagulants are effective in reducing stroke in atrial fibrillation; however, the benefits and risks rates in clinical trials show heterogeneity for each anticoagulant, and is unknown the cost influence on a model considering most of the treatment consequences. We designed a benefit-risk and cost assessment of oral anticoagulants. We followed the roadmap proposed by IMI-PROTECT and the considerations of emerged good practice to perform Multi-Criteria Decision Analysis (MCDA). The roadmap defines the following steps: (1) planning, (2) evidence gathering and data preparation, (3) analyses, (4) explorations, and (5) conclusions. We defined two reference points (0-100) to allocate numerical values for scores and weights, and used an analogue numeric scale to assess physicians' preferences. As benefits of the anticoagulant therapy, we included reductions in stroke and all-cause mortality; intracranial haemorrhage, gastrointestinal haemorrhage, minor bleeding and myocardial infarction were considered risks. We also made an estimation of the annual drug cost per person. The scores were: Apixaban 33, Dabigatrán 25, warfarin 18 and Rivaroxaban 14 this score reveals the most preferred up to the less preferred option, considering the benefit-risk ratio and drug costs altogether. The relative model weights were: 51.1% for risks, 40.4% for benefits and 8.5% for cost. The sensitivity analysis confirms the model robustness. From this analysis, apixaban should be considered as the preferred anticoagulant option -due to a better benefit-risk balance and a minor cost influence- followed by dabigatran, warfarin and rivaroxaban.

  20. Economic evaluation of the new oral anticoagulants for the prevention of thromboembolic events: a cost-minimization analysis.

    PubMed

    Marcolino, Milena Soriano; Polanczyk, Carisi Anne; Bovendorp, Ana Carolina Caixeta; Marques, Naiara Silveira; Silva, Lilian Azevedo da; Turquia, Cintia Proveti Barbosa; Ribeiro, Antonio Luiz

    2016-01-01

    Randomized clinical trials have shown that the new oral anticoagulants have at least similar impact regarding reduction of thromboembolic events, compared with warfarin, with similar or improved safety profiles. There is little data on real costs within clinical practice. Our aim here was to perform economic analysis on these strategies from the perspective of Brazilian society and the public healthcare system. Cost-minimization analysis; anticoagulation clinic of Hospital Municipal Odilon Behrens, Belo Horizonte, MG, Brazil. Patients at the anticoagulation clinic were recruited between August and October 2011, with minimum follow-up of four weeks. Operational and non-operational costs were calculated and corrected to 2015. This study included 633 patients (59% women) of median age 62 years (interquartile range -49-73). The mean length of follow-up was 64 ± 28 days. The average cost per patient per month was $ 54.26 (US dollars). Direct costs accounted for 32.5% of the total cost. Of these, 69.5% were related to healthcare professionals. With regards to indirect costs, 52.4% were related to absence from work and 47.6% to transportation. Apixaban, dabigatran and rivaroxaban were being sold to Brazilian public institutions, on average, for $ 49.87, $ 51.40 and $ 52.16 per patient per month, respectively, which was lower than the costs relating to warfarin treatment. In the Brazilian context, from the perspective of society and the public healthcare system, the cumulative costs per patient using warfarin with follow-up in anticoagulation clinics is currently higher than the strategy of prescribing the new oral anticoagulants.

  1. Adherence to recommendations of the Therapeutic Positioning Report about treatment with oral anticoagulants in elderly patients with atrial fibrillation. The ESPARTA study.

    PubMed

    Suárez Fernández, Carmen; Mostaza, Jose María; Castilla Guerra, Luis; Cantero Hinojosa, Jesus; Suriñach, Josep Maria; Acosta de Bilbao, Fernando; Tamarit, Juan José; Diaz Diaz, José Luis; Hernandez, Jose Luis; Cazorla, Daniel; Ràfols, Carles

    2017-10-06

    To evaluate the adherence to the recommendations in clinical practice performed by the Therapeutic Positioning Report (TPR) of the Spanish Agency of Medicines and Sanitary Products about the treatment with oral anticoagulants in patients aged≥75 years old with nonvalvular atrial fibrillation (NVAF) treated in Internal Medicine departments in Spain. Observational, cross-sectional and multicenter study in which 837 patients aged≥75 years old with NVAF, with stable treatment with oral anticoagulants at least 3 months before inclusion, and that had started treatment with oral anticoagulants before the inclusion period were included. Mean age was 83.0±5.0 years old, mean CHADS 2 score 3.2±1.2, mean CHA 2 DS 2 -VASc score 5.0±1.4, and mean HAS-BLED score 2.1±0.9. A percentage of 70.8 of patients were treated with vitamin K antagonists (VKA) and the rest of patients with direct oral anticoagulants (DOACs). A percentage of 65.6 of patients treated with VKA did not follow the recommendations made by the TPR compared with 43.0% of patients treated with DOACs (P<.0001). In the case of VKA, the main reason for being considered as not appropriate according to the TPR was having poor control of anticoagulation and not switching to DOACs, whereas in the case of DOACs, it was not receiving the adequate dose according to the TPR. In a high proportion of anticoagulated elderly patients with NVAF in Spain, the recommendations performed by the TPR are not followed, particularly with VKA, since patients are not switched to DOACs despite time in therapeutic range. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  2. Setting priorities in the health care sector - the case of oral anticoagulants in nonvalvular atrial fibrillation in Denmark.

    PubMed

    Poulsen, Peter Bo; Johnsen, Søren Paaske; Hansen, Morten Lock; Brandes, Axel; Husted, Steen; Harboe, Louise; Dybro, Lars

    2017-01-01

    Resources devoted to health care are limited, therefore setting priorities is required. It differs between countries whether decision-making concerning health care technologies focus on broad economic perspectives or whether focus is narrow on single budgets ("silo mentality"). The cost perspective as one part of the full health economic analysis is important for decision-making. With the case of oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF), the aim is to discuss the implication of the use of different cost perspectives for decision-making and priority setting. In a cost analysis, the annual average total costs of five oral anticoagulants (warfarin and non-vitamin K oral anticoagulants [NOACs; dabigatran, rivaroxaban, apixaban, and edoxaban]) used in daily clinical practice in Denmark for the prevention of stroke in NVAF patients are analyzed. This is done in pairwise comparisons between warfarin and each NOAC based on five potential cost perspectives, from a "drug cost only" perspective up to a "societal" perspective. All comparisons of warfarin and NOACs show that the cost perspective based on all relevant costs, ie, total costs perspective, is essential for the choice of therapy. Focusing on the reimbursement costs of the drugs only, warfarin is the least costly option. However, with the aim of therapy to prevent strokes and limit bleedings, including the economic impact of this, all NOACs, except rivaroxaban, result in slightly lower health care costs compared with warfarin. The same picture was found applying the societal perspective. Many broad cost-effectiveness analyses of NOACs exist. However, in countries with budget focus in decision-making this information does not apply. The present study's case of oral anticoagulants has shown that decision-making should be based on health care or societal cost perspectives for optimal use of limited resources. Otherwise, the risk is that suboptimal decisions will be likely.

  3. [Update on the control of patients on treatment with vitaminK antagonist oral anticoagulants in Primary Care].

    PubMed

    Fernández López, P; López Ramiro, M I; Merino de Haro, I; Cedeño Manzano, G; Díaz Siles, F J; Hermoso Sabio, A

    In Spain, more than 80% of patients with atrial fibrillation (AF) receive oral anticoagulant therapy (OAT), and 72% of these patients are followed up in the Primary Care (PC) setting. Recent studies have shown that there is insufficient control of patients on OAT. The objective of the present study was to obtain more detailed information on the state of control of patients on treatment with vitaminK antagonist (VKA) oral anticoagulants (OAC), on the diseases for which the therapy was indicated and on concomitant diseases. This was a retrospective, cross-sectional, observational study with the participation of patients from a single health area included in an OAT programme throughout 2014. In patients on treatment with OAC, International Normalised Ratio (INR) control was considered insufficient when the percentage time in therapeutic range (TTR) was below 65% during an evaluation period of at least 6months. A total of 368 patients were included in the study, where the most frequent indication for oral anticoagulation was non-valvular AF. A total of 5,128 INR controls were performed, of which 2,359 (46%) were outside the therapeutic range, and 2,769 (54%) were within range. The risk of thromboembolism was very high in 91% of patients on treatment with VKA OAC. The indication for anticoagulation is correct in our population, assuming a low-intermediate risk of haemorrhage in the majority of patients. Measurement of the TTR using the Rosendaal method shows that the control of patients on treatment with VKA OAC is insufficient. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  4. [Prophylaxis of thromboembolism in atrial fibrillation: new oral anticoagulants and left atrial appendage closure].

    PubMed

    Zeus, Tobias; Kelm, Malte; Bode, Christoph

    2015-08-01

    Thrombo-embolic prophylaxis is a key element within the therapy of atrial fibrillation/atrial flutter. Besides new oral anticoagulants the concept of left atrial appendage occlusion has approved to be a good alternative option, especially in patients with increased risk of bleeding. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Practical management of bleeding in patients receiving non-vitamin K antagonist oral anticoagulants.

    PubMed

    Weitz, Jeffrey I; Pollack, Charles V

    2015-11-25

    Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in the prevention and treatment of venous thromboembolism and in the prevention of stroke in patients with non-valvular atrial fibrillation. In phase III clinical trials and meta-analyses, the NOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with a similar or lower incidence of major bleeding, including consistent and significant decreases in intracranial bleeding, although with an increase in gastrointestinal bleeding for some agents compared with VKAs. Subsequent real-world evidence supports these outcomes. Despite this, physicians have concerns about serious bleeding or emergencies because there are no specific reversal agents for the NOACs. However, in clinical trials, patients receiving NOACs generally had similar or better outcomes after these events than those taking VKAs. As with any bleeding, anticoagulant-related bleeding should first be stratified according to severity and location; risk can be minimised by ongoing assessment. Management protocols for NOAC-related bleeding are similar to those for VKAs but should take into account the pharmacological profile of the specific drug. Because of their short half-lives, NOAC-related mild bleeding can often be controlled by temporarily withholding treatment. More severe bleeding requires standard escalating haemodynamic support measures, and non-specific reversal agents can be considered in life-threatening situations, based on limited clinical data. Specific and rapid reversal agents are not currently available for any oral anticoagulant and restoration of coagulation may not necessarily lead to better outcomes. Nevertheless, specific NOAC reversal agents are in development and show promise in healthy volunteers.

  6. Adverse Influence of Pre-Stroke Dementia on Short-Term Functional Outcomes in Patients with Acute Ischemic Stroke: The Fukuoka Stroke Registry.

    PubMed

    Wakisaka, Yoshinobu; Matsuo, Ryu; Hata, Jun; Kuroda, Junya; Kitazono, Takanari; Kamouchi, Masahiro; Ago, Tetsuro

    2017-01-01

    Dementia and stroke are major causes of disability in the elderly. However, the association between pre-stroke dementia and functional outcome after stoke remains unresolved. We aimed to determine this association in patients with acute ischemic stroke. Among patients registered in the Fukuoka Stroke Registry from June 2007 to May 2015, 4,237 patients with ischemic stroke within 24 h of onset, who were functionally independent before the onset, were enrolled in this study. Pre-stroke dementia was defined as any type of dementia that was present prior to the index stroke. Primary and secondary study outcomes were poor functional outcome (modified Rankin Scale 3-6) at 3 months after the stroke onset and neurological deterioration (≥2-point increases on the National Institutes of Health Stroke Scale score during hospitalization), respectively. For propensity score (PS)-matched cohort study to control confounding variables for pre-stroke dementia, 318 pairs of patients with and without pre-stroke dementia were also selected on the basis of 1:1 matching. Multivariable logistic regression models and conditional logistic regression analysis were used to quantify associations between pre-stroke dementia and study outcomes. Of all 4,237 participants, 347 (8.2%) had pre-stroke dementia. The frequencies of neurological deterioration and poor functional outcome were significantly higher in patients with pre-stroke dementia than in those without pre-stroke dementia (neurological deterioration, 16.1 vs. 7.1%, p < 0.01; poor functional outcome, 63.7 vs. 27.1%, p < 0.01). Multivariable analysis showed that pre-stroke dementia was significantly associated with neurological deterioration (OR 1.67; 95% CI 1.14-2.41; p < 0.01) and poor functional outcome (OR 2.91; 95% CI 2.17-3.91; p < 0.01). In the PS-matched cohort study, the same trends were observed between the pre-stroke dementia and neurological deterioration (OR 2.60; 95% CI 1.17-5.78; p < 0.01) and between the dementia and

  7. Underuse of Anticoagulation in Older Patients with Atrial Fibrillation and CHADS2 Score ≥ 2: Are We Doing Better Since the Marketing of Direct Oral Anticoagulants?

    PubMed

    Henrard, Séverine; Vandenabeele, Caroline; Marien, Sophie; Boland, Benoit; Dalleur, Olivia

    2017-11-01

    Our objectives were to (1) describe the evolution of the underuse of anticoagulants in older people with atrial fibrillation (AF) and a CHADS 2 score ≥ 2 since direct oral anticoagulants (DOACs) were introduced to the market and (2) describe factors associated with this underuse. We conducted a retrospective cross-sectional study including geriatric patients admitted during the pre-DOAC (2008-2011) and post-DOAC (2013-2015) periods in an academic hospital in Belgium. Five inclusion criteria were met: age ≥ 75 years, diagnosis of AF, indication for anticoagulation (CHADS 2 score ≥ 2), risk of functional decline (Identification of Seniors At Risk [ISAR] score ≥ 2), and comprehensive geriatric assessment. The use of anticoagulants and antiplatelets at home before admission was recorded. Risks of stroke and bleeding were calculated using CHADS 2 and HEMORR 2 HAGES scores, respectively. Three different logistic regression models were performed to describe the evolution of and factors associated with the underuse of anticoagulants after DOAC marketing. Anticoagulant underuse, present in 209 of 614 (34%) geriatric patients with AF, was lower in patients with a history of stroke (28.5%) or congestive heart failure (26.9%) but higher in those receiving antiplatelets (56.2%) and in older individuals. Anticoagulant underuse decreased significantly from the pre-DOAC (37.3%) to the post-DOAC (29.7%) era, as shown by two analyses using propensity scores. In older patients with AF, anticoagulant underuse was mainly associated with antiplatelet use. Anticoagulant underuse and antiplatelet use have both decreased since DOAC marketing. Underuse of anticoagulants was still a concern for three in ten geriatric patients with AF at high risk of stroke (CHADS 2 score ≥ 2).

  8. Risk of gastrointestinal bleeding during anticoagulant treatment.

    PubMed

    Lanas-Gimeno, Aitor; Lanas, Angel

    2017-06-01

    Gastrointestinal bleeding (GIB) is a major problem in patients on oral anticoagulation therapy. This issue has become even more pressing since the introduction of direct oral anticoagulants (DOACs) in 2009. Areas covered: Here we review current evidence related to GIB associated with oral anticoagulants, focusing on randomized controlled trials, meta-analyses, and post-marketing observational studies. Dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily increase the risk of GIB compared to warfarin. The risk increase with edoxaban is dose-dependent, while apixaban shows apparently, no increased risk. We summarize what is known about GIB risk factors for individual anticoagulants, the location of GIB in patients taking these compounds, and prevention strategies that lower the risk of GIB. Expert opinion: Recently there has been an important shift in the clinical presentation of GIB. Specifically, upper GIB has decreased with the decreased incidence of peptic ulcers due to the broad use of proton pump inhibitors and the decreased prevalence of H. pylori infections. In contrast, the incidence of lower GIB has increased, due in part to colonic diverticular bleeding and angiodysplasia in the elderly. In this population, the addition of oral anticoagulation therapy, especially DOACs, seems to increase the risk of lower GIB.

  9. [Physicians' Opinion on Health Care in Oral Anticoagulation].

    PubMed

    Eggebrecht, Lisa; Prochaska, Jürgen H; Schleuter, Leonie; Nagler, Markus; Hardt, Roland; Schinzel, Helmut; Münzel, Thomas; Wild, Philipp S

    2018-05-01

     The introduction of direct oral anticoagulants (DOAC) in addition to the established Vitamin K antagonist (VKA) has increased the complexity of antithrombotic therapy leading to numerous treatment options. Studies of the medical evaluation of the current treatment situation by health care providers, which are of great importance for the development of treatment strategies in addition to studies on pharmacovigilance, are limited in the literature.  11 700 physicians (Rhineland-Palatinate, Germany) were contacted to participate in the web-based survey on health care with oral anticoagulation (OAC). After detailed quality control, the study was analysed in synopsis with routine care data of VKA patients of the thrombEVAL study programme (N = 2.011).  In total, 512 physicians (mean age: 48.0 ± 9.6 years; 74.0 % male) participated in the study. In general, quality of OAC therapy was rated as "average/satisfactory" (2.9 ± 0.9). Comparison of physicians' perception with data from routine care highlighted marked differences regarding time in therapeutic range (+ 6.4 % [95 %-CI 2.7 %; 9.5 %]), duration of control intervals (- 35.0 % [28.0 %; 41.4 %]) and rate of OAC-related complications (+ 61.8 [37.8 %; 83.3 %], which differed additionally and statistically-significant between physician groups. The willingness to use DOAC was approximately 50 % lower in general physicians as compared to specialists (36.6 % [25.4 %; 47.8 %] vs. 72.4 % [66.0 %; 78.9 %]; p < 0.0001). Regarding management of OAC therapy, 73.8 % [69.7 %; 77.9 %] advocated the establishment of a service hotline and 67.3 % [62,9 %; 71.6 %] a specialized coagulation service.  The present survey among physicians reveals a need for optimization of OAC therapy in daily practice. Specialized care models might facilitate optimized OAC therapy with both VKAs and DOACs. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Cardiac arrest due to left circumflex coronary artery embolism as a complication of subtherapeutic oral anticoagulation in a patient with mitral and aortic mechanical valve prostheses

    PubMed Central

    Protasiewicz, Marcin; Gajek, Jacek; Mysiak, Andrzej

    2013-01-01

    We report a case of a 65-year-old female patient after replacement of aortic and mitral valve with mechanical prostheses and implantation of a pacemaker hospitalized in our clinic due to acute coronary syndrome complicated with cardiac arrest due to ventricular fibrillation. The electrocardiogram performed on admission showed signs of myocardial infarction with concomitant ventricular pacing. After successful resuscitation the coronary angiography was performed, which showed occlusion of the left circumflex artery (LCx) by thrombus. On the basis of intravascular ultrasound imaging the presence of vulnerable plaque, parietal thrombus and dissection of LCx were excluded. It suggested that occlusion of the LCx resulted from its embolism by left-sided heart thrombus due to subtherapeutic oral anticoagulation. In this case suboptimal anticoagulation was partially iatrogenic. Two weeks before the patient had been given vitamin K intravenously due to indeterminable international normalized ratio (INR) level, which caused transient resistance to oral anticoagulants. This case report illustrates tragic difficulties in the treatment with vitamin K antagonists, which concern as many as 2/3 of anticoagulated patients. These troubles contributed to the search for new, more efficient and safer anticoagulants. There are two classes of new oral anticoagulant drugs, which do not require monitoring of coagulation: direct thrombin inhibitors (e.g. dabigatran) and factor Xa inhibitors (e.g. rivaroxaban). In spite of their proven efficacy in the prevention of ischaemic stroke related to atrial fibrillation and prevention or treatment of deep vein thrombosis and pulmonary embolism, the use of new oral anticoagulants for the treatment of patients with mechanical valve prostheses needs further research. PMID:24570697

  11. Cardiac arrest due to left circumflex coronary artery embolism as a complication of subtherapeutic oral anticoagulation in a patient with mitral and aortic mechanical valve prostheses.

    PubMed

    Protasiewicz, Marcin; Rojek, Aleksandra; Gajek, Jacek; Mysiak, Andrzej

    2013-01-01

    We report a case of a 65-year-old female patient after replacement of aortic and mitral valve with mechanical prostheses and implantation of a pacemaker hospitalized in our clinic due to acute coronary syndrome complicated with cardiac arrest due to ventricular fibrillation. The electrocardiogram performed on admission showed signs of myocardial infarction with concomitant ventricular pacing. After successful resuscitation the coronary angiography was performed, which showed occlusion of the left circumflex artery (LCx) by thrombus. On the basis of intravascular ultrasound imaging the presence of vulnerable plaque, parietal thrombus and dissection of LCx were excluded. It suggested that occlusion of the LCx resulted from its embolism by left-sided heart thrombus due to subtherapeutic oral anticoagulation. In this case suboptimal anticoagulation was partially iatrogenic. Two weeks before the patient had been given vitamin K intravenously due to indeterminable international normalized ratio (INR) level, which caused transient resistance to oral anticoagulants. This case report illustrates tragic difficulties in the treatment with vitamin K antagonists, which concern as many as 2/3 of anticoagulated patients. These troubles contributed to the search for new, more efficient and safer anticoagulants. There are two classes of new oral anticoagulant drugs, which do not require monitoring of coagulation: direct thrombin inhibitors (e.g. dabigatran) and factor Xa inhibitors (e.g. rivaroxaban). In spite of their proven efficacy in the prevention of ischaemic stroke related to atrial fibrillation and prevention or treatment of deep vein thrombosis and pulmonary embolism, the use of new oral anticoagulants for the treatment of patients with mechanical valve prostheses needs further research.

  12. [Consensus statement: Management of oral anticoagulation for stroke prevention in patients with nonvalvular atrial fibrillation].

    PubMed

    Helms, Thomas Maria; Silber, Sigmund; Schäfer, Andreas; Masuhr, Florian; Palm, Frederick; Darius, Harald; Schrör, Karsten; Bänsch, Dietmar; Bramlage, Peter; Hankowitz, Johannes; Karle, Christoph A; Stargardt, Tom; Weil, Joachim; Geller, Johann Christoph

    2016-09-01

    With the introduction of edoxaban last year in Germany, four nonvitamin K antagonist oral anticoagulants are now available for stroke prevention in patients with nonvalvular atrial fibrillation. These novel oral anticoagulants (NOAC) represent an attractive new option compared to vitamin K antagonists (e.g., warfarin or phenprocoumon) due to simple use and fewer interactions with other drugs or food. Therefore, no INR monitoring and dosage adjustments are required for NOAC. The compelling clinical advantage of NOAC is the dramatic risk reduction of hemorhagic stroke and intracranial bleeding compared to current standard. In addition, total mortality is significantly reduced by 10 %. These effects are demonstrated for all four NOAC (dabigatran, rivaroxaban, apixaban and edoxaban). Therefore, current national and international guidelines recommend NOAC as the preferred option or at least as an attractive alternative compared to the former standard of vitamin K antagonists. The economic impact and reimbursement by Statutory Health Insurance (GKV) is of major importance for treatment in an outpatient setting. For apixaban and edoxaban, an additional benefit was granted by the institution of G‑BA and IQWiG in this clinical setting, whereas dabigatran and rivaroxaban were not assessed due to market entrance prior to 2011 before the AMNOG procedure was initiated. The members of this consensus paper recommend NOAC as the preferred option for patients with nonvalvular atrial fibrillation who are currently not treated with anticoagulant drugs in spite of clear indication for anticoagulation. For new patients with nonvalvular fibrillation, it should be decided on an individual basis which treatment option is adequate for the patient with their respective comorbidities.

  13. Comparison of estimated glomerular filtration rate equations for dosing new oral anticoagulants in patients with atrial fibrillation.

    PubMed

    Manzano-Fernández, Sergio; Andreu-Cayuelas, José M; Marín, Francisco; Orenes-Piñero, Esteban; Gallego, Pilar; Valdés, Mariano; Vicente, Vicente; Lip, Gregory Y H; Roldán, Vanessa

    2015-06-01

    New oral anticoagulants require dosing adjustment according to renal function. We aimed to determine discordance in hypothetical recommended dosing of these drugs using different estimated glomerular filtration rate equations in patients with atrial fibrillation. Cross-sectional analysis of 910 patients with atrial fibrillation and an indication for oral anticoagulation. The glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations. For dabigatran, rivaroxaban, and apixaban we identified dose discordance when there was disagreement in the recommended dose based on different equations. Among the overall population, relative to Cockcroft-Gault, discordance in dabigatran dosage was 11.4% for Modification of Diet in Renal Disease and 10% for Chronic Kidney Disease Epidemiology Collaboration, discordance in rivaroxaban dosage was 10% for Modification of Diet in Renal Disease and 8.5% for the Chronic Kidney Disease Epidemiology Collaboration. The lowest discordance was observed for apixaban: 1.4% for Modification of Diet in Renal Disease and 1.5% for the Chronic Kidney Disease Epidemiology Collaboration. In patients with Cockcroft-Gault<60mL/min or elderly patients, discordances in dabigatran and rivaroxaban dosages were higher, ranging from 13.2% to 30.4%. Discordance in apixaban dosage remained<5% in these patients. Discordance in new oral anticoagulation dosages using different equations is frequent, especially among elderly patients with renal impairment. This discordance was higher in dabigatran and rivaroxaban dosages than in apixaban dosages. Further studies are needed to clarify the clinical importance of these discordances and the optimal anticoagulant dosages depending on the use of different equations to estimate renal function. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Oral and parenteral anticoagulants: new kids on the block.

    PubMed

    Aditya, S

    2012-01-01

    Well-documented drawbacks of traditional anticoagulants have lead to the quest for an ideal anticoagulant resulting in a surge of novel anticoagulant molecules. These newer agents directly target specific steps in coagulation cascade and include newer low molecular weight heparins (adomiparin), ultra low molecular weight heparins (semuloparin, RO-14), inhibitors of activated factor II (dabigatran, AZD0837), X (rivaroxaban, apixaban, edoxaban, betrixaban), IX (REG1,2), XI (antisense oligonucleotides, BMS 262084, clavatadine A), VII/tissue factor (tifacogin, PCI 274836, and BMS 593214), V (recomodulin, solulin), VIII (TB402), dual thrombin/factor X inhibitors (EP21709, tanogitran), and newer vitamin K antagonists (tecarfarin). Direct thrombin inhibitors and Factor X inhibitors are the most clinically advanced. This article discusses the recent advances in the development of novel targets of anticoagulants. Medline, EMBASE, cochrane database, medscape, SCOPUS, and clinicaltrials.gov were searched using terms "anticoagulants", "blood coagulation inhibitors", "anticoagulants and venous thromboembolism", "anticoagulants and atrial fibrillation", and "'antithrombins." Journal articles published from 2007 to 2012 discussing pharmacology and/or clinical trials were screened.

  15. Cholesterol embolisms as possible adverse drug reaction of direct oral anticoagulants.

    PubMed

    Muller-Hansma, A H G; Daemen-Gubbels, C R G M; Schut, N H

    2018-04-01

    The Netherlands Pharmacovigilance Centre Lareb has received two reports of cholesterol crystal embolisms associated with the use of a direct oral anticoagulant (DOAC). The European pharmacovigilance database contains several other cases concerning this association, and one report was published in the scientific literature. Cholesterol crystal embolisms were described in association with the use of several other antithrombotic drugs, although the role as an independent risk factor is not conclusive. The case series described in this article, indicates the possibility of an adverse drug reaction when a patient develops cholesterol crystal embolisms while using a DOAC.

  16. Anticoagulant management in the cardiovascular setting.

    PubMed

    Verheugt, Freek W A

    2012-02-01

    Vitamin K antagonists have been used as oral anticoagulants (OACs) for over five decades, yet their use in real-world practice is problematic primarily because of their narrow therapeutic window, exacerbated by extensive food and drug interactions, necessitating regular coagulation monitoring and dose adjustment. Around half of patients receiving warfarin are within the therapeutic range, exposing them to the dangers of under-anticoagulation (i.e. thrombosis formation) or over-anticoagulation (i.e. bleeding). A new generation of OACs with improved pharmacology promises to revolutionize antithrombotic management. Rivaroxaban, apixaban (both oral direct Factor Xa inhibitors) and dabigatran (a direct thrombin inhibitor) all exhibit predictable anticoagulant responses and few drug-drug interactions and do not require routine coagulation monitoring. © 2011 The Author Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

  17. Development and validation of hospital information system-generated indicators of the appropriateness of oral anticoagulant prescriptions in hospitalised adults: the PACHA study protocol

    PubMed Central

    Petit-Monéger, Aurélie; Thiessard, Frantz; Jouhet, Vianney; Noize, Pernelle; Berdaï, Driss; Kret, Marion; Sitta, Rémi; Salmi, Louis-Rachid; Saillour-Glénisson, Florence

    2017-01-01

    Introduction The appropriateness of oral anticoagulant prescriptions is a major challenge to improve quality and safety of care. As indicators of the appropriateness of oral anticoagulant prescriptions are lacking, the aim of the study is to develop and validate a panel of such indicators, in hospitalised adults, from the hospital information system of two university hospitals in France. Methods and analysis The study will be carried out in four steps: (1) a literature review to identify indicators of the appropriateness of oral anticoagulant prescriptions and their conditions of appropriateness; (2) a Delphi consensus method to assess the potential utility and operational implementation of the selected indicators; (3) techniques of medical data search to implement indicators from the hospital information system and; (4) a cross-sectional study to assess the ability of indicators to detect inappropriate oral anticoagulant prescriptions, performance of medical data search techniques for tracking or retrieving information and the ability of tools to be transferred into other institutions. The fourth step will include up to 80 patient hospital stays for each indicator, depending on the prevalence of inappropriate prescriptions estimated in interim analyses. Ethics and dissemination This work addresses the current lack of quality indicators of the appropriateness of oral anticoagulant prescriptions. We aim to develop and validate such indicators for integrating them into hospital clinical practice, as part of a structured approach to improve quality and safety of care. As each hospital information system is different, we will propose tools transferable to other healthcare institutions to allow an automated construction of these indicators. The PACHA study protocol was approved by institutional review boards and ethics committees (CPP Sud-Ouest et Outre Mer III—DC 2016/119; CPP Ile-de-France II—CDW_2016_0014). Registration details Clinical Trial.gov registration

  18. [Comparison of quality and hemorragic risk of oral anticoagulant therapy using acenocoumarol versus warfarin].

    PubMed

    Oliva Berini, Elvira; Galán Alvarez, Pilar; Pacheco Onrubia, Ana María

    2008-06-21

    Long half life oral anticoagulants have shown a higher anticoagulation stability and a lower hemorragic risk than those of a short half life. We have compared therapeutic stability and hemorragic risk of acenocoumarol versus warfarin in 2 groups of patients on preventive anticoagulation because of atrial fibrilation (international normalised ratio [INR]: 2-3). Data on 120 patients treated with acenocoumarol and 120 on warfarin treatment who had started and continued treatment in our hospital for a minimum of a year was collected. The percentage of visits within the intended range of INR (2 to 3) was 65.5% with warfarin and 63.4% with acenocoumarol. Thirty percent of patients on warfarin had 75% or more of their controls within range, while for those treated with acenocoumarol this percentage was 22.5%. In the acenocoumarol group, 0.3 visits/patient/year presented an INR > or = 6 versus 0.07 in the warfarin group (p = 0.003). Patients treated with acenocoumarol show a higher risk of presenting with an INR > or = 6, but no statistically significant differences are observed in therapeutic stability.

  19. A Multilevel Analysis of Real-World Variations in Oral Anticoagulation Initiation for Atrial Fibrillation in Valencia, a European Region

    PubMed Central

    García-Sempere, Aníbal; Bejarano-Quisoboni, Daniel; Librero, Julián; Rodríguez-Bernal, Clara L.; Peiró, Salvador; Sanfélix-Gimeno, Gabriel

    2017-01-01

    Introduction: Beyond clinical trials, clinical practice guidelines, and administrative regulation, treatment decision-making can be influenced by individual and contextual factors. Our goal was to describe variations in the patterns of initiation of anticoagulation therapy in patients with atrial fibrillation by Health Areas (HA) in the region of Valencia in Spain and to quantify the influence of the HAs on variations in treatment choice. Methods: We conducted a population-based retrospective cohort study of all atrial fibrillation patients who started treatment with oral anticoagulants between November 2011 and February 2014 in each of the region's 24 HAs. We described patient and utilization characteristics per HA and initiation patterns over time, and we identified contextual and individual factors associated with differences in initiation patterns. Results: 21,879 patients initiated treatment with an oral anticoagulant in the 24 HAs. Initiation with direct oral anticoagulants (DOAC) in the first year was 14.6%. In November 2013 the ratio was 25.4%, with HA ratios ranging from 3.8 to 57.1%. DOAC-initiating patients had less comorbidity but were more likely to present episodes of previous ischemic stroke, hemorrhagic stroke, or TIA when compared with patients initiating with VKA treatment. Variability among HAs was statistically significant, with the majority of HAs ranking above or below the regional initiation average (ICC ≈ 8%). Conclusion: There was high variability in the percentage of DOAC initiation and in the choice of DOAC among HAs. Interventions aimed to improve DOAC initiation decision-making and to reduce variations should take into account the Health Area component. PMID:28883793

  20. A Multilevel Analysis of Real-World Variations in Oral Anticoagulation Initiation for Atrial Fibrillation in Valencia, a European Region.

    PubMed

    García-Sempere, Aníbal; Bejarano-Quisoboni, Daniel; Librero, Julián; Rodríguez-Bernal, Clara L; Peiró, Salvador; Sanfélix-Gimeno, Gabriel

    2017-01-01

    Introduction: Beyond clinical trials, clinical practice guidelines, and administrative regulation, treatment decision-making can be influenced by individual and contextual factors. Our goal was to describe variations in the patterns of initiation of anticoagulation therapy in patients with atrial fibrillation by Health Areas (HA) in the region of Valencia in Spain and to quantify the influence of the HAs on variations in treatment choice. Methods: We conducted a population-based retrospective cohort study of all atrial fibrillation patients who started treatment with oral anticoagulants between November 2011 and February 2014 in each of the region's 24 HAs. We described patient and utilization characteristics per HA and initiation patterns over time, and we identified contextual and individual factors associated with differences in initiation patterns. Results: 21,879 patients initiated treatment with an oral anticoagulant in the 24 HAs. Initiation with direct oral anticoagulants (DOAC) in the first year was 14.6%. In November 2013 the ratio was 25.4%, with HA ratios ranging from 3.8 to 57.1%. DOAC-initiating patients had less comorbidity but were more likely to present episodes of previous ischemic stroke, hemorrhagic stroke, or TIA when compared with patients initiating with VKA treatment. Variability among HAs was statistically significant, with the majority of HAs ranking above or below the regional initiation average (ICC ≈ 8%). Conclusion: There was high variability in the percentage of DOAC initiation and in the choice of DOAC among HAs. Interventions aimed to improve DOAC initiation decision-making and to reduce variations should take into account the Health Area component.

  1. Disadvantages of VKA and requirements for novel anticoagulants.

    PubMed

    Shameem, Raji; Ansell, Jack

    2013-06-01

    Vitamin K antagonists have been in wide use for over 70 years. Warfarin, the most commonly used vitamin K antagonist, has been shown to be highly effective in treating and preventing thrombosis. Despite this, warfarin has many disadvantages, which has led to the development of a new class of oral anticoagulants targeted to specific coagulation factors designated as target-specific oral anticoagulants (TSOAs). TSOAs include the thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). This chapter reviews the disadvantages of warfarin and evaluates both the advantages and disadvantages of the new oral anticoagulants. © 2013 Elsevier Ltd. All rights reserved.

  2. Managing bleeding and emergency reversal of newer oral anticoagulants: a review for primary care providers.

    PubMed

    Peacock, W Frank

    2014-10-01

    The therapeutic landscape for anticoagulation management is undergoing a shift from the use of traditional anticlotting agents such as heparins and warfarin as the only options to the growing adoption of newer target-specific oral anticoagulants (TSOACs) with novel mechanisms of action. Dabigatran, the first TSOAC approved for use in the United States, is a direct competitive inhibitor of thrombin. It has predictable kinetics, with an elimination half-life of 12 to 17 hours in healthy volunteers. Apixaban and rivaroxaban are selective inhibitors of factor Xa, and also display first-order kinetics. In younger healthy individuals, apixaban has an apparent half-life of approximately 12 hours, whereas rivaroxaban has an elimination half-life of 5 to 9 hours. Understanding the pharmacologic properties of these newer drugs can lead to better insights regarding their respective safety and efficacy profiles and their application in clinical practice. Laboratory assessments have been developed to measure the anticoagulant efficacy of these newer agents. However, the results of these tests can be highly variable, and are therefore not always useful for monitoring the anticoagulation effects of these agents. In addition, several strategies have been documented for the potential reversal of the anticoagulant effects of these drugs, from the temporary discontinuation of an agent before elective surgery to suggested emergency procedures in the case of major bleeding events. New, specific reversal agents for dabigatran, apixaban, and rivaroxaban are currently being developed, and dabigatran has received fast-track designation from the US Food and Drug Administration. Until comprehensive clinical guidelines are developed, institutions involved in emergency care should establish their own procedures for the management of patients undergoing anticoagulation who require emergency treatment. These protocols should include appropriate laboratory testing to assess anticoagulant activity

  3. Prestroke physical activity is associated with good functional outcome and arterial recanalization after stroke due to a large vessel occlusion.

    PubMed

    Ricciardi, Ana Clara; López-Cancio, Elena; Pérez de la Ossa, Natalia; Sobrino, Tomás; Hernández-Pérez, María; Gomis, Meritxell; Munuera, Josep; Muñoz, Lucía; Dorado, Laura; Millán, Mónica; Dávalos, Antonio; Arenillas, Juan F

    2014-01-01

    Although multiple studies and meta-analyses have consistently suggested that regular physical activity (PhA) is associated with a decreased stroke risk and recurrence, there is limited data on the possible preconditioning effect of prestroke PhA on stroke severity and prognosis. We aimed to study the association of prestroke PhA with different outcome variables in patients with acute ischemic stroke due to an anterior large vessel occlusion. The Prestroke Physical Activity and Functional Recovery in Patients with Ischemic Stroke and Arterial Occlusion trial is an observational and longitudinal study that included consecutive patients with acute ischemic stroke admitted to a single tertiary stroke center. Main inclusion criteria were: anterior circulation ischemic stroke within 12 h from symptom onset; presence of a confirmed anterior large vessel occlusion, and functional independence previous to stroke. Prestroke PhA was evaluated with the International Physical Activity Questionnaire and categorized into mild, moderate and high levels by means of metabolic equivalent (MET) minutes per week thresholds. The primary outcome measure was good functional outcome at 3 months (modified Rankin scale ≤2). Secondary outcomes were severity of stroke at admission, complete early recanalization, early dramatic neurological improvement and final infarct volume. During the study period, 159 patients fulfilled the above criteria. The mean age was 68 years, 62% were men and the baseline NIHSS score was 17. Patients with high levels of prestroke PhA were younger, had more frequently distal occlusions and had lower levels of blood glucose and fibrinogen at admission. After multivariate analysis, a high level of prestroke PhA was associated with a good functional outcome at 3 months. Regarding secondary outcome variables and after adjustment for relevant factors, a high level of prestroke PhA was independently associated with milder stroke severity at admission, early dramatic

  4. The efficacy and safety of novel oral anticoagulants for the preventive treatment in atrial fibrillation patients: a systematic review and meta-analysis.

    PubMed

    Liu, Guang Jian; Wang, Yun Fu; Chen, Ping You; Chang, Wei; Tu, Ming Li; Chang, Li Ying; Cheng, Ping; Luo, Jie

    2014-09-01

    Novel oral anticoagulants, including direct factor Xa inhibitors and direct factor IIa inhibitors, have been used to prevent stroke in patients with atrial fibrillation (AF) for a decade. In this study, the efficacy and safety of the novel oral anticoagulants were assessed in AF patients. No language restrictions were applied. Study selection and data extraction were carried out by searching PubMed, EMBASE, OVID, the BIOSIS, the Web of Science, Clinical Trials Registers, Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. Each database was searched from its inception date to June 2013. Using odds ratio (OR) as an indicator, we systematically evaluated the primary efficacy endpoints and safety endpoints, as well as 10 secondary endpoints. Compared to the control drugs, the novel oral anticoagulants showed an OR decreased by 26% (OR: 0.74, 95% confidence interval (CI): 0.62-0.88) for stroke or systemic embolism, decreased by 24% (OR: 0.76, 95% CI: 0.64-0.90) for major bleeding, decreased by 10% (OR: 0.90, 95% CI: 0.84-0.95) for death from any cause, decreased by 27% for disabling or fatal stroke (OR: 0.73, 95% CI: 0.54-0.97), decreased by 31% (OR: 0.69, 95% CI: 0.60-0.8) for fatal bleeding, and decreased by 8% (OR: 0.92, 95% CI: 0.88-0.95) for serious adverse events. However, there was no significant difference in acute myocardial infarction, systemic embolism, major bleeding or clinically relevant non-major, all bleeding events, all adverse events and liver function disorder, between the novel oral anticoagulants and control drugs (p > 0.05). Compared to the control drugs, the novel oral anticoagulants showed higher efficiency and safety in patients with AF, as evidenced by their superior performance not only in reducing the risk of stroke or systemic embolism with a lower risk of major bleeding but also in decreasing the incidence of death from any cause, disabling or fatal stroke, serious adverse events and

  5. Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants.

    PubMed

    Cuker, Adam; Siegal, Deborah M; Crowther, Mark A; Garcia, David A

    2014-09-16

    Non-vitamin K oral anticoagulants (NOACs) do not require routine laboratory monitoring. However, laboratory measurement may be desirable in special situations and populations. This study's objective was to systematically review and summarize current evidence regarding laboratory measurement of the anticoagulant activity of dabigatran, rivaroxaban, and apixaban. We searched PubMed and Web of Science for studies that reported a relationship between drug levels of dabigatran, rivaroxaban, and apixaban and coagulation assay results. Study quality was evaluated using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). We identified 17 eligible studies for dabigatran, 15 for rivaroxaban, and 4 for apixaban. For dabigatran, a normal thrombin time excludes clinically relevant drug concentrations. The activated partial thromboplastin time (APTT) and prothrombin time (PT) are less sensitive and may be normal at trough drug levels. The dilute thrombin time (R(2) = 0.92 to 0.99) and ecarin-based assays (R(2) = 0.92 to 1.00) show excellent linearity across on-therapy drug concentrations and may be used for drug quantification. For rivaroxaban and apixaban, anti-Xa activity is linear (R(2) = 0.89 to 1.00) over a wide range of drug levels and may be used for drug quantification. Undetectable anti-Xa activity likely excludes clinically relevant drug concentrations. The PT is less sensitive (especially for apixaban); a normal PT may not exclude clinically relevant levels. The APTT demonstrates insufficient sensitivity and linearity for quantification. Dabigatran, rivaroxaban, and apixaban exhibit variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in NOAC-treated patients. More information on the relationship between drug levels and clinical outcomes is needed. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  6. Anticoagulant and Antiplatelet Therapy in Patients with Atrial Fibrillation and Coronary Artery Disease

    PubMed Central

    Mischke, Karl; Knackstedt, Christian; Marx, Nikolaus

    2012-01-01

    Anticoagulation represents the mainstay of therapy for most patients with atrial fibrillation. Patients on oral anticoagulation often require concomitant antiplatelet therapy, mostly because of coronary artery disease. After coronary stent implantation, dual antiplatelet therapy is necessary. However, the combination of oral anticoagulation and antiplatelet therapy increases the bleeding risk. Risk scores such as the CHA2DS2-Vasc score and the HAS-BLED score help to identify both bleeding and stroke risk in individual patients. The guidelines of the European Society of Cardiology provide a rather detailed recommendation for patients on oral anticoagulation after coronary stent implantation. However, robust evidence is lacking for some of the recommendations, and especially for new oral anticoagulants and new antiplatelets few or no data are available. This review addresses some of the critical points of the guidelines and discusses potential advantages of new anticoagulants in patients with atrial fibrillation after stent implantation. PMID:22577538

  7. Reversal of Direct Oral Anticoagulants: Current Status and Future Directions.

    PubMed

    Weitz, Jeffrey I

    2017-02-01

    Direct oral anticoagulants (DOACs) are increasingly used for prevention and treatment of venous thromboembolism and for prevention of stroke in patients with nonvalvular atrial fibrillation. In phase III clinical trials that included more than 100,000 patients, the DOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with less serious bleeding, particularly less intracranial bleeding. Real-world evidence supports these outcomes. Despite this, some physicians and patients are concerned about serious bleeding or emergencies unless specific reversal agents for the DOACs are available. However, in clinical trials performed without reversal agents, the outcome of major bleeds was similar or better in patients receiving DOACs than in those taking VKAs. Because of their short half-lives, supportive measures are sufficient to manage most bleeds in patients receiving DOACs. Anticoagulant reversal should only be considered with life-threatening bleeds, with bleeds that fail to respond to usual measures and in patients requiring urgent surgery. Idarucizumab is licensed for dabigatran reversal and andexanet alfa is likely to be soon licensed for reversal of rivaroxaban, apixaban, and edoxaban. To ensure responsible use of these agents, every hospital needs a bleeding management algorithm that identifies patients eligible for reversal and outlines appropriate dosing regimens. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2

    PubMed Central

    Diener, Hans-Christoph; Aisenberg, James; Ansell, Jack; Atar, Dan; Breithardt, Günter; Eikelboom, John; Ezekowitz, Michael D.; Granger, Christopher B.; Halperin, Jonathan L.; Hohnloser, Stefan H.; Hylek, Elaine M.; Kirchhof, Paulus; Lane, Deirdre A.; Verheugt, Freek W.A.; Veltkamp, Roland; Lip, Gregory Y.H.

    2017-01-01

    The choice of oral anticoagulant (OAC) for patients with atrial fibrillation (AF) may be influenced by individual clinical features or by patterns of risk factors and comorbidities. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. non-vitamin K oral anticoagulants (NOACs) for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In addition, we discuss the timing of initiation of anticoagulation. In the second of a two-part review, we discuss the use of NOAC for stroke prevention in the following subgroups of patients with AF: (vii) secondary stroke prevention in patients after stroke or transient ischaemic attack (TIA), (viii) patients with acute stroke requiring thrombolysis or thrombectomy, (ix) those initiating or restarting OAC treatment after stroke or TIA, (x) those with renal impairment on dialysis, (xi) the elderly, (xii) those at high risk of gastrointestinal bleeding, and (xiii) those with hypertension. In addition, we discuss adherence and compliance. Finally, we present a summary of treatment suggestions. In specific subgroups of patients with AF, evidence supports the use of particular NOACs and/or particular doses of anticoagulant. The appropriate choice of treatment for these subgroups will help to promote optimal clinical outcomes. PMID:26848150

  9. The impact of pre-injury direct oral anticoagulants compared to warfarin in geriatric G-60 trauma patients.

    PubMed

    Barletta, J F; Hall, S; Sucher, J F; Dzandu, J K; Haley, M; Mangram, A J

    2017-08-01

    Pre-injury oral anticoagulants are associated with worse outcomes in geriatric (G-60) trauma patients, but there are limited data comparing warfarin with direct oral anticoagulants (DOAC). We sought to compare outcomes in G-60 trauma patients taking pre-injury DOACs vs. warfarin. All trauma patients, age ≥60 who were admitted to the hospital and taking an oral anticoagulant pre-injury were retrospectively identified. Patients were excluded if their reason for admission was a suicide attempt or penetrating extremity injury. Outcome measures included blood transfusions, hospital LOS, and mortality. A second analysis was performed, whereby patients were matched using ISS and age. There were 3,941 patients identified; 331 had documentation of anticoagulant use, pre-injury (warfarin, n = 237; DOAC, n = 94). Demographics were similar, but ISS [9 (4-13) vs. 8 (4-9), p = .027], initial INR [2.2 (1.8-2.9) vs. 1.2 (1.1-1.5), p < .001], and the use of pharmacologic reversal agents (48 vs. 14%, p < .001) were higher in the warfarin group. There was no difference in the use of blood transfusions (24 vs. 17%, p = .164) or mortality (5.9 vs. 4.3%, p = .789) between warfarin and DOAC groups, respectively. However, LOS was longer in the warfarin group [5 (3-7.5) vs. 4 (2-6.3) days, p = .02]. Matched analysis showed no difference in blood transfusions (23 vs. 17%, p = .276), mortality (2.1 vs. 4.3%, p = .682) or LOS [5 (3-7) vs. 4 (2-6.3) days, p = .158] between warfarin and DOAC groups, respectively. Pre-injury DOACs are not associated with worse clinical outcomes compared to warfarin in G-60 trauma patients. Higher use of pharmacologic reversal agents with warfarin may be related to differences in mechanism of action and effect on INR.

  10. Development and validation of hospital information system-generated indicators of the appropriateness of oral anticoagulant prescriptions in hospitalised adults: the PACHA study protocol.

    PubMed

    Petit-Monéger, Aurélie; Thiessard, Frantz; Jouhet, Vianney; Noize, Pernelle; Berdaï, Driss; Kret, Marion; Sitta, Rémi; Salmi, Louis-Rachid; Saillour-Glénisson, Florence

    2017-08-31

    The appropriateness of oral anticoagulant prescriptions is a major challenge to improve quality and safety of care. As indicators of the appropriateness of oral anticoagulant prescriptions are lacking, the aim of the study is to develop and validate a panel of such indicators, in hospitalised adults, from the hospital information system of two university hospitals in France. The study will be carried out in four steps: (1) a literature review to identify indicators of the appropriateness of oral anticoagulant prescriptions and their conditions of appropriateness; (2) a Delphi consensus method to assess the potential utility and operational implementation of the selected indicators; (3) techniques of medical data search to implement indicators from the hospital information system and; (4) a cross-sectional study to assess the ability of indicators to detect inappropriate oral anticoagulant prescriptions, performance of medical data search techniques for tracking or retrieving information and the ability of tools to be transferred into other institutions. The fourth step will include up to 80 patient hospital stays for each indicator, depending on the prevalence of inappropriate prescriptions estimated in interim analyses. This work addresses the current lack of quality indicators of the appropriateness of oral anticoagulant prescriptions. We aim to develop and validate such indicators for integrating them into hospital clinical practice, as part of a structured approach to improve quality and safety of care. As each hospital information system is different, we will propose tools transferable to other healthcare institutions to allow an automated construction of these indicators. The PACHA study protocol was approved by institutional review boards and ethics committees (CPP Sud-Ouest et Outre Mer III-DC 2016/119; CPP Ile-de-France II-CDW_2016_0014). Clinical Trial.gov registration: NCT02898090. © Article author(s) (or their employer(s) unless otherwise stated in the

  11. Novel Oral Anticoagulants in Atrial Fibrillation: Update on Apixaban

    PubMed Central

    Mezue, Kenechukwu; Obiagwu, Chukwudi; John, Jinu; Sharma, Abhishek; Yang, Felix; Shani, Jacob

    2017-01-01

    Almost 800,000 new or recurrent strokes occur every year. Atrial fibrillation, the most common cardiac arrhythmia, is a major risk factor for stroke, accounting for 15-20% of ischemic strokes. Apixaban is a direct inhibitor of Factor Xa that was approved in December 2012 by the US Food and Drug Administration (FDA) for the prevention of stroke in patients with non-valvular atrial fibrillation. It is part of a family of novel oral anticoagulants (NOACs) which has advantage over warfarin of less dosing variability, rapid onset of action and no INR monitoring required. Apixaban showed superiority to warfarin in both primary efficacy and primary safety outcomes by simultaneously showing both significantly lower rates of strokes and systemic embolism and a reduced risk of major clinical bleeding in clinical trials. Warfarin remains the anticoagulant of choice for patients with prosthetic heart valves and significant mitral stenosis. There are currently no head-to-head studies that directly compare the different NOACs with one another, but it is expected that there will be more trials in the future that will explore this comparison. Dabigatran is the only NOAC with an FDA approved reversal agent. However, a reversal agent for apixaban is being developed and was successful in recent clinical trials. This review summarizes the clinical trial data on apixaban for atrial fibrillation, compares apixaban to other NOACs and discusses apixaban use in clinical practice. PMID:27450450

  12. The use of novel oral anticoagulants for thromboprophylaxis after elective major orthopedic surgery

    PubMed Central

    Rachidi, Saleh; Aldin, Ehab Saad; Greenberg, Charles; Sachs, Barton; Streiff, Michael; Zeidan, Amer M

    2014-01-01

    Venous thromboembolism is a common cause of morbidity and mortality among patients undergoing elective orthopedic surgery. Due to the high incidence of venous thromboembolism in this setting, perioperative anticoagulation is the recommended approach for thromboprophylaxis. Low molecular weight heparin (LMWH), fondaparinux and warfarin are the agents commonly used for thromboprophylaxis. The well-recognized limitations of warfarin and the inconvenience and discomfort associated with the subcutaneous administration of low molecular weight heparin and fondaparinux inspired intense investigation to develop novel oral anticoagulants (NOACs) with more predictable pharmacokinetics, fewer drug interactions and no need for regular laboratory monitoring. Three NOACs have been demonstrated to be effective for thromboprophylaxis after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in large randomized controlled trials. Here we review the pharmacology of rivaroxaban, dabigatran, and apixaban, summarize the major clinical trials of these agents in thromboprophylaxis after THA and TKA, and discuss the clinical factors to be considered by providers when selecting a NOAC for their patients. PMID:24219550

  13. Odontostomatologic management of patients receiving oral anticoagulant therapy: a retrospective multicentric study

    PubMed Central

    2011-01-01

    Introduction Today, we frequently find patients taking oral anticoagulant therapy (OAT), a prophylaxis against the occurrence of thromboembolic events. An oral surgeon needs to know how to better manage such patients, in order to avoid hemorrhagic and thromboembolic complications. Materials and methods A group of 193 patients (119 men aged between 46 and 82 and 74 women aged between 54 and 76) undergoing OAT for more than 5 years were managed with a standardized management protocol and a 2-months follow-up. The aim of the present study was to apply a protocol, which could provide a safe intra- and postoperative management of patients on OAT. Results Among the 193 patients, only 2 had postoperative complications. Conclusions We think that the protocol used in the present study can be used for complete safety in the treatment of this type of patients. PMID:21771331

  14. Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

    PubMed

    Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

    2014-10-01

    The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. Thieme Medical Publishers

  15. Evaluation of the Ciba Corning Biotrack 512 coagulation monitor for the control of oral anticoagulation.

    PubMed Central

    Jennings, I; Luddington, R J; Baglin, T

    1991-01-01

    The Ciba Corning Biotrack 512 coagulation monitor requires a minimal degree of technical expertise to operate, and is already in use for near-patient testing. This study evaluated the monitor for possible use in decentralised control of oral anticoagulant treatment. The monitor compared well with Manchester Reagent, suggesting that it could be used in areas where this thromboplastin is used for centralised control. The inability of the monitor to allow for locally determined geometric mean normal prothrombin times in the calculation of the International Normalised Ratio (INR), and possibly the high International Sensitivity Index (ISI) of the thromboplastin used with the monitor, resulted in poor comparability with some other thromboplastins, particularly Thrombotest. These problems need to be addressed if the monitor is to be used for decentralised anticoagulant control. PMID:1752987

  16. Comparing intracerebral hemorrhages associated with direct oral anticoagulants or warfarin

    PubMed Central

    Kurogi, Ryota; Nishimura, Kunihiro; Nakai, Michikazu; Kada, Akiko; Kamitani, Satoru; Nakagawara, Jyoji; Toyoda, Kazunori; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Matsuda, Shinya; Yoshimura, Shinichi; Okuchi, Kazuo; Suzuki, Akifumi; Nakamura, Fumiaki; Onozuka, Daisuke; Ido, Keisuke; Kurogi, Ai; Mukae, Nobutaka; Nishimura, Ataru; Arimura, Koichi; Kitazono, Takanari; Hagihara, Akihito

    2018-01-01

    Objectives This cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)–associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database. Methods We analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge. Results DOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039). Conclusions This nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies. PMID:29490916

  17. Secondary prevention of recurrent venous thromboembolism after initial oral anticoagulation therapy in patients with unprovoked venous thromboembolism.

    PubMed

    Robertson, Lindsay; Yeoh, Su Ern; Ramli, Ahmad

    2017-12-15

    Currently, little evidence is available on the length and type of anticoagulation used for extended treatment for prevention of recurrent venous thromboembolism (VTE) in patients with unprovoked VTE who have completed initial oral anticoagulation therapy. To compare the efficacy and safety of available oral therapeutic options (aspirin, warfarin, direct oral anticoagulants (DOACs)) for extended thromboprophylaxis in adults with a first unprovoked VTE, to prevent VTE recurrence after completion of an acceptable initial oral anticoagulant treatment period, as defined in individual studies. For this review, the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (March 2017) as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2). We also searched trials registries (March 2017) and reference lists of relevant articles. We included randomised controlled trials in which patients with a first, symptomatic, objectively confirmed, unprovoked VTE, who had been initially treated with anticoagulants, were randomised to extended prophylaxis (vitamin K antagonists (VKAs), antiplatelet agents, or DOACs) versus no prophylaxis or placebo. We also included trials that compared one type of extended prophylaxis versus another type of extended prophylaxis. Two review authors independently selected studies, assessed quality, and extracted data. We resolved disagreements by discussion. Six studies with a combined total of 3436 participants met the inclusion criteria. Five studies compared extended prophylaxis versus placebo: three compared warfarin versus placebo, and two compared aspirin versus placebo. One study compared one type of extended prophylaxis (rivaroxaban) versus another type of extended prophylaxis (aspirin). For extended prophylaxis versus placebo, we downgraded the quality of the evidence for recurrent VTE and all-cause mortality to moderate owing to concerns arising from risks of selection and performance bias

  18. Acute management of stroke patients taking non-vitamin K antagonist oral anticoagulants Addressing Real-world Anticoagulant Management Issues in Stroke (ARAMIS) Registry: Design and rationale.

    PubMed

    Xian, Ying; Hernandez, Adrian F; Harding, Tina; Fonarow, Gregg C; Bhatt, Deepak L; Suter, Robert E; Khan, Yosef; Schwamm, Lee H; Peterson, Eric D

    2016-12-01

    Non-vitamin K antagonist oral anticoagulants (NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban) have been increasingly used as alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation. Yet there is substantial lack of information on how patients on NOACs are currently treated when they have an acute ischemic stroke and the best strategies for treating intracerebral hemorrhage for those on chronic anticoagulation with warfarin or a NOAC. These are critical unmet needs for real world clinical decision making in these emergent patients. The ARAMIS Registry is a multicenter cohort study of acute stroke patients who were taking chronic anticoagulation therapy prior to admission and are admitted with either an acute ischemic stroke or intracerebral hemorrhage. Built upon the existing infrastructure of American Heart Association/American Stroke Association Get With the Guidelines Stroke, the ARAMIS Registry will enroll a total of approximately 10,000 patients (5000 with acute ischemic stroke who are taking a NOAC and 5000 with anticoagulation-related intracerebral hemorrhage who are on warfarin or a NOAC). The primary goals of the ARAMIS Registry are to provide a comprehensive picture of current treatment patterns and outcomes of acute ischemic stroke patients on NOACs, as well as anticoagulation-related intracerebral hemorrhage in patients on either warfarin or NOACs. Beyond characterizing the index hospitalization, up to 2500 patients (1250 ischemic stroke and 1250 intracerebral hemorrhage) who survive to discharge will be enrolled in an optional follow-up sub-study and interviewed at 3 and 6 months after discharge to assess longitudinal medication use, downstream care, functional status, and patient-reported outcomes. The ARAMIS Registry will document the current state of management of NOAC treated patients with acute ischemic stroke as well as contemporary care and outcome of anticoagulation-related intracerebral hemorrhage. These

  19. International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: Results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries.

    PubMed

    Steinberg, Benjamin A; Gao, Haiyan; Shrader, Peter; Pieper, Karen; Thomas, Laine; Camm, A John; Ezekowitz, Michael D; Fonarow, Gregg C; Gersh, Bernard J; Goldhaber, Samuel; Haas, Sylvia; Hacke, Werner; Kowey, Peter R; Ansell, Jack; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Turpie, Alexander; Verheugt, Freek; Piccini, Jonathan P; Kakkar, Ajay; Peterson, Eric D; Fox, Keith A A

    2017-12-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment. Demographics, comorbidities, and stroke risk of the patients in the GARFIELD-AF (n=51,270), ORBIT-AF I (n=10,132), and ORBIT-AF II (n=11,602) registries were compared (overall N=73,004 from 35 countries). Stroke prevention therapies were assessed among patients with new-onset AF (≤6 weeks). Patients from GARFIELD-AF were less likely to be white (63% vs 89% for ORBIT-AF I and 86% for ORBIT-AF II) or have coronary artery disease (19% vs 36% and 27%), but had similar stroke risk (85% CHA 2 DS 2 -VASc ≥2 vs 91% and 85%) and lower bleeding risk (11% with HAS-BLED ≥3 vs 24% and 15%). Oral anticoagulant use was 46% and 57% for patients with a CHA 2 DS 2 -VASc=0 and 69% and 87% for CHA 2 DS 2 -VASc ≥2 in GARFIELD-AF and ORBIT-AF II, respectively, but with substantial geographic heterogeneity in use of oral anticoagulant (range: 31%-93% [GARFIELD-AF] and 66%-100% [ORBIT-AF II]). Among patients with new-onset AF, non-vitamin K antagonist oral anticoagulant use increased over time to 43% in 2016 for GARFIELD-AF and 71% for ORBIT-AF II, whereas use of antiplatelet monotherapy decreased from 36% to 17% (GARFIELD-AF) and 18% to 8% (ORBIT-AF I and II). Among new-onset AF patients, non-vitamin K antagonist oral anticoagulant use has increased and antiplatelet monotherapy has decreased. However, anticoagulation is used frequently in low-risk patients and inconsistently in those at high risk of stroke. Significant geographic variability in anticoagulation persists and represents an opportunity for improvement. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Dabigatran etexilate versus warfarin as the oral anticoagulant of choice? A review of clinical data.

    PubMed

    Ma, Terry K W; Yan, Bryan P; Lam, Yat-Yin

    2011-02-01

    For many years, warfarin was the only effective oral anticoagulant to prevent and treat thromboembolism. Nevertheless, its clinical use is limited by a narrow therapeutic window, extensive drug interactions, need of strict dietary control and frequent monitoring. The pharmacological response is also unpredictable and highly variable among patients. Suboptimal anticoagulation can lead to detrimental thromboembolic events or life-threatening bleeding. Direct thrombin inhibitor (DTI) activity represents a new class of anticoagulant activity that was intended to replace warfarin. Ximelagatran was the first DTI shown to have similar efficacy to warfarin, but failed to replace it because of a high incidence of liver toxicity. Dabigatran etexilate is another novel DTI with a more predictable pharmacokinetic profile and fewer drug interactions compared with warfarin. Recent large-scaled, randomized studies have shown that it does not share ximelagatran's hepatotoxicity, and is as effective as conventional anticoagulants for venous thromboembolism (VTE) and prophylaxis in atrial fibrillation (AF). These findings led to the approval of dabigatran etexilate for thromboprophylaxis following hip or knee replacement surgery in Europe, Canada and the United Kingdom. Here we summarize the latest evidence concerning the use of dabigatran etexilate in VTE (BISTRO, RE-MODEL, RE-NOVATE, RE-MOBILIZE and RECOVER) and AF (PETRO and RELY). Potential problems related to dabigatran use are also discussed to examine whether it can truly replace warfarin as the gold standard. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. New oral anticoagulants-TURKey (NOAC-TURK): Multicenter cross-sectional study.

    PubMed

    Altay, Servet; Yıldırımtürk, Özlem; Çakmak, Hüseyin Altuğ; Aşkın, Lütfü; Sinan, Ümit Yaşar; Beşli, Feyzullah; Gedikli, Ömer; Özden Tok, Özge

    2017-05-01

    New oral anticoagulants (NOACs) are increasingly used both for prevention of stroke in non-valvular atrial fibrillation (NVAF) and the treatment of venous thromboembolism (VTE). In this study, we aimed to evaluate the current patterns of NOACs treatment in Turkey. Moreover, demographic and clinical parameters and bleeding and/or embolic events under NOACs treatment were analyzed. The New Oral Anticoagulants-TURKey (NOAC-TURK) study was designed as a multicenter cross-sectional study. A total of 2,862 patients from 21 different centers of Turkey under the treatment of NOACs for at least three months were included in this study. Demographic, clinical, and laboratory characteristics of study participants with their medications used were obtained through the NOAC-TURK survey database. Additional necessary medical records were obtained from electronic health records of participating centers. Of the 2. 862 patients, 1.131 (39.5%) were male and the mean age was 70.3±10.2 years. Hypertension was found as the most frequent comorbidity (81%). The most common indication for NOACs was permanent atrial fibrillation (83.3%). NOACs were mainly preferred because of inadequate therapeutic range or overdose during warfarin usage. The most frequent complication was bleeding (n=217, 7.6%), and major bleeding was observed in 1.1% of the patients. Embolic events were observed in 37 patients (1.3%). Rivaroxaban and dabigatran were both more preferred than apixaban. Almost half of the patients (47.6%) were using lower doses of NOACs, which is definitely much more than expected. The NOAC-TURK study showed an important overview of the current NOACs treatment regimens in Turkey. Although embolic and bleeding complications were lower than or similar to previous studies, increased utilization of low-dose NOACs in this study should be considered carefully. According to the results of this study, NOACs treatment should be guided through CHA2DS2-VASc and HASBLED scores to ensure more benefit and

  2. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis.

    PubMed

    Pendlebury, Sarah T; Rothwell, Peter M

    2009-11-01

    Reliable data on the prevalence and predictors of post-stroke dementia are needed to inform patients and carers, plan services and clinical trials, ascertain the overall burden of stroke, and understand its causes. However, published data on the prevalence and risk factors for pre-stroke and post-stroke dementia are conflicting. We undertook this systematic review to assess the heterogeneity in the reported rates and to identify risk factors for pre-stroke and post-stroke dementia. Studies published between 1950 and May 1, 2009, were identified from bibliographic databases, reference lists, and journal contents pages. Studies were included if they were on patients with symptomatic stroke, were published in English, reported on a series of consecutive eligible patients or volunteers in prospective cohort studies, included all stroke or all ischaemic stroke, measured dementia by standard criteria, and followed up patients for at least 3 months after stroke. Pooled rates of dementia were stratified by study setting, inclusion or exclusion of pre-stroke dementia, and by first, any, or recurrent stroke. Pooled odds ratios were calculated for factors associated with pre-stroke and post-stroke dementia. We identified 22 hospital-based and eight population-based eligible cohorts (7511 patients) described in 73 papers. The pooled prevalence of pre-stroke dementia was higher (14.4%, 95% CI 12.0-16.8) in hospital-based studies than in population-based studies (9.1%, 6.9-11.3). Although post-stroke (pre-stroke dementia was excluded to 41.3% (29.6-53.1) in hospital-based studies of recurrent stroke in which pre-stroke dementia was included. The cumulative incidence of dementia after the first year was little greater (3.0%, 1.3-4.7) per year in hospital-based studies

  3. Adoption of direct oral anticoagulants for stroke prevention in atrial fibrillation.

    PubMed

    Baker, D; Wilsmore, B; Narasimhan, S

    2016-07-01

    Direct oral anticoagulants (DOAC) are being increasingly utilised for stroke prevention in atrial fibrillation (AF) and atrial flutter. To analyse the adoption and application of these drugs in a regional hospital inpatient cohort and compare with national prescribing data. Digital medical records identified prescribed anticoagulants for patients admitted with AF and atrial flutter during 2013-2014. Analysis of patient demographics and stroke risk identified trends in prescribing DOAC versus warfarin. For broader comparison, data from the Pharmaceuticals Benefits Scheme were sourced to determine the nation-wide adoption of DOAC. Of the 615 patients identified, 505 (255 in 2013, 250 in 2014) had sufficient records to include in the study. From 2013 to 2014, DOAC prescriptions increased from 9 to 28% (P < 0.001), warfarin and aspirin remained comparatively stable (38-34%, 22-20%), and those prescribed no medication declined (17-8%, P < 0.001). DOAC were prescribed to patients with lower CHA2 DS2 VASc scores than warfarin (3.6 vs 4.4; P = 0.005), lower HAS-BLED scores (1.7 vs 2.3; P < 0.01), higher glomerular filtration rates; 70 vs 63 ml/min; P = 0.002) and younger age (74 vs 77 years; P = 0.006). Nationally, warfarin prescriptions are higher in total numbers but increasing at a slower rate than DOAC, which increased 10-fold (101 158 in 2013, 1 095 985 in 2014). DOAC prescribing grew rapidly from 2013 to 2014, regionally and nationally. Warfarin prescriptions have remained stable, indicating that more patients are being appropriately anticoagulated for AF who previously were not. DOAC were found to be prescribed to patients with lower CHA2 DS2 VASc and HAS-BLED scores, younger age and higher glomerular filtration rates. Aspirin therapy remains over utilised in AF. © 2016 Royal Australasian College of Physicians.

  4. Use of oral anticoagulants in African-American and Caucasian patients with atrial fibrillation: is there a treatment disparity?

    PubMed Central

    Akinboboye, Olakunle

    2015-01-01

    Atrial fibrillation (AF) is a very common cardiac arrhythmia, and its prevalence is increasing along with aging in the developed world. This review discusses racial differences in the epidemiology and treatment of AF between African-American and Caucasian patients. Additionally, the effect of race on warfarin and novel oral anticoagulant use is discussed, as well as the role that physicians and patients play in achieving optimal treatment outcomes. Despite having a lower prevalence of AF compared with Caucasians, African-Americans suffer disproportionately from stroke and its sequelae. The possible reasons for this paradox include poorer access to health care, lower health literacy, and a higher prevalence of other stroke-risk factors among African-Americans. Consequently, it is important for providers to evaluate the effects of race, health literacy, access to health care, and cultural barriers on the use of anticoagulation in the management of AF. Warfarin-dose requirements vary across racial groups, with African-American patients requiring a higher dose than Caucasians to maintain a therapeutic international normalized ratio; the novel oral anticoagulants (dabigatran, rivaroxaban, and apixaban) seem to differ in this regard, although data are currently limited. Minority racial groups are not proportionally represented in either real-world studies or clinical trials, but as more information becomes available and other social issues are addressed, the treatment disparities between African-American and Caucasian patients should decrease. PMID:26056467

  5. NOACs replace VKA as preferred oral anticoagulant among new patients: a drug utilization study in 560 pharmacies in The Netherlands.

    PubMed

    van den Heuvel, J M; Hövels, A M; Büller, H R; Mantel-Teeuwisse, A K; de Boer, A; Maitland-van der Zee, A H

    2018-01-01

    In 2012, around 400.000 patients in the Netherlands were treated with Vitamin K Antagonists (VKA) for thromboembolic diseases. Since 2011, non-VKA oral anticoagulants (NOACs) are available. NOACs do not require frequent INR monitoring which benefits patients, but also imposes a risk of reduced therapy adherence. The objective of this study is to describe uptake and patient adherence of NOACs in The Netherlands until October 2016. Prescription data for 247.927 patients across 560 pharmacies were used to describe patient profiles, uptake of NOACs among new naive patients and switch between VKA and NOACs, and calculate therapy adherence as the Proportion of Days Covered (PDC). During the studied period the share of NOACs in oral anticoagulants has grown to 57% of prescriptions to new patients. More than 70% of new NOAC users were new naive patients and around 26% switched from VKA. The overall share of NOACs among starters is largest in the group of patients of 50-80 years. Calculated compliance rate for NOAC patients shows that 88% of all users are adherent with a PDC higher than 80%. NOAC have overtaken VKA as the major treatment prescribed to new oral anticoagulant patients, and the number of starters on VKA is decreasing. Patients are generally adherent to NOACs during the implementation phase, the period that the medication is used. Fear for inadherence by itself does not need to be a reason for not prescribing NOACs instead of VKA.

  6. Clinical effectiveness and cost-effectiveness of different models of managing long-term oral anticoagulation therapy: a systematic review and economic modelling.

    PubMed

    Connock, M; Stevens, C; Fry-Smith, A; Jowett, S; Fitzmaurice, D; Moore, D; Song, F

    2007-10-01

    To examine the clinical effectiveness and cost-effectiveness of self-testing and self-management of oral anticoagulation treatment compared with clinic-based monitoring. Major electronic databases were searched up to September 2005. A systematic review was undertaken of relevant data from selected studies. Results about complication events and deaths were pooled in meta-analyses using risk difference (RD) as the outcome statistic. Heterogeneity across trials and possible publication bias were statistically measured. Subgroup analyses (post hoc) were conducted to compare results of self-testing versus self-management, low versus high trial quality, trials conducted in the UK versus trials in other countries and industry versus other sponsors. A Markov-type, state-transition model was developed. Stochastic simulations using the model were conducted to investigate uncertainty in estimated model parameters. In the 16 randomised and eight non-randomised trials selected, patient self-monitoring of oral anticoagulation therapy was found to be more effective than poor-quality usual care provided by family doctors and as effective as good-quality specialised anticoagulation clinics in maintaining the quality of anticoagulation therapy. There was no significant RD of major bleeding events between patient self-monitoring and usual care controls and pooled analyses found that compared with primary care or anticoagulation control (AC) clinics, self-monitoring was statistically significantly associated with fewer thromboembolic events. However, the reduction in complication events and deaths was not consistently associated with the improvement of AC; in some trials this may be due to alternative explanations, including patient education and patient empowerment. Also, the improved AC and the reduction of major complications and deaths by patient self-monitoring were mainly observed in trials conducted outside the UK. According to UK-specific data, for every 100 eligible patients

  7. The effects of clopidogrel (Plavix) and other oral anticoagulants on early hip fracture surgery.

    PubMed

    Collinge, Cory A; Kelly, Kevin C; Little, Bert; Weaver, Tara; Schuster, Richard D

    2012-10-01

    Risk for bleeding complications during and after early hip fracture surgery for patients taking clopidogrel and other anticoagulants have not been defined. The purpose of this study is to assess the perioperative bleeding risks and clinical outcome after early hip fracture surgery performed on patients taking clopidogrel (Plavix) and other oral anticoagulants. Study design is a retrospective cohort analysis using data extracted from hospital records and state death records. Regional medical center (level II trauma). Data for 1118 patients ≥60 years of age who had surgical treatment for a hip fracture between 2004 and 2008 were reviewed. Eighty-two patients undergoing late surgery (>3 days after admission) were excluded. Patients taking clopidogrel were compared against those not taking clopidogrel. In addition, patients taking clopidogrel only were compared against cohorts of patients taking both clopidogrel and aspirin, aspirin only, warfarin only, or no anticoagulant. Seventy-four of 1036 patients (7%) were taking clopidogrel, although control groups included 253 patients on aspirin alone, 90 patients on warfarin, and 619 taking no anticoagulants. No significant differences were noted between patients taking clopidogrel and those not taking clopidogrel in estimated blood loss, transfusion requirement, final blood count, hematoma evacuation, hospital length of stay (LOS), or mortality while in hospital or at 1 year. A higher American Society of Anesthesiologists score was seen in the clopidogrel and warfarin groups (P = 0.05 each), increased LOS in the clopidogrel group (P = 0.05), and higher rate of deep vein thrombosis seen in those patients taking warfarin (P = 0.05). Clopidogrel only versus aspirin versus both aspirin and clopidogrel, versus no anticoagulant versus warfarin showed no significant differences in estimated blood loss, transfusion requirement, final blood count, bleeding or perioperative complications, or mortality. Patients undergoing early hip

  8. Real-life Use of Anticoagulants in Venous Thromboembolism With a Focus on Patients With Exclusion Criteria for Direct Oral Anticoagulants.

    PubMed

    Moustafa, Farès; Pesavento, Raffaele; di Micco, Pierpaolo; González-Martínez, José; Quintavalla, Roberto; Peris, Maria-Luisa; Porras, José Antonio; Falvo, Nicolas; Baños, Pilar; Monreal, Manuel

    2018-04-01

    We assessed the real-life use of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and exclusion criteria for randomized trials. From 2013 to 2016, 3,578 of 18,853 patients (19%) had exclusion criteria. Irrespective of which anticoagulant was chosen, they had more VTE recurrences (hazard ratio (HR): 3.10; 95% confidence interval (CI): 2.47-3.88), major bleeds (HR: 4.10; 95% CI: 3.38-4.96), and deaths (HR: 9.47; 95% CI: 8.46-10.6) than those without exclusion criteria. During initial therapy, no patient with exclusion criteria on DOACs (n = 115) recurred, but those on rivaroxaban bled less often (adjusted HR: 0.18; 95% CI: 0.04-0.79) than those on unfractionated heparin (n = 224) and similar to those (n = 3,172) on low-molecular-weight (LMWH) heparin. For long-term therapy, patients on rivaroxaban (n = 151) had nonsignificantly fewer VTE recurrences (adjusted HR: 0.74; 95% CI: 0.08-1.32) and major bleeds (adjusted HR: 0.41; 95% CI: 0.15-1.15) than those on LMWH (n = 2,071). The efficacy and safety of DOACs were similar to standard therapy. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  9. Intracranial hemorrhage in anticoagulated patients with mild traumatic brain injury: significant differences between direct oral anticoagulants and vitamin K antagonists.

    PubMed

    Cipriano, Alessandro; Pecori, Alessio; Bionda, Alessandra Eugenia; Bardini, Michele; Frassi, Francesca; Leoli, Francesco; Lami, Valentina; Ghiadoni, Lorenzo; Santini, Massimo

    2018-03-08

    Prognosis after mild traumatic brain injury (MTBI) on oral anticoagulant therapy (OAT) is uncertain. We evaluated the rate of immediate and delayed traumatic intracranial hemorrhage (ICH) comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) and the safety of a clinical management protocol. In this single-center prospective observational study, we enrolled 220 patients on OAT with MTBI. After a first negative CT scan, asymptomatic patients underwent a close neurological observation; if neurologically stable, they were discharged without a second CT scan and followed up for 1 month. Out of the 220 patients, 206 met the inclusion criteria. 23 of them (11.2%) had a positive first CT scan for ICH. Only 1 (0.5%, 95% CI 0.0-1.4%) died because of ICH; no one required neurosurgical intervention. The observed prevalence rate of immediate ICH resulted statistically higher in VKAs-treated patients compared to those treated with DOACs (15.7 vs. 4.7%, RR 3.34, 95% CI 1.18-9.46, P < 0.05). In the 1-month follow-up, 5 out of the 183 patients with a negative CT scan were lost. Out of the remaining 178 patients, only 3 showed a delayed ICH (1.7%, 95% CI 0.0-3.6%), 1 of them died (0.6%, 95% CI 0.5-1.7%) and the others did not require neurosurgical intervention. DOACs resulted safer than VKAs also in the setting of MTBI. In our observation, the rate of delayed hemorrhage was relatively low. Patients presenting with a negative first CT scan and without neurological deterioration could be safely discharged after a short period of in-ward observation with a low rate of complications and without a second CT scan.

  10. Tranexamic Acid Failed to Reverse the Anticoagulant Effect and Bleeding by an Oral Direct Factor Xa Inhibitor Edoxaban.

    PubMed

    Honda, Yuko; Furugohri, Taketoshi; Morishima, Yoshiyuki

    2018-01-01

    Agents to reverse the anticoagulant effect of edoxaban, an oral direct factor Xa inhibitor, would be desirable in emergency situations. The aim of this study is to determine the effect of tranexamic acid, an antifibrinolytic agent, on the anticoagulant activity and bleeding by edoxaban in rats. A supratherapeutic dose of edoxaban (3 mg/kg) was intravenously administered to rats. Three minutes after dosing, tranexamic acid (100 mg/kg) was given intravenously. Bleeding was induced by making an incision with a blade on the planta 8 min after edoxaban injection and bleeding time was measured. Prothrombin time (PT) and clot lysis were examined. A supratherapeutic dose of edoxaban significantly prolonged PT and bleeding time. Tranexamic acid did not affect PT or bleeding time prolonged by edoxaban, although tranexamic acid significantly inhibited clot lysis in rat plasma. An antifibrinolytic agent tranexamic acid failed to reverse the anticoagulant effect and bleeding by edoxaban in rats. © 2017 S. Karger AG, Basel.

  11. Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

    USGS Publications Warehouse

    Vyas, Nimish B.; Rattner, Barnett A.

    2012-01-01

    Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

  12. Emerging therapeutic uses of direct-acting oral anticoagulants: An evidence-based perspective.

    PubMed

    Raschi, Emanuel; Bianchin, Matteo; De Ponti, Roberto; De Ponti, Fabrizio; Ageno, Walter

    2017-06-01

    Direct-acting oral anticoagulants (DOACs) were claimed to cause a potential paradigm shift in the therapeutic scenario of patients requiring short- and long-term anticoagulation, by virtue of their pharmacological properties, perceived as innovative. The evidence gathered so far (from pre-approval pivotal trials to real-world post-marketing observational data) consistently confirmed that DOACs are overall comparable to vitamin-K antagonists (VKAs) in terms of safety, efficacy and effectiveness and unequivocally documented a consistent and clinically relevant reduced risk of intracranial bleeding in the settings of non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). Interestingly, two parallel paths can be identified in the current research scenario: A) in the aforementioned consolidated therapeutic indications, an innovative approach is directed towards tailored treatment strategies, to identify patients most likely to benefit from one of the different anticoagulant drugs, in particular subpopulations at increased risk of adverse events (e.g., bleeding); B) in unconventional settings, DOACs are gaining interest for potential use in emerging diseases characterized by arterial and venous thromboembolic risk. In these scenarios, the risk-benefit profile of DOACs, as compared to VKAs or heparins, is less defined. The aim of this review is to critically assess the body of evidence underlying emerging therapeutic uses of DOACs (e.g., heparin-induced thrombocytopenia, anti-phospholipid antibody syndrome), including evolving issues in special populations (e.g., patients with VTE and cancer or cirrhosis). This will be achieved by analyzing the strength (i.e., systematic reviews, randomized clinical trials, observational studies, case report/series) and consistency (i.e., concordance) of both published and unpublished evidence registered in major public repositories. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Is there a role for pharmacokinetic/pharmacodynamic-guided dosing for novel oral anticoagulants?

    PubMed

    Chan, Noel; Sager, Philip T; Lawrence, Jack; Ortel, Thomas's; Reilly, Paul; Berkowitz, Scott; Kubitza, Dagmar; Eikelboom, John; Florian, Jeffry; Stockbridge, Norman; Rose, Martin; Temple, Robert; Seltzer, Jonathan H

    2018-05-01

    The novel direct oral anticoagulants (NOACs) represent a major advance in oral anticoagulant therapy and are replacing vitamin K antagonists as the preferred options for many indications. Given in fixed doses without routine laboratory monitoring, they have been shown to be at least as effective in reducing thromboembolic stroke as dose-adjusted warfarin in phase 3 randomized trials and less likely to cause hemorrhagic stroke. Pharmacokinetic and/or pharmacodynamic subanalyses of the major NOAC trials in patients with atrial fibrillation have established relationships between clinical characteristics, and drug levels and/or pharmacodynamic responses with both efficacy and safety. Based on these analyses, pharmaceutical manufacturers and regulatory authorities have provided contraindications and dosing recommendations based on clinical characteristics that are associated with drug levels and/or pharmacodynamic responses, stroke reduction, and bleeding risk to optimize the risk-benefit profile of the NOACs in the real world. The current fixed-dosing strategy of NOACs has triggered discussions about the potential value of laboratory monitoring and dose adjustment in customizing drug exposure to further improve the safety and efficacy of the NOACs in patients with atrial fibrillation. As there is neither high-quality evidence nor consensus about the potential role of laboratory monitoring and dose adjustment for the NOACs, a Cardiac Research Safety Consortium "Think Tank" meeting was held at the American College of Cardiology Heart House in December 2015 to discussions these issues. This manuscript reports on the deliberations and the conclusions reached at that meeting. Copyright © 2017. Published by Elsevier Inc.

  14. Anticoagulant Preferences and Concerns among Venous Thromboembolism Patients.

    PubMed

    Lutsey, Pamela L; Horvath, Keith J; Fullam, Lisa; Moll, Stephan; Rooney, Mary R; Cushman, Mary; Zakai, Neil A

    2018-03-01

     Warfarin and direct oral anticoagulants (DOACs) are used for the initial treatment and secondary prevention of venous thromboembolism (VTE), and have similar efficacy. Patient concerns and preferences are important considerations when selecting an anticoagulant, yet these are not well studied.  VTE patients ( n  = 519) were surveyed from online sources (clotconnect.org, stoptheclot.org and National Blood Clot Alliance Facebook followers [ n  = 495]) and a haematology clinic in Vermont ( n  = 24).  Patients were 83% females and on average (±standard deviation [SD]) 45.7 ± 13.1 years; 65% self-reported warfarin as their initial VTE treatment and 35% a DOAC. Proportions reporting being extremely concerned about the following outcomes were as follows: recurrent VTE 33%, major bleeding 21%, moderate bleeding 16% and all-cause death 29%. When asked about oral anticoagulant characteristics, patients strongly preferred anticoagulants that are reversible (53%), and for which blood drug levels can be monitored (30%). Lower proportions agreed with statements that regular blood testing is inconvenient (18%), that they are comfortable using the newest drug versus an established drug (15%) and that it is difficult to change their diet to accommodate their anticoagulant (17%). In multivariable-adjusted models, patients tended to have had as their initial treatment, and to currently be taking, the oral anticoagulant option they personally preferred.  Patients held the greatest concern for recurrent VTE and mortality, regardless of which treatment they were prescribed. Potential weaknesses of warfarin (e.g., dietary restrictions, regular monitoring) were generally not considered onerous, while warfarin's advantages (e.g., ability to monitor) were viewed favourably. Schattauer GmbH Stuttgart.

  15. Direct Oral Anticoagulants in Emergency Trauma Admissions.

    PubMed

    Maegele, Marc; Grottke, Oliver; Schöchl, Herbert; Sakowitz, Oliver A; Spannagl, Michael; Koscielny, Jürgen

    2016-09-05

    Direct (non-vitamin-K-dependent) oral anticoagulants (DOAC) are given as an alternative to vitamin K antagonists (VKA) to prevent stroke and embolic disease in patients with atrial fibrillation that is not due to pathology of the heart valves. Fatal hemorrhage is rarer when DOACs are given (nonvalvular atrial fibrillation: odds ratio [OR] 0.68; 95% confidence interval [95% CI: 0.48; 0.96], and venous thromboembolism: OR 0.54; [0.22; 1.32]). 48% of emergency trauma patients need an emergency operation or early surgery. Clotting disturbances elevate the mortality of such patients to 43%, compared to 17% in patients without a clotting disturbance. This underscores the impor tance of the proper, targeted treatment of trauma patients who are aking DOAC. This review is based on articles retrieved by a selective search in PubMed and on a summary of expert opinion and the recommendations of the relevant medical specialty societies. Peak DOAC levels are reached 2-4 hours after the drug is taken. In patients with normal renal and hepatic function, no drug accumulation, and no drug interactions, the plasma level of DOAC 24 hours after administration is generally too low to cause any clinically relevant risk of bleeding. The risk of drug accumulation is higher in patients with renal dysfunction (creatinine clearance [CrCl] of 30 mL/min or less). Dabigatran levels can be estimated from the thrombin time, ecarin clotting time, and diluted thrombin time, while levels of factor Xa inhibitors can be estimated by means of calibrated chromogenic anti-factor Xa activity tests. Routine clotting studies do not reliably reflect the anticoagulant activity of DOAC. Surgery should be postponed, if possible, until at least 24-48 hours after the last dose of DOAC. For patients with mild, non-life threatening hemorrhage, it suffices to discontinue DOAC; for patients with severe hemorrhage, there are special treatment algorithms that should be followed. DOACs in the setting of hemorrhage are a

  16. Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies.

    PubMed

    Suleria, Hafiz Ansar Rasul; Masci, Paul P; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A; Gobe, Glenda C

    2017-08-04

    Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic.

  17. Venous hemostasis postcatheter ablation of atrial fibrillation while under therapeutic levels of oral and intravenous anticoagulation.

    PubMed

    Issa, Ziad F; Amr, Bashar S

    2015-11-01

    Catheter ablation of atrial fibrillation (AF) requires utilizing multiple venous femoral sheaths in conjunction with aggressive periprocedural anticoagulation, which can lead to increased risk of vascular access complications. The objective of this study is to evaluate the safety and efficacy of the "figure-of-eight" ("F-8") suture technique for femoral venous hemostasis while on therapeutic doses of intravenous anticoagulation at the time of sheath removal. In this case-control analysis, 376 consecutive patients underwent AF ablation while on uninterrupted oral anticoagulation and received intraprocedural heparin. In the first 253 patients (the control group), manual pressure was used for femoral venous hemostasis after reversal of heparin effects. The subsequent 123 patients (the F-8 group) had femoral venous hemostasis using the F-8 suture technique and while under therapeutic heparin effects. The F-8 subcutaneous suture technique achieved adequate venous hemostasis in 98.4% of patients. As compared to the control group, there was significantly less frequent utilization of the FemoStop compression assist device (1.2 vs. 16.8%, p < 0.0001) and in a significantly shorter interval (6.8 ± 5.7 vs. 50.7 ± 12.2 min, p < 0.0001). Vascular access complications and thromboembolic events occurred in 9.8% in the F-8 group vs. 13.0% in the control group (p = 0.678). Immediate hemostasis of the femoral venous access sites after insertion of multiple sheaths for AF ablation in the presence of anticoagulation can be safely and effectively achieved using the F-8 suture technique. This technique helps minimize the period of inadequate anticoagulation immediately following ablation and shortens the time required to achieve adequate hemostasis.

  18. Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review.

    PubMed

    Thibault, Nathan; Morrill, Amanda M; Willett, Kristine C

    The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants, the primary adverse event (AE) associated with dabigatran is bleeding. Until the FDA approval of idarucizumab, there had been no reversal agent for dabigatran-induced anticoagulation in patients with life-threatening or uncontrollable bleeding, or those requiring emergent procedures. The primary purpose of this review is to summarize the safety and efficacy of idarucizumab, a monoclonal antibody fragment, and its use as a reversal agent for dabigatran. A literature search was conducted through MEDLINE (1946 to November week 1 2015) and Embase (1980-2015 week 46) using the search term idarucizumab. Clinicaltrials.gov was consulted for a comprehensive list of ongoing and completed studies. Additional studies were identified through bibliographical citations. Clinical trials in animals and humans published in English evaluating the safety and efficacy of idarucizumab for reversal of anticoagulant treatment with dabigatran were included for review. Idarucizumab has been shown to significantly reverse the anticoagulant effects of dabigatran in both healthy volunteers and patients requiring a reversal agent because of either overt bleeding or an emergency surgery or invasive procedure. The most common AEs were headache, nasopharyngitis, back pain, skin irritation, hypokalemia, delirium, constipation, pyrexia, and pneumonia. Deaths reported in idarucizumab studies were attributed to either the index event or a preexisting comorbidity. Most adverse effects were minor, but 21 serious AEs have been reported in the published data including thrombotic events. Given the increased use of direct oral anticoagulants, such as dabigatran, a need for specific reversal agents exists. Idarucizumab has been shown to be safe and effective in the reversal of dabigatran-induced anticoagulation in patients requiring emergent

  19. Surgeon's guide to anticoagulant and antiplatelet medications part two: antiplatelet agents and perioperative management of long-term anticoagulation

    PubMed Central

    Yeung, Louise Y Y; Sarani, Babak; Weinberg, Jordan A; McBeth, Paul B; May, Addison K

    2016-01-01

    An increasing number of potent antiplatelet and anticoagulant medications are being used for the long-term management of cardiac, cerebrovascular, and peripheral vascular conditions. Management of these medications in the perioperative and peri-injury settings can be challenging for surgeons, mandating an understanding of these agents and the risks and benefits of various management strategies. In this two part review, agents commonly encountered by surgeons in the perioperative and peri-injury settings are discussed and management strategies for patients on long-term antiplatelet and anticoagulant therapy reviewed. In part one, we review warfarin and the new direct oral anticoagulants. In part two, we review antiplatelet agents and assessment of platelet function and the perioperative management of long-term anticoagulation and antiplatelet therapy. PMID:29767644

  20. Outcome of Secondary Stroke Prevention in Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants.

    PubMed

    Nakase, Taizen; Moroi, Junta; Ishikawa, Tatsuya

    2018-05-01

    Since non-vitamin K antagonist oral anticoagulants (NOACs) were released for clinical use, many studies have investigated its effectiveness in stroke prevention. In this study, to determine whether or not there is a difference in outcome in secondary stroke prevention between warfarin and NOACs, patients with embolic stroke with newly prescribed anticoagulants were prospectively analyzed. Patients with acute ischemic stroke, who newly started anticoagulant therapy, were consecutively asked to participate in this study. Enrolled patients (76.3 ± 11.0 years old) were classified into warfarin (n = 48), dabigatran (n = 73), rivaroxaban (n = 49), and apixaban (n = 65). The outcome in 1 year was prospectively investigated at outpatient clinic or telephone interview. Recurrence of stroke and death was considered as the critical incidence. The prevalence of risk factors was not different among all medicines. Patients with dabigatran showed significantly younger onset age (P < .001: 72.2 years old) and milder neurologic deficits than patients on other medicines (P < .001). Cumulative incident rates were 7.1%, 15.3%, 19.0%, and 29.7% for dabigatran, apixaban, rivaroxaban, and warfarin, respectively. Dabigatran showed relatively better outcome compared with warfarin (P = .069) and rivaroxaban (P = .055). All patients on NOACs presented lower cumulative stroke recurrence compared with warfarin. Even in the situation of secondary stroke prevention, noninferiority of NOACs to warfarin might be demonstrated. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type

    PubMed Central

    Wilson, Duncan; Charidimou, Andreas; Shakeshaft, Clare; Ambler, Gareth; White, Mark; Cohen, Hannah; Yousry, Tarek; Al-Shahi Salman, Rustam; Lip, Gregory Y.H.; Brown, Martin M.; Jäger, Hans Rolf

    2016-01-01

    Objective: To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non–vitamin K oral anticoagulants (NOAC)–associated ICH to warfarin-associated ICH. Methods: In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors. Results: We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3–5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0–21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037). Conclusions: In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH. PMID:26718576

  2. Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions.

    PubMed

    Ebner, Matthias; Birschmann, Ingvild; Peter, Andreas; Härtig, Florian; Spencer, Charlotte; Kuhn, Joachim; Blumenstock, Gunnar; Zuern, Christine S; Ziemann, Ulf; Poli, Sven

    2017-09-01

    In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation. Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations <30 ng/mL were calculated. Receiver operating characteristic analyses were used to define reagent-specific cutoff values. Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations <30 ng/mL (rivaroxaban/PT: specificity, 77%/sensitivity, 94%; apixaban/PT: specificity, 13%/sensitivity, 94%, dabigatran/aPTT: specificity, 49%/sensitivity, 91%). Normal TT was 100% specific for dabigatran, but sensitivity was 26%. In contrast, reagent-specific PT and aPTT cutoffs provided >95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established. Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02371044 and NCT02371070. © 2017 American Heart Association, Inc.

  3. Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type.

    PubMed

    Wilson, Duncan; Charidimou, Andreas; Shakeshaft, Clare; Ambler, Gareth; White, Mark; Cohen, Hannah; Yousry, Tarek; Al-Shahi Salman, Rustam; Lip, Gregory Y H; Brown, Martin M; Jäger, Hans Rolf; Werring, David J

    2016-01-26

    To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non-vitamin K oral anticoagulants (NOAC)-associated ICH to warfarin-associated ICH. In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors. We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3-5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0-21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037). In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH. © 2015 American Academy of Neurology.

  4. Risks of postextraction bleeding after receiving direct oral anticoagulants or warfarin: a retrospective cohort study

    PubMed Central

    Yagyuu, Takahiro; Kawakami, Mao; Ueyama, Yoshihiro; Imada, Mitsuhiko; Kurihara, Miyako; Matsusue, Yumiko; Imai, Yuichiro; Yamamoto, Kazuhiko; Kirita, Tadaaki

    2017-01-01

    Objective The effect of direct oral anticoagulants (DOACs) on the risk of bleeding after tooth extraction remains unclear. This study aimed to evaluate the incidence of postextraction bleeding among patients who received DOAC and vitamin K antagonists (VKAs), such as warfarin. Design This study was a retrospective cohort analysis. Incidence rates and propensity score-matched regression models were used to compare the risks of bleeding after tooth extractions involving DOACs and VKAs. Setting The study took place in a single university hospital in Japan. Participants Between April 2013 and April 2015, 543 patients underwent a total of 1196 simple tooth extractions. Primary outcome measure The primary outcome measure was the occurrence of postextraction bleeding, which was defined as bleeding that could not be stopped by biting down on gauze and required medical treatment between 30 min and 7 days after the extraction. Results A total of 1196 tooth extractions (634 procedures) in 541 patients fulfilled the study criteria, with 72 extractions (41 procedures) involving DOACs, 100 extractions (50 procedures) involving VKAs and 1024 extractions (543 procedures) involving no anticoagulants. The incidences of postextraction bleeding per tooth for the DOAC, VKA and no anticoagulant extractions were 10.4%, 12.0% and 0.9%, respectively. The incidences of postextraction bleeding per procedure for DOACs, VKAs and no anticoagulants were 9.7%, 10.0% and 1.1%, respectively. In comparison to the VKA extractions, the DOAC extractions did not significantly increase the risk of postextraction bleeding (OR 0.69, 95% CIs 0.24 to 1.97; p=0.49). Conclusions The risk of postextraction bleeding was similar for DOAC and VKA extractions. PMID:28827248

  5. [Quality control of oral anticoagulant therapy in Primary Care in Madrid City, Spain: CHRONOS-TAO study].

    PubMed

    Alonso Roca, Rafael; Figueroa Guerrero, Carmen Arlene; Mainar de Paz, Victoria; Arribas García, M Paz; Sánchez Perruca, Luis; Rodríguez Barrientos, Ricardo; Casado López, Mariano; Pedraza Flechas, Ana M

    2015-09-07

    To determine quality control of patients with oral anticoagulant treatment recruited in Primary Care (PC) using the Rosendaal method to estimate time in therapeutic range (TTR) and comparing it with fraction of international normalized ratio (INR) in range and cross-sectional analysis (last INR registred). A retrospective observational study based on electronic medical record in routine clinical practice. PC centers (262) in Madrid. We included all patients with acenocumarol treatment, with an INR therapeutic range established between 2 and 3. We excluded patients with valvular pathology and disrupted clinical follow up in PC (<3 INR determinations in the studied period, a period of>90 days or ≥ 3 periods of>60 days between 2 determinations). The final population was 49,312 patients. The variables considered were all INR values and their respective dates. TTR was calculated by the 3 methods above mentioned. We considered "therapeutic range" INR between 2-3 and "adjusted range" INR between 1.8-3.2. Optimal control for each patient was considered TTR>60%. By using Rosendaal method, TTR was 66.8% (81.7% adjusted), with a percentage of total INR in range was 58.8% (66.5% adjusted), and, with the cross-sectional analysis, it was 70.5% (76.8% adjusted). Mean TTR was 65% (standard deviation 20.3), and the percentage of patients with TTR>60% was 63.3% (88.1% adjusted). The quality control of patients with oral anticoagulants in PC in Madrid is acceptable, similar or higher to other studies and pivotal trials of new anticoagulants. Compared to the Rosendaal method, total fraction of INR underestimates quality control, and cross-sectional analysis slightly overestimates it. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  6. Hemostasis and Post-operative Care of Oral Surgical Wounds by Hemcon Dental Dressing in Patients on Oral Anticoagulant Therapy: A Split Mouth Randomized Controlled Clinical Trial.

    PubMed

    Kumar, K R Ashok; Kumar, Jambukeshwar; Sarvagna, Jagadesh; Gadde, Praveen; Chikkaboriah, Shwetha

    2016-09-01

    Hemostasis is a fundamental management issue post-operatively in minor oral surgical procedures. To ensure safety and therapeutic efficacy in patients, under oral anti coagulant therapy, is complicated by necessity for frequent determination of prothrombin time or international normalised ratio. The aim of the study was to determine whether early hemostasis achieved by using Hemcon Dental Dressing (HDD) will affect post-operative care and surgical healing outcome in minor oral surgical procedures. A total of 30 patients, aged 18 years to 90 years, except those allergic to seafood, who consented to participate, were enrolled into this study. Patients were required to have two or more surgical sites so that they would have both surgical and control sites. All patients taking Oral Anticoagulation Therapy (OAT) were included for treatment in the study without altering the anticoagulant regimens. Institutional Review Board approval was obtained for the same. The collected data was subjected to statistical analysis using unpaired t-test. All HDD surgically treated sites achieved hemostasis in 1.49 minutes and control wounds in 4.06 minutes (p < 0.001). Post-operative pain at HDD treated sites (1.87,1.27 on 1 st and 3 rd day respectively) was significantly lower than the control sites (4.0,1.87 on 1 st and 3 rd day respectively) p-value (0.001, 0.001 respectively). HDD treated oral surgery wounds achieved statistically significant improved healing both at 1 st and 3 rd post-operative days (p <0.0001). The HDD has been proven to be a clinically effective hemostatic dressing material that significantly shortens bleeding time following minor oral surgical procedures under local anaesthesia, including those patients taking OAT. Patients receiving the HDD had improved surgical wound healing as compared to controls.

  7. Management of Bleeding With Non-Vitamin K Antagonist Oral Anticoagulants in the Era of Specific Reversal Agents.

    PubMed

    Ruff, Christian T; Giugliano, Robert P; Antman, Elliott M

    2016-07-19

    Vitamin K antagonists are commonly used by clinicians to provide anticoagulation to patients who have or are at risk of having thrombotic events. In addition to familiarity with the dosing and monitoring of vitamin K antagonists, clinicians are accustomed to using vitamin K if there is a need to reverse the anticoagulant effect of vitamin K antagonists. There are now 4 new non-vitamin K antagonist oral anticoagulants (NOACs) that are attractive alternatives to vitamin K antagonists. Despite similar or lower rates of serious bleeding with NOACs in comparison with warfarin, there is a pressing need for strategies to manage bleeding when it does occur with NOACs and to reverse the pharmacological effect of these agents if needed. Important steps in minimizing bleeding risks with NOACs include dose adjustment of the agents in the setting of renal dysfunction and avoidance of the concomitant use of other antithrombotic agents if feasible. Laboratory measurement of the anticoagulant effect of NOACs is best accomplished with specialized assays, although some of the more widely available coagulation tests can provide information that is potentially useful to clinicians. Nonspecific hemostatic agents such as prothrombin complex concentrates and recombinant factor VIIa can be used to reverse the effect of NOACs. More specific reversing agents include the approved humanized monoclonal antibody fragment idarucizumab for reversing the effects of dabigatran, the investigational factor Xa decoy andexanet alfa, and the synthetic small molecule ciraparantag. Both andexanet and ciraparantag have been reported to reverse the effects of the anti-Xa NOACs (rivaroxaban, apixaban, and edoxaban), and a number of other anticoagulant agents in common clinical use, as well. © 2016 American Heart Association, Inc.

  8. Use of novel oral anticoagulants for the treatment of venous thromboembolism and its considerations in Asian patients

    PubMed Central

    Lee, Yun-Jeong

    2014-01-01

    Parenteral anticoagulation followed by warfarin has been conventionally used for the treatment of venous thromboembolism (VTE). However, there are numerous troublesome characteristics of warfarin that prompted the development of novel oral anticoagulants (NOACs) for the treatment of VTE. Asians are reported to be at an increased risk of bleeding with warfarin, and while the reported incidence of VTE in Asians is lower than in Caucasians, the annual rate of VTE in Asia is rising along with the need for better oral anticoagulant options. Recently, several Phase III clinical trials with NOACs for the treatment and prevention of VTE recurrence have been published. For the treatment of VTE, the four NOACs – dabigatran, rivaroxaban, apixaban, and edoxaban – each showed comparable efficacy outcomes while resulting in better safety outcomes when compared with conventional treatment. In these trials, Asian patients had comparable efficacy and safety outcomes as other races, except in the edoxaban trial, in which the Asian subgroup had better safety profiles than other races, although further confirmation is necessary. For secondary prevention, dabigatran was compared with conventional treatment and showed similar efficacy and safety outcomes. When NOACs were compared with placebo for secondary prevention of VTE, they showed superior efficacy and increased bleeding except for apixaban, which showed comparable major bleeding and composite of major and clinically relevant nonmajor bleeding rates as placebo. No significant differences in the outcomes based on race were observed in the Asian subgroups for secondary prevention. Therefore, NOACs can be used with similar efficacy and at least similar or superior safety compared with conventional treatment in the treatment of VTE, and at no increased risk in Asian patients. PMID:25328399

  9. Fitting the right non-vitamin K antagonist oral anticoagulant to the right patient with non-valvular atrial fibrillation: an evidence-based choice.

    PubMed

    Li, Yan-Guang; Pastori, Daniele; Lip, Gregory Y H

    2018-06-01

    Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with an increased risk of ischemic stroke (IS) and systemic embolism (SE). Stroke prevention is a key element for the overall management of AF patients. The non-vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, apixaban and edoxaban, are at least as effective as warfarin in reducing IS/SE with a lower rate of major bleeding. Various analyses from the large Phase III randomized trials demonstrated different efficacy and safety of NOACs in specific subgroups of patients. The randomized trials are supplemented by effectiveness and safety data from real-world observational cohorts following the availability of these drugs for use in everyday clinical practice. Given the clinical heterogeneity of AF patients, the available data from trials and real-world studies allow us to fit the right NOAC to the particular patient's characteristics, with the aim of optimizing outcomes for the individual patient. This review article aims to provide a summary of the evidence on the performance of NOACs in AF patients with specific clinical characteristics. Evidence-based suggestions are presented to provide a simple and viable strategy for clinicians for the choice of a particular NOAC. KEY MESSAGE Given the different performance of the new-oral anticoagulants in patients with the different clinical situation, evidence-based choice of fitting the right new-oral anticoagulants to the patients is provided in this review article.

  10. Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies

    PubMed Central

    Masci, Paul P.; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A.; Gobe, Glenda C.

    2017-01-01

    Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic. PMID:28777290

  11. Novel anticoagulants for stroke prevention in patients with atrial fibrillation.

    PubMed

    Jalota, A; Scarabelli, T M; Saravolatz, L; Bakhsh, M U; Agrawal, P; Jalota, R; Chen-Scarabelli, C; Fuster, V; Halperin, J

    2014-06-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia that can potentially result in stroke. Vitamin K antagonists (VKA) like warfarin were for many decades the only oral anticoagulants available for stroke prevention in patients with non-valvular atrial fibrillation (AF) at high risk of stroke. Recently, new oral anticoagulants (NOACS) have been introduced that act via direct inhibition of thrombin (dabigatran) or activated factor X (edoxaban, rivaroxaban and apixaban). Unlike VKAs, these anticoagulants do not require routine INR monitoring and posses favorable pharmacological properties. NOACs act rapidly, and have a stable and predictable dose-related anticoagulant effect with few clinically relevant drug-drug interactions. Phase III trials comparing these agents to warfarin for stroke prevention in patients with non-valvular AF demonstrated that they are at least as efficacious and safe as warfarin. Evolution of clinical guidelines to incorporate the new anticoagulants for stroke prevention in non-valvular AF may result in a reduction in the incidence of AF-related strokes. Safe and effective use of these new drugs in clinical practice requires understanding of their distinct pharmacological properties.

  12. Effects of Prehospital Thrombolysis in Stroke Patients With Prestroke Dependency.

    PubMed

    Nolte, Christian H; Ebinger, Martin; Scheitz, Jan F; Kunz, Alexander; Erdur, Hebun; Geisler, Frederik; Braemswig, Tim-Bastian; Rozanski, Michal; Weber, Joachim E; Wendt, Matthias; Zieschang, Katja; Fiebach, Jochen B; Villringer, Kersten; Grittner, Ulrike; Kaczmarek, Sabina; Endres, Matthias; Audebert, Heinrich J

    2018-03-01

    Data on effects of intravenous thrombolysis on outcome of patients with ischemic stroke who are dependent on assistance in activities of daily living prestroke are scarce. Recent registry based analyses in activities of daily -independent patients suggest that earlier start of intravenous thrombolysis in the prehospital setting leads to better outcomes when compared with the treatment start in hospital. We evaluated whether these observations can be corroborated in patients with prestroke dependency. This observational, retrospective analysis included all patients with acute ischemic stroke depending on assistance before stroke who received intravenous thrombolysis either on the Stroke Emergency Mobile (STEMO) or through conventional in-hospital care (CC) in a tertiary stroke center (Charité, Campus Benjamin Franklin, Berlin) during routine care. Prespecified outcomes were modified Rankin Scale scores of 0 to 3 and survival at 3 months, as well as symptomatic intracranial hemorrhage. Outcomes were adjusted in multivariable logistic regression. Between February 2011 and March 2015, 122 of 427 patients (28%) treated on STEMO and 142 of 505 patients (28%) treated via CC needed assistance before stroke. Median onset-to-treatment times were 97 (interquartile range, 69-159; STEMO) and 135 (interquartile range, 98-184; CC; P <0.001) minutes. After 3 months, modified Rankin Scale scores of 0 to 3 was observed in 48 STEMO patients (39%) versus 35 CC patients (25%; P =0.01) and 86 (70%, STEMO) versus 85 (60%, CC) patients were alive ( P =0.07). After adjustment, STEMO care was favorable with respect to modified Rankin Scale scores of 0 to 3 (odds ratio, 1.99; 95% confidence interval, 1.02-3.87; P =0.042) with a nonsignificant result for survival (odds ratio, 1.73; 95% confidence interval, 0.95-3.16; P =0.07). Symptomatic intracranial hemorrhage occurred in 5 STEMO versus 12 CC patients (4.2% versus 8.5%; P =0.167). The results of this study suggest that earlier, prehospital

  13. The prevalence of oral anticoagulation in patients with atrial fibrillation in Portugal: Systematic review and meta-analysis of observational studies.

    PubMed

    Caldeira, Daniel; Barra, Márcio; David, Cláudio; Costa, João; Ferreira, Joaquim J; Pinto, Fausto J

    2014-09-01

    Oral anticoagulation (OAC) is an effective treatment in the prevention of thromboembolic events in patients with atrial fibrillation (AF). The aim of this review was to estimate the prevalence of OAC therapy in patients with AF in Portugal. MEDLINE, the Index of Portuguese Medical Journals and SIBUL (the Bibliographic Catalog of the Integrated Library System of the University of Lisbon) were searched for Portuguese observational studies reporting the proportion of anticoagulated patients with AF. The pooled estimated prevalence of anticoagulated patients and respective 95% confidence interval (CI) were determined by means of a meta-analysis. Seven studies were included for analysis, of which four were conducted in a hospital environment and three in the general community. These studies enrolled a total of 891 patients with AF. The pooled estimated prevalence of anticoagulated patients was 40% (95% CI: 32-48%). The prevalence of OAC in Portuguese AF patients is low. There is a need to promote change in OAC prescribing habits for AF patients in Portugal, in accordance with international guidelines. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  14. Treating pulmonary embolism in Pacific Asia with direct oral anticoagulants.

    PubMed

    Cohen, Alexander; Jeyaindran, Sinnadurai; Kim, Jae Yeol; Park, Kihyuk; Sompradeekul, Suree; Tambunan, Karmel L; Tran, Huyen; Tsai, I-Chen; Ward, Christopher; Wong, Raymond

    2015-08-01

    Pulmonary embolism (PE) is the principal preventable cause of in-hospital deaths. Prevalence of PE in Asians is uncertain but undoubtedly underestimated. Asians and Caucasians have similar non-genetic risk factors for PE, and there is mounting evidence that PE affects Asians much more commonly than previously supposed; incidence, especially among high-risk patients, may approach that in Caucasians. Furthermore, PE incidence in Asia is increasing, due to both increased ascertainment, and also population ageing and growing numbers of patients with predisposing risk factors. Despite being warranted, thromboprophylaxis for high-risk patients is not routine in Pacific Asian countries/regions. There also appears to be scope to implement venous thromboembolism (VTE) management guidelines more assiduously. Anticoagulants, primarily heparins and warfarin, have been the mainstays of VTE management for years; however, these agents have limitations that complicate routine use. The complexity of current guidelines has been another barrier to applying evidence-based recommendations in everyday practice. Updated management approaches have considerable potential to improve outcomes. New oral anticoagulants that are easier to administer, require no, or much less, monitoring or dose-adjustment and have a favourable risk/benefit profile compared with conventional modalities, may offer an alternative with the potential to simplify VTE management. However, more information is required on practical management and the occurrence and treatment of bleeding complications. Increasing recognition of the burden of PE and new therapeutic modalities are altering the VTE management landscape in Pacific Asia. Consequently, there is a need to further raise awareness and bridge gaps between the latest evidence and clinical practice. Copyright © 2015. Published by Elsevier Ltd.

  15. Use of Oral Anticoagulant Therapy in Older Adults with Atrial Fibrillation after Acute Ischemic Stroke

    PubMed Central

    McGrath, Emer R.; Go, Alan S.; Chang, Yuchiao; Borowsky, Leila H.; Fang, Margaret C.; Reynolds, Kristi; Singer, Daniel E.

    2016-01-01

    Objective To explore barriers to anticoagulation among older atrial fibrillation (AF) patients at high risk for stroke and identify opportunities where interventions might increase use of oral anticoagulants (OAC). Design Retrospective cohort study Setting Two large community-based AF cohorts Participants 1405 patients (mean age 79 years) with ischemic stroke surviving hospitalization. Measurements Using structured chart review, we identified reasons for non-use of OACand assessed one-year post-stroke survival. Logistic regression identified correlates of OAC non-use. Results The median CHA2DS2-VASc score was 5, yet 44% of patients were not prescribed OAC at discharge. The most frequent (non-mutually exclusive) physician reasons for non-prescription of OAC included fall risk (26.7%), poor prognosis (19.3%), bleeding history (17.1%), patient/family refusal (14.9%), older age (11.0%) and dementia (9.4%). Older age (OR 8.96, 95% CI 5.01–16.04 for age ≥85 vs. age <65 years) and increased disability (OR 12.58, 95% CI 5.82–27.21 for severe vs. no deficit) were the most important independent predictors of non-use of OAC. By one year, 42.5% of those not receiving OAC at discharge had died versus 19.1% of those receiving OAC (p<0.0001), far higher than recurrent stroke rates. Conclusion Despite very high stroke risk, over 40% of patients were not discharged on OAC. Dominant reasons included fall risk, poor prognosis, older age, and dementia. These patients’ elevated 1-year mortality rate confirmed their high level of comorbidity. Future work to improve outcomes and clinical decisions regarding anticoagulation in this patient population should focus on: mitigation of fall risk, better assessment and decision tools for determining risk/benefit in individual patients, and determining whether newer anticoagulants are safer in complex elderly and/or frail patients. PMID:28039855

  16. Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant.

    PubMed

    Minhas, Anum S; Jiang, Qingmei; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Krol, Gregory D; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

    2016-11-01

    All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance <50 mL/min and 23 (12.2 %) experienced important fluctuations in renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

  17. Point-of-Care Coagulation Tests Monitoring of Direct Oral Anticoagulants and Their Reversal Therapy: State of the Art.

    PubMed

    Iapichino, Giacomo E; Bianchi, Paolo; Ranucci, Marco; Baryshnikova, Ekaterina

    2017-06-01

    Direct oral anticoagulants (DOACs) exert similar anticoagulant effects to vitamin K antagonists and are increasingly used worldwide. Nevertheless, an evidence-based approach to patients receiving DOACs when any unplanned urgent surgery or bleeding (either spontaneous or traumatic) occurs is still missing. In this review, we investigate the role of point-of-care coagulation tests when other, more specific tests are not available. Indeed, thromboelastography and activated clotting time can detect dabigatran-induced coagulopathy, while their accuracy is limited for apixaban and rivaroxaban, mostly in cases of low drug plasma concentrations. These tests can also be used to guide the reversal of DOAC-induced coagulopathy providing a quick, before-and-after picture in case of therapeutic use of hemostatic compounds. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  18. Screening test for direct oral anticoagulants with the dilute Russell viper venom time.

    PubMed

    Pratt, Jackie; Crispin, Philip

    2018-06-01

    To evaluate the dilute Russell viper venom time (DRVVT) for the detection of direct-acting oral anticoagulants (DOACs) and to investigate the effect of DOACS on coagulation assays. Patients with DOACs and controls had plasma levels determined by an anti-Xa assay and dilute thrombin clotting time (TCT). Levels were correlated with the DRVVT as well as TCT, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, protein C, protein S and antithrombin levels. The utility of the DRVVT for detecting clinically significant levels of DOACs was evaluated. There were 44 samples from patients taking dabigatran, 83 with rivaroxaban, 18 with apixaban and 55 controls. The PT and APTT failed to detect clinically significant doses of anticoagulants adequately. The TCT was increased in patients taking dabigatran and normal in controls and patients on FXa inhibitors. There was a linear correlation with all DOAC levels and the DRVVT, with moderate precision, but it showed high sensitivity (95%) and specificity (90%) for clinically significant DOAC levels. The DRVVT detects clinically significant levels of DOACs and, in conjunction with the TCT, may be used as a screen for the presence and type of DOAC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Simple and rapid assay for effect of the new oral anticoagulant (NOAC) rivaroxaban: preliminary results support further tests with all NOACs

    PubMed Central

    2014-01-01

    Background New oral anticoagulant (NOAC) drugs are known to influence the results of some routine hemostasis tests. Further data are needed to enable routine assessment of the effects of NOAC on clotting parameters in some special circumstances. Methods Following administration of rivaroxaban to patients, at the likely peak and trough activity times, we assessed the effects on prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and clotting time using Russell’s viper venom, and in the presence of phospholipids and calcium reagent available as DVVreagent® and DVVconfirm®. The data were used to determine an adequate NOAC plasma level based on anticoagulant activities expressed as a ratio (patients/normal, R-C). Results DVVconfirm as R-C could be rapidly performed, and the results were reasonably sensitive for rivaroxaban and probably for other FX inhibitors. This assay is not influenced by lupus anticoagulant and heparin, does not require purified NOAC as control, and will measure whole-plasma clotting activity. Conclusions We propose a cut-off R-C value of 4.52 ± 0.33 for safety, but clinical studies are needed to establish whether this cut-off is useful for identifying patients at increased risk of hemorrhage or exhibiting low anticoagulation effect. It also seems possible that normal R-C could indicate an absence of anticoagulant activity when rivaroxaban is discontinued due to episodes of uncontrolled bleeding during anticoagulation or for emergency surgery. PMID:24656069

  20. Prestroke CHA2DS2-VASc Score and Severity of Acute Stroke in Patients with Atrial Fibrillation: Findings from RAF Study.

    PubMed

    Acciarresi, Monica; Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Morotti, Andrea; Costa, Paolo; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; D'Amore, Cataldo; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Lees, Kennedy R

    2017-06-01

    The aim of this study was to investigate for a possible association between both prestroke CHA 2 DS 2 -VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA 2 DS 2 -VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS ≥10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS <3 or ≥3). Multiple logistic regression was used to correlate prestroke CHA 2 DS 2 -VASc and severity of stroke, as well as disability and mortality at 90 days. Of the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS ≥3. A linear correlation was found between the prestroke CHA 2 DS 2 -VASc score and severity of stroke (P = .001). On multivariate analysis, CHA 2 DS 2 -VASc score correlated with severity of stroke (P = .041) and adverse functional outcome (mRS ≥3) (P = .001). A logistic regression with the receiver operating characteristic graph procedure (C-statistics) evidenced an area under the curve of .60 (P = .0001) for severe stroke. Furthermore, a correlation was found between prestroke CHA 2 DS 2 -VASc score and lesion size. In patients with AF, in addition to the risk of stroke, a high CHA 2 DS 2 -VASc score was independently associated with both stroke severity at onset and disability and mortality at 90 days. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Prestroke Proteomic Changes in Cerebral Microvessels in Stroke-Prone, Transgenic[hCETP]-Hyperlipidemic, Dahl Salt-Sensitive Hypertensive Rats

    PubMed Central

    Bergerat, Agnes; Decano, Julius; Wu, Chang-Jiun; Choi, Hyungwon; Nesvizhskii, Alexey I; Moran, Ann Marie; Ruiz-Opazo, Nelson; Steffen, Martin; Herrera, Victoria LM

    2011-01-01

    Stroke is the third leading cause of death in the United States with high rates of morbidity among survivors. The search to fill the unequivocal need for new therapeutic approaches would benefit from unbiased proteomic analyses of animal models of spontaneous stroke in the prestroke stage. Since brain microvessels play key roles in neurovascular coupling, we investigated prestroke microvascular proteome changes. Proteomic analysis of cerebral cortical microvessels (cMVs) was done by tandem mass spectrometry comparing two prestroke time points. Metaprotein-pathway analyses of proteomic spectral count data were done to identify risk factor–induced changes, followed by QSPEC-analyses of individual protein changes associated with increased stroke susceptibility. We report 26 cMV proteome profiles from male and female stroke-prone and non–stroke-prone rats at 2 months and 4.5 months of age prior to overt stroke events. We identified 1,934 proteins by two or more peptides. Metaprotein pathway analysis detected age-associated changes in energy metabolism and cell-to-microenvironment interactions, as well as sex-specific changes in energy metabolism and endothelial leukocyte transmigration pathways. Stroke susceptibility was associated independently with multiple protein changes associated with ischemia, angiogenesis or involved in blood brain barrier (BBB) integrity. Immunohistochemical analysis confirmed aquaporin-4 and laminin-α1 induction in cMVs, representative of proteomic changes with >65 Bayes factor (BF), associated with stroke susceptibility. Altogether, proteomic analysis demonstrates significant molecular changes in ischemic cerebral microvasculature in the prestroke stage, which could contribute to the observed model phenotype of microhemorrhages and postischemic hemorrhagic transformation. These pathways comprise putative targets for translational research of much needed novel diagnostic and therapeutic approaches for stroke. PMID:21519634

  2. Percutaneous left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation and contraindication for anticoagulation.

    PubMed

    Grosset-Janin, D; Barth, E; Bertrand, B; Detante, O

    2015-05-01

    Stroke, as the third cause of death in developed countries, is a public health issue. Atrial fibrillation is an important cause of ischemic stroke and its prevention is efficient with oral anticoagulation. However, oral anticoagulation can be contraindicated because of hemorrhagic risk related to these treatments. Percutaneous left atrial appendage occlusion is a new alternative of oral anticoagulation for patients with atrial fibrillation and high risk of cardio-embolic stroke but contraindicated for oral anticoagulation. We describe in this paper the procedure of left atrial appendage occlusion with the Amplatzer cardiac plug device, used in our center in Grenoble university hospital, for the first three patients who have been treated with this device. These three patients (one man and two women) have all atrial fibrillation with neurological complication of this arrhythmia, as ischemic stroke. Oral anticoagulation is indicated to prevent another ischemic stroke. However, they all have a high risk of cerebral bleeding for different reasons (cavernomatosis, history of intracerebral hemorrhage and aneurysm of the polygon of Willis). Consequently, they have a high risk of cardio-embolic complication but contraindication for oral anticoagulation. They have been treated by left atrial appendage occlusion with Amplatzer cardiac plug device by percutaneous and trans-septal access. Then, they have been followed by neurologist and cardiologist, with clinical and paraclinical evaluation by echocardiography. Our three first patients have been successfully implanted, without periprocedural complication. No latest adverse event was observed, and particularly no cardiac or neurologic adverse event. The technique of left atrial appendage occlusion is a very interesting and promising technique for ischemic stroke prevention in patient with high risk of cardio-embolic complication because of atrial fibrillation, but high risk of bleeding and contraindication for oral

  3. Direct oral anticoagulants and digestive bleeding: therapeutic management and preventive measures.

    PubMed

    Deutsch, David; Boustière, Christian; Ferrari, Emile; Albaladejo, Pierre; Morange, Pierre-Emmanuel; Benamouzig, Robert

    2017-06-01

    The use of direct oral anticoagulants (DOACs) was an important step forward in the management of atrial fibrillation and venous thromboembolism (VTE). The DOACs, anti-IIa for dabigatran and anti-Xa for rivaroxaban, apixaban and edoxaban, all have a rapid onset of action and a short half life. There is no need for routine hemostasis testing for treatment monitoring of a DOAC. Compared with vitamin K antagonists (VKAs), DOACs may increase the risk of gastrointestinal bleeding (relative risk 1.25). Withholding the DOAC treatment, evaluating the time of the last intake and estimating the patient's renal function are the first steps in the management of gastrointestinal bleeding. For patients without impaired renal function, achieving low coagulation takes around 24 h after the last intake of a DOAC. The use of DOAC antagonists will be helpful in controlling bleeding in the most severe and urgent situations. Idarucizumab is available for clinical use for dabigatran and andexanet is currently being reviewed by drug agencies for rivaroxaban, apixaban and edoxaban. It is important to assess the bleeding risk associated with the planned procedure, and the patient's renal function before withholding DOAC therapy for a scheduled intervention. It is mandatory to strengthen the local hemostasis strategies in DOAC-treated patients undergoing a therapeutic endoscopic procedure. Resuming or not resuming anticoagulation with a DOAC after bleeding or a risky procedure depends on the thrombotic and bleeding risk as well as the procedure involved. This discussion should always involve the cardiologist and decisions should be taken by a pluridisciplinary team.

  4. Coagulation Testing in Acute Ischemic Stroke Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants.

    PubMed

    Purrucker, Jan C; Haas, Kirsten; Rizos, Timolaos; Khan, Shujah; Poli, Sven; Kraft, Peter; Kleinschnitz, Christoph; Dziewas, Rainer; Binder, Andreas; Palm, Frederick; Jander, Sebastian; Soda, Hassan; Heuschmann, Peter U; Veltkamp, Roland

    2017-01-01

    In patients who present with acute ischemic stroke while on treatment with non-vitamin K antagonist oral anticoagulants (NOACs), coagulation testing is necessary to confirm the eligibility for thrombolytic therapy. We evaluated the current use of coagulation testing in routine clinical practice in patients who were on NOAC treatment at the time of acute ischemic stroke. Prospective multicenter observational RASUNOA registry (Registry of Acute Stroke Under New Oral Anticoagulants; February 2012-2015). Results of locally performed nonspecific (international normalized ratio, activated partial thromboplastin time, and thrombin time) and specific (antifactor Xa tests, hemoclot assay) coagulation tests were documented. The implications of test results for thrombolysis decision-making were explored. In the 290 patients enrolled, nonspecific coagulation tests were performed in ≥95% and specific coagulation tests in 26.9% of patients. Normal values of activated partial thromboplastin time and international normalized ratio did not reliably rule out peak drug levels at the time of the diagnostic tests (false-negative rates 11%-44% [95% confidence interval 1%-69%]). Twelve percent of patients apparently failed to take the prescribed NOAC prior to the acute event. Only 5.7% (9/159) of patients in the 4.5-hour time window received thrombolysis, and NOAC treatment was documented as main reason for not administering thrombolysis in 52.7% (79/150) of patients. NOAC treatment currently poses a significant barrier to thrombolysis in ischemic stroke. Because nonspecific coagulation test results within normal range have a high false-negative rate for detection of relevant drug concentrations, rapid drug-specific tests for thrombolysis decision-making should be established. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850797. © 2016 American Heart Association, Inc.

  5. Cost-effectiveness of non-vitamin K antagonist oral anticoagulants for atrial fibrillation in Portugal.

    PubMed

    Costa, João; Fiorentino, Francesca; Caldeira, Daniel; Inês, Mónica; Lopes Pereira, Catarina; Pinheiro, Luís; Vaz-Carneiro, António; Borges, Margarida; Gouveia, Miguel

    2015-12-01

    Recently, three novel non-vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non-valvular atrial fibrillation (AF). It is therefore important to evaluate the relative cost-effectiveness of these new oral anticoagulants in Portuguese AF patients. A Markov model was used to analyze disease progression over a lifetime horizon. Relative efficacy data for stroke (ischemic and hemorrhagic), bleeding (intracranial, other major bleeding and clinically relevant non-major bleeding), myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban, dabigatran and rivaroxaban using warfarin as a common comparator. Data on resource use were obtained from the database of diagnosis-related groups and an expert panel. Model outputs included life years gained, quality-adjusted life years (QALYs), direct healthcare costs and incremental cost-effectiveness ratios (ICERs). Apixaban provided the most life years gained and QALYs. The ICERs of apixaban compared to warfarin and dabigatran were €5529/QALY and €9163/QALY, respectively. Apixaban was dominant over rivaroxaban (greater health gains and lower costs). The results were robust over a wide range of inputs in sensitivity analyses. Apixaban had a 70% probability of being cost-effective (at a threshold of €20 000/QALY) compared to all the other therapeutic options. Apixaban is a cost-effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare decision-makers. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  6. Anticoagulation knowledge in patients with atrial fibrillation: An Australian survey.

    PubMed

    Obamiro, Kehinde O; Chalmers, Leanne; Lee, Kenneth; Bereznicki, Bonnie J; Bereznicki, Luke R E

    2018-03-01

    Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia in clinical practice, and is associated with a significant medical and economic burden. Anticoagulants reduce the risk of stroke and systemic embolism by approximately two-thirds compared with no therapy. Knowledge regarding anticoagulant therapy can influence treatment outcomes in patients with AF. To measure the level of anticoagulation knowledge in patients with AF taking oral anticoagulants (OACs), investigate the association between patient-related factors and anticoagulation knowledge, and compare these results in patients taking warfarin and direct-acting oral anticoagulant (DOACs). Participants were recruited for an online survey via Facebook. Survey components included the Anticoagulation Knowledge Tool, the Perception of Anticoagulant Treatment Questionnaires (assessing treatment expectations, convenience and satisfaction), a modified Cancer Information Overload scale and the Morisky Medication Adherence Scale. Treatment groups were compared and predictors of OAC knowledge were identified. Participants taking warfarin had a higher knowledge score compared with those taking DOACs (n = 386, 73% ± 13% vs 66% ± 14%, P<.001). Advancing age, type of OAC, health information overload and ease of OAC use (treatment expectation) were significant predictors of knowledge. Treatment expectation, including the belief that OAC treatment would cause bleeding side effects, varied significantly between participants taking warfarin and DOACs (P = .011). The study identified knowledge gaps in patients taking OACs, and these deficiencies appeared to be greater in participants taking DOACs. Knowledge assessment should be integrated into patient counselling sessions to help identify and resolve knowledge deficits. © 2018 John Wiley & Sons Ltd.

  7. Differences in the INR evaluation of two different thromboplastins in patients with positivity to lupus anticoagulant in ongoing oral anticoagulation.

    PubMed

    Ferrazzi, Paola; Colombo, Anna; Di Micco, Pierpaolo; Lodigiani, Corrado; Librè, Luca; Rota, Lidia Luciana; Montanelli, Alessandro; Quaglia, Ilaria

    2010-01-01

    A possible interference between lupus anticoagulant (LAC), a well characterized clotting inhibitor, in the International Normalized Ratio (INR) determination during oral anticoagulation (OA) has been reported in the literature. Few data are available about the relationship between this kind of interference and the daily clinical management of oral anticoagulation. The aim of the study is to evaluate the role of two different thromboplastins-RecombiPlasTin 2G and HepatoComplex-in the determination of INR values of several patients' ongoing OA for a previous thrombotic disorder with and without positivity to LAC, and to evaluate possible interferences in the daily therapeutic approach. We selected 16 patients (13 females and 3 males, mean age 59 ± 16 years) with LAC positivity ongoing OA and 11 control subjects (7 females and 4 males, mean age 58 ± 14.5 years) with similar characteristics (ie, ethnic background and weight) with LAC negativity ongoing OA. 165 assays for INR determination were analyzed from both groups. Statistical analysis was performed using STATA 10 software. P values were considered significant if <0.05. Mean values of INR for patients with LAC positivity were 3.79 ± 1.63 when tested with RecombiPlasTin 2G vs 3.18 ± 1.15 when tested with HepatoComplex (P < 0.001, s); while mean values of INR for patients with antiphospholipid syndrome (APS) with LAC negativity were 3.54 ± 1.39 when tested with RecombiPlasTin 2G vs 3.23 ± 1.14 when tested with HepatoComplex (P < 0.002, s). An INR value > than 4.5 was found in 31/165 samples in 9 subjects, 8 patients with LAC positivity, and 1 control group subject with LAC negativity. There was a great difference in INR values in these subjects if we use the common thromboplastin (ie, RecombiPlasTin 2G) with a INR range varying from 5.14 ± 0.35 vs 3.79 ± 0.38 if we use another thromboplastin (ie, HepatoComplex) (P < 0.001, s). A change in the therapeutic approach for OA is possible in these cases because

  8. Peri-procedural interrupted oral anticoagulation for atrial fibrillation ablation: comparison of aspirin, warfarin, dabigatran, and rivaroxaban

    PubMed Central

    Winkle, Roger A.; Mead, R. Hardwin; Engel, Gregory; Kong, Melissa H.; Patrawala, Rob A.

    2014-01-01

    Aims Atrial fibrillation ablation requires peri-procedural oral anticoagulation (OAC) to prevent thromboembolic events. There are several options for OAC. We evaluate peri-procedural AF ablation complications using a variety of peri-procedural OACs. Methods and results We examined peri-procedural OAC and groin, bleeding, and thromboembolic complications for 2334 consecutive AF ablations using open irrigated-tip radiofrequency (RF) catheters. Pre-ablation OAC was warfarin in 1113 (47.7%), dabigatran 426 (18.3%), rivaroxaban 187 (8.0%), aspirin 472 (20.2%), and none 136 (5.8%). Oral anticoagulation was always interrupted and intraprocedural anticoagulation was unfractionated heparin (activated clotting time, ACT = 237 ± 26 s). Pre- and post-OAC drugs were the same for 1591 (68.2%) and were different for 743 (31.8%). Following ablation, 693 (29.7%) were treated with dabigatran and 291 (12.5%) were treated with rivaroxaban. There were no problems changing from one OAC pre-ablation to another post-ablation. Complications included 12 (0.51%) pericardial tamponades [no differences for dabigatran (P = 0.457) or rivaroxaban (P = 0.163) compared with warfarin], 12 (0.51%) groin complications [no differences for rivaroxaban (P = 0.709) and fewer for dabigatran (P = 0.041) compared with warfarin]. Only 5 of 2334 (0.21%) required blood transfusions. There were two strokes (0.086%) and no transient ischaemic attacks (TIAs) in the first 48 h post-ablation. Three additional strokes (0.13%), and two TIAs (0.086%) occurred from 48 h to 30 days. Only one stroke had a residual deficit. Compared with warfarin, the neurologic event rate was not different for dabigatran (P = 0.684) or rivaroxaban (P = 0.612). Conclusion Using interrupted OAC, low target intraprocedural ACT, and irrigated-tip RF, the rate of peri-procedural groin, haemorrhagic, and thromboembolic complications was extremely low. There were only minimal differences between OACs. Low-risk patients may remain on aspirin

  9. Breast hematoma complicating anticoagulant therapy: management and literature review.

    PubMed

    Salemis, Nikolaos S

    2012-01-01

    Anticoagulant-induced spontaneous breast hematoma is a very rare clinical entity with only a few cases reported in the literature so far. We describe a case of a spontaneous breast hematoma in a female patient under combined oral anticoagulant and antiplatelet therapy. Physicians should be aware of this possibility in patients under anticoagulant treatment presenting with sudden onset of breast pain and a palpable mass. Repeat imaging is mandatory until complete clinical and imaging resolution of the hematoma. If an abnormality persists, further investigation is needed to exclude an underlying malignancy.

  10. Successful treatment of deep vein thrombosis caused by iliac vein compression syndrome with a single-dose direct oral anti-coagulant.

    PubMed

    Nakashima, Naoya; Sueta, Daisuke; Kanemaru, Yusuke; Takashio, Seiji; Yamamoto, Eiichiro; Hanatani, Shinsuke; Kanazawa, Hisanori; Izumiya, Yasuhiro; Kojima, Sunao; Kaikita, Koichi; Hokimoto, Seiji; Tsujita, Kenichi

    2017-01-01

    Although vein stenting is popular for treatment for venous thromboembolism due to mechanical compression, some cases are forced to avoid inserting align agents because of immunodeficiency. An 82-year-old man with left extremity redness and swelling presented to a hospital for a medical evaluation. The patient was immunodeficient because of the adverse effects of his treatment for Castleman's disease. A contrast-enhanced computed tomography scan revealed a venous thromboembolism in inferior vena cava and the left lower extremity. Magnetic resonance venography showed that the iliac artery was compressing the iliac vein. We were reluctant to place a stent in the iliac vein has because of the patient's immunodeficient status. Three months of treatment using single-dose edoxaban (30 mg daily) resulted in complete resolution of the thrombus. This is the first report demonstrating that single-dose edoxaban without acute-phase parenteral anticoagulation is effective in the treatment of iliac vein compression. A single-dose direct oral anti-coagulant without acute-phase parenteral anticoagulation is effective for mechanical compression.

  11. Rivaroxaban as an oral anticoagulant for stroke prevention in atrial fibrillation

    PubMed Central

    Turpie, Alexander GG

    2014-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia in the developed world and is associated with a fivefold increase in the risk of stroke, accounting for up to 15% of strokes in the general population. The European Society of Cardiology now recommends direct oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran, in preference to vitamin K antagonist therapy for the prevention of stroke in patients with A F. This review focuses on the direct Factor Xa inhibitor rivaroxaban, summarizing the properties that make rivaroxaban appropriate for anticoagulant therapy in this indication (including its predictable pharmacokinetic and pharmacodynamic profile and once-daily dosing regimen) and describing data from the Phase III ROCKET AF trial, which showed once-daily rivaroxaban to be noninferior to warfarin for the prevention of stroke in patients with nonvalvular AF. In this trial, similar rates of major and nonmajor clinically relevant bleeding were observed; however, when compared with warfarin, rivaroxaban was associated with clinically significant reductions in intracranial and fatal bleeding. On the basis of these results, rivaroxaban was approved in both the United States and the European Union for the prevention of stroke and systemic embolism in patients with nonvalvular AF. Subanalyses of ROCKET AF data showed rivaroxaban to have consistent efficacy and safety across a wide range of patients, and studies to confirm these results in real-world settings are underway. This review also describes practical considerations for treatment with rivaroxaban in clinical practice (including dose reductions in specific high-risk patients, eg, those with renal impairment), recommendations for the transition from vitamin K antagonists to rivaroxaban, the management of bleeding events, and the measurement of rivaroxaban exposure. PMID:24711702

  12. Reduced-dose direct oral anticoagulants in the extended treatment of venous thromboembolism: a systematic review and meta-analysis.

    PubMed

    Vasanthamohan, L; Boonyawat, K; Chai-Adisaksopha, C; Crowther, M

    2018-05-17

    Essentials In venous thromboembolism (VTE), benefits of extended treatment are balanced by bleeding risks. This is a meta-analysis of reduced-dose direct oral anticoagulants (DOACs) in extended treatment. Reduced-dose DOACs are as effective as full anticoagulation with bleeding risks similar to placebo. Reduced-dose DOACs are an attractive option for patients in the extended phase of VTE treatment. Background Extended-duration anticoagulation is beneficial for preventing recurrent venous thromboembolism (VTE). Reduced-dose direct oral anticoagulants (DOACs) may be preferable if they preserve efficacy and cause less bleeding. We conducted a systematic review and meta-analysis of trials comparing reduced-dose DOACs with full-dose DOACs and aspirin or placebo in the extended phase of VTE treatment. Methods A literature search was conducted by use of the MEDLINE, EMBASE and CINAHL databases, supplemented by hand-searching. One thousand three hundred and ninety-nine titles were screened, with data from accepted studies being extracted by two independent reviewers. Major outcomes analyzed included recurrent VTE and major and clinically relevant non-major bleeding events, presented as risk ratios (RRs) and 95% confidence intervals (CI). Results Two trials met the prespecified inclusion criteria. Data from 5847 patients were analyzed for efficacy outcomes, and from 5842 patients for safety outcomes. Reduced-dose DOACs were as effective as full-dose treatment in preventing recurrent VTE at 1 year (RR 1.12 [95% CI 0.67-1.87]), and more effective than aspirin or placebo (RR 0.26 [95% CI 0.14-0.46]). Rates of major or clinically relevant non-major bleeding events were similar between patients receiving reduced-dose DOACs and and those receiving aspirin or placebo (RR 1.19 [95% CI 0.81-1.77]). There was a trend towards less bleeding when reduced-dose and full-dose DOACs were compared (RR 0.74 [95% CI 0.52-1.05]). Conclusions Extended-duration treatment of VTE with

  13. International Council for Standardization in Haematology (ICSH) Recommendations for Laboratory Measurement of Direct Oral Anticoagulants.

    PubMed

    Gosselin, Robert C; Adcock, Dorothy M; Bates, Shannon M; Douxfils, Jonathan; Favaloro, Emmanuel J; Gouin-Thibault, Isabelle; Guillermo, Cecilia; Kawai, Yohko; Lindhoff-Last, Edelgard; Kitchen, Steve

    2018-03-01

    This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH) for providing haemostasis-related guidance documents for clinical laboratories. This inaugural coagulation ICSH document was developed by an ad hoc committee, comprised of international clinical and laboratory direct acting oral anticoagulant (DOAC) experts. The committee developed consensus recommendations for laboratory measurement of DOACs (dabigatran, rivaroxaban, apixaban and edoxaban), which would be germane for laboratories assessing DOAC anticoagulation. This guidance document addresses all phases of laboratory DOAC measurements, including pre-analytical (e.g. preferred time sample collection, preferred sample type, sample stability), analytical (gold standard method, screening and quantifying methods) and post analytical (e.g. reporting units, quality assurance). The committee addressed the use and limitations of screening tests such as prothrombin time, activated partial thromboplastin time as well as viscoelastic measurements of clotting blood and point of care methods. Additionally, the committee provided recommendations for the proper validation or verification of performance of laboratory assays prior to implementation for clinical use, and external quality assurance to provide continuous assessment of testing and reporting method. Schattauer GmbH Stuttgart.

  14. Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1

    PubMed Central

    Diener, Hans-Christoph; Aisenberg, James; Ansell, Jack; Atar, Dan; Breithardt, Günter; Eikelboom, John; Ezekowitz, Michael D.; Granger, Christopher B.; Halperin, Jonathan L.; Hohnloser, Stefan H.; Hylek, Elaine M.; Kirchhof, Paulus; Lane, Deirdre A.; Verheugt, Freek W.A.; Veltkamp, Roland; Lip, Gregory Y.H.

    2017-01-01

    Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic embolism. Today's clinician is faced with the difficult task of selecting a suitable OAC for a patient with a particular clinical profile or a particular pattern of risk factors and concomitant diseases. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. NOACs for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In the first of a two-part review, we discuss the choice of NOAC for stroke prevention in the following subgroups of patients with AF: (i) stable coronary artery disease or peripheral artery disease, including percutaneous coronary intervention with stenting and triple therapy; (ii) cardioversion, ablation and anti-arrhythmic drug therapy; (iii) mechanical valves and rheumatic valve disease, (iv) patients with time in therapeutic range of >70% on warfarin; (v) patients with a single stroke risk factor (CHA2DS2VASc score of 1 in males, 2 in females); and (vi) patients with a single first episode of paroxysmal AF. Although there are no major differences in terms of efficacy and safety between the NOACs for some clinical scenarios, in others we are able to suggest that particular drugs and/or doses be prioritized for anticoagulation. PMID:26848149

  15. Managing hip fracture and lower limb surgery in the emergency setting: Potential role of non-vitamin K antagonist oral anticoagulants.

    PubMed

    Fisher, William

    2017-06-01

    Trauma, immobilization, and subsequent surgery of the hip and lower limb are associated with a high risk of developing venous thrombo-embolism (VTE). Individuals undergoing hip fracture surgery (HFS) have the highest rates of VTE among orthopedic surgery and trauma patients. The risk of VTE depends on the type and location of the lower limb injury. Current international guidelines recommend routine pharmacological thromboprophylaxis based on treatment with heparins, fondaparinux, dose-adjusted vitamin K antagonists and acetylsalicylic acid for patients undergoing emergency HFS; however, not all guidelines recommend pharmacological prophylaxis for patients with lower limb injuries. Non-vitamin K antagonist oral anticoagulants (NOACs) are indicated for VTE prevention after elective hip or knee replacement surgery, but at present are not widely recommended for other orthopedic indications despite their advantages over conventional anticoagulants and promising real-world evidence. In patients undergoing HFS or lower limb surgery, decisions on whether to anticoagulate and the most appropriate anti-coagulation strategy can be guided by weighing the risk of thromboprophylaxis against the benefit in relation to each patient's medical history and age. In addition, the nature and location of the fracture, operating times and times before fracture fixation should be considered. The current review discusses the need for anticoagulation in patients undergoing emergency HFS or lower limb surgery together with the current guidelines and available evidence on the use of NOACs in this setting. Appropriate thromboprophylactic strategies and practical advice on the peri-operative management of patients who present to the Emergency Department on a NOAC before emergency surgery are further outlined.

  16. Biobarcode assay for the oral anticoagulant acenocoumarol.

    PubMed

    Broto, Marta; Salvador, J Pablo; Galve, Roger; Marco, M Pilar

    2018-02-01

    A novel approach for therapeutic drug monitoring of oral anticoagulants (OA) in clinical samples is reported, based on a NP-based biobarcode assay. The proposed strategy uses specific antibodies for acenocumarol (ACL) covalently bound to magnetic particles (pAb236-MP) and a bioconjugate competitor (hACL-BSA) linked to encoded polystyrene probes (hACL-BSA-ePSP) on a classical competitive immunochemical format. By using this scheme ACL can be detected in low nM range (LOD, 0.96 ± 0.26, N = 3, in buffer) even in complex samples such as serum or plasma (LOD 4 ± 1). The assay shows a high reproducibility (%CV 1.1 day-to-day) and is robust, as it is demonstrated by the fact that ACL can be quantified in complex biological samples with a very good accuracy (slope = 0.97 and R 2 = 0.91, of the linear regression obtained when analyzing spiked vs measured values). Moreover, we have demonstrated that the biobarcode approach has the potential to overcome one of the main challenges of the multiplexed diagnostic, which is the possibility to measure in a single run biomarker targets present at different concentration ranges. Thus, it has been proven that the signal and the detectability can be modulated by just modifying the oligonucleotide load of the encoded probes. This fact opens the door for combining in the same assay encoded probes with the necessary oligonucleotide load to achieve the detectability required for each biomarker target. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Management of Periprocedural Anticoagulation: A Survey of Contemporary Practice.

    PubMed

    Flaker, Greg C; Theriot, Paul; Binder, Lea G; Dobesh, Paul P; Cuker, Adam; Doherty, John U

    2016-07-12

    Interruption of oral anticoagulation (AC) for surgery or an invasive procedure is a complicated process. Practice guidelines provide only general recommendations, and care of such patients occurs across multiple specialties. The availability of direct oral anticoagulants further complicates decision making and guidance here is limited. To evaluate current practice patterns in the United States for bridging AC, a survey was developed by the American College of Cardiology Anticoagulation Work Group. The goal of the survey was to assess how general and subspecialty cardiologists, internists, gastroenterologists, and orthopedic surgeons currently manage patients who receive AC and undergo surgery or an invasive procedure. The survey was completed by 945 physicians involved in the periprocedural management of AC. The results provide a template for educational and research projects geared toward the development of clinical pathways and point-of-care tools to improve this area of health care. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. The effect of bariatric surgery on direct-acting oral anticoagulant drug levels.

    PubMed

    Rottenstreich, Amihai; Barkai, Aviv; Arad, Ariela; Raccah, Bruria Hirsh; Kalish, Yosef

    2018-03-01

    To determine direct-acting oral anticoagulant (DOAC) blood levels in post-bariatric surgery (BS) patients treated with long-term anticoagulation therapy. We identified from medical records patients who underwent BS during 2005-2016 and who were treated with DOACs. We offered testing DOAC blood levels to these patients and to age, sex, body mass index, and serum creatinine-matched individuals treated by DOACs who did not undergo BS. Overall, 36 individuals were enrolled, 18 post-BS patients and 18 control subjects. Of the post-BS patients, 12 underwent laparoscopic sleeve gastrectomy, 4 laparoscopic adjustable gastric banding and 2 laparoscopic Roux-en-Y gastric bypass surgery. Median time lapsed from surgery until study inclusion was 4.9years. Five post-BS patients had peak drug levels below expected levels compared to none of the control subjects (P=0.05). For patients who used apixaban (n=9) and dabigatran (n=2), peak drug levels were within the expected range. In contrast, for the 7 patients who used rivaroxaban, levels were below the expected range in 5, including all four who underwent sleeve gastrectomy and one following adjustable gastric banding. Peak rivaroxaban levels were significantly lower in the post-BS than the control group (P=0.02). This preliminary study suggests that all DOACs, particularly rivaroxaban, be cautiously used following BS, if used at all. Given that vitamin-K antagonists can be easily monitored, they may be a better choice, until more data on DOAC use in this patient population are available. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events.

    PubMed

    Mekaj, Ymer H; Mekaj, Agon Y; Duci, Shkelzen B; Miftari, Ermira I

    2015-01-01

    Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required

  20. New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events

    PubMed Central

    Mekaj, Ymer H; Mekaj, Agon Y; Duci, Shkelzen B; Miftari, Ermira I

    2015-01-01

    Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required

  1. Athletes and blood clots: individualized, intermittent anticoagulation management.

    PubMed

    Berkowitz, J N; Moll, S

    2017-06-01

    Essentials Athletes on anticoagulants are typically prohibited from participation in contact sports. Short-acting anticoagulants allow for reconsideration of this precedent. An individualized pharmacokinetic/pharmacodynamics study can aid patient-specific management. Many challenges and unresolved issues exist regarding such tailored intermittent dosing. Athletes with venous thromboembolism (VTE) are typically prohibited from participating in contact sports during anticoagulation therapy, but such mandatory removal from competition can cause psychological and financial detriments for athletes and overlooks patient autonomy. The precedent of compulsory removal developed when options for anticoagulation therapy were more limited, but medical advances now allow for rethinking of the management of athletes with VTE. We propose a novel therapeutic approach to the treatment of athletes who participate in contact sports and require anticoagulation. A personalized pharmacokinetic/pharmacodynamics study of a direct oral anticoagulant can be performed for an athlete, which can inform the timing of medication dosing. Managed carefully, this can allow athletic participation when plasma drug concentration is minimal (minimizing bleeding risk) and prompt resumption of treatment after the risk of bleeding sufficiently normalizes (maximizing therapeutic time). © 2017 International Society on Thrombosis and Haemostasis.

  2. Major bleeding complications in patients treated with direct oral anticoagulants: One-year observational study in a Paris Hospital.

    PubMed

    Deville, L; Konan, M; Hij, A; Goldwirt, L; Peyrony, O; Fieux, F; Faure, P; Madelaine, I; Villiers, S; Farge-Bancel, D; Frère, C

    Direct oral anticoagulants (DAOC) are indicated for the treatment of venous thromboembolism and the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. Given their advantages and friendly use for patient, the prescription of long term DOAC therapy has rapidly increased both as first line treatment while initiating anticoagulation and as a substitute to vitamins K antagonist (VKA) in poorly controlled patients. However, DOAC therapy can also be associated with significant bleeding complications, and in the absence of specific antidote at disposal, treatment of serious hemorrhagic complications under DOAC remains complex. We report and discuss herein five cases of major hemorrhagic complications under DOAC, which were reported to the pharmacological surveillance department over one year at Saint-Louis University Hospital (Paris, France). We further discuss the need for careful assessment of the risk/benefit ratio at time of starting DOAC therapy in daily clinical practice. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Optical profiling of anticoagulation status (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.

    2016-02-01

    Defective blood coagulation resulting from excessive procoagulant activity often leads to thrombotic disorders such as stroke and myocardial infarction. A variety of oral and injectable anticoagulant drugs are prescribed to prevent or treat life-threatening thrombosis. However, due to bleeding complications often associated with anticoagulant treatment, routine monitoring and accurate dosing of anticoagulant therapy is imperative. We have developed Optical thromboelastography (OTEG), a non-contact approach that utilizes a drop of whole blood to measure blood coagulation status in patients. Here, we demonstrate the capability of OTEG for rapidly monitoring anticoagulation in whole blood samples. OTEG monitors coagulation status by assessing changes in blood viscosity from temporal intensity fluctuations of laser speckle patterns during clotting. In OTEG a blood drop is illuminated with coherent light and the blood viscosity is measured from the speckle intensity autocorrelation curve, g2 (t). The metrics, clotting time (R+k), clot progression (angle) and maximum clot stiffness (MA) are then extracted. The aim of the current study was to evaluate the accuracy of OTEG in assessing anticoagulation status of common anticoagulants including heparin, argatroban and rivaroxaban status. A dose-dependent prolongation of R+k was observed in anticoagulated blood, which closely corresponded with standard-reference Thromboelastography (TEG) (r 0.87-0.99, P>0.01 for all cases). OTEG angle was unaltered by anticoagulation whereas TEG angle presented a dose-dependent diminution probably linked to clot rupture. In both OTEG and TEG, MA was unaffected by heparin, argatroban or rivaroxaban. We conclude that OTEG can accurately monitor anticoagulation status following treatment, potentially providing a powerful tool for routine monitoring of patients in the doctor's office or in the home setting.

  4. New oral anticoagulants in patients with cancer: current state of evidence.

    PubMed

    Sardar, Partha; Chatterjee, Saurav; Herzog, Eyal; Pekler, Gerald; Mushiyev, Savi; Pastori, Luciano J; Visco, Ferdinand; Aronow, Wilbert S

    2015-01-01

    Effectiveness of new oral anticoagulants (NOAC) in patients with cancer is not clearly defined. There remain concerns of doubtful benefit and chances of potential harm with newer agents. In this meta-analysis, we evaluated the efficacy and safety of NOAC in patients with cancer. PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL databases were searched from January 01, 2001 through February 28, 2013. Randomized controlled trials reporting efficacy and safety data of NOACs (rivaroxaban, dabigatran, and apixaban) with control (low-molecular-weight heparin/vitamin K antagonists/placebo) for patients with cancer were included. Primary efficacy outcome was venous thromboembolism (VTE) or VTE-related death, and primary safety outcome was clinically relevant bleeding. We used random-effects models. Six trials randomized 19,832 patients, and 1197 patients had cancer. Risk of VTE or VTE-related death was not significantly different with NOAC versus control [odds ratio (OR), 0.80; 95% confidence interval (CI), 0.39-1.65] in patients with cancer. Separate analysis for individual effects showed similar results for rivaroxaban (OR, 1.08; 95% CI, 0.60-1.94) and dabigatran (OR, 0.91; 95% CI, 0.21-3.91). Clinically relevant bleeding was not higher with NOAC compared with control (OR, 1.49; 95% CI, 0.82-2.71); individual effect of rivaroxaban showed similar results. No statistically significant difference of efficacy and safety with NOAC was found between patients with and without cancer. Rivaroxaban might be equally effective and safe as vitamin K antagonist in patients with cancer. Dabigatran is as effective as comparator; however, safety profile of dabigatran is unknown. Randomized trials of new anticoagulants specific to the cancer population are necessary, and NOAC also need to be evaluated against low-molecular-weight heparin.

  5. INR goal attainment and oral anticoagulation knowledge of patients enrolled in an anticoagulation clinic in a Veterans Affairs medical center.

    PubMed

    Baker, Jennifer W; Pierce, Kristi L; Ryals, Casey A

    2011-03-01

    In January 2009, the Joint Commission implemented a National Patient Safety Goal (NPSG) for ambulatory care, NPSG 3E, intended to reduce harm associated with the use of anticoagulation therapy. The 2011 NPSG 3E encompasses 8 elements of performance, including requirements that each organization (a) provide education regarding anticoagulation therapy to staff, patients, and families and (b) evaluate its safety practices and take appropriate action to improve its practices. The Alvin C. York (ACY) outpatient anticoagulation clinic provides education to new patients and their families at the initial clinic visit, with follow-up reinforcement of education as needed throughout their care. To (a) assess the knowledge level of patients receiving warfarin therapy in an anticoagulation clinic using the validated Anticoagulation Knowledge Assessment (AKA) questionnaire and (b) examine the relationship between patient anticoagulation knowledge and anticoagulation control as measured by the international normalized ratio (INR). All ACY Veterans Affairs (VA) anticoagulation clinic patients seen during their routine visit within an 8-week recruitment period from February 2010 to April 2010 were asked to complete the AKA questionnaire. Upon voluntary consent, the questionnaire was completed by the patient either during the clinic visit or returned later by mail. Demographic and clinical data were manually extracted from the computerized patient record system and included age, gender, indication for and duration of anticoagulation therapy, goal INR range, and the 10 INR values preceding the date of consent. A passing score was defined as at least 21 correct responses on the 29-item AKA questionnaire (72.4% correct). Statistical analyses included comparisons of demographic and clinical characteristics for patients with passing versus failing scores, assessed with Pearson chi-square and Fisher's exact test, and bivariate analyses of INR control with anticoagulation knowledge

  6. Evaluation of the antithrombotic abilities of non-vitamin K antagonist oral anticoagulants using the Total Thrombus-formation Analysis System®.

    PubMed

    Idemoto, Yoshiaki; Miura, Shin-Ichiro; Norimatsu, Kenji; Suematsu, Yasunori; Hitaka, Yuka; Shiga, Yuhei; Morii, Joji; Imaizumi, Satoshi; Kuwano, Takashi; Iwata, Atsushi; Zhang, Bo; Ogawa, Masahiro; Saku, Keijiro

    2017-03-01

    The Total Thrombus-formation Analysis System (T-TAS ® ) is a novel automated microchip flow-chamber system for the quantitative evaluation of thrombus formation under blood flow conditions. T-TAS ® uses two types of microchip to evaluate thrombus formation: the AR-chip quantifies white thrombus formation and the PL-chip quantifies platelet thrombus formation. We assessed the antithrombotic abilities of various non-vitamin K antagonist oral anticoagulants (NOACs) using T-TAS ® . One hundred and three consecutive patients who were hospitalized with cardiovascular diseases were enrolled. We divided the patients into 2 groups; a control group that did not receive an anticoagulant (non-AC group) and an anticoagulant group (AC group). The AC group was further divided into warfarin, dabigatran, rivaroxaban and apixaban groups. We performed common coagulation tests and evaluated the area under the flow pressure curve (AR-AUC and PL-AUC) to quantify antithrombotic ability using T-TAS ® at the trough. There were no significant differences in patient characteristics between the non-AC and AC groups. Only 55.1 % of patients in the AC group achieved the target blood pressure (BP) of less than 130/80 mmHg. Compared with the non-AC group, AR-AUC was significantly decreased in the AC, warfarin, dabigatran and apixaban groups. Only the rivaroxaban group did not show a significant decrease in AR-AUC. NOACs showed a significant decrease in PL-AUC compared with the non-AC group. In conclusion, T-TAS ® was a useful tool for evaluating anticoagulation activity. NOACs was significantly effective as an antiplatelet agent. BP control should be a higher priority than the selection of an anticoagulant drug, especially NOACs.

  7. Discrepancies between Patients' Preferences and Educational Programs on Oral Anticoagulant Therapy: A Survey in Community Pharmacies and Hospital Consultations.

    PubMed

    Macquart de Terline, Diane; Hejblum, Gilles; Fernandez, Christine; Cohen, Ariel; Antignac, Marie

    2016-01-01

    Oral anticoagulation therapy is increasingly used for the prevention and treatment of thromboembolic complications in various clinical situations. Nowadays, education programs for patients treated with anticoagulants constitute an integrated component of their management. However, such programs are usually based on the healthcare providers' perceptions of what patients should know, rather than on patients' preferences. To investigate patients' viewpoints on educational needs and preferred modalities of information delivery. We conducted an observational study based on a self-administered questionnaire. To explore several profiles of patients, the study was designed for enrolling patients in two settings: during outpatient consultations in a cardiology department (Saint Antoine Hospital, Paris, France) and in community pharmacies throughout France. Of the 371 patients who completed the questionnaire, 187 (50.4%) were recruited during an outpatient consultation and 184 (49.6%) were recruited in community pharmacies. 84.1% of patients were receiving a vitamin K antagonist and 15.6% a direct oral anticoagulant. Patients ranked 16 of 21 (76.2%) questionnaire items on information about their treatment as important or essential; information on adverse effects of treatment was the highest ranked domain (mean score 2.38, 95% CI 2.30-2.46). Pharmacists (1.69, 1.58-1.80), nurses (1.05, 0.95-1.16), and patient associations (0.36, 0.29-0.44), along with group sessions (0.85, 0.75-0.95), the internet (0.77, 0.67-0.88), and delivery of material at the patient's home (1.26, 1.14-1.38), were ranked poorly in terms of delivering educational material. This study revealed substantial discrepancies between patient preferences and current educational programs. These findings should be useful for tailoring future educational programs that are better adapted to patients, with a potential associated enhancement of their effectiveness.

  8. Development of Quality Indicators to Assess Oral Anticoagulant Management in Community Pharmacies for Patients with Atrial Fibrillation.

    PubMed

    Chartrand, Mylène; Guénette, Line; Brouillette, Denis; Côté, Stéphane; Huot, Roger; Landry, Jérôme; Martineau, Josée; Perreault, Sylvie; White-Guay, Brian; Williamson, David; Martin, Élisabeth; Gagnon, Marie-Mireille; Lalonde, Lyne

    2018-04-01

    Few studies have evaluated the quality of oral anticoagulant management by community pharmacists. There is no complete set of quality indicators available for this purpose. To develop a set of specific quality indicators to assess oral anticoagulant management by community pharmacists for patients with atrial fibrillation (AF). Quality indicators were developed in 3 phases. In phase 1, potential quality indicators were generated based on clinical guidelines and a literature review. In phase 2, a modified RAND appropriateness method involving 2 rounds was implemented with 9 experts, who judged the appropriateness of quality indicators generated in phase 1 based on the extent to which they were accurate, based on evidence, relevant, representative of best practices, and measurable in community pharmacies. Phase 3 consisted of a feasibility assessment in 5 community pharmacies on 2 patients each. The final set included 38 quality indicators grouped into 6 categories: documentation (n = 29), risk assessment (n = 3), clinical control (n = 1), clinical follow-up (n = 15), choice of therapy (n = 11), and interaction management (n = 8). The quality indicators referred to process of care (n = 34), clinical outcomes (n = 2), or structure of care (n = 2). There were 24 quality indicators related to vitamin K antagonists (VKAs), and 17 were related to direct oral anticoagulants (DOACs). To assess quality indicators, a questionnaire was developed for completion by community pharmacists for each patient, which included 17 questions about VKA patients and 12 questions about DOAC patients. A first set of quality indicators is now available to assess the quality of oral anticoagulant management by community pharmacists for patients with AF. This research was supported by the Réseau Québécois de recherche sur le médicament (RQRM); the Blueprint for Pharmacy in collaboration with Pfizer Canada; and the Cercle du Doyen of the Faculty of Pharmacy, University of Montreal. The study

  9. Non-Vitamin K Oral Anticoagulants (NOACs) A Review of Clinical Management and Laboratory Issues.

    PubMed

    Blann, Andrew

    2016-01-01

    The non-vitamin K oral anticoagulants (NOACs) are set to replace vitamin K antagonists (principally warfarin), unfractionated heparin and low molecular weight heparin as the leading antithrombotic prophylaxis in several medical and surgical settings. As a group, NOACs have a better safety profile and at least an equivalent (and sometimes superior) efficacy profile than their comparator. The objective of this review is to provide the practitioner with a comprehensive, balanced and contemporary view of these drugs and their applications. More specifically, it focuses on the evidence base for their licences, use in clinical practice (such as in renal dysfunction, orthopaedic surgery, atrial fibrillation, and venous thromboembolism, and the effects of co-medications), responses to actual or perceived haemorrhage, and the role of the laboratory.

  10. [Oral anticogulation for non-valvular atrial fibrilation in the elderly].

    PubMed

    Veiga Fernández, Fernando; Malfeito Jiménez, María del Rocío; Barros Cerviño, Sonia María; Magariños Losada, María del Mar

    2015-01-01

    Anticoagulation in elderly people with non-valvular atrial afibrillation (AF) is a challenge, due to the thromboembolic, as well as the haemorrhagic risks. The correct use of anticoagulants in these patients has shown a higher net clinical benefit when comparing it with a younger population. Non-vitamin K antagonist oral anticoagulants (NOACs) have been compared to oral vitamin K antagonists in several studies that included a sufficient number of elderly people. Favourable results for non-vitamin K antagonist oral anticoagulants were obtained in these studies, making them the preferred treatment for this group of patients. Basing the estimations on indirect comparisons, the ideal anticoagulant and the specific dose for each particular case has been determined. Finally, a new algorithm has been developed that relates these parameters. Geriatric assessment is the key to the indication for an anticoagulation, the type of anticoagulant needed, and also the best way to optimise all the factors for a safe anticoagulation. The arrival of non-vitamin K antagonist oral anticoagulants will enhance the efficient thromboembolic prophylaxis rate in elderly people with AF. This new treatment will remove different controversial prophylaxis, such as antiaggregants. Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

  11. Determination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system.

    PubMed

    Bliden, Kevin P; Chaudhary, Rahul; Mohammed, Nafees; Muresan, Adina A; Lopez-Espina, Carlos G; Cohen, Eli; Raviv, Gabriel; Doubleday, Marc; Zaman, Fowzia; Mathew, Blessy; Tantry, Udaya S; Gurbel, Paul A

    2017-05-01

    Non vitamin K oral anticoagulants (NOACs) do not require regular monitoring but information about their pharmacodynamic effect may be importantin situations like trauma, stroke oremergent surgery. Currently, no standardized point-of-care test is available to evaluate the anticoagulant effects of NOACs. We evaluated the anticoagulant effect of NOACs with the next generation point-of-care TEG assay (TEG® 6S) based on a fully-automated thrombelastography system. We used two TEG® 6S assays, the DTI assay and Anti-Factor Xa (AFXa) assay, to detect anticoagulant effects and classify NOACs. Blood from healthy volunteers (n = 26) was used to obtain a baseline reference range. Data derived from patients on factor Xa inhibitors (FXi) (rivaroxaban and apixaban) (n = 39), and direct thrombin inhibitors (DTIs) (dabigatran) (n = 25) were compared against the reference range for detection of drug effect and drug classification. TEG®6s R-time highly correlated to each NOAC. Presence of NOACs caused elongation of R-time on the AFXa assay compared to the reference range (4.3 ± 1.7 vs. 1.3 ± 0.3 min. for FXi, p < 0.001 and 3.5 ± 1.2 vs. 1.3 ± 0.3 min. for DTI, p < 0.001). R-time on the DTI assay was elongated only in presence of a DTI (3.4 ± 1.0 vs. 1.5 ± 0.2 min, p < 0.001). The cutoff for detection of a DTI effect was an R time of 1.9 min and for anti-Xa effect was 1.95 min. For detection of NOAC therapy, there was ≥92% sensitivity and ≥95% specificity. The automated TEG®6s NOAC assay may be an effective tool to identify an anticoagulant effect from NOAC therapy and facilitate care of patients with bleeding or at risk of bleeding in the event of needing emergency surgery.

  12. Evaluating the impact of new anticoagulants in the hospital setting

    PubMed Central

    Braidy, Nady; Bui, Khai; Bajorek, Beata

    2010-01-01

    The short-comings of current anticoagulants have led to the development of newer, albeit more expensive, oral alternatives. Objective To explore the potential impact the new anticoagulants dabigatran and rivaroxaban in the local hospital setting, in terms of utilisation and subsequent costing. Method A preliminary costing analysis was performed based on a prospective 2-week clinical audit (29th June - 13th July 2009). Data regarding current anticoagulation management were extracted from the medical files of patients admitted to Ryde Hospital. To model potential costing implications of using the newer agents, the reported incidence of VTE/stroke and bleeding events were obtained from key clinical trials. Results Data were collected for 67 patients treated with either warfarin (n=46) or enoxaparin (n=21) for prophylaxis of VTE/stroke. At least two-thirds of all patients were deemed suitable candidates for the use of newer oral anticoagulants (by current therapy: warfarin: 65.2% (AF), 34.8% (VTE); enoxaparin: 100%, (VTE)). The use of dabigatran in VTE/stroke prevention was found to be more cost- effective than warfarin and enoxaparin due to significantly lower costs of therapeutic monitoring and reduced administration costs. Rivaroxaban was more cost-effective than warfarin and enoxaparin for VTE/stroke prevention when supplier-rebates (33%) were factored into costing. Conclusion This study highlights the potential cost- effectiveness of newer anticoagulants, dabigatran and rivaroxaban, compared to warfarin and enoxaparin. These agents may offer economic advantages, as well as clinical benefits, in the hospital-based management of anticoagulated patients. PMID:25132883

  13. Causes of Death in Patients with Venous Thromboembolism Anticoagulated with Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis.

    PubMed

    Gómez-Outes, Antonio; Terleira-Fernández, Ana Isabel; Lecumberri, Ramón; Suárez-Gea, Mª Luisa; Calvo-Rojas, Gonzalo; Vargas-Castrillón, Emilio

    2018-06-01

    Death is more frequent than nonfatal recurrent venous thromboembolism (VTE) and major bleeding after acute VTE. The analysis of the causes of death is fundamental to explore new strategies to reduce mortality rates in these patients. The authors performed a meta-analysis to analyze mortality and independently adjudicated causes of death in anticoagulated patients due to VTE, and to evaluate potential differences between different anticoagulant schemes. They searched MEDLINE and CENTRAL, from January 1, 2000, to January 31, 2017, and performed additional searches in Web sites of regulatory agencies, clinical trial registers, and conference proceedings. Two investigators independently selected studies and extracted the data. Study quality was assessed with the Cochrane Collaboration's tool for assessing the risk of bias in randomized studies. Seven prospective randomized trials in 29,844 patients (22,025 patient-year follow-up) were included, comparing dabigatran, rivaroxaban, apixaban, and edoxaban with the standard anticoagulant treatment of VTE. A total of 718 patients died during the follow-up (3.4% per year; 95% confidence interval [CI]: 2.3-4.8). The most frequent causes of death were cancer (42%), followed by VTE (20%), infections (13%), hemorrhage (6%), heart disease (4%), and stroke (2%). There were no differences in the overall survival and causes of death according to the anticoagulant type. Concomitant active cancer during the study was significantly associated with death (odds ratio: 15.2; 95% CI: 9.2-25.1). Cancer is the leading cause of death in contemporary VTE trials. Interventions beyond anticoagulation, particularly in patients with active cancer, are needed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.

    PubMed

    Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Gorst-Rasmussen, Anders; Rasmussen, Lars Hvilsted; Lip, Gregory Y H

    2015-08-11

    Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting. Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39-0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33-1.03) and 0.55 (95% confidence interval, 0.37-0.82), respectively. Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality

  15. The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands.

    PubMed

    Ten Cate, V; Ten Cate, H; Verheugt, F W A

    2016-10-01

    There are over 385,000 cases of atrial fibrillation (AF) in the Netherlands, with over 45,000 new cases each year. Among other things, AF patients are at high risk of stroke. Patients are often prescribed oral anticoagulation, such as vitamin K antagonists (VKA), to mitigate these risks. A recently introduced class of oral anticoagulants, non-vitamin K antagonists (NOAC), is quickly gaining currency in global clinical practice. This study provides insight into the changes these new drugs will bring about in Dutch clinical practice.GARFIELD-AF is a large-scale observational AF patient registry initiated in 2009 to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF in particular. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalised ratio fluctuations; and (3) therapy compliance and persistence patterns. The results in this paper provide the baseline characteristics of the first cohorts of Dutch participants in this registry and discuss some of the consequences of the changes in anticoagulation practice.Although VKA therapy remains overwhelmingly favoured by Dutch practitioners, NOACs are clearly gaining in popularity. Between 2011 and 2014, NOACs constituted an increasingly large proportion of prescriptions for oral anticoagulants.The insights provided by the GARFIELD-AF registry can be used by healthcare systems to inform better budgetary strategies, by practitioners to better tailor treatment pathways to patients, and finally to promote awareness of the various available treatment options and their associated risks and benefits for patients.

  16. [Secondary osteoporosis induced by anticoagulants?].

    PubMed

    Riess, H; Loew, A; Himmelreich, G

    2001-07-01

    Generalized osteoporosis is a result of different causes and pathogenic mechanisms, which often combine forces to become clinically relevant. Among the different exogenic factors, drugs play an important role, frequently in connection with other factors such as immobilization or pregnancy. It has been suggested that anticoagulation therapy with heparins or coumarins may induce osteoporotic changes or enhance the development of osteoporosis for other reasons. According to in vitro experiments, preclinical trials, and clinical investigations, it seems reasonable to assume that heparins induce increased bone loss in a time- and dose-related manner. Low-molecular-weight heparins most likely have less effect on bone turnover when compared to unfractionated heparin. Oral anticoagulation therapy with vitamin K-antagonists is believed to have a weak effect on induction of osteoporosis, but clinical studies are contradictory. In spite of the fact that a relevant effect of these drugs on the induction of osteoporosis is questionable, it must be taken into consideration that anticoagulant drugs may enhance the negative effects on bone density of other risk factors capable of inducing osteoporosis such as immobilization, pregnancy, or endocrinological disorders.

  17. Mild brain injury and anticoagulants: Less is enough.

    PubMed

    Campiglio, Laura; Bianchi, Francesca; Cattalini, Claudio; Belvedere, Daniela; Rosci, Chiara Emilia; Casellato, Chiara Livia; Secchi, Manuela; Saetti, Maria Cristina; Baratelli, Elena; Innocenti, Alessandro; Cova, Ilaria; Gambini, Chiara; Romano, Luca; Oggioni, Gaia; Pagani, Rossella; Gardinali, Marco; Priori, Alberto

    2017-08-01

    Despite the higher theoretical risk of traumatic intracranial hemorrhage (ICH) in anticoagulated patients with mild head injury, the value of sequential head CT scans to identify bleeding remains controversial. This study evaluated the utility of 2 sequential CT scans at a 48-hour interval (CT1 and CT2) in patients with mild head trauma (Glasgow Coma Scale 13-15) taking oral anticoagulants. We retrospectively evaluated the clinical records of all patients on chronic anticoagulation treatment admitted to the emergency department for mild head injury. A total of 344 patients were included, and 337 (97.9%) had a negative CT1. CT2 was performed on 284 of the 337 patients with a negative CT1 and was positive in 4 patients (1.4%), but none of the patients developed concomitant neurologic worsening or required neurosurgery. Systematic routine use of a second CT scan in mild head trauma in patients taking anticoagulants is expensive and clinically unnecessary.

  18. Optimal duration of anticoagulation in patients with venous thromboembolism

    PubMed Central

    Prandoni, Paolo; Piovella, Chiara; Spiezia, Luca; Valle, Fabio Dalla; Pesavento, Raffaele

    2011-01-01

    The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE. PMID:21808129

  19. Optimal duration of anticoagulation in patients with venous thromboembolism.

    PubMed

    Prandoni, Paolo; Piovella, Chiara; Spiezia, Luca; Dalla Valle, Fabio; Pesavento, Raffaele

    2011-07-01

    The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE.

  20. Satisfaction, quality of life and perception of patients regarding burdens and benefits of vitamin K antagonists compared with direct oral anticoagulants in patients with nonvalvular atrial fibrillation.

    PubMed

    Contreras Muruaga, Ma Del Mar; Vivancos, José; Reig, Gemma; González, Ayoze; Cardona, Pere; Ramírez-Moreno, José Mª; Martí, Joan; Suárez Fernández, Carmen

    2017-06-01

    To compare the satisfaction of patients treated with vitamin K antagonists (VKA) with that of patients treated with direct oral anticoagulants (DOACs) and to determine the impact on quality of life of both treatments in patients with nonvalvular atrial fibrillation (NVAF). Cross-sectional multicenter study in which outpatients with NVAF completed the ACTS (Anti-Clot Treatment Scale), SAT-Q (Satisfaction Questionnaire) and EQ-5D-3L (EuroQol 5 dimensions questionnaire, 3 level version) questionnaires. The study population comprised 1337 patients, of whom 587 were taking DOACs and 750 VKAs. Compared with VKAs, DOACs were more commonly prescribed in patients with a history of stroke and in patients with a higher thromboembolic risk. The study scores were as follows: SAT-Q: 63.8 ± 17.8; EQ-5D-3L total score: 75.6 ± 20.9; visual analog scale: 63.1 ± 20.6; ACTS Burdens: 51.8 ± 8.4 and ACTS Benefits: 11.9 ± 2.4. The ACTS Burdens score and ACTS Benefits score were higher with DOACs than with VKAs (54.83 ± 6.11 vs 49.50 ± 9.15; p < 0.001 and 12.36 ± 2.34 vs 11.48 ± 2.46; p < 0.001 respectively). NVAF patients treated with oral anticoagulants had many comorbidities and a high thromboembolic risk. Satisfaction and quality of life with oral anticoagulants were high, although they were both better with DOACs than with VKAs.

  1. Bleeding events associated with novel anticoagulants: a case series.

    PubMed

    Mirzaee, Sam; Tran, Tara Thi Thien; Amerena, John

    2013-12-01

    Until lately warfarin was the only valuable oral anticoagulant in stroke reduction in high risk cases with non valvular atrial fibrillation (NVAF). Although with warfarin the rate of stroke reduced notably, the major concern is the risk of serious bleeding and difficulty of establishing and maintaining the international normalised ratio (INR) within the therapeutic range. With the development of the novel anticoagulants we now have for the first time since the innovation of Warfarin feasible alternatives to it to decrease stroke rates in high risk patients with NVAF. To diminish adverse bleeding events with the novel anticoagulant proper selection of patients prior starting treatment is essential. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  2. Appropriateness of Oral Anticoagulants for the Long-Term Treatment of Atrial Fibrillation in Older People: Results of an Evidence-Based Review and International Consensus Validation Process (OAC-FORTA 2016).

    PubMed

    Wehling, Martin; Collins, Ronan; Gil, Victor M; Hanon, Olivier; Hardt, Roland; Hoffmeister, Martin; Monteiro, Pedro; Quinn, Terence J; Ropers, Dieter; Sergi, Giuseppe; Verheugt, Freek W A

    2017-07-01

    Age appropriateness of anticoagulants for stroke prevention in atrial fibrillation is uncertain. To review oral anticoagulants for the treatment of atrial fibrillation in older (age >65 years) people and to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability using the Fit-fOR-The-Aged (FORTA) classification. We performed a structured comprehensive review of controlled clinical trials and summaries of individual product characteristics to assess study and total patient numbers, quality of major outcome data and data of geriatric relevance. The resulting evidence was discussed in a round table with an interdisciplinary panel of ten European experts. Decisions on age appropriateness were made using a Delphi process. For the eight drugs included, 380 citations were identified. The primary outcome results were reported in 32 clinical trials with explicit and relevant data on older people. Though over 24,000 patients aged >75/80 years were studied for warfarin, data on geriatric syndromes were rare (two studies reporting on frailty/falls/mental status) and missing for all other compounds. Apixaban was rated FORTA-A (highly beneficial). Other non-vitamin K antagonist oral anticoagulants (including low/high-intensity dabigatran and high-intensity edoxaban) and warfarin were assigned to FORTA-B (beneficial). Phenprocoumon, acenocoumarol and fluindione were rated FORTA-C (questionable), mainly reflecting the absence of data. All non-vitamin K antagonist oral anticoagulants and warfarin were classified as beneficial or very beneficial in older persons (FORTA-A or -B), underlining the overall positive assessment of the risk/benefit ratio for these drugs. For other vitamin-K antagonists regionally used in Europe, the lack of evidence should challenge current practice.

  3. Clinical characteristics and management of patients with atrial fibrillation treated with direct oral anticoagulants according to blood pressure control.

    PubMed

    de la Figuera, M; Cinza, S; Egocheaga, I; Marín, N; Prieto, M A

    2018-02-14

    To determine the clinical characteristics and management of hypertensive patients with nonvalvular atrial fibrillation (AF) treated with direct oral anticoagulants (DOACs) according to blood pressure (BP) control. For this purpose, data from two observational, cross-sectional and multicenter studies were combined. In both studies, patients on chronic treatment with anticoagulants and that were on current treatment with DOACs at least for 3 months were included. Adequate BP was defined as a systolic BP<140mmHg and a diastolic BP<90mmHg (<140/85mmHg if diabetes). Overall, 1036 patients were included. Of these, 881 (85%) had hypertension that were finally analyzed. The presence of other risk factors and cardiovascular disease was common. Mean BP was 132.6±14.3/75.2±9.2mmHg and 70.5% of patients achieved BP goals. Those patients with a poor BP control had more frequently diabetes, and a history of prior labile INR. Patients had a high thromboembolic risk, but without significant differences according to BP control. By contrast, more patients with a poor BP control had a higher bleeding risk (HAS-BLED ≥3: 24.0% vs 35.4%; P<0.001). HAS-BLED score was an independent predictor of poor BP control (odds ratio 1.435; 95% confidence interval 1.216-1.693; P<0.001). Satisfaction with anticoagulant treatment was independent of BP control. More than two thirds of our patients with hypertension and AF anticoagulated with DOACs achieve BP targets, what is clearly superior to that reported in the general hypertensive population. Copyright © 2018 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. [Concepts in anticoagulant therapy - past, present, and future].

    PubMed

    Graf, L

    2012-11-01

    The understanding of the clotting system emerged in parallel to the development of anticoagulants. In contrast to vitamin K-antagonists and heparins that where discovered by chance, new anticoagulants have been systematically designed to specifically inhibit single clotting factors. Both clotting factors Xa (FXa) and thrombin play a crucial role within the new cell-based model of hemostasis. Thus it is obvious that FXa and thrombin turned out to be ideal targets for anticoagulation. The proof of the concept of selective inhibition of thrombin and FXa has been provided by hirudin and fondaparinux, respectively. By now, a whole group of new oral anticoagulants has been licensed: the direct FXa-inhibitors rivaroxaban, apixaban, and edoxaban as well as the direct thrombin dabigatran etexilate. Furthermore, a bundle of FXa- and thrombin-inhibitors that differ from the so far licensed products mainly in pharmacokinetics are in an advanced phase of development. A further innovative concept of anticoagulation that entered its clinical phase of development is the inhibition of factor VIII. Other new concepts such as inhibition of initiation of coagulation by blocking factor VIIa, inhibition of contact factor XII, or inhibition of factor IX are in an early phase of development.

  5. Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: An updated systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Ntaios, George; Papavasileiou, Vasileios; Diener, Hans-Chris; Makaritsis, Konstantinos; Michel, Patrik

    2017-08-01

    Background In a previous systematic review and meta-analysis, we assessed the efficacy and safety of nonvitamin-K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and stroke or transient ischemic attack. Since then, new information became available. Aim The aim of the present work was to update the results of the previous systematic review and meta-analysis. Methods We searched PubMed until 24 August 2016 for randomized controlled trials using the following search items: "atrial fibrillation" and "anticoagulation" and "warfarin" and "previous stroke or transient ischemic attack." Eligible studies had to be phase III trials in patients with atrial fibrillation comparing warfarin with nonvitamin-K antagonist oral anticoagulants currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause, and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding, and major gastrointestinal bleeding. We performed fixed effects analyses on intention-to-treat basis. Results Among 183 potentially eligible articles, four were included in the meta-analysis. In 20,500 patients, compared to warfarin, nonvitamin-K antagonist oral anticoagulants were associated with a significant reduction of stroke/systemic embolism (relative risk reduction: 13.7%, absolute risk reduction: 0.78%, number needed to treat to prevent one event: 127), hemorrhagic stroke (relative risk reduction: 50.0%, absolute risk reduction: 0.63%, number needed to treat: 157), any stroke (relative risk reduction: 13.1%, absolute risk reduction: 0.7%, number needed to treat: 142), and intracranial hemorrhage (relative risk reduction: 46.1%, absolute risk reduction: 0.88%, number needed

  6. Efficacy and Safety of Oral Anticoagulants Versus Aspirin for Patients With Atrial Fibrillation

    PubMed Central

    Zhang, Jing-Tao; Chen, Ke-Ping; Zhang, Shu

    2015-01-01

    Abstract The purpose of this study was to perform a meta-analysis comparing the effectiveness and safety of anticoagulation to antiplatelet therapy for the prevention of thromboembolic events in patients with atrial fibrillation (AF). MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched for studies published through May 31, 2014. Randomized controlled trials comparing anticoagulants (warfarin) and antiplatelet therapy in patients with AF were included. The primary outcomes were the rates of stroke and systemic embolism. Secondary outcomes included the rates of hemorrhage/major bleeding and death. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Nine reports of 8 trials that enrolled 4363 patients (2169 patients received anticoagulation and 2194 antiplatelet therapy) were included. All of the studies compared adjusted-dose warfarin or with aspirin, and the majority of the patients were >70 years of age. Anticoagulants were titrated to an international normalized ratio (INR) of 2.0 to 4.5, and aspirin was administered at a dosage of 75 to 325 mg/d. Death occurred in 206 participants treated with an anticoagulant and 229 participants treated with antiplatelet therapy. There was no significant difference in the overall stroke rate between the groups (OR = 0.667, 95% CI 0.426–1.045, P = 0.08); however, patients with nonrheumatic AF (NRAF) treated with an anticoagulant had a lower risk of stroke (OR = 0.557, 95% CI 0.411–0.753, P < 0.001). Anticoagulants were associated with a lower risk of embolism (OR = 0.616, 95% CI = 0.392–0.966, P = 0.04), and this finding persisted in patients with NRAF (OR = 0.581, 95% CI 0.359–0.941, P = 0.03). No significant difference in the rate of hemorrhage/major bleeding was noted (OR = 1.497, 95% CI 0.730–3.070, P = 0.27), and this finding persisted on subgroup analysis. Anticoagulants appear to be more effective than aspirin in preventing

  7. Aligning health care policy with evidence-based medicine: the case for funding direct oral anticoagulants in atrial fibrillation.

    PubMed

    Stone, James A; Earl, Karen M; O'Neill, Blair J; Sharma, Mukul; Huynh, Thao; Leblanc, Kori; Ward, Richard; Teal, Philip A; Cox, Jafna L

    2014-10-01

    Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guideline-based therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes are preventable with appropriate anticoagulation, this has historically been underprescribed and poorly managed. National and international guidelines endorse the direct oral anticoagulants as first-line therapy for this indication. However, no Canadian province has provided these agents with an unrestricted listing. These decisions appear to be founded on silo-based cost assessment-the drug costs rather than the total system costs-and thus overlook several important cost-drivers in stroke. The discordance between best scientific evidence and public policy requires health care providers to use a potentially suboptimal therapy in contravention of guideline recommendations. It represents a significant obstacle for knowledge translation efforts that aim to increase the appropriate anticoagulation of Canadians with AF. As health care professionals, we have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  8. New oral anticoagulants in the treatment of heparin-induced thrombocytopenia.

    PubMed

    Sharifi, Mohsen; Bay, Curt; Vajo, Zoltan; Freeman, Wilbur; Sharifi, Mirali; Schwartz, Frederic

    2015-04-01

    Heparin induced thrombocytopenia (HIT) is a potentially catastrophic syndrome with a high incidence of vascular thrombosis. There are little data on the efficacy of new oral anticoagulants (NOAC) in this setting. This study reports on the outcome of patients with HIT, treated with NOAC. We retrospectively identified 22 patients with HIT who were treated by our group with a combination of NOAC and a short course of argatroban. These patients were evaluated in a prospective fashion for development of outcomes at a mean follow up of 19±3 months. There were a total of 5 deep and 2 superficial vein thromboses diagnosed at index hospitalization. No patient developed arterial thrombosis. All patients tolerated NOAC and their platelet count normalized before discharge. At 19 months of follow-up, 6 patients had died of non-thrombotic causes. There was no bleeding, limb loss or recurrent venous thromboembolism in any patient. In patients with HIT, a short course of parenteral treatment with argatroban followed by administration of a NOAC is highly safe and effective in prevention of thrombosis and normalization of platelet count. Development of HIT however, portends a poor prognosis independent of vascular thrombosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Meta-Analysis of Effectiveness and Safety of Oral Anticoagulants in Atrial Fibrillation With Focus on Apixaban.

    PubMed

    Bai, Ying; Shi, Xu-Bo; Ma, Chang-Sheng; Lip, Gregory Y H

    2017-11-01

    We performed a meta-analysis of data on the effectiveness and safety of apixaban compared with other oral anticoagulants (warfarin or rivaroxaban or dabigatran or edoxaban) for stroke prevention in atrial fibrillation (AF) in different settings of randomized controlled trials, real-world studies, and radiofrequency ablation (RFA). Thirty studies were searched in PubMed, the Cochrane Library, and Clinicaltrials.gov databases reporting comparative effectiveness and safety of apixaban with warfarin (n = 23), rivaroxaban (n = 12), dabigatran (n = 13), or edoxaban (n = 2) for stroke prevention in AF. In real-world estimates, apixaban was similar to warfarin for the prevention of stroke or systematic thromboembolism (hazard ratio 0.93, 95% CI 0.71 to 1.14, I 2  = 82.9%, N = 7), and safer than warfarin in the risks of major bleeding (hazard ratio 0.62, 95% CI 0.54 to 0.70, I 2  = 18.7%, N = 9) in patients with AF. The risk of stroke or thromboembolism with apixaban was similar to rivaroxaban, dabigatran, and edoxaban in the settings of real-world studies and RFA. Major bleeding with apixaban was generally lower than rivaroxaban (relative risks 0.45, 95% CI 0.38 to 0.53, I 2  = 0%, N = 5) and similar to dabigatran in real-world studies (relative risks 1.44, 95% CI 0.33 to 6.30, I 2  = 97.7%, N = 5), but similar to rivaroxaban, dabigatran, and edoxaban in RFA. In conclusion, our meta-analysis provides a comprehensive estimate of the effectiveness and safety of apixaban compared with other oral anticoagulants (warfarin, rivaroxaban, dabigatran, and edoxaban) in patients with AF in different settings of randomized controlled trial, real-world studies, and RFA. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Atrial Fibrillation.

    PubMed

    Cha, Myung-Jin; Choi, Eue-Keun; Han, Kyung-Do; Lee, So-Ryoung; Lim, Woo-Hyun; Oh, Seil; Lip, Gregory Y H

    2017-11-01

    There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with nonvalvular atrial fibrillation. We aimed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population, with particular focus on high-risk patients. Using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH) events, and all-cause death in NOAC users (n=11 611 total, n=5681 taking rivaroxaban, n=3741 taking dabigatran, and n=2189 taking apixaban) compared with propensity score-matched warfarin users (n=23 222) among patients with high-risk atrial fibrillation (CHA 2 DS 2 -VASc score ≥2) between 2014 and 2015. NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin. All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin. Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome (ischemic stroke, ICH, and all-cause death) compared with warfarin, whereas this was nonsignificant for rivaroxaban. Among previously oral anticoagulant-naive patients (n=23 262), dabigatran and apixaban were superior to warfarin for ICH prevention, whereas rivaroxaban and warfarin were associated with similar risk of ICH. In real-world practice among a high-risk Asian atrial fibrillation population, all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin. All-cause mortality was significantly lower only with dabigatran and apixaban. © 2017 American Heart Association, Inc.

  11. Evaluation of the predictive performance of bleeding risk scores in patients with non-valvular atrial fibrillation on oral anticoagulants.

    PubMed

    Beshir, S A; Aziz, Z; Yap, L B; Chee, K H; Lo, Y L

    2018-04-01

    Bleeding risk scores (BRSs) aid in the assessment of oral anticoagulant-related bleeding risk in patients with atrial fibrillation. Ideally, the applicability of a BRS needs to be assessed, prior to its routine use in a population other than the original derivation cohort. Therefore, we evaluated the performance of 6 established BRSs to predict major or clinically relevant bleeding (CRB) events associated with the use of oral anticoagulant (OAC) among Malaysian patients. The pharmacy supply database and the medical records of patients with non-valvular atrial fibrillation (NVAF) receiving warfarin, dabigatran or rivaroxaban at two tertiary hospitals were reviewed. Patients who experienced an OAC-associated major or CRB event within 12 months of follow-up, or who have received OAC therapy for at least 1 year, were identified. The BRSs were fitted separately into patient data. The discrimination and the calibration of these BRSs as well as the factors associated with bleeding events were then assessed. A total of 1017 patients with at least 1-year follow-up period, or those who developed a bleeding event within 1 year of OAC use, were recruited. Of which, 23 patients experienced a first major bleeding event, whereas 76 patients, a first CRB event. Multivariate logistic regression results show that age of 75 or older, prior bleeding and male gender are associated with major bleeding events. On the other hand, prior gastrointestinal bleeding, a haematocrit value of less than 30% and renal impairment are independent predictors of CRB events. All the BRSs show a satisfactory calibration for major and CRB events. Among these BRSs, only HEMORR 2 HAGES (C-statistic = 0.71, 95% CI 0.60-0.82, P < .001) and ATRIA score (C-statistic = 0.70, 95% CI 0.58-0.82, P < .001) show acceptable discrimination performance for major bleeding events. All the 6 BRSs, however, lack acceptable predictive performance for CRB events. To the best of our knowledge, this is the first

  12. Safety profile of the direct oral anticoagulants: an analysis of the WHO database of adverse drug reactions.

    PubMed

    Monaco, Luca; Biagi, Chiara; Conti, Valentino; Melis, Mauro; Donati, Monia; Venegoni, Mauro; Vaccheri, Alberto; Motola, Domenico

    2017-07-01

    Direct oral anticoagulants (DOACs) have shown noninferiority to warfarin for stroke prevention in nonvalvular atrial fibrillation (AF) and a more promising safety profile. Unanswered safety aspects remain to be addressed and available evidence on the risk associated with these drugs are conflicting. In order to contribute to the debate on their safety profile, we conducted a comparative analysis of the reports of suspected adverse drug reactions (ADRs) associated with DOACs in VigiBase. Study based on reports of suspected ADRs held in VigiBase as at December 2014, in which a DOAC or warfarin were administered in patients with nonvalvular AF and listed as suspected/interacting drugs. Medical Dictionary for Regulatory Activities was used to classify ADRs. Reporting odds ratio (ROR) with 95% confidence interval were calculated. Results with P ≤ 0.05 were statistically significant. We retrieved 32 972 reports. We identified 204 ADRs with a ROR >1 (P ≤ 0.05) and we focused on 105 reactions. Positive ROR emerged for DOACs and gastrointestinal haemorrhage compared with warfarin [(1.6 (1.47-1.75)], but no disproportionality with cerebral haemorrhage was found [0.31 (0.28-0.34)]. We identified other potential signals that have not been associated with DOACs previously. As well as premarketing authorization clinical trial studies, we found a reduced risk of intracranial haemorrhage, but an increased risk of gastrointestinal haemorrhage in patients treated with DOACs compared to warfarin. We provide new data and we highlight several differences between the three novel oral anticoagulants, in the rate and type of ADRs occurred. © 2017 The British Pharmacological Society.

  13. [Drug compliance of patients on anticoagulant treatment].

    PubMed

    Gadó, Klára; Kocsis, Eszter; Zelkó, Romána; Hankó, Balázs; Kovácsné Balogh, Judit; Forczig, Mónika; Domján, Gyula

    2015-08-09

    Despite several therapeutic possibilities the morbidity and mortality of thromboembolic disorders remain high. Improving drug compliance - i. e. keeping up the doctor's prescriptions - may be an effective tool to reach better results. To improve patients' compliance, the risk factors of non-compliance should be recognized. Among these patients' fear of adverse effects of drugs, their lack of knowledge about their illness and medication, forgetfulness, and other social, economic factors may be the most important. Furthermore, adherence may be worsened when the patient feels that the decision has been made over his/her head. Sustained medical adherence is important because anticoagulation may be a life-long treatment. The new oral anticoagulants make the matter of compliance to be current. These new type of drugs do not need regular laboratory monitoring and, therefore, compliance cannot be strictly followed. There are several studies concerning drug compliance to anticoagulant medications. Improvement of adherence is based on regular patient education after reviewing the factors of non-compliance, which needs teamwork with important roles of doctors, pharmacists, dietetics and nurses. Careful and accurate work of the participants of primary care might be complemented by the activity of anticoagulant clinics.

  14. Combined Aspirin and Anticoagulant Therapy in Patients with Atrial Fibrillation

    PubMed Central

    So, Charlotte H.; Eckman, Mark H.

    2016-01-01

    Background The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. Objective (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Design and Participants Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Main Measures Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Key Results Of 948 patients receiving OAC, 430 (45%) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49% and 42% of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27% had a diagnosis of CAD and 14% had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn’t discontinued. A surprisingly large proportion of patients (22.8%) had no obvious indication for dual therapy. Conclusions Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or

  15. NP-184[2-(5-methyl-2-furyl) benzimidazole], a novel orally active antithrombotic agent with dual antiplatelet and anticoagulant activities.

    PubMed

    Kuo, Heng-Lan; Lien, Jin-Cherng; Chung, Ching-Hu; Chang, Chien-Hsin; Lo, Shyh-Chyi; Tsai, I-Chun; Peng, Hui-Chin; Kuo, Sheng-Chu; Huang, Tur-Fu

    2010-06-01

    The established antiplatelet and anticoagulant agents show beneficial effects in the treatment of thromboembolic diseases; however, these drugs still have considerable limitations. The effects of NP-184, a synthetic compound, on platelet functions, plasma coagulant activity, and mesenteric venule thrombosis in mice were investigated. NP-184 concentration-dependently inhibited the human platelet aggregation induced by collagen, arachidonic acid (AA), and U46619, a thromboxane (TX)A(2) mimic, with IC(50) values of 4.5 +/- 0.2, 3.9 +/- 0.1, and 9.3 +/- 0.5 microM, respectively. Moreover, NP-184 concentration-dependently suppressed TXA(2) formations caused by collagen and AA. In exploring effects of NP-184 on enzymes involved in TXA(2) synthesis, we found that NP-184 selectively inhibited TXA(2) synthase activity with an IC(50) value of 4.3 +/- 0.2 microM. Furthermore, NP-184 produced a right shift of the concentration-response curve of U46619, indicating a competitive antagonism on TXA(2)/prostaglandin H(2) receptor. Intriguingly, NP-184 also caused a concentration-dependent prolongation of the activated partial thromboplastin time (aPTT) with no changes in the prothrombin and thrombin time, indicating that it selectively impairs the intrinsic coagulation pathway. Oral administration of NP-184 significantly inhibited thrombus formation of the irradiated mesenteric venules in fluorescein sodium-treated mice without affecting the bleeding time induced by tail transection. However, after oral administration, NP-184 inhibited the ex vivo mouse platelet aggregation triggered by collagen and U46619 and also prolonged aPTT. Taken together, the dual antiplatelet and anticoagulant activities of NP-184 may have therapeutic potential as an oral antithrombotic agent in the treatment of thromboembolic disorders.

  16. Photodegradation of novel oral anticoagulants under sunlight irradiation in aqueous matrices.

    PubMed

    Yassine, Montaha; Fuster, Laura; Dévier, Marie-Hélène; Geneste, Emmanuel; Pardon, Patrick; Grélard, Axelle; Dufourc, Erick; Al Iskandarani, Mohamad; Aït-Aïssa, Selim; Garric, Jeanne; Budzinski, Hélène; Mazellier, Patrick; Trivella, Aurélien S

    2018-02-01

    Kinetics of photodegradation of novel oral anticoagulants dabigatran, rivaroxaban, and apixaban were studied under simulated solar light irradiation in purified, mineral, and river waters. Dabigatran and rivaroxaban underwent direct photolysis with polychromatic quantum yields of 2.2 × 10 -4 and 4.4 × 10 -2 , respectively. The direct photodegradation of apixaban was not observed after 19 h of irradiation. Kinetics of degradation of rivaroxaban was not impacted by the nature of the aqueous matrix while photosensitization from nitrate ions was observed for dabigatran and apixaban dissolved in a mineral water. The photosensitized reactions were limited in the tested river water (Isle River, Périgueux, France) certainly due to the hydroxyl radical scavenging effect of the dissolved organic matter. The study of photoproduct structures allowed to identify two compounds for dabigatran. One of them is the 4-aminobenzamidine while the second one is a cyclization product. In the case of rivaroxaban, as studied by very high field NMR, only one photoproduct was observed i.e. a photoisomer. Finally, seven photoproducts were clearly identified from the degradation of apixaban under simulated solar light. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine.

    PubMed

    Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

    2017-01-02

    Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1 H nuclear magnetic resonance ( 1 H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity and the feeding indexes of R 1 and R 2 were tested. The result of the experiment proved that the new synthesis of 1, 3 - indan diketone for maternal new anticoagulant rodenticide can replace the current 4 - hydroxyl coumarin as the mother of the second generation anticoagulant rodenticide and 1, 3 - indan diketone for maternal new anticoagulant rodenticides will have a good development prospect.

  18. Areas of improvement in anticoagulant safety. Data from the CACAO study, a cohort in general practice

    PubMed Central

    Cogneau, Joël; Gaboreau, Yoann; Abenhaïm, Nathan; Bayen, Marc; Calafiore, Matthieu; Guichard, Claude; Jacquet, Jean-Pierre; Lacoin, François; Bertoletti, Laurent

    2017-01-01

    Background Real-world studies on anticoagulants are mostly performed on health insurance databases, limited to reported events, and sometimes far from every-day issues in family practice. We assess the presence of data for safe monitoring of oral anticoagulants in general practice, and compare patients’ knowledge of taking an anticoagulant between vitamin K antagonists (VKA) and direct anticoagulants (DOAC), and the general practitioner’s perception of their adherence to anticoagulation. Methods The CACAO study is a national cohort study, conducted by general practitioners on ambulatory patients under oral anticoagulant. In the first phase, investigators provided safety data available from medical records at inclusion. They also evaluated patients’ knowledge about anticoagulation and graded their perception of patients’ adherence. Results Between April and December 2014, 463 general practitioners included 7154 patients. Renal and hepatic function tests were respectively unavailable in 109 (7.5%) and 359 (24.7%) DOAC patients. Among patients with atrial fibrillation, 345 patients (6.9%) had a questionable indication of anticoagulant (CHA2DS2-Vasc<2). One hundred and thirty-three VKA patients (2.3%) and 70 DOAC patients (4.9%) answered they took no anticoagulant (p<0.0001). According to general practitioners’ perception, 430 patients (6.1%) were classified as “not very” or “not adherent”, with no difference between groups. Conclusions Our results highlight the efforts needed to improve anticoagulant safety in daily practice: decreasing the rate of unknown biological data in patients with DOACs or the rate of patients with VKA with no strong indication of anticoagulation, and improving patient knowledge with regard to their anticoagulant. Patients’ adherence seems highly over-estimated by the general practitioners. Clinical trial registration ClinicalTrials.gov NCT02376777 PMID:28384199

  19. The safety and persistence of non-vitamin-K-antagonist oral anticoagulants in atrial fibrillation patients treated in a well structured atrial fibrillation clinic.

    PubMed

    Al-Khalili, Faris; Lindström, Catrine; Benson, Lina

    2016-01-01

    To examine the long-term persistence and safety of the non-vitamin-K-antagonist oral anticoagulants (NOACs) dabigatran (D), rivaroxaban (R) and apixaban (A) in patients with non-valvular atrial fibrillation (AF) treated in the framework of a well structured, nurse-based AF unit for initiation and follow-up of NOAC. Retrospective clinical data were collected for 766 consequent patients from a single cardiology outpatient clinic incorporating the AF unit. The follow-up time, median (q1-q3), was 367 days (183-493) for D patients (n = 233), 432 days (255-546) for R patients (n = 282) and 348 days (267-419) for A patients (n = 251). No significant differences were found between the three groups with regard to age, sex, renal function, or CHA2DS2-VASc score. For all bleeding events the incidence rates per 100 patient-years of follow-up (95% confidence interval [CI], p-value) were reported more often for treatment with R (17.2, 12.7-22.8) than for D (7.0, 4.0-11.3, p = 0.001) and A (8.7, 5.2-13.6, p = 0.013). The differences remained significant after adjustment for clinically relevant variables. Discontinuation rates (n = 167) were lower for A (11.5, 7.5-16.8) than for D (30, 23.4-37.9, p < 0.001) and R (23.9, 18.6-30.1, p = 0.001), and were mainly attributed to drug-specific side effects and bleedings. The majority of discontinued patients (n = 142, 85%) proceeded with other types of oral anticoagulants. The main limitation of the study is the small patient population with a short follow-up time. In a retrospective study at a single AF clinic, NOACs showed significantly different bleeding rates and varied discontinuation rates when compared to each other, related mainly to agent-specific side effects and bleedings. The majority of patients that discontinued proceeded with other types of oral anticoagulant.

  20. Injuries and outcomes associated with traumatic falls in the elderly population on oral anticoagulant therapy.

    PubMed

    Boltz, Melissa M; Podany, Abigail B; Hollenbeak, Christopher S; Armen, Scott B

    2015-09-01

    Fall risk for older adults is a multi-factorial public health problem as 90% of geriatric injuries are caused by traumatic falls. The CDC estimated 33% of adults >65 years incurred a fall in 2011, with 30% resulting in moderate injury. While much has been written about overall risk to trauma patients on oral anticoagulant (OAC) therapy, less has been reported on outcomes in the elderly trauma population. We used data from the National Trauma Data Bank (NTDB) to identify the types of injury and complications incurred, length of stay, and mortality associated with OACs in elderly patients sustaining a fall. Using standard NTDB practices, data were collected on elderly patients (≥65 years) on OACs with diagnosis of fall as the primary mechanism of injury from 2007 to 2010. Univariate analysis was used to determine patient variables influencing risk of fall on OACs. Odds ratios were calculated for types of injury sustained and post-trauma complications. Logistic regression was used to determine mortality associated with type of injury incurred. Of 118,467 elderly patients sampled, OAC use was observed in 444. Predisposing risk factors for fall on OACs were >1 comorbidity (p<0.0001). Patients on OACs were 188% and 370% more likely to develop 2 and >3 complications (p<0.0001); the most significant being ARDS and ARF (p<0.0001). The mortality rate on OACs was 16%. Injuries to the GI tract, liver, spleen, and kidney (p<0.0002) were more likely to occur. However, if patients suffered a mortality, the most significant injuries were skull fractures and intracranial haemorrhage (p<0.0001). Risks of anticoagulation in elderly trauma patients are complex. While OAC use is a predictor of 30-day mortality after fall, the injuries sustained are markedly different between the elderly who die and those who do not. As a result there is a greater need for healthcare providers to identify preventable and non-preventable risks factors indicative of falls in the anti-coagulated elderly

  1. Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy.

    PubMed

    Labovitz, Daniel L; Shafner, Laura; Reyes Gil, Morayma; Virmani, Deepti; Hanina, Adam

    2017-05-01

    This study evaluated the use of an artificial intelligence platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants, while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding. A randomized, parallel-group, 12-week study was conducted in adults (n=28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the artificial intelligence platform (intervention) or to no daily monitoring (control). The artificial intelligence application visually identified the patient, the medication, and the confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups. For all patients (n=28), mean (SD) age was 57 years (13.2 years) and 53.6% were women. Mean (SD) cumulative adherence based on the artificial intelligence platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively. Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving direct oral anticoagulants, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on direct oral anticoagulant therapy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259. © 2017 American Heart Association, Inc.

  2. Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine

    PubMed Central

    Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

    2017-01-01

    ABSTRACT Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1H nuclear magnetic resonance (1H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity and the feeding indexes of R1 and R2 were tested. The result of the experiment proved that the new synthesis of 1, 3 - indan diketone for maternal new anticoagulant rodenticide can replace the current 4 - hydroxyl coumarin as the mother of the second generation anticoagulant rodenticide and 1, 3 - indan diketone for maternal new anticoagulant rodenticides will have a good development prospect. PMID:27759485

  3. Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol

    PubMed Central

    Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

    2016-01-01

    Introduction Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12–15% of patients with SSc and accounts for 30–40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. Methods and analysis This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethics and dissemination Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. Trial registration number ACTRN12614000418673, Pre-results. PMID:27932335

  4. Cross-cultural adaptation and psychometric properties of the Brazilian-Portuguese version of the Duke Anticoagulation Satisfaction Scale.

    PubMed

    Pelegrino, Flávia M; Dantas, Rosana A S; Corbi, Inaiara S A; da Silva Carvalho, Ariana R; Schmidt, André; Pazin Filho, Antônio

    2012-09-01

    The aim of this study was to evaluate the internal reliability and validity of the Brazilian-Portuguese version of Duke Anticoagulation Satisfaction Scale (DASS) among cardiovascular patients. Oral anticoagulation is widely used to prevent and treat thromboembolic events in several conditions, especially in cardiovascular diseases; however, this therapy can induce dissatisfaction and reduce the quality of life. Methodological and cross-sectional research design. The cultural adaptation of the DASS included the translation and back-translation, discussions with healthcare professionals and patients to ensure conceptual equivalence, semantic evaluation and instrument pretest. The Brazilian-Portuguese version of the DASS was tested among subjects followed in a university hospital anticoagulation outpatient clinic. The psychometric properties were assessed by construct validity (convergent, known groups and dimensionality) and internal consistency/reliability (Cronbach's alpha). A total of 180 subjects under oral anticoagulation formed the baseline validation population. DASS total score and SF-36 domain correlations were moderate for General health (r=-0.47, p<0.01), Vitality (r=-0.44, p<0.01) and Mental health (r=-0.42, p<0.01) (convergent). Age and length on oral anticoagulation therapy (in years) were weakly correlated with total DASS score and most of the subscales, except Limitation (r=-0.375, p<0.01) (Known groups). The Cronbach's alpha coefficient was 0.79 for the total scale, and it ranged from 0.76 (hassles and burdens)-0.46 (psychological impact) among the domains, confirming the internal consistency reliability. The Brazilian-Portuguese version of the DASS has shown levels of reliability and validity comparable with the original English version. Healthcare practitioners and researchers need internationally validated measurement tools to compare outcomes of interventions in clinical management and research tools in oral anticoagulation therapy. © 2011

  5. Management of novel oral anticoagulants in emergency and trauma surgery.

    PubMed

    Pinho-Gomes, Ana-Catarina; Hague, Adam; Ghosh, Jonathan

    2016-08-01

    The compelling safety, efficacy and predictable effect of novel oral anticoagulants (NOACs) is driving a rapid expansion in their therapeutic indications. Management of the increasing number of patients on those new agents in the setting of emergency or trauma surgery can be challenging and the absence of specific reversal agents has been a matter of concern. This review summarises the key principles that underpin the management of those patients with a particular emphasis on the recent development of specific antidotes. As of 2015, a new line of antidotes, specific for these drugs, are at different stages of their development with their release imminent. However, as NOACs are innately reversible due to their short half-life, the use of reversal agents will probably be restricted to a few exceptional cases. Post-marketing surveillance will be paramount to better clarify the role of these promising drugs. Management of patients on NOACs in the context of emergency or trauma surgery relies on best supportive care in combination with the blood products and/or specific antidotes as required. Familiarity with the new reversal agents is essential but further evidence on their indications, safety and efficacy as well as consensus guidelines are warranted prior to widespread adoption. Copyright © 2016 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  6. ANMCO Position Paper: the use of non-vitamin K dependent new oral anticoagulant(s) in pulmonary embolism therapy and prevention

    PubMed Central

    Roncon, Loris; Azzarito, Michele; Becattini, Cecilia; Bongarzoni, Amedeo; Casazza, Franco; Cuccia, Claudio; D’Agostino, Carlo; Rugolotto, Matteo; Vatrano, Marco; Vinci, Eugenio; Fenaroli, Paride; Formigli, Dario; Silvestri, Paolo; Nardi, Federico; Vedovati, Maria Cristina; Scherillo, Marino

    2017-01-01

    Abstract The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including (i) their mechanism of action, pharmacodynamics, and pharmacokinetics; (ii) the use in the acute phase with the ‘double drug single dose’ approach or with ‘single drug double dose’; (iii) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; (iv) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance > 30 mL/min), the elderly (>75 years); (v) they propose a possible laboratory clinical pathway for follow-up; and (vi) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the use of NOACs both in the acute phase and in the extended phase is equally effective to conventional therapy and associated with fewer major bleeding events, which make their use in patients at higher risk of recurrences safer. PMID:28751847

  7. Comparison of Direct Oral Anticoagulants and Warfarin in the Treatment of Deep Venous Thrombosis in the Chronic Phase.

    PubMed

    Wakakura, Shingo; Hara, Fumihiko; Fujino, Tadashi; Hamai, Asami; Ohara, Hiroshi; Kabuki, Takayuki; Harada, Masahiko; Ikeda, Takanori

    2018-01-27

    We assessed the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of deep venous thrombosis (DVT) in the chronic phase through comparison with conventional warfarin therapy.A total of 807 consecutive patients who were diagnosed with having DVT in the chronic phase were included (484 patients to warfarin therapy and 323 patients to DOAC therapy). The condition of leg veins was assessed 3 to 6 months after starting the therapies by ultrasound examination. Major bleeding and mortality during the therapies were followed-up.There was no significant difference between the two groups in the thrombosis improvement rate (DOAC group: 91.2% versus warfarin group: 88.9%). There was no significant difference between the two groups in major bleeding (DOAC group: 1.8% versus warfarin group: 1.8%). In patients with active cancer, the DOAC group had a borderline higher thrombosis improvement rate than the warfarin group (92.1% versus 80.0%, P = 0.05). The proportion of major bleeding in the patients with active cancer was slightly higher in the warfarin group than in the DOAC group (4.3% versus 2.8%; P = 0.71). Active cancer was not an independent risk factor for major bleeding and recurrence in the DOAC group (OR 2.68, 95% CI 0.51-14.1; P = 0.24 and OR 0.65, 95% CI 0.20-2.07; P = 0.47).In treatment using oral anticoagulants for DVT in the chronic phase, DOACs exhibited equal efficacy and safety as warfarin did. Particularly DOACs appear to be an attractive therapeutic option for cancer-associated DVT in chronic phase, with relatively low anticipated rates of recurrence and major bleeding.

  8. The cost savings of newer oral anticoagulants in atrial fibrillation-related stroke prevention
.

    PubMed

    Masbah, Norliana; Macleod, Mary Joan

    2017-03-01

    Newer oral anticoagulants (NOACs) are considered as better alternatives compared to warfarin for stroke prevention in atrial fibrillation (AF) in terms of clinical effectiveness although the drug acquisition cost is more substantial. This study determined the direct stroke costs based on inpatient hospitalization in a subgroup of the National Health Service (NHS) Grampian, Scotland, stroke patients, to evaluate the differences in costs related to AF stroke, and to ascertain whether the use of NOACs within this study population would produce greater cost savings. Hospitalization records over 5 years involving 3,601 stroke patients were analyzed. Direct costs were based on the costs of inpatient length of stay per day. The potential cost savings if AF patients had been on NOACs were estimated using efficacy data from a landmark clinical trial involving rivaroxaban. Out of the total stroke cases, 29.5% of total stroke cases were secondary to AF, and these cases were more severe with longer hospitalizations. Only 254 patients (39.4%) with confirmed AF were anticoagulated with warfarin prior to admission. AF patients incurred higher median costs (£4,719 (interquartile range (IQR) £1,815 - £12,452) compared to non-AF patients (£3,267 (IQR £1,175 - £11,368)), although the association was statistically insignificant. The use of NOACs in AF-related patients with ischemic strokes would potentially prevent more strokes (leading to 58 fewer cases in comparison to warfarin), resulting in 17.1% in total cost reduction. AF stroke patients incurred higher total direct costs compared to non-AF cases. However, more cost savings were evident with NOACs, due to more strokes being prevented through the use of NOACs compared to warfarin.
.

  9. Catheter ablation for atrial fibrillation on uninterrupted direct oral anticoagulants: A safe approach.

    PubMed

    Sawhney, V; Shaukat, M; Volkova, E; Jones, N; Providencia, R; Honarbakhsh, S; Dhillon, G; Chow, A; Lowe, M; Lambiase, P; Dhinoja, M; Sporton, S; Earley, M J; Schilling, R J; Hunter, R J

    2018-05-16

    Current consensus guidelines suggest DOACs are interrupted peri-procedurally for catheter ablation (CA) of AF. However, this may predispose patients to thromboembolic complications. This study investigates the safety of CA for AF on uninterrupted DOACs compared to uninterrupted warfarin. Single centre, retrospective study of consecutive patients undergoing CA for AF. All patients were heparinised prior to trans-septal puncture with a target activated clotting time (ACT) of 300-350 seconds. Patients who had procedures performed on continuous DOAC were compared to those on continuous warfarin. Clinical, procedural data and complications occurring up to 3 months were analysed from a prospective registry with additional review of electronic health records. 1884 procedures were performed over 28 months: 761(609 patients) on uninterrupted warfarin and 1123(900 patients) on uninterrupted DOAC (rivaroxaban 64%, apixaban 32% and dabigatran 4%). There was no difference in the composite end point of death, thromboembolism or major bleeding complication(2.2% vs 1.4%, p = 0.20). There was no difference in the complications comprising this including tamponade, haematoma, pseudoaneurysm, transfusion(p-values 0.28, 0.13, 0.45 and 0.36). There were no strokes, TIAs or other thromboembolic complications. There was no difference between groups in the proportion of tamponades requiring reversal of oral anticoagulation, the volume of blood lost, the proportion transfused, or the proportion drained percutaneously(p-values 0.50, 0.51, 0.36, 0.38). Catheter ablation for AF can be performed safely and effectively in patients anticoagulated with DOACs and heparinised with a therapeutic ACT. There is no increased risk of peri-procedural bleeding when compared to uninterrupted warfarin. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Clinicians-related Determinants of Anticoagulation Therapy and Prophylaxis in Nigeria

    PubMed Central

    Anakwue, Raphael; Nwagha, Theresa; Ukpabi, Ogba J.; Obeka, Ndudim; Onwubuya, Emmanuel; Onwuchekwa, Uwa; Azubuike, Benjamin; Okoye, Innocent

    2017-01-01

    Background: Thromboembolic and hypercoagulable diseases are common life-threatening but treatable problems in hospital practice. Fortunately, anticoagulation is an efficacious management practice indicated for arterial, venous, and intracardiac thromboembolism. Clinicians in developing countries may have gaps in their knowledge of anticoagulation therapy/prophylaxis which could affect their clinical decision. Objectives: The study examined the knowledge and attitude of clinicians to anticoagulation therapy/prophylaxis in some tertiary hospitals in Nigeria. Methodology: The study was a multicenter survey. A pretested questionnaire was administered to clinicians in six tertiary hospitals in Southeast Nigeria. Results: A total of 528 questionnaires were returned by 419 (79.4%) residents and 109 (20.6%) consultants. We observed significant abysmal knowledge and lack of awareness of direct oral anticoagulants (DOACs) among most respondents irrespective of their job grades (P = 0.02, odds ratio [OR] 0.59, 95% confidence interval [CI] 0.38–0.90). Their knowledge of anti-Xa assay as laboratory monitoring tool was also significantly inadequate (P = 0.001, OR 0.23, 95% CI 0.10–0.51). On statement analysis on their attitude to anticoagulation therapy/prophylaxis, “Do you think anticoagulation therapy/prophylaxis is clinically relevant” had the highest mean of 4.60, P = 0.01, and a high degree of agreement; while “Should hospital inpatient with > 3 days admission routinely receive anticoagulation/prophylaxis?” had the lowest mean of 2.27, P = 0.02, and a low degree of agreement. Conclusion: There is the need to upscale knowledge of anticoagulation agents and an attitude change to anticoagulation therapy/prophylaxis, especially on the DOACs through continuing medical education activities in emerging countries such as Nigeria. PMID:29063899

  11. New oral anticoagulant and antiplatelet agents for neurosurgeons.

    PubMed

    Kimpton, George; Dabbous, Bassam; Leach, Paul

    2015-01-01

    Until recently, warfarin, clopidogrel and aspirin have provided the mainstay for prevention of thrombotic disease in cardiac patients. However, new classes of drugs have recently emerged that promise better clinical outcomes and lower risks. Use of such agents has increased, but increased risk and severity of intra-cranial haemorrhage (ICH) still remain. These cases of intra-cranial bleeds present as emergencies to neurosurgical units. It is of paramount importance that neurosurgical practitioners are aware of those new drugs, useful monitoring tests and available emergency reversal options in case the patient needs emergency intervention. In this review we survey newly available agents in the U.K. at the time of publication. We look at the data provided by the manufacturers, related publications and international guidelines for their use and reversal. New anticoagulants offer a lower incidence of ICH compared with warfarin. Advanced and accurate monitoring tests are emerging, as are prospective data on reversal of anticoagulation in bleeding. Some standard coagulation tests may be of use, whilst reversal agents are available and being evaluated. The trial data shows that new antiplatelet agents have similar or increased incidence and severity of intra-cranial ICH compared with clopidogrel. There is currently limited data on monitoring or reversal. We suggest they may be managed similarly to clopidogrel by using platelet reactivity assays, optimising platelet count and using platelet transfusion with adjunctive agents.

  12. Consensus recommendations for preventing and managing bleeding complications associated with novel oral anticoagulants in singapore.

    PubMed

    Ng, Heng Joo; Chee, Yen Lin; Ponnudurai, Kuperan; Lim, Lay Cheng; Tan, Daryl; Tay, Jam Chin; Handa, Pankaj Kumar; Akbar Ali, Mufeedha; Lee, Lai Heng

    2013-11-01

    Novel oral anticoagulants (NOACs) have at least equivalent efficacy compared to standard anticoagulants with similar bleeding risk. Optimal management strategies for bleeding complications associated with NOACs are currently unestablished. A working group comprising haematologists and vascular medicine specialists representing the major institutions in Singapore was convened to produce this consensus recommendation. A Medline and EMBASE search was conducted for articles related to the 3 available NOACs (dabigatran, rivaroxaban, apixaban), bleeding and its management. Additional information was obtained from the product monographs and bibliographic search of articles identified. The NOACs still has substantial interactions with a number of drugs for which concomitant administration should best be avoided. As they are renally excreted, albeit to different degrees, NOACs should not be prescribed to patients with creatinine clearance of <30 mLs/min. Meticulous consideration of risk versus benefits should be exercised before starting a patient on a NOAC. In patients presenting with bleeding, risk stratification of the severity of bleeding as well as identification of the source of bleeding should be performed. In life-threatening bleeds, recombinant activated factor VIIa and prothrombin complex may be considered although their effectiveness is currently unsupported by firm clinical evidence. The NOACs have varying effect on the prothrombin time and activated partial thromboplastin time which has to be interpreted with caution. Routine monitoring of drug level is not usually required. NOACs are an important advancement in antithrombotic management and careful patient selection and monitoring will permit optimisation of their potential and limit bleeding events.

  13. Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: A meta-analysis of contemporary randomized controlled trials.

    PubMed

    Wang, Kang-Ling; Giugliano, Robert P; Goto, Shinya; Chiu, Chun-Chih; Lin, Chun-Yi; Lai, En-Yu; Chiang, Chern-En

    2016-12-01

    Although randomized controlled trials (RCTs) indicated that standard dose non-vitamin K antagonist oral anticoagulants (NOACs) were more compelling, low dose NOACs are commonly used in clinical practice in Asia. The purpose of this study was to assess the relative therapeutic benefit and risk of standard dose vs low dose NOACs in Asian patients enrolled in contemporary RCTs. We performed a prespecified meta-analysis of 3155 Asian patients with NOACs in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) and ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trials. Efficacy and safety with standard dose vs low dose NOACs were compared by risk ratios (RRs) and 95% confidence intervals (CIs) in a random-effects model. An evidence network incorporating additional Asian patients from ROCKET AF, J- ROCKET AF, and ARISTOTLE was constructed with the Bayesian method. Risks of stroke or systemic embolism and ischemic stroke were significantly reduced with standard dose vs low dose NOACs (RR 0.62, 95% CI 0.45-0.85; and RR 0.55, 95% CI 0.38-0.79, respectively). Rates of major, intracranial, and life-threatening bleeding with 2 dosing regimens were broadly similar (RR 1.31, 95% CI 0.74-2.33; RR 1.54, 95% CI 0.72-3.30; and RR 1.49, 95% CI 0.87-2.55, respectively). Absolute rates of all-cause mortality and the net clinical outcome with standard dose NOACs were lower but not statistically significant (absolute reduction 0.4% per year and 1.1% per year, respectively). Network meta-analyses demonstrated that standard dose NOACs had the most favorable risk-benefit profile among oral anticoagulants. In Asian patients, standard dose NOACs represent a more appealing therapeutic option than low dose NOACs, with a significant reduction in ischemic stroke without an excess of major bleeding. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  14. Liver Cirrhosis in Patients With Atrial Fibrillation: Would Oral Anticoagulation Have a Net Clinical Benefit for Stroke Prevention?

    PubMed

    Kuo, Ling; Chao, Tze-Fan; Liu, Chia-Jen; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Lip, Gregory Y H; Chen, Shih-Ann

    2017-06-23

    Patients with liver cirrhosis have been excluded from randomized clinical trials of oral anticoagulation therapy for stroke prevention in atrial fibrillation. We hypothesized that patients with liver cirrhosis would have a positive net clinical benefit for oral anticoagulation when used for stroke prevention in atrial fibrillation. This study used the National Health Insurance Research Database in Taiwan. Among 289 559 atrial fibrillation patients aged ≥20 years, there were 10 336 with liver cirrhosis, and 9056 of them having a CHA 2 DS 2 -VASc score ≥2 were divided into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Patients with liver cirrhosis had a higher risk of ischemic stroke (hazard ratio=1.10, P =0.046) and intracranial hemorrhage (hazard ratio=1.20, P =0.043) compared with those without. Among patients with liver cirrhosis, patients taking antiplatelet therapy had a similar risk of ischemic stroke (hazard ratio=1.02, 95%CI=0.88-1.18) compared to those without antithrombotic therapies, but the risk was significantly lowered among warfarin users (hazard ratio=0.76, 95%CI=0.58-0.99). For intracranial hemorrhage, there were no significant differences between those untreated and those taking antiplatelet therapy or warfarin. The use of warfarin was associated with a positive net clinical benefit compared with being untreated or receiving only antiplatelet therapy. For atrial fibrillation patients with liver cirrhosis in the current analysis of an observational study, warfarin use was associated with a lower risk of ischemic stroke and a positive net clinical benefit compared with nontreatment, and thus, thromboprophylaxis should be considered for such patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  15. Direct Oral Anticoagulant- or Warfarin-Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study.

    PubMed

    Xu, Yan; Schulman, Sam; Dowlatshahi, Dar; Holbrook, Anne M; Simpson, Christopher S; Shepherd, Lois E; Wells, Philip S; Giulivi, Antonio; Gomes, Tara; Mamdani, Muhammad; Khuu, Wayne; Frymire, Eliot; Johnson, Ana P

    2017-07-01

    Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in < 40% of cases, raising concerns about the generalizability of this finding. Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases. Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarin bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Standards of care issues with anticoagulation in real-world populations.

    PubMed

    2015-01-01

    Current guidelines recommend anticoagulants for reducing the risk of stroke in appropriate patients with nonvalvular atrial fibrillation (NVAF) and for the acute treatment of venous thromboembolism (VTE) and the prevention of recurrent VTE. Warfarin is the standard of care for both NVAF and VTE, yet International Normalized Ratio (INR) control remains suboptimal, even in the clinical trial setting. Maintaining INR within the recommended therapeutic range is associated with better outcomes in these distinct populations. In VTE, high rates of recurrence have been reported during the first few weeks of treatment, emphasizing the importance of surveillance during this time and of early optimization of anticoagulation therapy. The NVAF population tends to have more comorbidities and requires longer-term therapy. It is important to keep in mind that real-world patient populations are more complex than those in controlled studies. Patients with multiple comorbidities are particularly challenging, and physicians may focus on clinically urgent issues rather than anticoagulation optimization. Despite the many complexities associated with the use of warfarin, it remains a mainstay of anticoagulation therapy. Aligning financial incentives and improving care coordination are important factors in moving toward better outcomes for patients who need anticoagulation therapy. The increased focus on value-based care and evolving approaches to patient treatment could lead more physicians and payers to consider alternatives to warfarin, including the use of novel oral anticoagulants.

  17. SMART: self-management of anticoagulation, a randomised trial [ISRCTN19313375].

    PubMed

    McCahon, Deborah; Fitzmaurice, David A; Murray, Ellen T; Fuller, Christopher J; Hobbs, Richard F D; Allan, Teresa F; Raftery, James P

    2003-09-18

    Oral anticoagulation monitoring has traditionally taken place in secondary care because of the need for a laboratory blood test, the international normalised ratio (INR). The development of reliable near patient testing (NPT) systems for INR estimation has facilitated devolution of testing to primary care. Patient self-management is a logical progression from the primary care model. This study will be the first to randomise non-selected patients in primary care, to either self-management or standard care. The study was a multi-centred randomised controlled trial with patients from 49 general practices recruited. Those suitable for inclusion were aged 18 or over, with a long term indication for oral anticoagulation, who had taken warfarin for at least six months. Patients randomised to the intervention arm attended at least two training sessions which were practice-based, 1 week apart. Each patient was assessed on their capability to undertake self management. If considered capable, they were given a near patient INR testing monitor, test strips and quality control material for home testing. Patients managed their own anticoagulation for a period of 12 months and performed their INR test every 2 weeks. Control patients continued with their pre-study care either attending hospital or practice based anticoagulant clinics. The methodology used in this trial will overcome concerns from previous trials of selection bias and relevance to the UK health service. The study will give a clearer understanding of the benefits of self-management in terms of clinical and cost effectiveness and patient preference.

  18. European cardiac nurses' current practice and knowledge on anticoagulation therapy.

    PubMed

    Oterhals, Kjersti; Deaton, Christi; De Geest, Sabina; Jaarsma, Tiny; Lenzen, Mattie; Moons, Philip; Mårtensson, Jan; Smith, Karen; Stewart, Simon; Strömberg, Anna; Thompson, David R; Norekvål, Tone M

    2014-06-01

    Successful management of warfarin, new anti-thrombotic agents and self-monitoring devices requires that health care professionals effectively counsel and educate patients. Previous studies indicate that health care professionals do not always have the knowledge to provide patients with the correct information. The purpose of this study was to investigate European cardiovascular nurses' knowledge on the overall management of anticoagulation therapy and examine if this knowledge was influenced by level of education and years in clinical practice. A questionnaire including 47 items on practice patterns and knowledge on warfarin, new anticoagulants, warfarin-drug and warfarin-food interactions, and self-management of International Normalized Ratio (INR) was distributed to the attendants at a European conference in 2012. The response rate was 32% (n=206), of whom 84% reported having direct patient contact. Warfarin was the most common used oral anticoagulation in daily practice. One third offered their patients both patient self-testing and patient self-management of INR. The mean total score on the knowledge questions was 28±6 (maximum possible score 53). Nurses in direct patient care had a higher mean score (p=0.011). Knowledge on warfarin and medication-interactions were low, but knowledge on warfarin-diet interactions and how to advise patients on warfarin as somewhat better. European cardiac nurses need to improve their knowledge and practice patterns on oral anticoagulation therapy. This area of knowledge is important in order to deliver optimal care to cardiac patients and to minimise adverse effects of the treatment.

  19. Percutaneous Occlusion of the Left Atrial Appendage with the Watchman Device in an Active Duty Sailor with Atrial Fibrillation and Recurrent Thromboembolism Despite Appropriate Use of Oral Anticoagulation.

    PubMed

    Cox, Justin M; Choi, Anthony J; Oakley, Luke S; Francisco, Gregory M; Nayak, Keshav R

    2018-05-23

    Atrial fibrillation is the most common significant cardiac arrhythmia and is associated with a five-fold increased risk of stroke from thromboembolism. Over 94% of these emboli arise from the left atrial appendage. Systemic embolic phenomena are rare, accounting for less than 1 out of 10 of all embolic events, but have a similar prevention strategy. Anticoagulation significantly reduces the risk of these events, and thus forms the cornerstone of therapy for most patients with atrial fibrillation. Left atrial appendage occlusion with the Watchman device is a recently approved alternative for stroke prevention in selected patients. We present a case of an active duty U.S. Navy sailor at low risk for thromboembolism who nonetheless suffered recurrent thromboembolic events despite appropriate anticoagulation, and thus underwent Watchman implantation. The therapy in this case will ideally provide a lifetime of protection from recurrent systemic embolization while allowing the patient to continue his active duty military career without restriction due to oral anticoagulation.

  20. Stratifying the risks of oral anticoagulation in patients with liver disease.

    PubMed

    Efird, Lydia M; Mishkin, Daniel S; Berlowitz, Dan R; Ash, Arlene S; Hylek, Elaine M; Ozonoff, Al; Reisman, Joel I; Zhao, Shibei; Jasuja, Guneet K; Rose, Adam J

    2014-05-01

    Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin. Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases-Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases-Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P<0.001) and more hemorrhages (hazard ratio, 2.02; P<0.001). Among patients with liver disease, serum albumin and creatinine levels were the strongest predictors of both outcomes. We created a 4-point score system: patients received 1 point each for albumin (2.5-3.49 g/dL) or creatinine (1.01-1.99 mg/dL), and 2 points each for albumin (<2.5 g/dL) or creatinine (≥2 mg/dL). This score predicted both anticoagulation control and hemorrhage. When compared with patients without liver disease, those with a score of zero had modestly lower time in therapeutic range (56.7%) and no increase in hemorrhages (hazard ratio, 1.16; P=0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P<0.001). Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes. © 2014 American

  1. Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol.

    PubMed

    Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

    2016-12-08

    Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. ACTRN12614000418673, Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

  2. Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE). Methods and design This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a

  3. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review.

    PubMed

    Warkentin, Theodore E; Pai, Menaka; Linkins, Lori-Ann

    2017-08-31

    Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, ON, Canada, since January 1, 2015 (when we completed our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT (4Ts score ≥4 points; positive platelet factor 4 [PF4]/heparin immunoassay, positive serotonin-release assay). We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabigatran, edoxaban). We focused on patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary therapy (group B; initial treatment using a non-DOAC/non-heparin anticoagulant with transition to a DOAC during HIT-associated thrombocytopenia). Our primary end point was occurrence of objectively documented thrombosis during DOAC therapy for acute HIT. We found that recovery without new, progressive, or recurrent thrombosis occurred in all 10 Hamilton patients with acute HIT treated with rivaroxaban. Data from the literature review plus these new data identified a thrombosis rate of 1 of 46 patients (2.2%; 95% CI, 0.4%-11.3%) in patients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage was seen in 0 of 46 patients. Similar outcomes in smaller numbers of patients were observed with apixaban (n = 12) and dabigatran (n = 11). DOACs offer simplified management of selected patients, as illustrated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel waning of serum-induced heparin-independent serotonin release) with successful outpatient rivaroxaban management of HIT-associated thrombosis. Evidence supporting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for rivaroxaban. © 2017 by The American Society of Hematology.

  4. Percutaneous closure of the left atrial appendage for prevention of thromboembolism in atrial fibrillation for patients with contraindication to or failure of oral anticoagulation: a single-center experience.

    PubMed

    Faustino, Ana; Paiva, Luís; Providência, Rui; Trigo, Joana; Botelho, Ana; Costa, Marco; Leitão-Marques, António

    2013-06-01

    In non-valvular atrial fibrillation 90% of thrombi originate in the left atrial appendage (LAA). Percutaneous LAA closure has been shown to be non-inferior to warfarin for prevention of thromboembolism. To evaluate the initial experience of a single center in percutaneous LAA closure in patients with high thromboembolic risk and in whom oral anticoagulation was impractical or contraindicated or had failed. Patients with non-valvular atrial fibrillation and CHADS2 score ≥2 in whom oral anticoagulation was impractical or contraindicated or had failed underwent percutaneous LAA closure according to the standard technique. After the procedure, dual antiplatelet therapy was maintained for one month, followed by single antiplatelet therapy indefinitely. Patients were followed by clinical assessment and transthoracic and transesophageal echocardiography. The procedure was performed in 22 of the 23 selected patients (95.7%), mean age 70±9 years, CHADS2 score 3.2±0.9 and CHA2DS2-VASC score 4.7±1.4. Intraprocedural device replacement was necessary only in the first patient, due to oversizing. The following periprocedural complications were observed: one femoral pseudoaneurysm, three femoral hematomas and two minor oropharyngeal bleeds, resolved by local hemostatic measures. During a 12±8 month follow-up a mild peri-device flow and a thrombus adhering to the device, resolved under with enoxaparin therapy, were identified. The rate of transient ischemic attack (TIA)/stroke was lower than expected according to the CHADS2 score (0 vs. 6.7±2.2%). In our initial experience, this procedure proved to be a feasible, safe and effective alternative for atrial fibrillation patients in whom oral anticoagulation is not an option. Only relatively minor complications were observed, with a lower than expected TIA/stroke rate. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  5. Reduced Anticoagulant Effect of Dabigatran in a Patient Receiving Concomitant Phenytoin.

    PubMed

    Wiggins, Barbara S; Northup, Amanda; Johnson, Dominic; Senfield, Jeffrey

    2016-02-01

    Dabigatran, a direct thrombin inhibitor, is an oral anticoagulant indicated for the prevention of stroke in patients with atrial fibrillation (AF) and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. Dabigatran, as well as the other new anticoagulants-rivaroxaban, apixaban, and edoxaban-are substrates for P-glycoprotein (P-gp). Although the U.S. labeling for rivaroxaban and apixaban states to avoid concomitant use with phenytoin, a known P-gp inducer, the U.S. labeling for dabigatran and edoxaban are less clear. We describe the first case report, to our knowledge, documenting a drug interaction between phenytoin and dabigatran by using laboratory measurements of dabigatran serum concentrations. A 45-year-old African-American man was admitted to the inpatient cardiology service following defibrillations from his implantable cardioverter defibrillator. The patient was evaluated and received appropriate antitachycardia pacing for atrial tachyarrhythmias for an episode of ventricular tachycardia (VT), and antiarrhythmic therapy with sotalol was initiated to reduce both his AF and VT burden. On review of the patient's medications for potential interactions, it was discovered that the patient was taking both dabigatran and phenytoin. To determine the magnitude of this drug interaction prior to making a change in his anticoagulation regimen, a dabigatran serum concentration was measured. This concentration was undetectable, indicating that phenytoin had a significant influence on dabigatran's metabolism and that this patient was at high risk for stroke. Clinicians should be aware of this interaction between phenytoin and dabigatran as well as with all other new oral anticoagulants. In patients taking phenytoin who require an anticoagulant, only warfarin should be prescribed to minimize the risk of stroke. In addition, the prescribing information for dabigatran should be updated to include other medications that result in a significant

  6. The clinical evaluation of International Normalized Ratio variability and control in conventional oral anticoagulant administration by use of the variance growth rate.

    PubMed

    Ibrahim, S; Jespersen, J; Poller, L

    2013-08-01

    The time in target International Normalized Ratio (INR) range (TIR) is used to assess the control and intensity of oral anticoagulation, but it does not measure variation in the INR. The value of assessing INR variability by use of the variance growth rate (VGR) as a predictor of events was investigated in patients treated with warfarin. Three different methods of VGR determination (A, B1, and B2) together with the TIR were studied. Method A measures both INR variability and control, but methods B1 and B2 measure variability only. The VGR and TIR were determined over three time periods: overall follow-up to an event, and 6 months and 3 months before an event. Six hundred and sixty-one control patients were matched to 158 cases (bleeding, thromboembolism, or death). With all VGR methods, the risk of an event was greater in unstable patients at 6 months before an event than in stable patients. Method A demonstrated the greatest risk 3 months before an event in the unstable VGR group as compared with the stable group (odds ratio 3.3, 95% confidence interval 1.9-5.7, P < 0.005). The risk of an event was 1.9 times greater in patients with a low TIR (< 39%) than in those with a high TIR (> 80%) in the 3-month period (P = 0.02). Risk of bleeding was significantly greater in the 3-month period in patients with unstable VGR, with the greatest risk found with method B2 (P < 0.01). Patients with unstable anticoagulation have a significantly increased risk of 'clinical events' at 3 and 6 months before an event. The VGR can be incorporated into computer-dosage programs, and may offer additional safety when oral anticoagulation is monitored. © 2013 International Society on Thrombosis and Haemostasis.

  7. Emergency admissions for major haemorrhage associated with direct oral anticoagulants.

    PubMed

    Bouget, Jacques; Oger, Emmanuel

    2015-12-01

    To describe the population admitted in an emergency department of a teaching hospital for severe bleeding associated with direct oral anticoagulants (DOAC). During a three-year period (2012-2014) patients older than 16 years were prospectively identified by haemorrhagic symptoms from computerised requests. At least one of the following criteria defined major haemorrhage: haemorrhagic shock, unstable haemodynamic, need for transfusion or haemostatic procedure, or a life threatening location. Fifty four patients, 23 receiving dabigatran, 30 rivaroxaban and one apixaban were included, 2 in 2012, 35 in 2013 and 17 in 2014. Median age was 84 years (range 63-99) with a sex ratio of 1.16. Haemorrhagic complications were gastrointestinal (n=27), intracranial (n=12) or miscellaneous (n=15). Indication of DOAC was stroke prevention in atrial fibrillation in 49 cases and deep vein thrombosis in 5 cases. Hospitalization was required for 45 patients (83%) with a mean length of stay of 8.5 days. Sixteen patients needed intensive care. Reversal therapy was prescribed in 11 patients. At 1 month, overall mortality was 24%, reaching 41.7% for intracranial haemorrhage. Among surviving patients, DOAC was stopped in 10 cases, continued in 17 patients and switched for other antithrombotic in 17 patients. Our study contributes to the post marketing surveillance of major haemorrhagic complications associated with DOAC. It takes part to the knowledge about the course of this severe event in emergencies. Careful awareness in risk benefit assessment, especially in elderly, is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Controversies regarding the new oral anticoagulants for stroke prevention in patients with atrial fibrillation.

    PubMed

    Mohanty, Bibhu D; Looser, Patrick M; Gokanapudy, Lakshmi R; Handa, Rishi; Mohanty, Sudipta; Choi, Sharon S; Goldman, Martin E; Fuster, Valentin; Halperin, Jonathan L

    2014-06-01

    Increasing use of the new oral anticoagulants (NOACs) - dabigatran, rivaroxaban, and apixaban - has prompted considerable discussion in the medical community even as warfarin remains the mainstay of therapy. This article raises 10 controversial issues regarding the use of NOACs for stroke prevention in patients with atrial fibrillation, and offers a review of the latest available evidence. We provide a brief overview of the mechanism and dosing of these drugs, as well as a summary of the key clinical trials that have brought them into the spotlight. Comparative considerations relative to warfarin such as NOAC safety, efficacy, bleeding risk, reversibility, drug-transitioning and use in patients well controlled on warfarin are addressed. Use in select populations such as the elderly, those with coronary disease, renal impairment, or on multiple anti-platelet drugs is also discussed. Finally, we consider such specific issues as comparative efficacy, off-label use, cost, rebound and management during events. Ultimately, the rise of the NOACs to mainstream use will depend on further data and clinical experience amongst the medical community. © The Author(s) 2014.

  9. Outpatient management of oral vitamin K antagonist therapy: defining and measuring high-quality management.

    PubMed

    Phillips, Katherine W; Ansell, Jack

    2008-01-01

    Oral anticoagulation therapy with warfarin is the mainstay of prevention and treatment of thromboembolic disease. However, it remains one of the leading causes of harmful medication errors and medication-related adverse events. The beneficial outcomes of oral anticoagulation therapy are directly dependent upon the quality of dose and anticoagulation management, but the literature is not robust with regards to what constitutes such management. This review focuses on, and attempts to define, the parameters of high-quality anticoagulation management and identifies the appropriate outcome measures constituting high-quality management. Elements discussed include the most fundamental measure, time in therapeutic range, along with other parameters including therapy initiation, time to therapeutic range, dosing management when patients are not in therapeutic range, perioperative dosing management, patient education, and other important outcome measures. Healthcare providers who manage oral anticoagulation therapy should utilize these parameters as a measure of their performance in an effort to achieve high-quality anticoagulation management.

  10. The business case for quality improvement: oral anticoagulation for atrial fibrillation.

    PubMed

    Rose, Adam J; Berlowitz, Dan R; Ash, Arlene S; Ozonoff, Al; Hylek, Elaine M; Goldhaber-Fiebert, Jeremy D

    2011-07-01

    The potential to save money within a short time frame provides a more compelling "business case" for quality improvement than merely demonstrating cost-effectiveness. Our objective was to demonstrate the potential for cost savings from improved control in patients anticoagulated for atrial fibrillation. Our population consisted of 67 077 Veterans Health Administration patients anticoagulated for atrial fibrillation between October 1, 2006, and September 30, 2008. We simulated the number of adverse events and their associated costs and utilities, both before and after various degrees of improvement in percent time in therapeutic range (TTR). The simulation had a 2-year time horizon, and costs were calculated from the perspective of the payer. In the base-case analysis, improving TTR by 5% prevented 1114 adverse events, including 662 deaths; it gained 863 quality-adjusted life-years and saved $15.9 million compared with the status quo, not accounting for the cost of the quality improvement program. Improving TTR by 10% prevented 2087 events, gained 1606 quality-adjusted life-years, and saved $29.7 million. In sensitivity analyses, costs were most sensitive to the estimated risk of stroke and the expected stroke reduction from improved TTR. Utilities were most sensitive to the estimated risk of death and the expected mortality benefit from improved TTR. A quality improvement program to improve anticoagulation control probably would be cost-saving for the payer, even if it were only modestly effective in improving control and even without considering the value of improved health. This study demonstrates how to make a business case for a quality improvement initiative.

  11. Management and Outcomes of Bleeding Events in Patients in the Emergency Department Taking Warfarin or a Non-Vitamin K Antagonist Oral Anticoagulant.

    PubMed

    Singer, Adam J; Quinn, Adam; Dasgupta, Neil; Thode, Henry C

    2017-01-01

    Most comparisons of bleeding patients who are taking warfarin or a non-vitamin K oral anticoagulant (NOAC) have been limited to admitted patients and major bleeding events in well-controlled, clinical trial settings. We describe the clinical characteristics, interventions, and outcomes in patients who are taking warfarin or a NOAC who presented to the emergency department (ED) with any bleeding event. We conducted a structured, retrospective, observational study of nonvalvular atrial fibrillation, pulmonary embolism, or deep vein thrombosis warfarin- or NOAC-treated patients presenting with any bleeding event to a large, academic ED between January 2012 and March 2015. We used descriptive statistics to summarize baseline characteristics, treatments, and outcomes and performed subgroup analyses based on the type of anticoagulant and site of bleeding. The electronic search yielded 95 cases of patients taking a NOAC (i.e., dabigatran [33], rivaroxaban [32], or abixaban [30]) and 342 patients taking warfarin. Reversal agents were rarely used in all anticoagulant groups. Case fatality rates were similar among warfarin- and NOAC-treated patients for gastrointestinal bleeding (7% vs. 7%) and intracranial hemorrhage (18% vs. 4%), respectively. After adjustment for other factors, only intracranial hemorrhage (odds ratio 4.4; 95% confidence interval 1.4-13.3) was associated with mortality. Despite the rare use of reversal strategies, mortality was low and outcomes were comparable among patients with bleeding events presenting to the ED while taking a NOAC compared with warfarin. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial.

    PubMed

    Åsberg, Signild; Hijazi, Ziad; Norrving, Bo; Terént, Andreas; Öhagen, Patrik; Oldgren, Jonas

    2017-12-02

    Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design

  13. Anticoagulant and Antiplatelet Prescribing Patterns for Patients with Atrial Fibrillation after Percutaneous Coronary Intervention.

    PubMed

    Woods, Erin A; Ackman, Margaret L; Graham, Michelle M; Koshman, Sheri L; Boswell, Rosaleen M; Barry, Arden R

    2016-01-01

    Current guidelines recommend triple antithrombotic therapy (TAT), defined as acetylsalicylic acid (ASA), clopidogrel, and warfarin, for patients with nonvalvular atrial fibrillation who have undergone percutaneous coronary intervention with stent implantation. The choice of anticoagulant/antiplatelet therapy in this population is ambiguous and complex, and prescribing patterns are not well documented. To characterize local prescribing patterns for anticoagulant/antiplatelet therapy after percutaneous coronary intervention in patients with nonvalvular atrial fibrillation. A chart review was conducted at a single quaternary cardiology centre. Patients with nonvalvular atrial fibrillation were identified via medical records, and those who underwent percutaneous coronary intervention were identified using a local clinical patient registry. Adult inpatients with nonvalvular atrial fibrillation and a CHADS2 score (based on congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) of 1 or higher who underwent percutaneous coronary intervention from 2011 to 2013 were included. Patients undergoing cardiovascular surgery or transcatheter aortic valve replacement, those with mechanical devices requiring anticoagulation, and those with an allergy to any component of TAT were excluded. Seventy patients were included. The median age was 75 years, and 52 (74%) were men. At discharge, 30 (43%) were receiving TAT and 27 (39%) were receiving dual antiplatelet therapy (clopidogrel and ASA). No patients received the combination of warfarin and clopidogrel. Among those who received TAT, 90% (19 of 21) who received a bare metal stent had a recommended duration of 1 month, and 75% (6 of 8) who received a drug-eluting stent had a recommended duration of 1 year. Direct-acting oral anticoagulants with 2 antiplatelet drugs were prescribed for 9% (6 of 70) of the patients, and 10% (7 of 70) received ticagrelor and ASA with or without warfarin. Overall, the

  14. Anticoagulation Quality Assessment in Patients with Nonvalvular Atrial Fibrillation (NVAF) and Comparison with Major Trials of Direct-Acting Oral Anticoagulants

    DTIC Science & Technology

    2016-04-22

    Purpose: The benefits of warfarin anticoagulation therapy are strongly correlated with the ability to maintain patients’ INR goal, known as the time...Rosendaal). Differences in TTR calculations could alter perceptions about the effectiveness of warfarin therapy.

  15. Delivery of optimized inpatient anticoagulation therapy: consensus statement from the anticoagulation forum.

    PubMed

    Nutescu, Edith A; Wittkowsky, Ann K; Burnett, Allison; Merli, Geno J; Ansell, Jack E; Garcia, David A

    2013-05-01

    To provide recommendations for optimized anticoagulant therapy in the inpatient setting and outline broad elements that need to be in place for effective management of anticoagulant therapy in hospitalized patients; the guidelines are designed to promote optimization of patient clinical outcomes while minimizing the risks for potential anticoagulation-related errors and adverse events. The medical literature was reviewed using MEDLINE (1946-January 2013), EMBASE (1980-January 2013), and PubMed (1947-January 2013) for topics and key words including, but not limited to, standards of practice, national guidelines, patient safety initiatives, and regulatory requirements pertaining to anticoagulant use in the inpatient setting. Non-English-language publications were excluded. Specific MeSH terms used include algorithms, anticoagulants/administration and dosage/adverse effects/therapeutic use, clinical protocols/standards, decision support systems, drug monitoring/methods, humans, inpatients, efficiency/ organizational, outcome and process assessment (health care), patient care team/organization and administration, program development/standards, quality improvement/organization and administration, thrombosis/ drug therapy, thrombosis/prevention and control, risk assessment/standards, patient safety/standards, and risk management/methods. Because of this document's scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent the consensus opinion of all authors and are endorsed by the Board of Directors of the Anticoagulation Forum, an organization dedicated to optimizing anticoagulation care. The board is composed of physicians, pharmacists, and nurses with demonstrated expertise and experience in the management of

  16. Patient education about anticoagulant medication: is narrative evidence or statistical evidence more effective?

    PubMed

    Mazor, Kathleen M; Baril, Joann; Dugan, Elizabeth; Spencer, Frederick; Burgwinkle, Pamela; Gurwitz, Jerry H

    2007-12-01

    To determine the relative impact of incorporating narrative evidence, statistical evidence or both into patient education about warfarin, a widely used oral anticoagulant medication. 600 patients receiving anticoagulant therapy were randomly assigned to view one of three versions of a video depicting a physician-patient encounter where anticoagulation treatment was discussed, or usual care (no video). The videos differed in whether the physician used narrative evidence (patient anecdotes), statistical evidence, or both to highlight key information. 317 patients completed both the baseline and post-test questionnaires. Questions assessed knowledge, beliefs and adherence to medication and laboratory monitoring regimens. All three approaches positively effected patients' warfarin-related knowledge, and beliefs in the importance of lab testing; there was also some indication that viewing a video strengthened belief in the benefits of warfarin. There was some indication that narrative evidence had a greater impact than statistical evidence on beliefs about the importance of lab testing and on knowledge. No other evidence of the differential effectiveness of either approach was found. No statistically significant effect was found on intent to adhere, or documented adherence to lab monitoring. Videos depicting a physician-patient dialogue about warfarin were effective in educating patients about anticoagulant medication, and had a positive impact on their beliefs. The use of narrative evidence in the form of patient anecdotes may be more effective than statistical evidence for some patient outcomes. Patients on oral anticoagulant therapy may benefit from periodic educational efforts reinforcing key medication safety information, even after initial education and ongoing monitoring. Incorporating patient anecdotes into physician-patient dialogues or educational materials may increase the effectiveness of the message.

  17. Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry.

    PubMed

    Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph Gabriel

    2015-01-01

    Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. ISRCTN registry of clinical trials: ISRCTN43070564.

  18. Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry

    PubMed Central

    Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M.; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph. Gabriel

    2015-01-01

    Background Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. Methods and Findings CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. Conclusions In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. Trial Registration ISRCTN registry of clinical trials: ISRCTN43070564. PMID:25915904

  19. Dental management of patients receiving anticoagulant and/or antiplatelet treatment

    PubMed Central

    Chaveli-López, Begonya; Gavaldá-Esteve, Carmen

    2014-01-01

    Introduction: Adequate hemostasis is crucial for the success of invasive dental treatment, since bleeding problems can give rise to complications associated with important morbidity-mortality. The dental treatment of patients who tend to an increased risk of bleeding due to the use of anticoagulant and/or antiplatelet drugs raises a challenge in the daily practice of dental professionals. Adequate knowledge of the mechanisms underlying hemostasis, and the optimized management of such patients, are therefore very important issues. Objectives: A study is made of the anticoagulant / antiplatelet drugs currently available on the market, with evaluation of the risks and benefits of suspending such drugs prior to invasive dental treatment. In addition, a review is made of the current management protocols used in these patients. Material and Methods: A literature search was made in the PubMed, Cochrane Library and Scopus databases, covering all studies published in the last 5 years in English and Spanish. Studies conducted in humans and with scientific evidence levels 1 and 2 (metaanalyses, systematic reviews, randomized phase 1 and 2 trials, cohort studies and case-control studies) were considered. The keywords used for the search were: tooth extraction, oral surgery, hemostasis, platelet aggregation inhibitors, antiplatelet drugs, anticoagulants, warfarin, acenocoumarol. Results and Conclusions: Many management protocols have been developed, though in all cases a full clinical history is required, together with complementary hemostatic tests to minimize any risks derived from dental treatment. Many authors consider that patient medication indicated for the treatment of background disease should not be altered or suspended unless so indicated by the prescribing physician. Local hemostatic measures have been shown to suffice for controlling possible bleeding problems resulting from dental treatment. Key words:Tooth extraction, oral surgery, hemostasis, platelet

  20. Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study.

    PubMed

    Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Acciarresi, Monica; D'Amore, Cataldo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Bubba, Valentina; Silvestri, Ilenia; Lees, Kennedy R

    2015-08-01

    The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered

  1. Periprocedural Management of Non-Vitamin K Oral Anticoagulants in Chronic Kidney Disease: A Review of Existing Heterogeneity and Contemporary Evidence.

    PubMed

    Gunasekaran, Prasad; Parashara, Deepak K

    2015-12-01

    Non vitamin-K oral anticoagulants (NOAC) have considerably enhanced anticoagulation practice for non-valvular atrial fibrillation with specific advantages of fixed dosing, non-fluctuant therapeutic levels and obviation of therapeutic level monitoring. NOAC pharmacology is remarkable for considerable renal excretion. Heterogeneity in the precise time cut-offs for discontinuation of NOACs prior to elective surgical or percutaneous procedures arise from the non-linear variations of drug excretion with different levels of creatinine clearances as in chronic kidney disease. Multiple authors have suggested cut-offs leading to ambiguity among practicing clinicians. Recent data pertaining to systemic thromboembolism, stroke and major bleeding derived from randomized controlled clinical trials have simplified the periprocedural management of NOACs. This review focusses on heterogeneity in the management of NOACs in patients with CKD in this peculiar scenario and highlights the contemporary evidence to support a unified approach towards perioperative management of NOACs. Multiple antidotes targeted towards binding of specific NOACs have been developed and are in the testing phase, thereby offering immense potential for rapid and complete reversal of NOAC activity in emergent procedures and major bleeding episodes. Targeted research on thromboembolism, stroke and major bleeding following temporary periprocedural interruption of NOACs using multicentric registries could further expand the clinical utility of these agents.

  2. Differentiation of parenteral anticoagulants in the prevention and treatment of venous thromboembolism.

    PubMed

    Fareed, Jawed; Adiguzel, Cafer; Thethi, Indermohan

    2011-03-28

    The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available. MEDLINE and EMBASE databases were searched to identify relevant original articles. Low-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding. Parenteral anticoagulants should be prescribed in accordance with recommended dose regimens

  3. Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

    PubMed

    Miyamoto, Koji; Aiba, Takeshi; Arihiro, Shoji; Watanabe, Makoto; Kokubo, Yoshihiro; Ishibashi, Kohei; Hirose, Sayako; Wada, Mitsuru; Nakajima, Ikutaro; Okamura, Hideo; Noda, Takashi; Nagatsuka, Kazuyuki; Noguchi, Teruo; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kamakura, Shiro; Shimizu, Wataru; Miyamoto, Yoshihiro; Toyoda, Kazunori; Kusano, Kengo

    2016-08-01

    Renal function is crucial for patients with non-valvular atrial fibrillation (NVAF) using non-vitamin K antagonist oral anticoagulants (NOAC). The incidence of renal function deterioration during anticoagulation therapy and its impact of adverse events are unknown. In 807 consecutive NVAF patients treated with NOAC and with estimated creatinine clearance (eCCr) ≥ 50 ml/min (mean age 68 ± 11 years, mean CHADS2 score = 1.8 ± 1.4, CHA2DS2-VASc score = 2.8 ± 1.8, HAS-BLED score = 1.7 ± 1.1), we analyzed the time course of renal function and clinical outcomes, and compared these with the data of general Japanese inhabitants from the Suita Study (n = 2140). Of the 807 patients, 751 (93 %) maintained eCCr ≥ 50 ml/min (group A) whereas the remaining 56 (7 %) fell into the eCCr < 50 ml/min (group B) during the 382 ± 288 days of follow-up. Multivariate logistic regression analysis revealed that advanced age, lower body weight, and congestive heart failure were independent predictors for renal function deterioration in patients with eCCr ≥ 50 ml/min at baseline. Major and/or minor bleedings were more commonly observed in group B than in group A (21 vs. 8 %; P = 0.0004). The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were also significant predictors of renal function deterioration (P < 0.0001). The incidences of renal function deterioration were 1.4, 3.4, 10.5 and 11.7 % in patients with CHADS2 score of 0, 1, 2 and ≥3, respectively. As to CHA2DS2-VASc score, renal function deterioration occurred in 0, 1.7, 9.8 and 15.0 % with a score of 0, 1-2, 3-4 and ≥5, respectively. In the Suita Study of the general population, on the other hand, 122 of 2140 participants with eCCr ≥ 50 ml/min at baseline (5.7 %) fell into the eCCr < 50 ml/min during about 2 years. The incidence of renal function deterioration increased with the CHADS2 score in the general population as well as in our patients. Renal function deterioration was

  4. Early Initiation of Anticoagulation with Direct Oral Anticoagulants in Patients after Transient Ischemic Attack or Ischemic Stroke.

    PubMed

    Macha, Kosmas; Volbers, Bastian; Bobinger, Tobias; Kurka, Natalia; Breuer, Lorenz; Huttner, Hagen B; Schwab, Stefan; Köhrmann, Martin

    2016-09-01

    Direct oral anticoagulants (DOACs) are increasingly used for secondary prevention of cardioembolic stroke. While DOACs are associated with a long-term reduced risk of intracranial hemorrhage compared to vitamin K antagonists, pivotal trials avoided the very early period after stroke and few data exist on early initiation of DOAC therapy post stroke. We retrospectively analyzed data from our prospective database of all consecutive transient ischemic attack (TIA) or ischemic stroke patients with atrial fibrillation treated with DOACs during hospital stay. As per our institutional treatment algorithm for patients with cardioembolic ischemia DOACs are started immediately in TIA and minor stroke (group 1), within days 3-5 in patients with infarcts affecting one third or less of the middle cerebral artery, the anterior cerebral artery, or the posterior cerebral artery territories (group 2) as well as in infratentorial stroke (group 3) and after 1-2 weeks in patients with large infarcts (>⅓MCA territory, group 4). We investigated baseline characteristics, time to initiation of DOAC therapy after symptom onset, and hemorrhagic complications. In 243 included patients, administration of DOAC was initiated 40.5 hours (interquartile range [IQR] 23.0-65.5) after stroke onset in group 1 (n = 41) and after 76.7 hours (IQR 48.0-134.0), 108.4 hours (IQR 67.3-176.4), and 161.8 hours (IQR 153.9-593.8) in groups 2-4 (n = 170, 28, and 4), respectively. Two cases of asymptomatic intracranial hemorrhage (.8%) and 1 case of symptomatic intracranial hemorrhage (.4%) were observed, both in group 2. No severe safety issues were observed in early initiation of DOACs for secondary prevention after acute stroke in our in-patient cohort. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Implementation of non-vitamin K antagonist oral anticoagulants in daily practice: the need for comprehensive education for professionals and patients.

    PubMed

    Heidbuchel, Hein; Berti, Dana; Campos, Manuel; Desteghe, Lien; Freixo, Ana Parente; Nunes, António Robalo; Roldán, Vanessa; Toschi, Vincenzo; Lassila, Riitta

    2015-01-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for the prevention and treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation. NOACs do not require routine coagulation monitoring, creating a challenge to established systems for patient follow-up based on regular blood tests. Healthcare professionals (HCPs) are required to cope with a mixture of patients receiving either a vitamin K antagonist or a NOAC for the same indications, and both professionals and patients require education about the newer drugs. A European working group convened to consider the challenges facing HCPs and healthcare systems in different countries and the educational gaps that hinder optimal patient management. Group members emphasised the need for regular follow-up and noted national, regional and local variations in set-up and resources for follow-up. Practical incorporation of NOACs into healthcare systems must adapt to these differences, and practical follow-up that works in some systems may not be able to be implemented in others. The initial prescriber of a NOAC should preferably be a true anticoagulation specialist, who can provide initial patient education and coordinate the follow-up. The long-term follow-up care of patients can be managed through specialist coagulation nurses, in a dedicated anticoagulation clinic or by general practitioners trained in NOAC use. The initial prescriber should be involved in educating those who perform the follow-up. Specialist nurses require access to tools, potentially including specific software, to guide systematic patient assessment and workflow. Problem cases should be referred for specialist advice, whereas in cases for which minimal specialist attention is required, the general practitioner could take responsibility for patient follow-up. Hospital departments and anticoagulation clinics should proactively engage with all downstream HCPs (including pharmacists) to ensure

  6. Lupus anticoagulants and antiphospholipid antibodies

    MedlinePlus

    Blood clots - lupus anticoagulants; DVT - anticoagulants ... Most often, lupus anticoagulants and aPL are found in people with diseases such as systemic lupus erythematosus (SLE). Lupus anticoagulants and ...

  7. How to Invest in Getting Cost-effective Technologies into Practice? A Framework for Value of Implementation Analysis Applied to Novel Oral Anticoagulants.

    PubMed

    Faria, Rita; Walker, Simon; Whyte, Sophie; Dixon, Simon; Palmer, Stephen; Sculpher, Mark

    2017-02-01

    Cost-effective interventions are often implemented slowly and suboptimally in clinical practice. In such situations, a range of implementation activities may be considered to increase uptake. A framework is proposed to use cost-effectiveness analysis to inform decisions on how best to invest in implementation activities. This framework addresses 2 key issues: 1) how to account for changes in utilization in the future in the absence of implementation activities; and 2) how to prioritize implementation efforts between subgroups. A case study demonstrates the framework's application: novel oral anticoagulants (NOACs) for the prevention of stroke in the National Health Service in England and Wales. The results suggest that there is value in additional implementation activities to improve uptake of NOACs, particularly in targeting patients with average or poor warfarin control. At a cost-effectiveness threshold of £20,000 per quality-adjusted life-year (QALY) gained, additional investment in an educational activity that increases the utilization of NOACs by 5% in all patients currently taking warfarin generates an additional 254 QALYs, compared with 973 QALYs in the subgroup with average to poor warfarin control. However, greater value could be achieved with higher uptake of anticoagulation more generally: switching 5% of patients who are potentially eligible for anticoagulation but are currently receiving no treatment or are using aspirin would generate an additional 4990 QALYs. This work can help health services make decisions on investment at different points of the care pathway or across disease areas in a manner consistent with the value assessment of new interventions.

  8. [Multidisciplinary meeting about the use of direct oral anticoagulants in nonvalvular atrial fibrillation].

    PubMed

    Rodríguez-Reyes, Humberto; Arauz-Góngora, Antonio; Asensio-Lafuente, Enrique; Celaya-Cota, Manuel de Jesús; Cordero-Cabra, Alejandro; Guevara-Valdivia, Milton; Izaguirre-Avila, Raúl; Lara-Vaca, Susano; Mariona-Moreno, Vitelio; Martínez-Flores, Enrique; Nava-Townsend, Santiago; Pozas-Garza, Gerardo; Rodríguez-Diez, Gerardo

    Knowing the real impact of atrial fibrillation in the stroke, the Sociedad Mexicana of Electrofisiología y Estimulación Cardiaca (SOMEEC) had the initiative to develop a multidisciplinary meeting of experts the with the purpose to update the available scientific evidence from clinical practice guidelines, meta-analyses, controlled clinical trials, and complementing with the experience and views of a group of experts. To meet this goal, SOMEEC gathered a group of specialists in the area of cardiology, electrophysiology, neurology and hematology that given their experience in certain areas, they share the scientific evidence with the panel of experts to leave open a discussion about the information presented in this article. This document brings together the best scientific evidence available and aims to be a useful tool in the decision to use of new oral anticoagulants in nonvalvular atrial fibrillation and ischemic heart disease, or relating to the management of patients with stroke or renal failure, and even those that will be submitted to elective surgery and invasive procedures. In the same, they handled comparative schemes of follow-up and treatment which simplifies the decision making by the specialists participants. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  9. Trial Protocol: A randomised controlled trial of extended anticoagulation treatment versus routine anticoagulation treatment for the prevention of recurrent VTE and post thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (The ExACT Study)

    PubMed Central

    2013-01-01

    Background Venous thromboembolism comprising pulmonary embolism and deep vein thrombosis is a common condition with an incidence of approximately 1 per 1,000 per annum causing both mortality and serious morbidity. The principal aim of treatment of a venous thromboembolism with heparin and warfarin is to prevent extension or recurrence of clot. However, the recurrence rate following a deep vein thrombosis remains approximately 10% per annum following treatment cessation irrespective of the duration of anticoagulation therapy. Patients with raised D-dimer levels after discontinuing oral anticoagulation treatment have also been shown to be at high risk of recurrence. Post thrombotic syndrome is a complication of a deep vein thrombosis which can lead to chronic venous insufficiency and ulceration. It has a cumulative incidence after 2 years of around 25% and it has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure. Methods/design Patients with a first idiopathic venous thromboembolism will be recruited through anticoagulation clinics and randomly allocated to either continuing or discontinuing warfarin treatment for a further 2 years and followed up on a six monthly basis. At each visit D-dimer levels will be measured using a Roche Cobas h 232 POC device. In addition a venous sample will be taken for laboratory D-dimer analysis at the end of the study. Patients will be examined for signs and symptoms of PTS using the Villalta scale and complete VEINES and EQ5D quality of life questionnaires. Discussion The primary aim of the study is to investigate whether extending oral anticoagulation treatment (prior to discontinuing treatment) beyond 3–6 months for patients with a first unprovoked proximal deep vein thrombosis or pulmonary embolism prevents recurrence. The study will also determine the role of extending anticoagulation for patients with elevated D-dimer levels prior to discontinuing treatment and

  10. Oral contraceptives and the prothrombin time.

    PubMed

    Pangrazzi, J; Roncaglioni, M C; Donati, M B

    1980-02-02

    Dr. De Teresa and others reported that mean prothrombin time ratio of 12 patients on long-term anticoagulation with warfarin was significantly higher when they were also taking oral contraceptives (OCs). A study of prothrombin complex activity was recently conducted in female rats treated with an estrogen-progestogen combination (lynestrenol 5 mg; mestranol 0.3 mg/kg body weight) which resulted in a 100% infertility in this species. After 1 treatment for only 1 estral cycle, OC-treated rats had a significantly longer Normotest clotting time (37.7+ or-0.5 sec) than control rats (31.0+or-0.4); the difference was even more notable after 10 cycles. Although this finding has not been reported in women on OCs, it may be that the estrogen-induced "lability" of the prothrombin complex occurs in humans only in special conditions, such as anticoagulation. Alternatively, liver dysfunction occurring among women on OCs may be responsible for reduced metabolism of warfarin, contributing to the effectiveness of the anticoagulation. Further pharmacology studies should be done to clarify the interaction between OCs and oral anticoagulants.

  11. Acute Pulmonary Embolism in Emergency Department Patients Despite Therapeutic Anticoagulation.

    PubMed

    Liu, Michelle Y; Ballard, Dustin W; Huang, Jie; Rauchwerger, Adina S; Reed, Mary E; Bouvet, Sean C; Vinson, David R

    2018-05-01

    Emergency department (ED) patients with acute pulmonary embolism (PE) despite therapeutic anticoagulation at the time of diagnosis are uncommonly encountered and present a diagnostic and management challenge. Their characterization and outcomes are poorly described. We sought to describe the prevalence and characteristics of therapeutically anticoagulated patients among a population of patients with acute PE in a community setting and to describe treatment changes and 30-day outcomes. From a large retrospective cohort of adults with acute, objectively-confirmed PE across 21 EDs between 01/2013 and 04/2015, we identified patients who arrived on direct oral or injectable anticoagulants, or warfarin with an initial ED international normalized ratio (INR) value ≥2.0. Patients were excluded from the larger cohort if they had received a diagnosis of venous thromboembolism (VTE) in the prior 30 days. We gathered demographic and clinical variables from electronic health records and structured manual chart review. We report discharge anticoagulation regimens and major 30-day adverse outcomes. Among 2,996 PE patients, 36 (1.2%) met study criteria. Mean age was 63 years. Eleven patients (31%) had active cancer and 25 (69%) were high risk on the PE Severity Index (Classes III-V), comparable to the larger cohort (p>0.1). Reasons for pre-arrival anticoagulation were VTE treatment or prevention (n=21), and atrial fibrillation or flutter (n=15). All patients arrived on warfarin and one was also on enoxaparin: 32 had a therapeutic INR (2.0-3.0) and four had a supratherapeutic INR (>3.0). Fifteen patients (42%) had at least one subtherapeutic INR (<2.0) in the 14 days preceding their diagnostic visit. Two patients died during hospitalization. Of the 34 ultimately discharged, 22 underwent a change in anticoagulation drug or dosing, 19 of whom received injectables, either to replace or to supplement warfarin. Four patients also received inferior vena cava filters. Thirty

  12. Posttraumatic gastric wall hematoma in a patient under anticoagulant therapy. Case report and literature review.

    PubMed

    Mânzat Saplacan, Roberta Maria; Catinean, Adrian; Manole, Simona; Valean, Simona Doina; Chira, Romeo Ioan; Mircea, Petru Adrian

    2011-06-01

    We report the clinical observation of a 58-year old patient who presented with upper abdominal pain and a small ecchymosis located in the umbilical area. Personal history of the patient revealed ischemic heart disease and chronic atrial fibrillation. He was under treatment with oral anticoagulants (coumarins). The clinical data and especially the imaging investigations led to a diagnosis of gastric wall hematoma, possibly occurring post-traumatically in a patient under anticoagulant treatment. A conservative therapeutic approach was adopted and ultrasound surveillance. After 6 months the gastric parietal collection manifested complete resorption, spontaneously. In relation to the case presentation, we also discuss some issues on the frequency, diagnosis and therapeutic attitude in this rare complication of anticoagulant therapy.

  13. Outcome of intracerebral hemorrhage associated with different oral anticoagulants.

    PubMed

    Wilson, Duncan; Seiffge, David J; Traenka, Christopher; Basir, Ghazala; Purrucker, Jan C; Rizos, Timolaos; Sobowale, Oluwaseun A; Sallinen, Hanne; Yeh, Shin-Joe; Wu, Teddy Y; Ferrigno, Marc; Houben, Rik; Schreuder, Floris H B M; Perry, Luke A; Tanaka, Jun; Boulanger, Marion; Al-Shahi Salman, Rustam; Jäger, Hans R; Ambler, Gareth; Shakeshaft, Clare; Yakushiji, Yusuke; Choi, Philip M C; Staals, Julie; Cordonnier, Charlotte; Jeng, Jiann-Shing; Veltkamp, Roland; Dowlatshahi, Dar; Engelter, Stefan T; Parry-Jones, Adrian R; Meretoja, Atte; Werring, David J

    2017-05-02

    In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non-vitamin K antagonist oral anticoagulation-related ICH (NOAC-ICH) and vitamin K antagonist-associated ICH (VKA-ICH). We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours. We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6-38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0-27.9) for VKA-ICH ( p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [ p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52-1.64] [ p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [ p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18-1.19 [ p = 0.11]). In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  14. Pre-Stroke Weight Loss is Associated with Post-Stroke Mortality among Men in the Honolulu-Asia Aging Study

    PubMed Central

    Bell, Christina L.; Rantanen, Taina; Chen, Randi; Davis, James; Petrovitch, Helen; Ross, G. Webster; Masaki, Kamal

    2013-01-01

    Objective To examine baseline pre-stroke weight loss and post-stroke mortality among men. Design Longitudinal study of late-life pre-stroke body mass index (BMI), weight loss and BMI change (midlife to late-life), with up to 8-year incident stroke and mortality follow-up. Setting Honolulu Heart Program/Honolulu-Asia Aging Study. Participants 3,581 Japanese-American men aged 71–93 years and stroke-free at baseline. Main Outcome Measure Post-stroke Mortality: 30-day post-stroke, analyzed with stepwise multivariable logistic regression and long-term post-stroke (up to 8-year), analyzed with stepwise multivariable Cox regression. Results Weight loss (10-pound decrements) was associated with increased 30-day post-stroke mortality (aOR=1.48, 95%CI 1.14–1.92), long-term mortality after incident stroke (all types n=225, aHR=1.25, 95%CI=1.09–1.44) and long-term mortality after incident thromboembolic stroke (n=153, aHR 1.19, 95%CI-1.01–1.40). Men with overweight/obese late-life BMI (≥25kg/m2, compared to normal/underweight BMI) had increased long-term mortality after incident hemorrhagic stroke (n=54, aHR=2.27, 95%CI=1.07–4.82). Neither desirable nor excessive BMI reductions (vs. no change/increased BMI) were associated with post-stroke mortality. In the overall sample (n=3,581), nutrition factors associated with increased long-term mortality included 1) weight loss (10-pound decrements, aHR=1.15, 1.09–1.21); 2) underweight BMI (vs. normal BMI, aHR=1.76, 1.40–2.20); and 3) both desirable and excessive BMI reductions (vs. no change or gain, separate model from weight loss and BMI, aHRs=1.36–1.97, p<0.001). Conclusions Although obesity is a risk factor for stroke incidence, pre-stroke weight loss was associated with increased post-stroke (all types and thromboembolic) mortality. Overweight/obese late-life BMI was associated with increased post-hemorrhagic stroke mortality. Desirable and excessive BMI reductions were not associated with post-stroke mortality

  15. Rapid bedside coagulometry prior to urgent neurosurgical procedures in anticoagulated patients.

    PubMed

    Beynon, Christopher; Jakobs, Martin; Rizos, Timolaos; Unterberg, Andreas W; Sakowitz, Oliver W

    2014-01-01

    With the increased use of oral anticoagulation with vitamin K antagonists, emergency physicians encounter a growing number of patients requiring a rapid reversal of anticoagulant effects in order to perform urgent surgical procedures. Initiation of these procedures can be delayed because the coagulation status has to be assessed through examination of blood samples in central laboratories (CL). This delay may lead to negative effects, especially in potentially life-threatening conditions such as intracranial haemorrhage. Point-of-care (POC) devices for assessment of international normalized ratio (POC INR) have improved the management of anticoagulation therapy in the outpatient setting. The use of these devices may also have beneficial effects in the treatment of anticoagulated patients requiring urgent neurosurgical procedures. The primary aim of this study was to analyse the potential of POC-guided assessment of INR to reduce time to potentially life-saving neurosurgery in this setting. Feasibility and accuracy as well as the gain of time through the use of this device were analysed. The POC coagulometer CoaguChek XS(®) was used in 17 patients with a history of anticoagulant use and a condition requiring urgent anticoagulant reversal prior to neurosurgical procedures (burr-hole trepanation: n = 8, craniotomy: n = 7, laminectomy: n = 2). No technical difficulties occurred and rapid assessment of INR was achieved in all cases within 2 min. POC INR values correlated well with CL INR assessment with a mean INR deviation of 0.036 ± 0.12. The mean gain of time through the use of the POC INR device compared with CL assessment of INR was 47 ± 6 min (range: 37-61 min). Our initial experiences with a POC INR device in anticoagulated patients undergoing urgent neurosurgical procedures demonstrate that its use may contribute to an improved management of these patients.

  16. Patient preferences and willingness to pay for different options of anticoagulant therapy.

    PubMed

    Moia, Marco; Mantovani, Lorenzo Giovanni; Carpenedo, Monica; Scalone, Luciana; Monzini, Mara Silvia; Cesana, Giancarlo; Mannucci, Pier Mannuccio

    2013-04-01

    New anticoagulant drugs alternative to vitamin K antagonists are currently under clinical evaluation. Patient's preferences should be considered in the development of new therapeutic strategies. Our study aim was to elicit patient preferences, and estimate their willingness to pay for the different treatment options. A Discrete Choice Experiment was administered to patients consecutively attending an anticoagulation clinic, either on stable oral anticoagulant therapy, or during their first visit at the time of starting therapy. Six treatment characteristics were analysed: route and number of medication administrations, frequency of monitoring, risk of some minor bleeding, the amount of attention required for drug/food interactions, requirement for dose adjustment, and out-of-pocket treatment cost. Relationships between patient's preferences and their characteristics were analysed. 255 patients participated (55 % men, with a mean age 64 years; 35.7 % on stable therapy). A statistically significant importance was attributed to all but two characteristics (the amount of attention required for interaction with other drugs/food and for dose adjustment.) Monthly patient willingness to pay was 79 for tablets versus injections; 41 for once-daily versus twice-daily tablets, 25 for drugs without risk of minor bleeding events and 20 for once-monthly versus twice-monthly monitoring. Patients on stable therapy considered more important the amount of attention required for drug/food interactions than did the starters. Younger or working patients considered the reduction of monitoring frequency more important than did the older or not working patients (retired, housewives). This study elicited preferences from patients on oral anticoagulant therapy with a simple and well established method, which allows to obtain information warranted for planning optimal healthcare.

  17. The Indian consensus guidance on stroke prevention in atrial fibrillation: An emphasis on practical use of nonvitamin K oral anticoagulants.

    PubMed

    Dalal, Jamshed; Bhave, Abhay; Oomman, Abraham; Vora, Amit; Saxena, Anil; Kahali, Dhiman; Poncha, Fali; Gambhir, D S; Chaudhuri, Jaydip Ray; Sinha, Nakul; Ray, Saumitra; Iyengar, S S; Banerjee, Suvro; Kaul, Upendra

    2015-12-01

    The last ten years have seen rapid strides in the evolution of nonvitamin K oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF). For the preparation of this consensus, a comprehensive literature search was performed and data on available trials, subpopulation analyses, and case reports were analyzed. This Indian consensus document intends to provide guidance on selecting the right NOAC for the right patients by formulating expert opinions based on the available trials and Asian/Indian subpopulation analyses of these trials. A section has been dedicated to the current evidence of NOACs in the Asian population. Practical suggestions have been formulated in the following clinical situations: (i) Dose recommendations of the NOACs in different clinical scenarios; (ii) NOACs in patients with rheumatic heart disease (RHD); (iii) Monitoring anticoagulant effect of the NOACs; (iv) Overdose of NOACs; (v) Antidotes to NOACs; (vi) Treatment of hypertrophic cardiomyopathy (HCM) with AF using NOACs; (vii) NOACs dose in elderly, (viii) Switching between NOACs and vitamin K antagonists (VKA); (ix) Cardioversion or ablation in NOAC-treated patients; (x) Planned/emergency surgical interventions in patients currently on NOACs; (xi) Management of bleeding complications of NOACs; (xii) Management of acute coronary syndrome (ACS) in AF with NOACs; (xiii) Management of acute ischemic stroke while on NOACs. Copyright © 2015. Published by Elsevier B.V.

  18. Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy.

    PubMed

    Maas, Angela H E M; Euler, Mia von; Bongers, Marlies Y; Rolden, Herbert J A; Grutters, Janneke P C; Ulrich, Lian; Schenck-Gustafsson, Karin

    2015-12-01

    A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis.

    PubMed

    Xu, Wei-Wei; Hu, Shen-Jiang; Wu, Tao

    2017-07-01

    Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs. We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo. Bayesian network meta-analysis of two different evidence networks was performed using a binomial likelihood model, based on a network in which different agents (and doses) were treated as separate nodes. Odds ratios (ORs) and 95% confidence intervals (CIs) were modeled using Markov chain Monte Carlo methods. Indirect comparisons with the Bayesian model confirmed that aspirin+clopidogrel significantly increased the risk of GIB in AF patients compared to the placebo (OR 0.33, 95% CI 0.01-0.92). Warfarin was identified as greatly increasing the risk of ICH compared to edoxaban 30 mg (OR 3.42, 95% CI 1.22-7.24) and dabigatran 110 mg (OR 3.56, 95% CI 1.10-8.45). We further ranked the NOACs for the lowest risk of GIB (apixaban 5 mg) and ICH (apixaban 5 mg, dabigatran 110 mg, and edoxaban 30 mg). Bayesian network meta-analysis of treatment of non-valvular AF patients with anticoagulants suggested that NOACs do not increase risks of GIB and/or ICH, compared to each other.

  20. Continuing or Temporarily Stopping Prestroke Antihypertensive Medication in Acute Stroke: An Individual Patient Data Meta-Analysis.

    PubMed

    Woodhouse, Lisa J; Manning, Lisa; Potter, John F; Berge, Eivind; Sprigg, Nikola; Wardlaw, Joanna; Lees, Kennedy R; Bath, Philip M; Robinson, Thompson G

    2017-05-01

    Over 50% of patients are already taking blood pressure-lowering therapy on hospital admission for acute stroke. An individual patient data meta-analysis from randomized controlled trials was undertaken to determine the effect of continuation versus temporarily stopping preexisting antihypertensive medication in acute stroke. Key databases were searched for trials against the following inclusion criteria: randomized design; stroke onset ≤48 hours; investigating the effect of continuation versus stopping prestroke antihypertensive medication; and follow-up of ≥2 weeks. Two randomized controlled trials were identified and included in this meta-analysis of individual patient data from 2860 patients with ≤48 hours of acute stroke. Risk of bias in each study was low. In adjusted logistic regression and multiple regression analyses (using random effects), we found no significant association between continuation of prestroke antihypertensive therapy (versus stopping) and risk of death or dependency at final follow-up: odds ratio 0.96 (95% confidence interval, 0.80-1.14). No significant associations were found between continuation (versus stopping) of therapy and secondary outcomes at final follow-up. Analyses for death and dependency in prespecified subgroups revealed no significant associations with continuation versus temporarily stopping therapy, with the exception of patients randomized ≤12 hours, in whom a difference favoring stopping treatment met statistical significance. We found no significant benefit with continuation of antihypertensive treatment in the acute stroke period. Therefore, there is no urgency to administer preexisting antihypertensive therapy in the first few hours or days after stroke, unless indicated for other comorbid conditions. © 2017 American Heart Association, Inc.

  1. Recurrence of ICH after resumption of anticoagulation with VK antagonists: CHIRONE study.

    PubMed

    Poli, Daniela; Antonucci, Emilia; Dentali, Francesco; Erba, Nicoletta; Testa, Sophie; Tiraferri, Eros; Palareti, Gualtiero

    2014-03-25

    To evaluate the risk of recurrent intracranial hemorrhage (ICH) in patients on vitamin K antagonists (VKAs) after a first episode of ICH. The Cerebral Haemorrhage in patients Restarting Oral Anticoagulant Therapy (CHIRONE) Study collected data of patients eligible for the study from the database of 27 centers affiliated with the Italian Federation of Anticoagulation Clinics. We enrolled 267 patients (163 male, median age 73.9 years) who had received VKA anticoagulation after an ICH event. During the total period of follow-up (778 patient-years), ICH recurred in 20 patients (7.5%; rate 2.56 × 100 patient-years) at a median time of 16.5 months, and was fatal in 5 patients (25%; rate 0.4 × 100 patient-years). Male sex, hypertension, prosthetic valves, previous ischemic stroke, renal failure, cancer, and spontaneous events were associated with the risk of recurrence, though none of them in isolation reached statistical significance. More than one-third of spontaneous recurrences occurred in patients with a posttraumatic index event. Our results show that patients with a history of ICH carry a significant risk of recurrent ICH when treated with VKA anticoagulation. The risk is also present, though to a lower degree, in patients with previous posttraumatic events. All patients with a history of ICH require a careful evaluation of their thromboembolic risk to estimate the net clinical benefit of (re)starting anticoagulation with VKAs.

  2. Technology-assisted self-testing and management of oral anticoagulation therapy: a qualitative patient-focused study.

    PubMed

    Kuljis, Jasna; Money, Arthur G; Perry, Mark; Barnett, Julie; Young, Terry

    2017-09-01

    Oral anticoagulation therapy requires regular blood testing to ensure therapeutic levels are maintained and excessive bleeding/clotting is avoided. Technology-assisted self-testing and management is seen as one of the key areas in which quality of care can be improved whilst reducing costs. Nevertheless, levels of patient engagement in self-testing and management remain low. To date, little research emphasis has been placed on understanding the patients' perspectives for low engagement. The typical approach adopted by healthcare providers is to provide patient education programmes, with the expectation that individual patients will change their behaviour and adopt new self-care strategies. However, if levels of patient engagement are to be increased, healthcare providers must also develop a better understanding of how their clinical service provision is perceived by patients and make adaptations. To explore patient views, needs and expectations of an anticoagulation service and the self-testing and management services provided. Interviews were conducted with 17 patients who currently engage in international normalised ratio (INR) self-testing and management. Thematic coding and analysis were carried out on the interview transcripts. Four high-level themes emerged from interviews: (i) role of clinic, (ii) motivations for self-testing, (iii) managing INR and (iv) trust. The clinic was seen as adding value in terms of specifying testing frequency, dosage profiles and calibrating equipment. Prompt communication from clinic to patient was also valued, although more personalised/real-time communication would help avoid feelings of isolation. Patients felt more in control as self-tester/managers and often took decisions about treatment adjustments themselves. However, some also manipulated their own test results to avoid 'unnecessary' interventions. More personalised/real-time communication, pragmatic and collaborative patient-clinician partnerships and recognition of

  3. [Real-world data on novel oral anticoagulants: the added value of registries and observational studies. Focus on apixaban].

    PubMed

    Pelliccia, Francesco; Tanzilli, Gaetano; Schiariti, Michele; Viceconte, Nicola; Greco, Cesare; Gaudio, Carlo

    2016-12-01

    Anticoagulant therapy has been used with great effect for decades for the prevention of stroke among patients with atrial fibrillation. In recent years, the therapeutic armamentarium has been strengthened considerably, with the addition of anticoagulants acting through novel pathways. The currently available novel agents are apixaban, rivaroxaban and dabigatran. These novel oral anticoagulants (NOACs) were approved for use on the basis of major clinical trials clearly demonstrating improved risk reductions compared to warfarin for stroke and/or major bleeding events. In these studies, apixaban and dabigatran 150 mg each significantly reduced the risk of stroke, while apixaban and dabigatran 110 mg reduced the risk of major bleeding compared to warfarin. Extrapolating the results of the randomized clinical trials on NOACs to all patients is not possible, as the strict design of clinical trials yields information that is directly applicable to a relatively narrow spectrum of patients. To control for confounding variables, randomized studies restrict enrolment to a prespecified set of criteria that do not necessarily reflect the profiles of all those who could potentially benefit from these agents. Research continues using the trial databases, in an attempt to better identify patient subgroups who do or do not benefit from each of the agents. At the European Society of Cardiology (ESC) annual meetings in London in 2015 and in Rome in 2016, there were several presentations and posters providing this type of evidence. Perhaps more important, as real-world experience with these agents grows, we are beginning to obtain meaningful new information about the NOACs in everyday use. This has involved the study of large databases including patients receiving these medications in clinical situations less stringently defined than in the randomized clinical trials. These include purpose-built registries, observational studies, and analyses of healthcare administrative databases

  4. Monitoring therapeutic anticoagulation with low molecular weight heparins: is it useful or misleading?

    PubMed

    Hammerstingl, C

    2008-10-01

    Weight adapted low molecular weight heparin (LMWH) treatment is recommended as initial anticoagulant therapy of deep vein thrombosis, pulmonary embolism, in patients with myocardial ischemia or when oral anticoagulation (OAC) must be interrupted peri- operatively. Traditionally unfractioned heparin (UFH) was used as standard short acting anticoagulant, with the therapy monitored by frequent laboratory testing. Currently LMWH have broadly replaced UFH as first- choice anticoagulant due to more preferable pharmacokinetics and a better safety profile. Therapeutic anticoagulation with LMWH can be achieved by subcutaneous weight adapted application and measurement of anti-factor Xa- activity (anti-Xa) has been established as gold standard for LMWH- monitoring. However, since almost all LMWH dosing regimens have been developed empirically without laboratory monitoring, there is still a debate ongoing about the usefulness and impact of anti-Xa-testing. Data are lacking that prove a clear correlation between obtained levels of anti-Xa and the patients' clinical outcome. Newer methods have been developed aiming to determine a broader spectrum of LMWH depending anticoagulant activity. Even though there are some promising preliminary results, these alternative methods are not ready for routine clinical use yet. Nevertheless, current guidelines advise determination of anti-Xa in special patient populations with markedly altered LMWH metabolism or to exclude residual LMWH- activity before surgery at very high risk of bleeding. The aim of this article is to review critically the usefulness of anti- Xa guidance of LMWH- therapy and to give new perspectives on upcoming methods of LMWH- monitoring.

  5. Acute Pulmonary Embolism in Emergency Department Patients Despite Therapeutic Anticoagulation

    PubMed Central

    Liu, Michelle Y.; Ballard, Dustin W.; Huang, Jie; Rauchwerger, Adina S.; Reed, Mary E.; Bouvet, Sean C.

    2018-01-01

    Introduction Emergency department (ED) patients with acute pulmonary embolism (PE) despite therapeutic anticoagulation at the time of diagnosis are uncommonly encountered and present a diagnostic and management challenge. Their characterization and outcomes are poorly described. We sought to describe the prevalence and characteristics of therapeutically anticoagulated patients among a population of patients with acute PE in a community setting and to describe treatment changes and 30-day outcomes. Methods From a large retrospective cohort of adults with acute, objectively-confirmed PE across 21 EDs between 01/2013 and 04/2015, we identified patients who arrived on direct oral or injectable anticoagulants, or warfarin with an initial ED international normalized ratio (INR) value ≥2.0. Patients were excluded from the larger cohort if they had received a diagnosis of venous thromboembolism (VTE) in the prior 30 days. We gathered demographic and clinical variables from electronic health records and structured manual chart review. We report discharge anticoagulation regimens and major 30-day adverse outcomes. Results Among 2,996 PE patients, 36 (1.2%) met study criteria. Mean age was 63 years. Eleven patients (31%) had active cancer and 25 (69%) were high risk on the PE Severity Index (Classes III–V), comparable to the larger cohort (p>0.1). Reasons for pre-arrival anticoagulation were VTE treatment or prevention (n=21), and atrial fibrillation or flutter (n=15). All patients arrived on warfarin and one was also on enoxaparin: 32 had a therapeutic INR (2.0–3.0) and four had a supratherapeutic INR (>3.0). Fifteen patients (42%) had at least one subtherapeutic INR (<2.0) in the 14 days preceding their diagnostic visit. Two patients died during hospitalization. Of the 34 ultimately discharged, 22 underwent a change in anticoagulation drug or dosing, 19 of whom received injectables, either to replace or to supplement warfarin. Four patients also received inferior vena

  6. Differences in attitude, education, and knowledge about oral anticoagulation therapy among patients with atrial fibrillation in Europe: result of a self-assessment patient survey conducted by the European Heart Rhythm Association.

    PubMed

    Hernández Madrid, Antonio; Potpara, Tatjana S; Dagres, Nikolaos; Chen, Jian; Larsen, Torben B; Estner, Heidi; Todd, Derick; Bongiorni, Maria G; Sciaraffia, Elena; Proclemer, Alessandro; Cheggour, Saida; Amara, Walid; Blomstrom-Lundqvist, Carina

    2016-03-01

    The purpose of this patient survey was to analyse the knowledge about blood thinning medications relative to gender, age, education, and region of residence in patients with atrial fibrillation (AF). A total of 1147 patients with AF [mean age 66 ± 13 years, 529 (45%) women] from eight European countries responded to this survey. Most patients understood that the indication for anticoagulation therapy was to 'thin the blood', but 8.1% responded that the purpose of the medication was to treat the arrhythmia. Patients with college or university grades reported less frequent deviations from their target INR range compared with those without schooling (2.8% vs. 5.1%, P < 0.05). The awareness of anticoagulation-related risk of bleedings was lowest in patients without schooling (38.5%) and highest in those with college and university education (57.0%), P < 0.05. The same pattern was also observed regarding patient's awareness of non-vitamin K antagonist oral anticoagulants (NOACs): 56.5% of the patients with university education and only 20.5% of those without schooling (P < 0.05) knew about NOACs, indicating that information about new anticoagulation therapies remains well below the target. Bleeding events were statistically less frequent in patients on NOACs compared with vitamin K antagonists. The education level and patients' knowledge have a direct influence on the global management of the anticoagulation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  7. Needs and barriers to improve the collaboration in oral anticoagulant therapy: a qualitative study

    PubMed Central

    2011-01-01

    Background Oral anticoagulant therapy (OAT) involves many health care disciplines. Even though collaboration between care professionals is assumed to improve the quality of OAT, very little research has been done into the practice of OAT management to arrange and manage the collaboration. This study aims to identify the problems in collaboration experienced by the care professionals involved, the solutions they proposed to improve collaboration, and the barriers they encountered to the implementation of these solutions. Methods In the Netherlands, intensive follow-up of OAT is provided by specialized anticoagulant clinics (ACs). Sixty-eight semi-structured face-to-face interviews were conducted with 103 professionals working at an AC. These semi-structured interviews were transcribed verbatim and analysed inductively. Wagner's chronic care model (CCM) and Cabana's framework for improvement were used to categorize the results. Results AC professionals experienced three main bottlenecks in collaboration: lack of knowledge (mostly of other professionals), lack of consensus on OAT, and limited information exchange between professionals. They mentioned several solutions to improve collaboration, especially solutions of CCM's decision support component (i.e. education, regular meetings, and agreements and protocols). Education is considered a prerequisite for the successful implementation of other proposed solutions such as developing a multidisciplinary protocol and changing the allocation of tasks. The potential of the health care organization to improve collaboration seemed to be underestimated by professionals. They experienced several barriers to the successful implementation of the proposed solutions. Most important barriers were the lack motivation of non-AC professionals and lack of time to establish collaboration. Conclusions This study revealed that the collaboration in OAT is limited by a lack of knowledge, a lack of consensus, and a limited information

  8. Safety and Efficacy of Novel Oral Anticoagulants vs Low Molecular Weight Heparin for Thromboprophylaxis in Large-Volume Liposuction and Body Contouring Procedures.

    PubMed

    Morales, Rolando; Ruff, Eric; Patronella, Christopher; Mentz, Henry; Newall, Germán; Hustak, Kristi L; Fortes, Paul; Bush, Amelia

    2016-04-01

    Preventing venous thromboembolism (VTE) remains an important topic in the plastic surgery community. However, there is little consensus regarding appropriate VTE prophylaxis for patients undergoing common body contouring procedures. This study compared the use of two novel oral anticoagulants (Rivaroxaban and Apixiban) vs low molecular weight heparin (LMWH) for postoperative chemical prophylaxis in body contouring plastic surgery procedures. A single center retrospective chart review of 1572 patients who underwent body contouring plastic surgery procedures from January 2012 to February 2015 was performed. Major complications associated with chemical prophylaxis were reviewed including hematomas requiring surgical evacuation, acute blood loss anemia requiring transfusions, and thrombotic or hemorrhagic events. Drug-related adverse events occurred in 1.27% (n = 20) of patients. The complications encountered by the 454 patients on LMWH consisted of 0.88% (n = 4) with hematomas requiring surgical evacuation, 0.44% (n = 2) with decreased hemoglobin requiring transfusions, and 0.22% (n = 1) with a deep vein thrombosis (DVT). The complications encountered by 703 patients on with Rivaroxaban consisted of 1.3% (n = 9) with hematomas requiring surgical evacuation, 0.43% (n = 3) with decreased hemoglobin requiring transfusions, and 0.1% (n = 1) with a DVT and pulmonary embolism. The complications encountered by 415 patients on with Apixaban consisted of 0.48% (n = 2) with a DVT. Novel oral anticoagulants (Rivaroxaban and Apixiban) are comparable to LMWH for chemical prophylaxis after body contouring procedures with similar rates of drug-related complications. Further investigation is warranted with more clinical cases in order to recommend the use of this medication for routine postoperative chemical prophylaxis after body contouring procedures. 3 Therapeutic. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  9. Thrombosis, Hypercoagulable States, and Anticoagulants.

    PubMed

    Hollenhorst, Marie A; Battinelli, Elisabeth M

    2016-12-01

    Patients with derangements of secondary hemostasis resulting from inherited or acquired thrombophilias are at increased risk of venous thromboemboli (VTE). Evaluation of a patient with suspected VTE proceeds via evidence-based algorithms that involve computing a pretest probability based on the history and physical examination; this guides subsequent work-up, which can include D dimer and/or imaging. Testing for hypercoagulable disorders should be pursued only in patients with VTE with an increased risk for an underlying thrombophilia. Direct oral anticoagulants are first-line VTE therapies, but they should be avoided in patients who are pregnant, have active cancer, antiphospholipid antibody syndrome, severe renal insufficiency, or prosthetic heart valves. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Predictors of self-reported adherence to direct oral anticoagulation in a population of elderly men and women with non-valvular atrial fibrillation.

    PubMed

    Rossi, Andrea P; Facchinetti, Roberto; Ferrari, Elena; Nori, Nicole; Sant, Selena; Masciocchi, Elena; Zoico, Elena; Fantin, Francesco; Mazzali, Gloria; Zamboni, Mauro

    2018-05-14

    There is a general lack of studies evaluating medication adherence with self-report scales for elderly patients in treatment with direct oral anticoagulants (DOACs). The aim of the study was to assess the degree of adherence to DOAC therapy in a population of elderly outpatients aged 65 years or older affected by non-valvular atrial fibrillation (NVAF), using the 4-item Morisky Medication Adherence Scale, and to identify potential factors, including the geriatric multidimensional evaluation, which can affect adherence in the study population. A total of 103 subjects, anticoagulated with DOACs for NVAF in primary or secondary prevention, were eligible; 76 showed adequate adhesion to anticoagulant therapy, while 27 showed inadequate adherence. Participants underwent biochemical assessment and Morisky Scale, Instrumental Activities of Daily Living, CHA2DS2-VASc, HAS-BLED, mental status and nutritional evaluations were performed. 2% of subjects assumed Dabigatran at low dose, while 7.8% at standard dose, 9.7% assumed low-dose of Rivaroxaban and 30.1% at standard dose, 6.8% assumed Apixaban at low dose and 39.7% at standard dose, and finally 1% assumed Edoxaban at low dose and 2.9% at standard dose. Most subjects took the DOACs without help (80.6%), while 16 subjects were helped by a family member (15.5%) and 4 were assisted by a caregiver (3.9%). Binary logistic regression considered inappropriate adherence as a dependent variable, while age, male sex, polypharmacotherapy, cognitive decay, caregiver help for therapy assumption, duration of DOAC therapy and double daily administration were considered as independent variables. The double daily administration was an independent factor, determining inappropriate adherence with an OR of 2.88 (p = 0.048, CI 1.003-8.286).

  11. Impact of oral anticoagulation on morbidity of transurethral resection of the prostate.

    PubMed

    Descazeaud, Aurélien; Robert, Gregoire; Lebdai, Souhil; Bougault, Alain; Azzousi, Abdel Rahmene; Haillot, Olivier; Devonec, Marian; Fourmarier, Marc; Saussine, Christian; Barry-Delongchamps, Nicolas; de la Taille, Alexandre

    2011-04-01

    To assess the impact of oral anticoagulation (OA) on morbidity of transurethral resection of the prostate (TURP). OA included warfarin and platelet aggregation inhibitors (PAI). Multicenter analysis of patients operated for symptomatic benign prostatic hyperplasia (BPH) by TURP. Patients under OA were compared to those with no OA. Out of 612 patients included in the analysis, 206 (33%) were on OA prior surgery (55 warfarin, 142 PAI, and 9 warfarin and PAI). No patient continued warfarin and clopidogrel during the operating period. Patients under OA were significantly older (75 vs. 71 yo, P < 0.001), had larger prostate volume (56 vs. 49 ml, P = 0.05), and had higher rate of bladder catheter prior surgery (26 vs. 17%, P = 0.02). At 3 months follow-up, patients in the OA group had a higher weight of resected tissue (24 vs. 21.7 g, P < 0.001), a longer duration of hospitalization (6.4 vs. 4.7 days P < 0.001), a higher rate of bladder clots (13 vs. 4.7%, P < 0.001), red cell transfusion (1.9 vs. 1.0%, P = 0.026), late hematuria (15.0 vs. 8.4%, P = 0.004), and thromboembolic events (2.4 vs. 0.7, P = 0.02). In multivariable analysis, OA status was the sole independent parameter associated with bladder clots (P = 0.004) and with late hematuria (P = 0.03). OA had a significant and independent impact on TURP outcome in terms of bleeding complications. This data could be used for treatment decision and for patient's information prior BPH surgery.

  12. [Appropriateness of the prescriptions of conventional versus new oral anticoagulants at discharge from a department of internal medicine].

    PubMed

    Bochatay, L; Beney, J; Jordan-von Gunten, V; Petignat, P A; Roulet, L

    2016-09-01

    The recently introduced oral direct anticoagulants (ODAs), presumably safer, and with comparable efficacy to the vitamin K antagonists (VKAs), may reshape the world of anticoagulation medicine. This study aimed to assess the prescription appropriateness of ODAs and VKAs at discharge from hospital. We performed a one year retrospective study between August 2012 and July 2013 in the department of internal medicine of a regional hospital (HVs Sion) using Electronic Medical Records. All patients receiving an ODA were included and matched to a patient treated with a VKA. The appropriateness of prescription at discharge was defined by an adequate indication and dosing, the absence of contraindication, a minimal risk of drug-drug interactions and no major bleeding or venous thromboembolism during the hospitalization. The bleeding risk was evaluated with the HAS-BLED score when the indication was atrial fibrillation (AF). Out of the 44patients included (22 with an ODA and 22 with a VKA), 38 received an appropriate prescription according to all criteria. Two patients had an inadequate dosing. A potential drug-drug interaction was detected in 3patients receiving a VKA and in 1patient receiving an ODA. No major contraindication was found, but a relative contraindication was discussed in 3cases. The majority of patients receiving an ODA for an AF had a minor bleeding risk. No significant difference was ascertained between the two groups regarding the appropriateness of prescription. Our results suggest that ODAs were cautiously used in our setting. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  13. Management of major bleedings during anticoagulant treatment with the oral direct thrombin inhibitor ximelagatran or warfarin.

    PubMed

    Fernlöf, Gunilla; Sjöström, Britta M; Lindell, Klas M; Wall, Ulrika E

    2009-12-01

    Several new oral anticoagulants are currently investigated in phase III programmes, mainly with inhibition of factor Xa or thrombin as their pharmacological target. Advantages are expected with these new drugs compared with vitamin K antagonists, but one potential drawback is the lack of specific antidotes. During the clinical studies with ximelagatran, an oral direct thrombin inhibitor withdrawn due to hepatic side effects, investigators were instructed to manage bleedings with routine measures. We have retrospectively tried to assess whether this was sufficient or whether there was a need for reversal strategies. The study population consisted of patients with major bleedings in three long-term studies (104 ximelagatran, 155 warfarin). All individual patient narratives were reviewed with respect to management of the bleeding. Complementary data were retrieved from the data-based case report forms. Approximately, two of three of the patients in both groups were subject to some kind of treatment. One-third (1/3) in both groups had transfusions documented and/or received specific medication. Vitamin K was given more often to warfarin patients. Two ximelagatran patients received prothrombin complex (four-factor concentrate), but one was a patient with a severe hepatopathy suspected to be drug-induced. Overall, the case descriptions did not reveal any apparent differences in the course of events between groups. We found no indications that the lack of an antidote posed a clinical problem in patients treated with ximelagatran as compared with warfarin. The relatively short half-life of melagatran, the active metabolite of ximelagatran, may have contributed to these results.

  14. Cerebral amyloid angiopathy, cerebral microbleeds and implications for anticoagulation decisions: The need for a balanced approach.

    PubMed

    Charidimou, Andreas; Shoamanesh, Ashkan; Al-Shahi Salman, Rustam; Cordonnier, Charlotte; Perry, Luke A; Sheth, Kevin N; Biffi, Alessandro; Rosand, Jonathan; Viswanathan, Anand

    2018-02-01

    Cerebral amyloid angiopathy is a common hemorrhagic small vessel disease of the brain, often associated with high risk of spontaneous lobar intracerebral hemorrhage. When the suspicion of cerebral amyloid angiopathy is raised, clinicians are hesitant in prescribing oral anticoagulation in patients in whom it is otherwise indicated, including the case of non-valvular atrial fibrillation. This is one of the thorniest clinical dilemmas in the field currently. In this short Leading Opinion piece by an international panel of clinicians-researchers active in the field, we present our consistent approach and future outlook on oral anticoagulation post intracerebral hemorrhage and in the setting of clinical-radiologic evidence of cerebral amyloid angiopathy. We discuss recent advances and support a more balanced approach with implications for the wider neurological clinical community in regards to successful recruiting this patient population in ongoing and future randomized trials.

  15. New Oral Anticoagulants May Be Particularly Useful for Asian Stroke Patients

    PubMed Central

    Bang, Oh Young; Hong, Keun-Sik; Heo, Ji Hoe; Koo, Jaseong; Kwon, Sun U.; Yu, Kyung-Ho; Bae, Hee-Joon; Lee, Byung-Chul; Yoon, Byung-Woo

    2014-01-01

    Atrial fibrillation (AF) is an emerging epidemic in both high-income and low-income countries, mainly because of global population aging. Stroke is a major complication of AF, and AF-related ischemic stroke is more disabling and more fatal than other types of ischemic stroke. However, because of concerns about bleeding complications, particularly intracranial hemorrhage, and the limitations of a narrow therapeutic window, warfarin is underused. Four large phase III randomized controlled trials in patients with non-valvular AF (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48) demonstrated that new oral anticoagulants (NOACs) are superior or non-inferior to warfarin as regards their efficacy in preventing ischemic stroke and systemic embolism, and superior to warfarin in terms of intracranial hemorrhage. Among AF patients receiving warfarin, Asians compared to non-Asians are at higher risk of stroke or systemic embolism and are also more prone to develop major bleeding complications, including intracranial hemorrhage. The extra benefit offered by NOACs over warfarin appears to be greater in Asians than in non-Asians. In addition, Asians are less compliant, partly because of the frequent use of herbal remedies. Therefore, NOACs compared to warfarin may be safer and more useful in Asians than in non-Asians, especially in stroke patients. Although the use of NOACs in AF patients is rapidly increasing, guidelines for the insurance reimbursement of NOACs have not been resolved, partly because of insufficient understanding of the benefit of NOACs and partly because of cost concerns. The cost-effectiveness of NOACs has been well demonstrated in the healthcare settings of developed countries, and its magnitude would vary depending on population characteristics as well as treatment cost. Therefore, academic societies and regulatory authorities should work together to formulate a scientific healthcare policy that will effectively reduce the burden of AF-related stroke in

  16. Oral anticoagulation in elderly patients as secondary prevention of cardioembolic strokes

    PubMed Central

    2010-01-01

    Background Stroke incidence increases with age. Atrial fibrillation (AF) is an important risk factor for ischemic stroke and its incidence also increases with age. However oral anticoagulant therapy (OAT) tends to be underused in the elderly population. Methods Elderly patients (> = 80 years) with an ischemic stroke admitted in our department between 1/7/2003 and 31/6/2005 were prospectively evaluated. Baseline characteristics, risk factors, treatment and etiology according to TOAST criteria were recorded. Patients treated with OAT were followed up in order to assess any side effect and stroke recurrence. Mean follow-up was of 19.5 months (7-45) from discharge. Results Sixty four out of a hundred and fifty nine elderly patients (40.25%) were classified as cardioembolic; mean age was 84.5 years (80-97) and 64.6% were women. AF had been previously identified in 60% of them (16.9% were on OAT and 40.6% on antiplatelet therapy). At discharge, 32 patients (49.2%) were on OAT. In the follow-up 4 patients (12.5%) suffered systemic haemorrhages (3 urinary, 1 gastrointestinal bleeding), with no change in their functional status. Mean INR in this group was 5.9 [3-11] and, in 3 of them, OAT was cancelled. No brain haemorrhages were recorded. Ischemic stroke recurred in 4 patients (INR < 1.8 in 3 of them; the other, INR 2.35). Three patients had died at the end of the follow-up, one of them as a consequence of ischemic stroke recurrence. Discussion Twenty eight point eight of stroke patients admitted in the period of study were >80 years. The high proportion of cardioembolic strokes in this age segment contrasts with the general underuse of OAT as antithrombotic prophylaxis. Our study suggests that OAT is a safe strategy when carefully prescribed, even for elderly patients. PMID:20525389

  17. Impact of video technology on efficiency of pharmacist-provided anticoagulation counseling and patient comprehension.

    PubMed

    Moore, Sarah J; Blair, Elizabeth A; Steeb, David R; Reed, Brent N; Hull, J Heyward; Rodgers, Jo Ellen

    2015-06-01

    Discharge anticoagulation counseling is important for ensuring patient comprehension and optimizing clinical outcomes. As pharmacy resources become increasingly limited, the impact of informational videos on the counseling process becomes more relevant. To evaluate differences in pharmacist time spent counseling and patient comprehension (measured by the Oral Anticoagulation Knowledge [OAK] test) between informational videos and traditional face-to-face (oral) counseling. This prospective, open, parallel-group study at an academic medical center randomized 40 individuals-17 warfarin-naïve ("New Start") and 23 with prior warfarin use ("Restart")-to receive warfarin discharge education by video or face-to-face counseling. "Teach-back" questions were used in both groups. Although overall pharmacist time was reduced in the video counseling group (P < 0.001), an interaction between prior warfarin use and counseling method (P = 0.012) suggests the difference between counseling methods was smaller in New Start participants. Following adjustment, mean total time was reduced 8.71 (95% CI = 5.15-12.26) minutes (adjusted P < 0.001) in Restart participants and 2.31 (-2.19 to 6.81) minutes (adjusted P = 0.472) in New Start participants receiving video counseling. Postcounseling OAK test scores did not differ. Age, gender, socioeconomic status, and years of education were not predictive of total time or OAK test score. Use of informational videos coupled with teach-back questions significantly reduced pharmacist time spent on anticoagulation counseling without compromising short-term patient comprehension, primarily in patients with prior warfarin use. Study results demonstrate that video technology provides an efficient method of anticoagulation counseling while achieving similar comprehension. © The Author(s) 2015.

  18. A new instrument for measuring anticoagulation-related quality of life: development and preliminary validation

    PubMed Central

    Samsa, Greg; Matchar, David B; Dolor, Rowena J; Wiklund, Ingela; Hedner, Ewa; Wygant, Gail; Hauch, Ole; Marple, Cheryl Beadle; Edwards, Roger

    2004-01-01

    Background Anticoagulation can reduce quality of life, and different models of anticoagulation management might have different impacts on satisfaction with this component of medical care. Yet, to our knowledge, there are no scales measuring quality of life and satisfaction with anticoagulation that can be generalized across different models of anticoagulation management. We describe the development and preliminary validation of such an instrument – the Duke Anticoagulation Satisfaction Scale (DASS). Methods The DASS is a 25-item scale addressing the (a) negative impacts of anticoagulation (limitations, hassles and burdens); and (b) positive impacts of anticoagulation (confidence, reassurance, satisfaction). Each item has 7 possible responses. The DASS was administered to 262 patients currently receiving oral anticoagulation. Scales measuring generic quality of life, satisfaction with medical care, and tendency to provide socially desirable responses were also administered. Statistical analysis included assessment of item variability, internal consistency (Cronbach's alpha), scale structure (factor analysis), and correlations between the DASS and demographic variables, clinical characteristics, and scores on the above scales. A follow-up study of 105 additional patients assessed test-retest reliability. Results 220 subjects answered all items. Ceiling and floor effects were modest, and 25 of the 27 proposed items grouped into 2 factors (positive impacts, negative impacts, this latter factor being potentially subdivided into limitations versus hassles and burdens). Each factor had a high degree of internal consistency (Cronbach's alpha 0.78–0.91). The limitations and hassles factors consistently correlated with the SF-36 scales measuring generic quality of life, while the positive psychological impact scale correlated with age and time on anticoagulation. The intra-class correlation coefficient for test-retest reliability was 0.80. Conclusions The DASS has

  19. The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism - still a challenging issue.

    PubMed

    Elmi, Giovanna; Di Pasquale, Giuseppe; Pesavento, Raffaele

    2017-03-01

    As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

  20. 2017 Scientific Sessions Sol Sherry Distinguished Lecture in Thrombosis: Factor XI as a Target for New Anticoagulants.

    PubMed

    Weitz, Jeffrey I; Fredenburgh, James C

    2018-02-01

    The goal of anticoagulant therapy is to attenuate thrombosis without compromising hemostasis. Although the direct oral anticoagulants are associated with less intracranial hemorrhage than vitamin K antagonists, bleeding remains their major side effect. Factor XI has emerged as a promising target for anticoagulants that may be safer than those currently available. The focus on factor XI stems from epidemiological evidence of its role in thrombosis, the observation of attenuated thrombosis in factor XI-deficient mice, identification of novel activators, and the fact that factor XI deficiency is associated with only a mild bleeding diathesis. Proof-of-concept comes from the demonstration that compared with enoxaparin, factor XI knockdown reduces venous thromboembolism without increasing bleeding after elective knee arthroplasty. This article rationalizes the selection of factor XI as a target for new anticoagulants, reviews the agents under development, and outlines a potential path forward for their development. © 2017 American Heart Association, Inc.

  1. Novel thrombin and factor Xa inhibitors: challenges to reversal of their anticoagulation effects.

    PubMed

    Yates, Sean; Sarode, Ravi

    2013-11-01

    Warfarin has been the sole oral anticoagulant used in the management of thromboembolic disorders for over 60 years. Target-specific oral anticoagulants (TSOAs) have recently emerged as alternatives to warfarin, because they do not require laboratory monitoring. Nevertheless, with the rising use of TSOAs, there is growing concern among clinicians regarding management of bleeding in patients taking them. Unlike warfarin, there is no antidote or reversal agent for TSOAs. This review summarizes recent developments and attempts to provide a systematic approach to patients on TSOAs presenting with bleeding complications. Currently, data involving clinical management of TSOAs are limited and primarily based on ex-vivo or animal models using hemostatic agents with uncertain implications in bleeding patients. There is a pressing need for randomized clinical trials evaluating the safety and efficacy of hemostatic agents. Without evidence-based guidelines for TSOA management, appropriate patient care requires an understanding of TSOA pharmacology, their effect on coagulation tests and, hence, a correct interpretation of test results, as well as a systematic approach to bleeding complications.

  2. Trends in initiation of direct oral anticoagulant therapies for atrial fibrillation in a national population-based cross-sectional study in the French health insurance databases

    PubMed Central

    Huiart, Laetitia; Ferdynus, Cyril; Renoux, Christel; Beaugrand, Amélie; Lafarge, Sophie; Bruneau, Léa; Suissa, Samy; Maillard, Olivier; Ranouil, Xavier

    2018-01-01

    Objective Unlike several other national health agencies, French health authorities recommended that the newer direct oral anticoagulant (DOAC) agents only be prescribed as second choice for the treatment of newly diagnosed non-valvular atrial fibrillation (NVAF), with vitamin K antagonists (VKA) remaining the first choice. We investigated the patterns of use of DOACs versus VKA in the treatment of NVAF in France over the first 5 years of DOAC availability. We also identified the changes in patient characteristics of those who initiated DOAC treatment over this time period. Methods Based on the French National Health Administrative Database, we constituted a population-based cohort of all patients who were newly treated for NVAF between January 2011 and December 2015. Trends in drug use were described as the percentage of patients initiating each drug at the time of treatment initiation. A multivariate analysis using logistic regression model was performed to identify independent sociodemographic and clinical predictors of initial anticoagulant choice. Results The cohort comprised 814 446 patients who had received a new anticoagulant treatment for NVAF. The proportion of patients using DOACs as initial anticoagulant therapy reached 54% 3 months after the Health Ministry approved the reimbursement of dabigatran for NVAF, and 61% by the end of 2015, versus VKA use. In the multivariate analysis, we found that DOAC initiators were younger and healthier overall than VKA initiators, and this tendency was reinforced over the 2011–2014 period. DOACs were more frequently prescribed by cardiologists in 2012 and after (adjusted OR in 2012: 2.47; 95% CI 2.40 to 2.54). Conclusion Despite recommendations from health authorities, DOACs have been rapidly and massively adopted as initial therapy for NVAF in France. Observational studies should account for the fact that patients selected to initiate DOAC treatment are healthier overall, as failure to do so may bias the risk

  3. Evaluating the potential for pharmacists to prescribe oral anticoagulants for atrial fibrillation

    PubMed Central

    Sandhu, Roopinder K.; Guirguis, Lisa M.; Bungard, Tammy J.; Youngson, Erik; Brehaut, Jamie C.; Healey, Jeff S.; McAlister, Finlay A.

    2017-01-01

    Background: Oral anticoagulant therapy (OAC) to prevent atrial fibrillation (AF)–related strokes remains poorly used. Alternate strategies, such as community pharmacist prescribing of OAC, should be explored. Methods: Approximately 400 pharmacists, half with additional prescribing authority (APA), randomly selected from the Alberta College of Pharmacists, were invited to participate in an online survey over a 6-week period. The survey consisted of demographics, case scenarios assessing appropriateness of OAC (based on the 2014 Canadian Cardiovascular Society AF guidelines) and perceived barriers to prescribing. Regression analysis was performed to determine predictors of knowledge. Results: A total of 35% (139/397) of pharmacists responded to the survey, and 57% of these had APA. Depending on the case scenario, 55% to 92% of pharmacists correctly identified patients eligible for stroke prevention therapy, but only about a half selected the appropriate antithrombotic agent; there was no difference in the knowledge according to APA status. In multivariable analysis, predictors significantly associated with guideline-concordant prescribing were having the pharmacist interact as part of an interprofessional team (p = 0.04) and direct OAC (DOAC) self-efficacy (confidence in ability to extend, adapt, initiate or alter prescriptions; p = 0.02). Barriers to prescribing OAC for APA pharmacists included a lack of AF and DOAC knowledge and preference for consulting the physician first, but these same pharmacists also identified difficulty in contacting the physician as a major barrier. Interpretation and Conclusion: Community pharmacists can identify patients who would benefit from stroke prevention therapy in AF. However, physician collaboration and further training on AF and guidelines for prescribing OAC are needed. PMID:29317937

  4. Reported Prestroke Physical Activity Is Associated with Vascular Endothelial Growth Factor Expression and Good Outcomes after Stroke.

    PubMed

    López-Cancio, Elena; Ricciardi, Ana Clara; Sobrino, Tomás; Cortés, Jordi; de la Ossa, Natalia Pérez; Millán, Mónica; Hernández-Pérez, María; Gomis, Meritxell; Dorado, Laura; Muñoz-Narbona, Lucía; Campos, Francisco; Arenillas, Juan F; Dávalos, Antoni

    2017-02-01

    Physical activity (PhA) prior to stroke has been associated with good outcomes after the ischemic insult, but there is scarce data on the involved molecular mechanisms. We studied consecutive acute ischemic stroke patients admitted to a single tertiary stroke center. Prestroke PhA was evaluated with the International Physical Activity Questionnaire (metabolic equivalent of minutes/week). We studied several circulating angiogenic and neurogenic factors at different time points: vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and brain-derived neurotrophic factor (BDNF) at admission, day 7, and at 3 months. We considered good functional outcome at 3 months (modified Rankin scale  ≤ 2) as primary end point, and final infarct volume as secondary outcome. We studied 83 patients with at least 2 time point serum determinations (mean age 69.6 years, median National Institutes of Health Stroke Scale 17 at admission). Patients more physically active before stroke had a significantly higher increment of serum VEGF on the seventh day when compared to less active patients. This increment was an independent predictor of good functional outcome at 3 months and was associated with smaller infarct volume in multivariate analyses adjusted for relevant covariates. We did not find independent associations of G-CSF or BDNF levels neither with level of prestroke PhA nor with stroke outcomes. Although there are probably more molecular mechanisms by which PhA exerts its beneficial effects in stroke outcomes, our observation regarding the potential role of VEGF is plausible and in line with previous experimental studies. Further research in this field is needed. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  5. Transition of patients from blinded study drug to open-label anticoagulation: the ENGAGE AF-TIMI 48 trial.

    PubMed

    Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Mercuri, Michele; Curt, Valentin; Betcher, Joshua; Grip, Laura; Cange, Abby L; Crompton, Andrea E; Murphy, Sabina A; Deenadayalu, Naveen; Antman, Elliott M

    2014-08-12

    At the end of 2 previous trials, an excess of stroke and bleeding was observed in patients with AF randomized to a new oral anticoagulant (NOAC) who transitioned to a vitamin K antagonist (VKA). The ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial compared once-daily edoxaban to warfarin for stroke prevention in patients with AF. An end-of-trial transition plan was developed to minimize the risks of stroke due to inadequate anticoagulation and bleeding from excessive anticoagulation during this critical period. All patients on the blinded study drug at the trial's conclusion were included in this analysis. In pre-specified analyses, stroke, bleeding, and death that occurred through 30 days after the end-of-trial visit were stratified by randomized treatment allocation and open-label anticoagulant selected post-trial. Of the 13,642 patients taking the blinded study drug at the end of the trial, 9,304 (68.2%) were transitioned to open-label VKA and 4,258 patients (31.2%) to an NOAC. There were 21 strokes evenly distributed across the 3 randomized treatment arms: warfarin 7 (1.90%/year), edoxaban high dose 7 (1.89%/year), edoxaban low dose 7 (1.85%/year). Major bleeding was also similar across the 3 treatment arms: warfarin 11 (2.98%/year), edoxaban high dose 10 (2.69%/year), edoxaban low dose 18 (4.76%/year). In patients transitioned to VKA, 85% of patients had at least 1 INR ≥ 2 by day 14 after the transition and 99% by day 30. The ENGAGE AF-TIMI 48 transition plan protected patients from an excess of thrombotic and bleeding events and should be helpful in clinical practice when patients are transitioned between oral anticoagulants. (Global Study to Assess the Safety and Effectiveness of Edoxaban [DU-176b] vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation [EngageAFTIMI48]; NCT00781391). Copyright © 2014 American College of Cardiology

  6. A promising oral fucoidan-based antithrombotic nanosystem: development, activity and safety

    NASA Astrophysics Data System (ADS)

    da Silva, L. C. R. P.; Todaro, V.; do Carmo, F. A.; Frattani, F. S.; de Sousa, V. P.; Rodrigues, C. R.; Sathler, P. C.; Cabral, L. M.

    2018-04-01

    Fucoidan-loaded nanoparticles emerge as great candidates for oral anticoagulant therapy, due to increases in the bioavailability and circulation time of this natural anticoagulant. Crosslinks between chitosan chains are performed using glutaraldehyde to confer higher gastric pH resistance to nanoparticle matrices. In this work, chitosan-fucoidan nanoparticles, without (NpCF) and with glutaraldehyde crosslink (NpCF 1% and NpCF 2%), were prepared to evaluate their anticoagulant, antithrombotic and hemorrhagic profiles. Nanoparticles were characterized by average diameter (AD), polydispersity index, zeta potential, Fourier transform infrared spectroscopy and fucoidan in vitro release. Anticoagulant and antithrombotic activities were determined by in vitro and in vivo models, respectively. Hemorrhagic profile was in vivo evaluated by tail bleeding assay. Preparations showed nanometric and homogeneous ADs. Zeta potentials of NpCF and NpCF 1% were stable over the gastrointestinal pH range, which was confirmed by low fucoidan release in gastric and enteric media. In pH 7.4, NpCF and NpCF 1% demonstrated fucoidan release of 65.5% and 60.6%, respectively, within the first 24 h. In comparison to fucoidan, NpCF and NpCF 1% showed increased in vitro anticoagulant activity. A significant difference in the oral antithrombotic profile of NpCF 1% was found in comparison to fucoidan. Bleeding profile of NpCF and NpCF 1% showed no differences to the control group, indicating the safety of these systems. Surprisingly, the oral antithrombotic profile of commercially available fucoidan, from Fucus vesiculosus, has not been previously determined, which reveals new possibilities. In this work, significant advances were observed in the anticoagulant and antithrombotic profiles of fucoidan through the preparation of NpCF 1%.

  7. Direct oral anticoagulant use in patients with thrombophilia, antiphospholipid syndrome or venous thrombosis of unusual sites: A narrative review.

    PubMed

    Bertoletti, Laurent; Benhamou, Ygal; Béjot, Yannick; Marechaux, Sylvestre; Cheggour, Saida; Aleil, Boris; Lellouche, Nicolas; Dillinger, Jean-Guillaume; Delluc, Aurélien

    2018-07-01

    Direct oral anticoagulants (DOACs) are indicated in the treatment and prevention of venous thromboembolism (VTE). However, the use of DOACs in unusual VTE, including cerebral venous thrombosis (CVT) and splanchnic venous thrombosis (SVT), and in patients with biological thrombophilia including minor thrombophilia (Factor V Leiden and prothrombin G20210A), major innate thrombophilia (protein C and S deficiency, and antithrombin) and major acquired thrombophilia (antiphospholipid syndrome [APS]), remains controversial due to the paucity of available data. There are some reports of DOACs use in the initial treatment or long-term maintenance of patients with either CVT or SVT, but their efficacy remains unclear. The efficacy of DOACs may be suitable in patients with biological minor or major thrombophilia. The use of DOACs for the long-term maintenance of patients with APS is more contentious. Randomized clinical trials, which are currently underway, should offer definitive insight into the efficacy and safety profiles of DOACs in these patient populations. Copyright © 2018. Published by Elsevier Ltd.

  8. Pre-stroke seizures: A nationwide register-based investigation.

    PubMed

    Zelano, Johan; Larsson, David; Kumlien, Eva; Åsberg, Signild

    2017-07-01

    The relationship between cerebrovascular disease and seizures is clearly illustrated by poststroke epilepsy. Seizures can also be the first manifestation of cerebrovascular disease and case-control studies have demonstrated that seizures carry an increased risk of subsequent stroke. Thus, seizures could serve as a marker for vascular risk that merits intervention, but more data is needed before proper trials can be conducted. The occurrence of pre-stroke seizures has not been assessed on a national scale. We asked what proportion of strokes in middle-aged and elderly patients was preceded by seizures. All patients over 60 years of age with first-ever stroke in 2005-2010 (n=92,596) were identified in the Swedish stroke register (Riksstroke) and cross-sectional data on a history of a first seizure or epilepsy diagnosis in the ten years preceding stroke were collected from national patient registers with mandatory reporting. 1372 patients (1.48%) had a first seizure or epilepsy diagnosis registered less than ten years prior to the index stroke. The mean latency between seizure and stroke was 1474days (SD 1029 days). Seizures or epilepsy preceded 1.48% of strokes in patients >60years of age. Based on recent national incidence figures, 5-20% of incident cases of seizures or epilepsy after 60 years of age could herald stroke, depending on age group. These proportions are of a magnitude that merit further study on how to reduce the risk of stroke in patients with late-onset seizures or epilepsy. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  9. A cost-analysis model for anticoagulant treatment in the hospital setting.

    PubMed

    Mody, Samir H; Huynh, Lynn; Zhuo, Daisy Y; Tran, Kevin N; Lefebvre, Patrick; Bookhart, Brahim

    2014-07-01

    Rivaroxaban is the first oral factor Xa inhibitor approved in the US to reduce the risk of stroke and blood clots among people with non-valvular atrial fibrillation, treat deep vein thrombosis (DVT), treat pulmonary embolism (PE), reduce the risk of recurrence of DVT and PE, and prevent DVT and PE after knee or hip replacement surgery. The objective of this study was to evaluate the costs from a hospital perspective of treating patients with rivaroxaban vs other anticoagulant agents across these five populations. An economic model was developed using treatment regimens from the ROCKET-AF, EINSTEIN-DVT and PE, and RECORD1-3 randomized clinical trials. The distribution of hospital admissions used in the model across the different populations was derived from the 2010 Healthcare Cost and Utilization Project database. The model compared total costs of anticoagulant treatment, monitoring, inpatient stay, and administration for patients receiving rivaroxaban vs other anticoagulant agents. The length of inpatient stay (LOS) was determined from the literature. Across all populations, rivaroxaban was associated with an overall mean cost savings of $1520 per patient. The largest cost savings associated with rivaroxaban was observed in patients with DVT or PE ($6205 and $2742 per patient, respectively). The main driver of the cost savings resulted from the reduction in LOS associated with rivaroxaban, contributing to ∼90% of the total savings. Furthermore, the overall mean anticoagulant treatment cost was lower for rivaroxaban vs the reference groups. The distribution of patients across indications used in the model may not be generalizable to all hospitals, where practice patterns may vary, and average LOS cost may not reflect the actual reimbursements that hospitals received. From a hospital perspective, the use of rivaroxaban may be associated with cost savings when compared to other anticoagulant treatments due to lower drug cost and shorter LOS associated with

  10. Recommendations for the use of new oral anticoagulants (NOACs) after TIA or stroke caused by atrial fibrillation (AF), after a consensus conference among Italian neurologists (the Venice group).

    PubMed

    Toso, Vito

    2014-05-01

    Vascular neurologists of Veneto and Friuli Venezia Giulia, north-east regions of Italy, have sought an agreement on the two following questions: (A) what prophylactic treatment should we recommend to patients with a stroke ascribed to atrial fibrillation (AF), who were not previously on antithrombotic treatment, to prevent further strokes? (B) What should we do in the event of an ischemic or hemorrhagic stroke associated with AF in patients who were already on antithrombotic treatment? There was a unanimous consensus for preferring the new oral anticoagulants (NOACs) in patients not taking any antithrombotics and in cases treated with antithrombotic drugs (coumadin and/or antiplatelets), due to a lower incidence of intracranial bleeding complications and a noninferiority for recurrent stroke or TIA. Even after intracranial bleeding complications, when it is useful or necessary to continue anticoagulant treatment, the group of experts preferred the NOACs, suggesting, however, to be very cautious in cases with widespread leukoaraiosis or microbleeds, practice frequent monitoring of creatinine clearance (CrCl) and avoid using NOACs when CrCl is <30 mL/min.

  11. Clinical Outcome of a Portosplenomesenteric Venous Thrombosis in Necrotizing Acute Pancreatitis with Protein C and S Deficiency Treated by Anticoagulation Therapy Alone.

    PubMed

    Ankouane, Firmin; Kowo, Mathurin; Ngo Nonga, Bernadette; Magny, Eric; Hell Medjo, Edith; Ndjitoyap Ndam, Elie Claude

    2015-01-01

    Cases of splanchnic venous thrombosis have not been described in Cameroon. Their prevalence in acute pancreatitis is variable. With the emergence of acute intra-abdominal infections including typhoid fever and peritoneal tuberculosis in situations of acquired immunodeficiency syndrome, these cases will become frequent. We report the case of a portosplenomesenteric venous thrombosis related to necrotizing acute pancreatitis associated with proteins C and S deficiency, in a 46-year-old Cameroonian man, without particular past medical history. He was admitted for abdominal pain which had been evolving for 3 weeks and accompanied by vomiting. In the absence of hemorrhagic risk factor, the patient received low molecular weight heparin followed by oral warfarin. The abdominal ultrasound check on the 12th day showed a partial recanalization of venous thrombosis. The abdominal contrast-enhanced CT scanner at day 30 on oral anticoagulation therapy showed collateral vessels and small bowel edema. At the same time the upper gastrointestinal endoscopy showed grade II esophageal varices. We have maintained oral anticoagulation therapy. This case highlights that an early effective anticoagulation heparin therapy is needed for a clear benefit in case of suspected PSMVT. It is certain that the sooner the treatment is given, the better outcome will be.

  12. Visual Aid Tool to Improve Decision Making in Anticoagulation for Stroke Prevention.

    PubMed

    Saposnik, Gustavo; Joundi, Raed A

    2016-10-01

    The management of stroke prevention among patients with atrial fibrillation (AF) has changed in the last few years. Despite the benefits of new oral anticoagulants (NOACs), decisions about the optimal agent remain a challenge. We provide a visual aid tool to guide clinicians and patients in the decision process of selecting oral anticoagulants for stroke prevention. We created visual plots representing benefits of warfarin versus NOACs from a meta-analysis comprising 58,541 participants. Visual plots (Cates plots) were created using software available at nntonline.net. The primary outcome was stroke or systemic embolism during the study period. In the chosen meta-analysis, 29,312 participants received a NOAC and 29,229 participants received warfarin. For every 1000 patients with AF, 38 would have a stroke or systemic embolic event in the warfarin group compared to 31 in the NOAC group (RR .81; 95% CI .73-.91). Fifteen patients would develop an intracranial hemorrhage in the warfarin group compared to 7 in the NOAC group (RR .48; 95% CI .39-.59). Conversely, 25 patients would develop gastrointestinal bleeding in the NOAC group compared to 20 in the warfarin group (RR 1.25; 95% CI 1.01-1.55). For every 1000 treated individuals with AF, NOACs would prevent stroke or systemic embolism in 7 additional patients and cerebral hemorrhage in 8 additional patients compared to warfarin. On the other hand, 5 more patients would develop gastrointestinal bleeding with NOACs compared to warfarin. These data are visually shown in Cates plots, facilitating conversations with patients regarding anticoagulation decisions. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  13. Kidney function monitoring and nonvitamin K oral anticoagulant dosage in atrial fibrillation.

    PubMed

    Andreu Cayuelas, Jose Manuel; Caro Martínez, Cesar; Flores Blanco, Pedro Jose; Elvira Ruiz, Gines; Albendin Iglesias, Helena; Cerezo Manchado, Juan Jose; Bailen Lorenzo, Jose Luis; Januzzi, James L; García Alberola, Arcadio; Manzano-Fernández, Sergio

    2018-06-01

    Clinical practice guidelines recommend regular kidney function monitoring in atrial fibrillation patients on nonvitamin K oral anticoagulants (NOAC); however, information regarding compliance with these recommendations in daily life conditions is scarce. We sought to determine the compliance with kidney function monitoring recommendations in nonvalvular atrial fibrillation (NVAF) patients starting NOAC and its implication on the appropriateness of NOAC dosage. This study involves the retrospective analysis of a multicentre registry including consecutive NVAF patients who started NOAC (n = 692). Drug dosage changes and serum creatinine determinations were recorded during 1-year follow-up. European Heart Rhythm Association criteria were used to define the appropriateness of kidney function monitoring as well as adequate NOAC dosage. During the follow-up (334 ± 89 days), the compliance with kidney function monitoring recommendations was 61% (n = 425). After multivariate adjustment, age (OR × year: 0.92 (CI 95%: 0.89-0.95) P < .001), creatinine clearance (OR × mL/min: 1.02 (CI 95%: 1.01-1.03) P < .001) and adequate NOAC dosage at baseline (OR: 1.54 (CI 95%: 1.06-2.23), P = .024) were independent predictors of appropriate kidney function monitoring. Compliance with kidney function monitoring recommendations was independently associated with change to appropriate NOAC dose after 1 year (OR: 2.80 (CI 95%: 1.01-7.80), P = .049). Noncompliance with kidney function monitoring recommendations is common in NVAF patients starting NOAC, especially in elderly patients with kidney dysfunction. Compliance with kidney function monitoring recommendations was associated with adequate NOAC dosage at 1-year follow-up. Further studies are warranted to evaluate the implication of kidney function monitoring on prognosis. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

  14. Anticoagulation beyond direct thrombin and factor Xa inhibitors: indications for targeting the intrinsic pathway?

    PubMed

    van Montfoort, Maurits L; Meijers, Joost C M

    2013-08-01

    Antithrombotic drugs like vitamin K antagonists and heparin have been the gold standard for the treatment and prevention of thromboembolic disease for many years. Unfortunately, there are several disadvantages of these antithrombotic drugs: they are accompanied by serious bleeding problems, it is necessary to monitor the therapeutic window, and there are various interactions with food and other drugs. This has led to the development of new oral anticoagulants, specifically inhibiting either thrombin or factor Xa. In terms of effectiveness, these drugs are comparable to the currently available anticoagulants; however, they are still associated with issues such as bleeding, reversal of the drug and complicated laboratory monitoring. Vitamin K antagonists, heparin, direct thrombin and factor Xa inhibitors have in common that they target key proteins of the haemostatic system. In an attempt to overcome these difficulties we investigated whether the intrinsic coagulation factors (VIII, IX, XI, XII, prekallikrein and high-molecular-weight kininogen) are superior targets for anticoagulation. We analysed epidemiological data concerning thrombosis and bleeding in patients deficient in one of the intrinsic pathway proteins. Furthermore, we discuss several thrombotic models in intrinsic coagulation factor-deficient animals. The combined results suggest that intrinsic coagulation factors could be suitable targets for anticoagulant drugs.

  15. Direct oral anticoagulants for extended thromboprophylaxis in medically ill patients: meta-analysis and risk/benefit assessment.

    PubMed

    Al Yami, Majed S; Kurdi, Sawsan; Abraham, Ivo

    2018-01-01

    Standard-duration (7-10 days) thromboprophylaxis with low molecular weight heparin, low dose unfractionated heparin, or fondaparinux in hospitalized medically ill patients is associated with ~50% reduction in venous thromboembolism (VTE) risk. However, these patients remain at high risk for VTE post-discharge. The direct oral anticoagulants (DOACs) apixaban, rivaroxaban and betrixaban have been evaluated for extended-duration (30-42 days) thromboprophylaxis in this population. We review the efficacy and safety results from the 3 pivotal trials of extended-duration DOAC thromboprophylaxis in medically ill patients. We performed a meta-analysis of these pivotal trials focusing on 6 VTE (efficacy) and three bleeding outcomes (safety). These results were integrated into a quantitative risk/benefit assessment. The trials evaluating extended-duration DOAC thromboprophylaxis in medically ill patients failed to establish clear efficacy and/or safety signals for each agent. Our meta-analysis shows that, as a class, DOACs have selective and partial extended-duration prophylactic activity in preventing VTE events. However, this is associated with a marked increase in the risk of various bleeding events. The risk/benefit analyses fail to show a consistent net clinical benefit of extended-duration DOAC prophylaxis in medically ill patients. At this time, the evidence of safe and effective extended-duration thromboprophylaxis with DOACs in this population is inconclusive.

  16. Cost Effectiveness of Implantable Cardiac Monitor-Guided Intermittent Anticoagulation for Atrial Fibrillation: An Analysis of the REACT.COM Pilot Study.

    PubMed

    Steinhaus, Daniel A; Zimetbaum, Peter J; Passman, Rod S; Leong-Sit, Peter; Reynolds, Matthew R

    2016-08-30

    Anticoagulation guidelines for patients with atrial fibrillation (AF) disregard AF burden. A strategy of targeted anticoagulation with novel oral anticoagulants (NOACs) based on continuous rhythm assessment with an implantable cardiac monitor (ICM) has recently been explored. We evaluated the potential cost-effectiveness of this strategy versus projected outcomes with continuous anticoagulation. We developed a Markov model using data from the Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring (REACT.COM) pilot study (N = 59) and prior NOAC trials to calculate the costs and quality-adjusted life years (QALYs) associated with ICM-guided intermittent anticoagulation for AF versus standard care during a 3-year time horizon. Health state utilities were estimated from the pilot study population using the SF-12. Costs were based on current Medicare reimbursement. Over 14 ± 4 months of follow-up, 18 of 59 patients had 35 AF episodes. The ICM-guided strategy resulted in a 94% reduction in anticoagulant use relative to continuous treatment. There were no strokes, 3 (5.1%) TIAs, 2 major bleeding events (on aspirin) and 3 minor bleeding events with the ICM-guided strategy. The projected total 3-year costs were $12,535 for the ICM-guided strategy versus $13,340 for continuous anticoagulation. Projected QALYs were 2.45 for both groups. Based on a pilot study, a strategy of ICM-guided anticoagulation with NOACs may be cost-saving relative to expected outcomes with continuous anticoagulation, with similar quality-adjusted survival. This strategy could be attractive from a health economic perspective if shown to be safe and effective in a rigorous clinical trial. © 2016 Wiley Periodicals, Inc.

  17. Cost Effectiveness of Implantable Cardiac Monitor-Guided Intermittent Anticoagulation for Atrial Fibrillation: An Analysis of the REACT.COM Pilot Study

    PubMed Central

    Steinhaus, Daniel A; Zimetbaum, Peter J; Passman, Rod S; Leong-Sit, Peter; Reynolds, Matthew R.

    2016-01-01

    Introduction Anticoagulation guidelines for patients with atrial fibrillation (AF) disregard AF burden. A strategy of targeted anticoagulation with novel oral anticoagulants (NOACs) based on continuous rhythm assessment with an implantable cardiac monitor (ICM) has recently been explored. We evaluated the potential cost-effectiveness of this strategy versus projected outcomes with continuous anticoagulation. Methods and Results We developed a Markov model using data from the Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring (REACT.COM) pilot study (N=59) and prior NOAC trials to calculate the costs and quality-adjusted life years (QALYs) associated with ICM-guided intermittent anticoagulation for AF vs. standard care over a 3-year time horizon. Health state utilities were estimated from the pilot study population using the SF-12. Costs were based on current Medicare reimbursement. Over 14±4 months of follow-up 18 of 59 patients had 35 AF episodes. The ICM-guided strategy resulted in a 94% reduction in anticoagulant use relative to continuous treatment. There were no strokes, 3 (5.1%) TIAs, 2 major bleeding events (on aspirin) and 3 minor bleeding events with the ICM-guided strategy. The projected total 3-year costs were $12,535 for the ICM-guided strategy vs. $13,340 for continuous anticoagulation. Projected QALYs were 2.45 for both groups. Conclusion Based on a pilot study, a strategy of ICM-guided anticoagulation with NOACs may be cost-saving relative to expected outcomes with continuous anticoagulation, with similar quality-adjusted survival. This strategy could be attractive from a health economic perspective if shown to be safe and effective in a rigorous clinical trial. PMID:27571718

  18. Comparative risk assessment of the first-generation anticoagulant rodenticide diphacinone to raptors

    USGS Publications Warehouse

    Rattner, Barnett A.; Lazarus, Rebecca S.; Eisenreich, Karen M.; Horak, Katherine E.; Volker, Steven F.; Campton, Christopher M.; Eisemann, John D.; Meteyer, Carol U.; Johnson, John J.

    2012-01-01

    New regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides in the United States, and in some situations this action may be offset by expanded use of first-generation compounds. We have recently conducted several studies with captive adult American kestrels and eastern screech-owls examining the toxicity of diphacinone (DPN) using both acute oral and short-term dietary exposure regimens. Diphacinone evoked overt signs of intoxication and lethality in these raptors at exposure doses that were 20 to 30 times lower than reported for traditionally used wildlife test species (mallard and northern bobwhite). Sublethal exposure of kestrels and owls resulted in prolonged clotting time, reduced hematocrit, and/or gross and histological evidence of hemorrhage at daily doses as low as 0.16 mg DPN/kg body weight. Findings also demonstrated that DPN was far more potent in short-term 7-day dietary studies than in single-day acute oral exposure studies. Incorporating these kestrel and owl data into deterministic and probabilistic risk assessments indicated that the risks associated with DPN exposure for raptors are far greater than predicted in analyses using data from mallards and bobwhite. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

  19. Adjusted indirect comparison of new oral anticoagulants for stroke prevention in atrial fibrillation.

    PubMed

    Testa, L; Agnifili, M; Latini, R A; Mattioli, R; Lanotte, S; De Marco, F; Oreglia, J; Latib, A; Pizzocri, S; Laudisa, M L; Brambilla, N; Bedogni, F

    2012-10-01

    Vit-K antagonists are the therapy of choice to prevent thromboembolic events due to atrial fibrillation since many years. New oral anticoagulants (NOA) showed encouraging results vs. warfarin but there are no data directly comparing different NOA. We performed an adjusted indirect meta-analysis. Randomized controlled trials (RCTs) were searched. Efficacy end points were the cumulative rate of thomboembolic stroke (TES) and systemic embolism (SE). Main safety end point was the rate of hemorrhagic stroke (HS). Three RCTs (50578 patients) were included. Overall, NOA were comparable to warfarin according to the cumulative risk of TES and SE, as well as for TES alone. NOA were associated with a reduced rate of SE [OR 0.64 (0.44, 0.94], P=0.02]. Compared to warfarin, NOA were associated with a significantly reduced risk of HS [OR 0.43 (0.34, 0.55), P<0.001, NNT to avoid a HS 153] and all cause death [OR 0.90 [0.84, 0.96], P=0.03, NNT to save one fatality 43]. Head to head comparison showed that in terms of cumulative rate of TES/SE, as well as of TES, none of the NOA was significantly superior to the others (all Ps>0.05). Rivaroxaban showed superiority in the prevention of SE. Dabigatran 150 mg/twice daily was associated with the largest reduction in the risk of HS vs. warfarin and vs. other NOA. Overall mortality was quite comparable across NOA. Overall superiority of NOA over warfarin is largely influenced by the reduction of HS. Dabigatran 150 mg/twice daily seems to have the best risk/benefit profile.

  20. Laboratory assessment of novel oral anticoagulants: method suitability and variability between coagulation laboratories.

    PubMed

    Helin, Tuukka A; Pakkanen, Anja; Lassila, Riitta; Joutsi-Korhonen, Lotta

    2013-05-01

    Laboratory tests to assess novel oral anticoagulants (NOACs) are under evaluation. Routine monitoring is unnecessary, but under special circumstances bioactivity assessment becomes crucial. We analyzed the effects of NOACs on coagulation tests and the availability of specific assays at different laboratories. Plasma samples spiked with dabigatran (Dabi; 120 and 300 μg/L) or rivaroxaban (Riva; 60, 146, and 305 μg/L) were sent to 115 and 38 European laboratories, respectively. International normalized ratio (INR) and activated partial thromboplastin time (APTT) were analyzed for all samples; thrombin time (TT) was analyzed specifically for Dabi and calibrated anti-activated factor X (anti-Xa) activity for Riva. We compared the results with patient samples. Results of Dabi samples were reported by 73 laboratories (13 INR and 9 APTT reagents) and Riva samples by 22 laboratories (5 INR and 4 APTT reagents). Both NOACs increased INR values; the increase was modest, albeit larger, for Dabi, with higher CV, especially with Quick (vs Owren) methods. Both NOACs dose-dependently prolonged the APTT. Again, the prolongation and CVs were larger for Dabi. The INR and APTT results varied reagent-dependently (P < 0.005), with less prolongation in patient samples. TT results (Dabi) and calibrated anti-Xa results (Riva) were reported by only 11 and 8 laboratories, respectively. The screening tests INR and APTT are suboptimal in assessing NOACs, having high reagent dependence and low sensitivity and specificity. They may provide information, if laboratories recognize their limitations. The variation will likely increase and the sensitivity differ in clinical samples. Specific assays measure NOACs accurately; however, few laboratories applied them. © 2013 American Association for Clinical Chemistry.

  1. Impact of CHA2DS2VASc Score on Candidacy for Anticoagulation in Patients With Atrial Fibrillation: A Multi-payer Analysis.

    PubMed

    Patel, Aarti A; Nelson, Winnie W; Schein, Jeff

    2016-10-01

    whom oral anticoagulation would be recommended. Additional research is needed to determine whether this paradigm shift to greater use of oral anticoagulants improves patient outcomes. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  2. Anticoagulant Medicine: Potential for Drug-Food Interactions

    MedlinePlus

    ... Medications Anticoagulants and Drug-Food Interactions Anticoagulants and Drug-Food Interactions Make an Appointment Ask a Question ... care provider before making the change. Anticoagulants and Medicine There are many medicines that can interact with ...

  3. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of deep vein thrombosis.

    PubMed

    Robertson, Lindsay; Kesteven, Patrick; McCaslin, James E

    2015-06-30

    Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately 1 in 1,000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of novel oral anticoagulants (NOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the treatment of DVT. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the treatment of DVT. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). We searched clinical trials databases for details of ongoing or unpublished studies and the reference lists of relevant articles retrieved by electronic searches for additional citations. We included randomised controlled trials in which people with a DVT confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor for the treatment of DVT. Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third review author (PK). We performed meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent VTE and PE. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes using an odds ratio (OR) with a 95% confidence interval (CI). We included

  4. Strengths and weaknesses of 'real-world' studies involving non-vitamin K antagonist oral anticoagulants.

    PubMed

    Camm, A John; Fox, Keith A A

    2018-01-01

    Randomised controlled trials (RCTs) provide the reference standard for comparing the efficacy of one therapy or intervention with another. However, RCTs have restrictive inclusion and exclusion criteria; thus, they are not fully representative of an unselected real-world population. Real-world evidence (RWE) studies encompass a wide range of research methodologies and data sources and can be broadly categorised as non-interventional studies, patient registries, claims database studies, patient surveys and electronic health record studies. If appropriately designed, RWE studies include a patient population that is far more representative of unselected patient populations than those of RCTs, but they do not provide a robust basis for comparing treatment strategies. RWE studies can have very large sample sizes, can provide information on treatments in patient groups that are usually excluded from RCTs, are generally less expensive and quicker than RCTs, and can assess a broad range of outcomes. Limitations of RWE studies can include low internal validity, lack of quality control surrounding data collection and susceptibility to multiple sources of bias for comparing outcomes. RWE studies can complement the findings from RCTs by providing valuable information on treatment practices and patient characteristics among unselected patients. This information is necessary to guide treatment decisions and for reimbursement and payment decisions. RWE studies have been extensively applied in the postmarketing approval assessment of non-vitamin K antagonist oral anticoagulants since 2010. However, the benefits, costs, limitations and methodological challenges associated with the different types of RWE must be considered carefully when interpreting the findings.

  5. Comparison between videotape and personalized patient education for anticoagulant therapy.

    PubMed

    Stone, S; Holden, A; Knapic, N; Ansell, J

    1989-07-01

    To assess the effectiveness of videotape patient education, 22 patients were randomized to receive either videotape or personalized teaching for oral anticoagulant (warfarin) therapy. Both groups scored significantly higher on a questionnaire designed to assess knowledge gained after instruction, with no significant difference between the two groups. Videotape instruction required substantially less nursing time. A second questionnaire assessed patient satisfaction with respect to both methods, which were rated equally effective and worthwhile. Videotape teaching is an effective and well-accepted alternative form of patient education requiring significantly less personnel time.

  6. Anticoagulation management associated with extracorporeal circulation.

    PubMed

    Sniecinski, Roman M; Levy, Jerrold H

    2015-06-01

    The use of extracorporeal circulation requires anticoagulation to maintain blood fluidity throughout the circuit, and to prevent thrombotic complications. Additionally, adequate suppression of hemostatic activation avoids the unnecessary consumption of coagulation factors caused by the contact of blood with foreign surfaces. Cardiopulmonary bypass represents the greatest challenge in this regard, necessitating profound levels of anticoagulation during its conduct, but also quick, efficient reversal of this state once the surgical procedure is completed. Although extracorporeal circulation has been around for more than half a century, many questions remain regarding how to best achieve anticoagulation for it. Although unfractionated heparin is the predominant agent used for cardiopulmonary bypass, the amount required and how best to monitor its effects are still unresolved. This review discusses the use of heparin, novel anticoagulants, and the monitoring of anticoagulation during the conduct of cardiopulmonary bypass. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Aspirin in stroke prevention in nonvalvular atrial fibrillation and stable vascular disease: an era of new anticoagulants.

    PubMed

    Turagam, Mohit K; Velagapudi, Poonam; Leal, Miguel A; Kocheril, Abraham G

    2012-04-01

    Atrial fibrillation (AF) is a major cause of ischemic stroke, especially in the elderly. There are currently enough data to support the notion that anticoagulation with warfarin or dabigatran is far superior to aspirin in the prevention of stroke or systemic embolism in AF. Aspirin is the preferred modality in patients who are either not candidates for anticoagulation, such as patients with increased risk for bleeding, low-risk patients based on the CHADS2 score or patients who have difficulty in maintaining a therapeutic international normalized ratio. There is no dispute on the recommendations regarding stroke prevention in high-risk patients (CHADS2 risk score of 2 and beyond) with AF. However, there is some controversy regarding the appropriate strategy (anticoagulation vs aspirin) for stroke prevention in low-risk patients (CHA2DS2-VASc score of 0-1). Novel oral anticoagulant drugs (direct thrombin inhibitors and Factor Xa inhibitors) might further diminish the role of aspirin for stroke prevention in AF due to their superior efficacy, lack of need for monitoring of therapeutic effects and lower bleeding risk when compared with warfarin, especially in patients with stable vascular disease.

  8. Anticoagulation and high dose liver radiation. A preliminary report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lightdale, C.J.; Wasser, J.; Coleman, M.

    Two groups of patients were observed for evidence of acute radiation hepatitis during high dose radiation to the liver. The first group of 18 patients with metastatic liver disease received an average of 4,050 rad to the whole liver. Half received anticoagulation with warfarin. One patient on anticoagulation developed evidence of acute radiation hepatitis while 2 patients did so without anticoagulation. Eleven patients with Hodgkin's disease received 4,000 rad to the left lobe of the liver during extended field radiation. Four of these 11 patients were anticoagulated to therapeutic range. Only one of the fully anticoagulated patients showed changes onmore » liver scan consistent with radiation hepatitis whereas three did so without anticoagulation. No serious sequelae from anticoagulation occurred in either group. These preliminary data suggest that anticoagulation may be safely administered with high dose hepatic radiation and that further trials with anticoagulation are warranted.« less

  9. Direct oral anticoagulants: analysis of worldwide use and popularity using Google Trends

    PubMed Central

    Mattiuzzi, Camilla; Cervellin, Gianfranco; Favaloro, Emmanuel J.

    2017-01-01

    Background Four direct oral anticoagulants (DOACs) have been approved for clinical use by many medicines regulatory agencies around the world. Due to increasing use of these drugs in routine practice, we planned an original study to investigate their worldwide diffusion using a popular Web-search engine. Methods Two electronic searches were performed using Google Trends, the former using the keywords “warfarin” AND “heparin” AND “fondaparinux”, and the latter using the keywords “warfarin” AND “dabigatran” AND “rivaroxaban” AND “apixaban” AND “edoxaban”, both using the search criterion “prescription drug”. No language restriction was applied, and the searches were carried out from the first date available in Google Trends (January 1st, 2004) to present time (June 1st, 2017). Results The median Google Trends score of warfarin (i.e., 86) was consistently higher than that of heparin (54; P<0.001), fondaparinux (6; P<0.001), dabigatran (11; P<0.001), rivaroxaban (5; P<0.001), apixaban (1; P<0.001) and edoxaban (1; P<0.001). Specific analysis of the trends shows that the score of warfarin exhibits a highly significant decrease over time (r=−0.40; P<0.001), whilst that of heparin has remained virtually unchanged (r=0.12; P=0.127), and that of fondaparinux has marginally increased (r=0.16; P=0.038). As regards DOACs, the scores of these drugs significantly increased during the search period (dabigatran, r=0.79; rivaroxaban, r=0.99; apixaban, r=0.98; edoxaban, r=0.78; all P<0.001). When the analysis was limited to the past five years, the dabigatran score significantly decreased (r=−0.57; P<0.001), whereas that of the other DOACs exhibited an even sharper increase. Most Google searches for DOACs were performed in North America, central-eastern Europe and Australia. Conclusions The results of our analysis suggest that the popularity of DOACs is constantly increasing around the world, whereas that of warfarin has exhibited a constant

  10. Direct oral anticoagulants: analysis of worldwide use and popularity using Google Trends.

    PubMed

    Lippi, Giuseppe; Mattiuzzi, Camilla; Cervellin, Gianfranco; Favaloro, Emmanuel J

    2017-08-01

    Four direct oral anticoagulants (DOACs) have been approved for clinical use by many medicines regulatory agencies around the world. Due to increasing use of these drugs in routine practice, we planned an original study to investigate their worldwide diffusion using a popular Web-search engine. Two electronic searches were performed using Google Trends, the former using the keywords "warfarin" AND "heparin" AND "fondaparinux", and the latter using the keywords "warfarin" AND "dabigatran" AND "rivaroxaban" AND "apixaban" AND "edoxaban", both using the search criterion "prescription drug". No language restriction was applied, and the searches were carried out from the first date available in Google Trends (January 1 st , 2004) to present time (June 1 st , 2017). The median Google Trends score of warfarin (i.e., 86) was consistently higher than that of heparin (54; P<0.001), fondaparinux (6; P<0.001), dabigatran (11; P<0.001), rivaroxaban (5; P<0.001), apixaban (1; P<0.001) and edoxaban (1; P<0.001). Specific analysis of the trends shows that the score of warfarin exhibits a highly significant decrease over time (r=-0.40; P<0.001), whilst that of heparin has remained virtually unchanged (r=0.12; P=0.127), and that of fondaparinux has marginally increased (r=0.16; P=0.038). As regards DOACs, the scores of these drugs significantly increased during the search period (dabigatran, r=0.79; rivaroxaban, r=0.99; apixaban, r=0.98; edoxaban, r=0.78; all P<0.001). When the analysis was limited to the past five years, the dabigatran score significantly decreased (r=-0.57; P<0.001), whereas that of the other DOACs exhibited an even sharper increase. Most Google searches for DOACs were performed in North America, central-eastern Europe and Australia. The results of our analysis suggest that the popularity of DOACs is constantly increasing around the world, whereas that of warfarin has exhibited a constant and inexorable decline.

  11. Impact of a pharmacist-led warfarin self-management program on quality of life and anticoagulation control: a randomized trial.

    PubMed

    Verret, Lucie; Couturier, Justine; Rozon, Andréanne; Saudrais-Janecek, Sarah; St-Onge, Amélie; Nguyen, Angela; Basmadjian, Arsène; Tremblay, Simon; Brouillette, Denis; de Denus, Simon

    2012-10-01

    To evaluate the impact of a pharmacist-led warfarin patient self-management program on quality of life and anticoagulation control compared with management in a physician-led specialized anticoagulation clinic. Prospective, randomized, controlled, open-label trial. Tertiary care academic medical center. A total of 114 patients aged 18-75 years who were followed at a specialized anticoagulation clinic, had received warfarin for at least 6 months, and were expected to continue warfarin for a minimum of 4 months. All patients attended an educational session on anticoagulation provided by a pharmacist. Patients randomized to the self-management group (58 patients) also received practical training to use the CoaguChek XS device and a self-management dosing algorithm. Patients in the control group (56 patients) continued to undergo standard management at the anticoagulation clinic. Patients completed a validated quality-of-life questionnaire and the validated Oral Anticoagulation Knowledge test at the beginning and end of the study. The quality of anticoagulation control was evaluated by using the time spent in therapeutic range. After 4 months of follow-up, a significant improvement in the self-management group was observed compared with the control group in four of the five quality-of-life topics (p<0.05). Improvements in knowledge were observed in both groups after the training session and persisted after 4 months (p<0.05 for all). The time spent in the therapeutic range (80.0% in the self-management group vs 75% in the control group, p=0.79) and in the extended therapeutic range ([target international normalized ratio ± 0.3] 93.2% in the self-management group vs 91.1% in the control group, p=0.30) were similar between groups. A self-management warfarin program led by pharmacists resulted in significant improvement in the quality of life of patients receiving warfarin therapy as well as a reduction in the time required for anticoagulation monitoring, while

  12. The Patterns of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Use in Patients with Atrial Fibrillation in Seven Balkan Countries: a Report from the BALKAN-AF Survey.

    PubMed

    Potpara, Tatjana S; Trendafilova, Elina; Dan, Gheorghe-Andrei; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Gjini, Viktor; Pojskic, Belma; Popescu, Mircea Ioakim; Georgescu, Catalina Arsenescu; Dimitrova, Elena S; Kamenova, Delyana; Ekmeciu, Uliks; Mrsic, Denis; Nenezic, Ana; Brusich, Sandro; Milanov, Srdjan; Zeljkovic, Ivan; Lip, Gregory Y H

    2017-08-01

    Data on management of atrial fibrillation (AF) in the Balkan Region are scarce. To capture the patterns in AF management in contemporary clinical practice in the Balkan countries a prospective survey was conducted between December 2014 and February 2015, and we report results pertinent to the use of non-vitamin K antagonist oral anticoagulants (NOACs). A 14-week prospective, multicenter survey of consecutive AF patients seen by cardiologists or internal medicine specialists was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania, and Serbia (a total of about 50 million inhabitants). Of 2712 enrolled patients, 2663 (98.2%) had complete data relevant to oral anticoagulant (OAC) use (mean age 69.1 ± 10.9 years, female 44.6%). Overall, OAC was used in 1960 patients (73.6%) of whom 338 (17.2%) received NOACs. Malignancy [odds ratio (OR), 95% confidence interval (CI) 2.06, 1.20-3.56], rhythm control (OR 1.64, 1.25-2.16), and treatment by cardiologists were independent predictors of NOAC use (OR 2.32, 1.51-3.54) [all p < 0.01)], whilst heart failure and valvular disease were negatively associated with NOAC use (both p < 0.01). Individual stroke and bleeding risk were not significantly associated with NOAC use on multivariate analysis. NOACs are increasingly used in AF patients in the Balkan Region, but NOAC use is predominantly guided by factors other than evidence-based decision-making (e.g., drug availability on the market or reimbursement policy). Efforts are needed to establish an evidence-based approach to OAC selection and to facilitate the optimal use of OAC, thus improving the outcomes in AF patients in this large region.

  13. Plasma clot formation and clot lysis to compare effects of different anticoagulation treatments on hemostasis in patients with atrial fibrillation.

    PubMed

    Königsbrügge, Oliver; Weigel, Günter; Quehenberger, Peter; Pabinger, Ingrid; Ay, Cihan

    2018-02-07

    The effect of direct oral anticoagulants (DOACs) on turbidimetric measurements of plasma clot formation and susceptibility to fibrinolysis may facilitate a comparison between different classes of anticoagulants in plasma samples. We obtained 424 citrate plasma samples from 226 atrial fibrillation patients on anticoagulation and 24 samples without anticoagulation serving as controls. As comparators, we measured the international normalized ratio (INR) for phenprocoumon samples (N = 166), anti-Xa for low molecular weight heparin (LMWH) samples (N = 42), and DOAC levels with mass spectrometry (dabigatran N = 40, rivaroxaban N = 110, apixaban N = 42). Plasma clot formation and lysis were recorded continuously on a photometer after addition of an activation mix (tissue factor 2 pmol/l and tissue plasminogen activator 333 ng/ml). We used linear regression and ANCOVA for correlation analysis. Clot formation lag phase was prolonged in the presence of anticoagulants in a concentration-dependent manner for DOACs (dabigatran Spearman r = 0.74; rivaroxaban r = 0.78; apixaban r = 0.72, all p < 0.0001), INR dependent for phenprocoumon (r = 0.59, p < 0.0001), anti-Xa level dependent in LMWH samples (r = 0.90, p < 0.0001). Maximum rate of clot formation and peak clot turbidity were reduced in the presence of anticoagulants, but correlated only moderately with the comparator measures of anticoagulation. The clot lysis time was inversely correlated with DOAC concentrations in the presence of recombinant thrombomodulin. A direct ex vivo comparison between the effects of different classes of anticoagulants is possible with turbidimetric measurement of plasma clot formation and lysis. Anticoagulation inhibited clot formation in a plasma concentration manner for DOACs, INR dependent for phenprocoumon, and anti-Xa dependent for LMWH. Susceptibility to fibrinolysis increased with increasing DOAC concentrations.

  14. Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.

    PubMed

    Sterne, Jonathan Ac; Bodalia, Pritesh N; Bryden, Peter A; Davies, Philippa A; López-López, Jose A; Okoli, George N; Thom, Howard Hz; Caldwell, Deborah M; Dias, Sofia; Eaton, Diane; Higgins, Julian Pt; Hollingworth, Will; Salisbury, Chris; Savović, Jelena; Sofat, Reecha; Stephens-Boal, Annya; Welton, Nicky J; Hingorani, Aroon D

    2017-03-01

    Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs. Novel oral anticoagulants (NOACs) have more rapid onset and offset of action than warfarin, and more predictable dosing requirements. To determine the best oral anticoagulant/s for prevention of stroke in AF and for primary prevention, treatment and secondary prevention of VTE. Four systematic reviews, network meta-analyses (NMAs) and cost-effectiveness analyses (CEAs) of randomised controlled trials. Hospital (VTE primary prevention and acute treatment) and primary care/anticoagulation clinics (AF and VTE secondary prevention). Patients eligible for anticoagulation with warfarin (stroke prevention in AF, acute treatment or secondary prevention of VTE) or LMWH (primary prevention of VTE). NOACs, warfarin and LMWH, together with other interventions (antiplatelet therapy, placebo) evaluated in the evidence network. Efficacy  Stroke, symptomatic VTE, symptomatic deep-vein thrombosis and symptomatic pulmonary embolism. Safety  Major bleeding, clinically relevant bleeding and intracranial haemorrhage. We also considered myocardial infarction and all-cause mortality and evaluated cost-effectiveness. MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library, reference lists of published NMAs and trial registries. We searched MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. The stroke prevention in AF review search was run on the 12 March 2014 and updated on

  15. Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF.

    PubMed

    Charidimou, Andreas; Karayiannis, Christopher; Song, Tae-Jin; Orken, Dilek Necioglu; Thijs, Vincent; Lemmens, Robin; Kim, Jinkwon; Goh, Su Mei; Phan, Thanh G; Soufan, Cathy; Chandra, Ronil V; Slater, Lee-Anne; Haji, Shamir; Mok, Vincent; Horstmann, Solveig; Leung, Kam Tat; Kawamura, Yuichiro; Sato, Nobuyuki; Hasebe, Naoyuki; Saito, Tsukasa; Wong, Lawrence K S; Soo, Yannie; Veltkamp, Roland; Flemming, Kelly D; Imaizumi, Toshio; Srikanth, Velandai; Heo, Ji Hoe

    2017-12-05

    To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking oral anticoagulants. This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models. We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval [CI] 1.19-6.01, p = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66, p = 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04-0.55) among CMB-negative patients to 0.81% (95% CI 0.17-1.45) in CMB-positive patients ( p = 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs ( p = 0.001). There was no association between CMBs and recurrent ischemic stroke. The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies. © 2017 American Academy of Neurology.

  16. Vena cava filter retrieval in therapeutically anticoagulated patients.

    PubMed

    Schmelzer, Thomas M; Christmas, A Britton; Taylor, Dennis A; Heniford, B Todd; Sing, Ronald F

    2008-12-01

    Vena cava filters (VCFs) are indicated in patients with active venous thromboembolism and are a contraindication to therapeutic anticoagulation. When patients can be anticoagulated, VCFs can be removed; however, patients often have anticoagulation discontinued during the retrieval procedure, leaving them at risk for pulmonary embolism (PE). The authors evaluated their experience with retrieving VCFs in therapeutically anticoagulated patients. Data from a prospectively collected database of patients with VCFs placed between January 2005 and September 2007 were reviewed. The retrievals in therapeutically anticoagulated patients (international normalized ratio, 2.0-3.4) were performed using a strict protocol, including preretrieval and postretrieval cavograms. All retrievals were performed in the operating room, and patients were discharged home the same day and examined within 7 to 14 days. Descriptive statistics including means and counts were calculated. One hundred thirteen VCF removals occurred during the study period; 62 were attempted on anticoagulated patients (42 male and 20 female patients; mean age, 36.5 years). Thirty-five patients (56%) had VCFs placed for prophylaxis, 22 (35%) had deep venous thromboses or PEs but had contraindications to anticoagulation, and 5 (8%) were on anticoagulation, which was discontinued perioperatively for major surgical operations. The mean time the filters were in place was 153.7 days (range, 22-684 days). No extravasation was seen on postretrieval cavography. Eight of 62 removal attempts in anticoagulated patients were unsuccessful. One patient had a postoperative pneumothorax that was successfully managed without intervention. There were no operative bleeding complications, and no hematomas or contusions were seen at follow-up. The retrieval of VCFs in therapeutically anticoagulated patients can be performed without complication. Given the perioperative risk for PE, anticoagulation should not be discontinued for VCF

  17. Oral anticoagulant re-initiation following intracerebral hemorrhage in non-valvular atrial fibrillation: Global survey of the practices of neurologists, neurosurgeons and thrombosis experts.

    PubMed

    Xu, Yan; Shoamanesh, Ashkan; Schulman, Sam; Dowlatshahi, Dar; Al-Shahi Salman, Rustam; Moldovan, Ioana Doina; Wells, Philip Stephen; AlKherayf, Fahad

    2018-01-01

    While oral anticoagulants (OACs) are highly effective for ischemic stroke prevention in atrial fibrillation, intracerebral hemorrhage (ICH) remains the most feared complication of OAC. Clinical controversy remains regarding OAC resumption and its timing for ICH survivors with atrial fibrillation because the balance between risks and benefits has not been investigated in randomized trials. To survey the practice of stroke neurologists, thrombosis experts and neurosurgeons on OAC re-initiation following OAC-associated ICH. An online survey was distributed to members of the International Society for Thrombosis and Haemostasis, Canadian Stroke Consortium, NAVIGATE-ESUS trial investigators (Clinicatrials.gov identifier NCT02313909) and American Association of Neurological Surgeons. Demographic factors and 11 clinical scenarios were included. Two hundred twenty-eight participants from 38 countries completed the survey. Majority of participants were affiliated with academic centers, and >20% managed more than 15 OAC-associated ICH patients/year. Proportion of respondents suggesting OAC anticoagulant resumption varied from 30% (for cerebral amyloid angiopathy) to 98% (for traumatic ICH). Within this group, there was wide distribution in response for timing of resumption: 21.4% preferred to re-start OACs after 1-3 weeks of incident ICH, while 25.3% opted to start after 1-3 months. Neurosurgery respondents preferred earlier OAC resumption compared to stroke neurologists or thrombosis experts in 5 scenarios (p<0.05 by Kendall's tau). Wide variations in current practice exist among management of OAC-associated ICH, with decisions influenced by patient- and provider-related factors. As these variations likely reflect the lack of high quality evidence, randomized trials are direly needed in this population.

  18. Ezetimibe enhances and stabilizes anticoagulant effect of warfarin.

    PubMed

    Hashikata, Takehiro; Yamaoka-Tojo, Minako; Kakizaki, Ryota; Nemoto, Teruyoshi; Fujiyoshi, Kazuhiro; Namba, Sayaka; Kitasato, Lisa; Hashimoto, Takuya; Ishii, Shunsuke; Kameda, Ryo; Shimohama, Takao; Tojo, Taiki; Ako, Junya

    2017-01-01

    Ezetimibe reduces plasma levels of low-density lipoprotein cholesterol by inhibiting Niemann-Pick C1-like protein 1 (NPC1L1). A recent study demonstrated that NPC1L1 plays an important role in absorption of fat-soluble vitamins including vitamin K. We evaluated whether the add-on treatment of ezetimibe affects anticoagulation in patients taking warfarin. Between October 2007 and March 2015, the administration of ezetimibe was started to a total of 101 outpatients who were already on oral anticoagulation with warfarin. We retrospectively analyzed blood lipid levels, prothrombin time international normalized ratio (PT-INR) and time in therapeutic INR range (TTR). Seventy-one patients (70 %) showed increase in PT-INR after ezetimibe treatment (1.96 ± 0.45 to 2.20 ± 0.61, p < 0.001). It was necessary to reduce the warfarin dose in 9 of 101 patients for clinical indication. There was a significant positive correlation between change in PT-INR and statin usage at baseline (p = 0.03). The mean value of changes in PT-INR of patients with taking statin was significantly larger than that of patients without taking statin (0.34 ± 0.54 vs. 0.06 ± 0.36, p = 0.03). There was an increase in the TTR (52 ± 26 to 61 ± 23 %, p < 0.0001) and a decrease in the frequency to change the dose of warfarin after the ezetimibe treatment [45 times of 735 examination days (6 %) to 20 times of 695 examination days (3 %), p = 0.02]. Our data suggest possible drug interaction between warfarin and ezetimibe. Ezetimibe may increase and stabilize the anticoagulant effect of warfarin, especially in patients taking statins.

  19. [Anticoagulation and peripartum management].

    PubMed

    Philippe, A; Ruivard, M; Auclair, C; Accoceberry, M; Bonnin, M; Pouly, J-L; Lémery, D; Philippe, P; Gallot, D

    2015-03-01

    To compare peripartum management of anticoagulated patients concerning locoregional analgesia, post-partum hemorrhage and thrombotic events according to planified interruption or not of antithrombotic therapy. We conducted a single tertiary care center retrospective study of all deliveries associated with antithrombotic therapy from January 2005 to September 2011. We identified 120 cases with prophylactic (71%) or curative (29%) anticoagulation. Two thrombotic events occurred. In case of curative therapy, the use of locoregional analgesia was lower (P<0.0001) and post-partum hemorrhage occurred more frequently (P=0.07) compared to prophylactic therapy. According to planified interruption or not of antithrombotic therapy, we observed a more prolonged duration of therapeutic interruption before delivery (55.6h±63.3 vs 26.4 h±11.6, P<0.0001), higher use of locoregional analgesia (83% vs 71%, P=0.02) but no difference concerning cesarean rate (35% vs 39%, P=0.8) or post-partum hemorrhage (13% vs 14%, P=0.9). In case of curative anticoagulation, plannified interruption favours the use of perimedullar analgesia after 24hour delay. In case of preventive anticoagulation, plannified interruption appears unnecessary as the 12hour delay is easier to reach. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  20. [Clinical characteristics of patients with atrial fibrillation treated with direct oral anticoagulants attended in primary care setting. The SILVER-AP study].

    PubMed

    de la Figuera, Mariano; Cinza, Sergio; Marín, Nuria; Egocheaga, Isabel; Prieto, Miguel Angel

    To analyse the clinical characteristics and management of patients with non-valvular atrial fibrillation (NVAF) treated with direct oral anticoagulants (DOAC). Observational, cross-sectional and multicentre study. Autonomous Communities in which the general practitioner can prescribe DOAC (n=9). The study included a total of 790 patients on chronic treatment with anticoagulants, and on whom therapy was changed, as well as being currently on treatment with DOAC for at least for 3 months. A record was made of the sociodemographic and clinical management date. Mean age was 78.6±8.4 years, and 50.5% of patients were men. Mean CHADS 2 score was 2.6±1.2, mean CHA 2 DS 2 -VASc score was 4.3±1.6, and the mean HAS-BLED score was 2.3±1.0. Mean duration of treatment with DOAC was 15.8±12.5 months. Rivaroxaban was the DOAC most frequently prescribed (57.8%), followed by dabigatran (23.7%), and apixaban (18.5%). Of the patients receiving rivaroxaban, 70.2% were taking the dose of 20mg/daily. Of the patients receiving dabigatran, 41.7% were taking the dose of 150mg twice daily, and in the case of apixaban, 56.2% were taking the dose of 5mg twice daily. Satisfaction (ACTS Burdens scale 52.0±7.2 and ACTS Benefits scale 12.1±2.2), and therapeutic adherence (97.8% of patients took their medication regularly) with DOAC were high. Patients treated with DOAC in Spain have a high thromboembolic risk. A significant proportion of patients receive a lower dose of DOAC than that recommended according to their clinical profile. Satisfaction and medication adherence are high. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  1. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of pulmonary embolism.

    PubMed

    Robertson, Lindsay; Kesteven, Patrick; McCaslin, James E

    2015-12-04

    Pulmonary embolism is a potentially life-threatening condition in which a clot can travel from the deep veins, most commonly in the leg, up to the lungs. Previously, a pulmonary embolism was treated with the anticoagulants heparin and vitamin K antagonists. Recently, however, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the long-term treatment (minimum duration of three months) of pulmonary embolism. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the long-term treatment of pulmonary embolism. The Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). Clinical trials databases were also searched for details of ongoing or unpublished studies. We searched the reference lists of relevant articles retrieved by electronic searches for additional citations. We included randomised controlled trials in which patients with a pulmonary embolism confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor for the long-term (minimum duration three months) treatment of pulmonary embolism. Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third author (PK). We used meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent venous thromboembolism and pulmonary embolism. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes

  2. A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System

    PubMed Central

    2012-01-01

    Introduction The Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens. Methods We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 ± 11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis. Results Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P < 0.001) but remained within a safe range. We observed no major adverse events. Conclusions Regional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with

  3. Secondary poisoning of owls by anticoagulant rodenticides

    USGS Publications Warehouse

    Mendenhall, Vivian M.; Pank, L.F.

    1980-01-01

    Anticoagulants-compounds that prevent clotting of the blood-are extensively used for control of small mammal pests. The potential secondary hazards of 6 anticoagulant rodenticides to birds of prey were examined in this study. Whole rats or mice were killed with each anticoagulant and were fed to 1-3 species of owls. Owls died of hemorrhaging after feeding on rats killed with bromadiolone, brodifacoum, or diphacinone; sublethal hemorrhaging occurred in owls fed rats killed with difenacoum. These results demonstrate potential secondary hazards of 4 anticoagulants to avian predators. No abnormalities were observed in owls fed rats killed with fumarin and chlorophacinone

  4. Practical management of anticoagulation in patients with atrial fibrillation.

    PubMed

    Kovacs, Richard J; Flaker, Greg C; Saxonhouse, Sherry J; Doherty, John U; Birtcher, Kim K; Cuker, Adam; Davidson, Bruce L; Giugliano, Robert P; Granger, Christopher B; Jaffer, Amir K; Mehta, Bella H; Nutescu, Edith; Williams, Kim A

    2015-04-07

    Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, management of major and minor bleeding, and treatment of special populations. The attendees continued to work toward consensus on these topics, and present the key findings of this roundtable in a state-of- the-art review focusing on the practical aspects of anticoagulation care for the patient with atrial fibrillation. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Strengths and weaknesses of ‘real-world’ studies involving non-vitamin K antagonist oral anticoagulants

    PubMed Central

    Camm, A John; Fox, Keith A A

    2018-01-01

    Randomised controlled trials (RCTs) provide the reference standard for comparing the efficacy of one therapy or intervention with another. However, RCTs have restrictive inclusion and exclusion criteria; thus, they are not fully representative of an unselected real-world population. Real-world evidence (RWE) studies encompass a wide range of research methodologies and data sources and can be broadly categorised as non-interventional studies, patient registries, claims database studies, patient surveys and electronic health record studies. If appropriately designed, RWE studies include a patient population that is far more representative of unselected patient populations than those of RCTs, but they do not provide a robust basis for comparing treatment strategies. RWE studies can have very large sample sizes, can provide information on treatments in patient groups that are usually excluded from RCTs, are generally less expensive and quicker than RCTs, and can assess a broad range of outcomes. Limitations of RWE studies can include low internal validity, lack of quality control surrounding data collection and susceptibility to multiple sources of bias for comparing outcomes. RWE studies can complement the findings from RCTs by providing valuable information on treatment practices and patient characteristics among unselected patients. This information is necessary to guide treatment decisions and for reimbursement and payment decisions. RWE studies have been extensively applied in the postmarketing approval assessment of non-vitamin K antagonist oral anticoagulants since 2010. However, the benefits, costs, limitations and methodological challenges associated with the different types of RWE must be considered carefully when interpreting the findings. PMID:29713485

  6. [Anticoagulation in the aged patient with atrial fibrillation: What are prescribing cardiologists, geriatricians and general practitioners?].

    PubMed

    Fuchs, P; Vogel, T; Lang, P-O

    2015-08-01

    To assess prescribing of anticoagulants in atrial fibrillation (AF) in the elderly, both a quantitative point of view (rate of anticoagulation) and qualitative (type of anticoagulation). Determinants of prescribing and non-prescribing were also analysed. Prospective survey of practice, based on one clinical case and questionnaire conducted in 60 practitioners (20 cardiologists [C], 20 geriatricians [G] and 20 general practitioners [GP]). In reading the clinical case, 88.3% of physicians would have initiated a treatment; three types of treatments would have been chosen: AVK (68.3%), ODA (20.0%) and platelet antiaggregant (11.7%). Criteria taken into account to initiate anticoagulation varied according to the specialty. Cardiologists considered more the age criteria (C: 95.0%, G: 75.0%, MG: 60.0%; P<0.05), diabetes (C: 90.0%, G: 60.0%, MG: 55.0%; P<0.05), hypertension (C: 85.0%, G: 55.0%, MG: 60.0%; P<0.05) and female gender (C: 80.0%, G: 35.0%, MG: 25.0%; P<0.05). The quality of renal function was however a more secondary criteria (C: 15.0%, G: 5.0%, MG: 0.0%; P<0.05). General practitioners considered most frequently the presence of underlying heart disease (C: 35.0%, G: 5.0%, MG: 45.0%; P<0.05) as well as usual cardiovascular risk factors (overweight, dyslipidaemia; P<0.05). Risk of bleeding, however, was observed by 76.7% of physicians in the clinical situation presented (C: 70.0%, G: 75.0%, MG: 85.0%; P<0.05). This survey confirms that the FA remains under anticoagulated in the elderly and the barriers to the prescription of oral anticoagulation are often without rational basis. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  7. The mythology of anticoagulation therapy interruption for dental surgery.

    PubMed

    Wahl, Michael J

    2018-01-01

    Continuous anticoagulation therapy is used to prevent heart attacks, strokes, and other embolic complications. When patients receiving anticoagulation therapy undergo dental surgery, a decision must be made about whether to continue anticoagulation therapy and risk bleeding complications or briefly interrupt anticoagulation therapy and increase the risk of developing embolic complications. Results from decades of studies of thousands of dental patients receiving anticoagulation therapy reveal that bleeding complications requiring more than local measures for hemostasis have been rare and never fatal. However, embolic complications (some of which were fatal and others possibly permanently debilitating) sometimes have occurred in patients whose anticoagulation therapy was interrupted for dental procedures. Although there is now virtually universal consensus among national medical and dental groups and other experts that anticoagulation therapy should not be interrupted for most dental surgery, there are still some arguments made supporting anticoagulation therapy interruption. An analysis of these arguments shows them to be based on a collection of myths and half-truths rather than on logical scientific conclusions. The time has come to stop anticoagulation therapy interruption for dental procedures. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

  8. Identification of potent orally active factor Xa inhibitors based on conjugation strategy and application of predictable fragment recommender system.

    PubMed

    Ishihara, Tsukasa; Koga, Yuji; Iwatsuki, Yoshiyuki; Hirayama, Fukushi

    2015-01-15

    Anticoagulant agents have emerged as a promising class of therapeutic drugs for the treatment and prevention of arterial and venous thrombosis. We investigated a series of novel orally active factor Xa inhibitors designed using our previously reported conjugation strategy to boost oral anticoagulant effect. Structural optimization of anthranilamide derivative 3 as a lead compound with installation of phenolic hydroxyl group and extensive exploration of the P1 binding element led to the identification of 5-chloro-N-(5-chloro-2-pyridyl)-3-hydroxy-2-{[4-(4-methyl-1,4-diazepan-1-yl)benzoyl]amino}benzamide (33, AS1468240) as a potent factor Xa inhibitor with significant oral anticoagulant activity. We also reported a newly developed Free-Wilson-like fragment recommender system based on the integration of R-group decomposition with collaborative filtering for the structural optimization process. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Overview of a pharmacist anticoagulation certificate program.

    PubMed

    Kirk, Julienne K; Edwards, Rebecca; Brewer, Andrew; Miller, Cathey; Bray, Bryan; Groce, James B

    2017-07-01

    To describe the design of an ongoing anticoagulation certificate program and annual renewal update for pharmacists. Components of the anticoagulation certificate program include home study, pre- and posttest, live sessions, case discussions with evaluation and presentation, an implementation plan, and survey information (program evaluation and use in practice). Clinical reasoning skills were assessed through case work-up and evaluation prior to live presentation. An annual renewal program requires pharmacists to complete home study and case evaluations. A total of 361 pharmacists completed the anticoagulation certificate program between 2002 and 2015. Most (62%) practiced in ambulatory care and 38% in inpatient care settings (8% in both). In the past four years, 71% were working in or starting anticoagulation clinics in ambulatory and inpatient settings. In their evaluations of the program, an average of 90% of participants agreed or strongly agreed the lecture material was relevant and objectives were met. Pharmacists are able to apply knowledge and skills in management of anticoagulation. This structured practice-based continuing education program was intended to enhance pharmacy practice and has achieved that goal. The certificate program in anticoagulation was relevant to pharmacists who attended the program. Copyright © 2017. Published by Elsevier Inc.

  10. Early initiation of new oral anticoagulants in acute stroke and TIA patients with nonvalvular atrial fibrillation.

    PubMed

    Shibazaki, Kensaku; Kimura, Kazumi; Aoki, Junya; Saji, Naoki; Sakai, Kenichiro

    2013-08-15

    The aim of this study was to investigate whether early initiation of new oral anticoagulants (NOAC) for acute stroke or transient ischemic attack (TIA) patients with nonvalvular atrial fibrillation (NVAF) are safe. Between March 2011 and September 2012, stroke or TIA patients with NVAF who started NOAC within 2 weeks were enrolled retrospectively. Symptomatic intracerebral hemorrhage (ICH), hemorrhagic transformation (HT) on T2*-weighted MRI, recurrence of stroke or TIA, systemic embolism and any bleeding complications after initiation of NOAC were evaluated. 41 patients (25 males; mean age 76.2 years) started NOAC; of which, 39 (95%) patients had stroke, and 2 (5%) had TIA. The median (interquartile range) interval from onset to treatment with NOAC was 2 (1-6) days. Symptomatic ICH was not observed. HT on initial T2* and new HT on follow-up T2* were 5 (12%) and 11 (31%), but it was asymptomatic. Of 5 patients who had HT on the initial T2*, enlargement of hemorrhage on follow-up T2* (hemorrhagic infarction (HI) Type 1→HI Type 2) was observed in 1 patient, but it was asymptomatic. None of the patients had recurrent stroke or TIA, systemic embolism, and any bleeding complications. The NOAC may be safe in acute stroke or TIA patients with NVAF. A large, prospective study is needed to confirm this. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Anticoagulants for secondary prevention after acute myocardial infarction: lessons from the past decade

    PubMed Central

    Atar, Dan; Bode, Christoph; Stuerzenbecher, André; Verheugt, Freek W A

    2014-01-01

    The impact of an acute coronary syndrome (ACS) event, such as an acute myocardial infarction (MI), is not limited to the acute management phase; patients face an elevated risk of residual atherothrombotic events that commonly requires chronic management for months or even years. Significant advances have been made in both the acute and chronic management of patients with acute MI over the past decade, resulting in improved prognoses. One of the hallmarks of modern treatment strategies is more aggressive antiplatelet treatment regimens. However, the risks of further ACS events, stroke and premature death remain elevated in these patients, and addressing this residual risk is challenging owing to interpatient variability, differences in management strategies between centres and countries, incomplete understanding of the specific pathophysiology of post-ACS thrombosis and limitations of current therapeutic approaches. The recent approval in Europe of the direct oral anticoagulant rivaroxaban for use in this setting in combination with clopidogrel and acetylsalicylic acid offers another strategy to consider in the management of these patients, and clinical strategies in this area continue to evolve. In this review, we chart the progress made over the past decade in reducing the burden of secondary thromboembolic events after acute MI and discuss the current position of and future perspectives on the inclusion of oral anticoagulants into care pathways in this setting. PMID:24494730

  12. Cost-effectiveness of pharmacogenetics-guided warfarin therapy vs. alternative anticoagulation in atrial fibrillation.

    PubMed

    Pink, J; Pirmohamed, M; Lane, S; Hughes, D A

    2014-02-01

    Pharmacogenetics-guided warfarin dosing is an alternative to standard clinical algorithms and new oral anticoagulants for patients with nonvalvular atrial fibrillation. However, clinical evidence for pharmacogenetics-guided warfarin dosing is limited to intermediary outcomes, and consequently, there is a lack of information on the cost-effectiveness of anticoagulation treatment options. A clinical trial simulation of S-warfarin was used to predict times within therapeutic range for different dosing algorithms. Relative risks of clinical events, obtained from a meta-analysis of trials linking times within therapeutic range with outcomes, served as inputs to an economic analysis. Neither dabigatran nor rivaroxaban were cost-effective options. Along the cost-effectiveness frontier, in relation to clinically dosed warfarin, pharmacogenetics-guided warfarin and apixaban had incremental cost-effectiveness ratios of £13,226 and £20,671 per quality-adjusted life year gained, respectively. On the basis of our simulations, apixaban appears to be the most cost-effective treatment.

  13. Prostate Histotripsy in an Anticoagulated Canine Model

    PubMed Central

    Wheat, Jeffery C.; Hall, Timothy L.; Hempel, Christopher R.; Cain, Charles A.; Xu, Zhen; Roberts, William W.

    2009-01-01

    Purpose Histotripsy is a non-invasive ultrasound technology which induces microbubble formation (cavitation) within tissues producing mechanical tissue fractionation. During initial in-vivo feasibility canine studies of prostate ablation, minimal hematuria was observed. In the current study, we sought to further explore this phenomenon by performing extensive prostate histotripsy treatments in anticoagulated canines. Materials and Methods Histotripsy was performed on 9 canine subjects pre-treated with 6 mg of oral warfarin for 3 to 5 days using an extracorporeal 750 kHz therapeutic ultrasound transducer delivering acoustic pulses to the prostatic urethra and periurethral parenchyma. After 7–28 days, the subjects were euthanized, transrectal prostate ultrasound was performed and the prostate was harvested. Serum hemoglobin and International Normalization Ratio (INR) were measured immediately prior to histotripsy treatment and at euthanasia. Results Mean treatment INR was 4.6 (median 2.4, range 1.2 to 11.3). There was no clinically significant change in hemoglobin concentration at euthanasia compared to baseline. At harvest, histologic sections of the prostate revealed a large cavity corresponding to the planned treatment volume incorporating the prostatic urethra and parenchyma in all subjects. Urine was clear within 2 days of treatment and no blood clots were seen. Conclusions Despite therapeutic and supratherapeutic anticoagulation, histotripsy resulted in minimal bleeding despite significant fractionation and tissue debulking of the prostate. These results have prompted further studies to understand the mechanism of non-thermal hemostasis underlying histotripsy. PMID:19931897

  14. Assessing Bleeding Risk in Patients Taking Anticoagulants

    PubMed Central

    Shoeb, Marwa; Fang, Margaret C.

    2013-01-01

    Anticoagulant medications are commonly used for the prevention and treatment of thromboembolism. Although highly effective, they are also associated with significant bleeding risks. Numerous individual clinical factors have been linked to an increased risk of hemorrhage, including older age, anemia, and renal disease. To help quantify hemorrhage risk for individual patients, a number of clinical risk prediction tools have been developed. These risk prediction tools differ in how they were derived and how they identify and weight individual risk factors. At present, their ability to effective predict anticoagulant-associated hemorrhage remains modest. Use of risk prediction tools to estimate bleeding in clinical practice is most influential when applied to patients at the lower spectrum of thromboembolic risk, when the risk of hemorrhage will more strongly affect clinical decisions about anticoagulation. Using risk tools may also help counsel and inform patients about their potential risk for hemorrhage while on anticoagulants, and can identify patients who might benefit from more careful management of anticoagulation. PMID:23479259

  15. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines.

    PubMed

    Veitch, Andrew M; Vanbiervliet, Geoffroy; Gershlick, Anthony H; Boustiere, Christian; Baglin, Trevor P; Smith, Lesley-Ann; Radaelli, Franco; Knight, Evelyn; Gralnek, Ian M; Hassan, Cesare; Dumonceau, Jean-Marc

    2016-04-01

    The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage vs. thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor): For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation);For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation).For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin: The advice for warfarin is fundamentally unchanged from BSG 2008 guidance. Direct Oral Anticoagulants (DOAC): For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation). For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥ 48 hours before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30 - 50 mL/min we recommend that the last dose of DOAC be taken 72 hours before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation). © Georg Thieme Verlag KG Stuttgart · New York.

  16. MARINE LEECH ANTICOAGULANT DIVERSITY AND EVOLUTION.

    PubMed

    Tessler, Michael; Marancik, David; Champagne, Donald; Dove, Alistair; Camus, Alvin; Siddall, Mark E; Kvist, Sebastian

    2018-03-16

    Leeches (Annelida: Hirudinea) possess powerful salivary anticoagulants and, accordingly, are frequently employed in modern, authoritative medicine. Members of the almost exclusively marine family Piscicolidae account for 20% of leech species diversity, and feed on host groups (e.g., sharks) not encountered by their freshwater and terrestrial counterparts. Moreover, some species of Ozobranchidae feed on endangered marine turtles and have been implicated as potential vectors for the tumor-associated turtle herpesvirus. In spite of their ecological importance and unique host associations, there is a distinct paucity of data regarding the salivary transcriptomes of either of these families. Using next generation sequencing, we profiled transcribed, putative anticoagulants and other salivary bioactive compounds that have previously been linked to bloodfeeding from 7 piscicolid species (3 elasmobranch-feeders; 4 non-cartilaginous fish-feeders) and 1 ozobranchid species (2 samples). In total, 149 putative anticoagulants and bioactive loci were discovered in varying constellations throughout the different samples. The putative anticoagulants showed a broad spectrum of described antagonistic pathways, such as inhibition of factor Xa and platelet aggregation, that likely have similar bioactive roles in marine fish and turtles. A transcript with homology to ohanin, originally isolated from king cobras, was found in Cystobranchus vividus but is otherwise unknown from leeches. Estimation of selection pressures for the putative anticoagulants recovered evidence for both positive and purifying selection along several isolated branches in the gene trees and positive selection was also estimated for a few select codons in a variety of marine species. Similarly, phylogenetic analyses of the amino acid sequences for several anticoagulants indicated divergent evolution.

  17. Recent progress and market analysis of anticoagulant drugs

    PubMed Central

    Fan, Ping; Gao, Yangyang; Zheng, Minglin; Xu, Ting; Schoenhagen, Paul

    2018-01-01

    This review describes epidemiology of thromboembolic disease in China and abroad, evaluates trends in the development of anticoagulant drugs, and analyzes the market situation based on large amounts of accumulated data. Specifically, we describe advances in clinical application of anticoagulants and analyze the most commonly used anticoagulants in the market systematically.

  18. Sustained impact of anticoagulant control achieved in an anticoagulation management service after transfer of management to the primary care physician.

    PubMed

    Bungard, Tammy J; Ritchie, Bruce; Garg, Sipi; Tsuyuki, Ross T

    2012-02-01

    To determine whether the impact of anticoagulant control achieved in an Anticoagulation Management Service (AMS) is sustained after transfer of anticoagulation management to the primary care physician (PCP), and to assess patient satisfaction with their anticoagulation management by both the AMS and PCP. Prospective, randomized trial. Pharmacist-directed ambulatory AMS located in a tertiary medical care facility and PCP practices in Canada. Sixty-two adults who had received at least 6 months of warfarin therapy managed by the AMS. Patients were randomly assigned to remain with AMS care (32 patients) or to transfer their anticoagulation management care to their PCP (30 patients). After 4.5 months of care, patients in both groups completed a validated survey instrument assessing their satisfaction with the management of their warfarin therapy. Of 295 patients screened, most were excluded from the study for denying consent or for having previous bleeding or clotting complications while taking warfarin. Patients in the AMS and PCP groups who completed the study were similar in age (median 70 and 76 yrs, respectively), and most had atrial fibrillation as an indication for warfarin (75% and 83%, respectively). The primary outcome measure-mean percentage of time within the desired international normalized ratio (INR) range after 6 months-was compared between the two groups, using both the actual range (INR 2.5 ± 0.5) and an expanded range (INR 2.5 ± 0.7). No significant difference was noted in this outcome between the groups (73.5 ± 19.1% vs 76.9 ± 24.5% for the AMS vs PCP groups, p=0.54). Other outcome measures were rates of thrombotic and hemorrhagic events resulting in emergency department visits or hospitalizations, patients' overall satisfaction with warfarin therapy, and patients' preferred anticoagulation management strategy. Two hemorrhagic events and one thrombotic event occurred in each group. Patients were more satisfied with their anticoagulant

  19. Anticoagulation Bridge Therapy in Patients with Atrial Fibrillation: Recent Updates Providing a Rebalance of Risk and Benefit.

    PubMed

    Garwood, Candice L; Korkis, Bianca; Grande, Domenico; Hanni, Claudia; Morin, Amy; Moser, Lynette R

    2017-06-01

    In 2011 we reviewed clinical updates and controversies surrounding anticoagulation bridge therapy in patients with atrial fibrillation (AF). Since then, options for oral anticoagulation have expanded with the addition of four direct oral anticoagulant (DOAC) agents available in the United States. Nonetheless, vitamin K antagonist (VKA) therapy continues to be the treatment of choice for patients who are poor candidates for a DOAC and for whom bridge therapy remains a therapeutic dilemma. This literature review identifies evidence and guideline and consensus statements from the last 5 years to provide updated recommendations and insight into bridge therapy for patients using a VKA for AF. Since our last review, at least four major international guidelines have been updated plus a new consensus document addressing bridge therapy was released. Prospective trials and one randomized controlled trial have provided guidance for perioperative bridge therapy. The clinical trial data showed that bridging with heparin is associated with a significant bleeding risk compared with not bridging; furthermore, data suggested that actual perioperative thromboembolic risk may be lower than previously estimated. Notably, patients at high risk for stroke have not been adequately represented. These findings highlight the importance of assessing thrombosis and bleeding risk before making bridging decisions. Thrombosis and bleeding risk tools have emerged to facilitate this assessment and have been incorporated into guideline recommendations. Results from ongoing trials are expected to provide more guidance on safe and effective perioperative management approaches for patients at high risk for stroke. © 2017 Pharmacotherapy Publications, Inc.

  20. Dual Antithrombotic Therapy with Clopidogrel and Novel Oral Anticoagulants in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Real-world Study.

    PubMed

    Kebernik, Julia; Borlich, Martin; Tölg, Ralph; El-Mawardy, Mohamed; Abdel-Wahab, Mohamed; Richardt, Gert

    2018-06-01

    For patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), proper antithrombotic therapy is equivocal. Current guidelines recommend triple therapy, which carries a high risk of bleeding. Recent large trials suggest that dual therapy (DT) with novel oral anticoagulant (NOAC) plus P2Y 12 inhibitor can be an appropriate alternative, but real-world data for this alternative are scarce and the optimal duration of DT has not yet been established. This analysis was performed in a single-center prospective cohort. We investigated 216 PCI patients with indication for anticoagulation due to AF. After PCI patients received DT with reduced doses NOAC plus P2Y 12 inhibitor for 6 months, which was followed by standard dose NOAC monotherapy. Efficacy endpoints were defined as cardiac death, myocardial infarction (MI), stent thrombosis (ST), and stroke. Safety endpoints were bleeding events as defined by Bleeding Academic Consortium (BARC). Baseline characteristics of our study population were described by a CHA 2 DS 2 -VASc score of greater than 4 and a HAS-BLED score of greater than 3. After a mean follow-up of 18.7 months, efficacy events occurred in 12 patients (5.6%). We observed three (1.4%) cardiac deaths, two (0.9%) MIs, six (2.8%) strokes, and one (0.5%) definite ST. After switching from DT to NOAC monotherapy after 6.3 ± 1.7 months, there was no rebound of ischemic events. Bleeding events occurred in 34 patients (15.7%) mainly under DT, while bleeding was less during NOAC monotherapy. In this long-term study of high-risk and real-world AF-patients with PCI, DT with NOAC and P2Y 12 inhibitor (6 months) followed by NOAC monotherapy was safe and effective.

  1. Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial.

    PubMed

    Boersma, Lucas V; Ince, Hueseyin; Kische, Stephan; Pokushalov, Evgeny; Schmitz, Thomas; Schmidt, Boris; Gori, Tommaso; Meincke, Felix; Protopopov, Alexey Vladimir; Betts, Timothy; Foley, David; Sievert, Horst; Mazzone, Patrizio; De Potter, Tom; Vireca, Elisa; Stein, Kenneth; Bergmann, Martin W

    2017-09-01

    Left atrial appendage (LAA) occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials. EWOLUTION was designed to provide data in routine practice from a prospective multicenter registry. A total of 1025 patients scheduled for a WATCHMAN implant were prospectively and sequentially enrolled at 47 centers. Indication for LAA closure was based on European Society of Cardiology guidelines. Follow-up and transesophageal echocardiography (TEE) were performed per local practice. The baseline CHA 2 DS 2 -VASc score was 4.5 ± 1.6; the mean age was 73.4 ± 9 years; previous transient ischemic attack/ischemic stroke was present in 312 (30.5%), 155 (15.1%) had previous hemorrhagic stroke, and 320 (31.3%) had a history of major bleeding; and 750 (73%) were deemed unsuitable for oral anticoagulation therapy. WATCHMAN implant succeeded in 1005 (98.5%) of patients, without leaks >5 mm in 1002 (99.7%) with at least 1 TEE follow-up in 875 patients (87%). Antiplatelet therapy was used in 784 (83%), while vitamin K antagonists were used in only 75 (8%). At 1 year, mortality was 98 (9.8%), reflecting the advanced age and comorbidities in this population. Device thrombus was observed in 28 patients at routine TEE (3.7%) and was not correlated with the drug regimen (P = .14). Ischemic stroke rate was 1.1% (relative risk 84% vs estimated historical data); the major bleeding rate was 2.6% and was predominantly (2.3%) nonprocedure/device related. LAA closure with the WATCHMAN device has a high implant and sealing success. This method of stroke risk reduction appears to be safe and effective with an ischemic stroke rate as low as 1.1%, even though 73% of patients had a contraindication to and were not using oral anticoagulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Anticoagulation by factor Xa inhibitors.

    PubMed

    Orfeo, T; Butenas, S; Brummel-Ziedins, K E; Gissel, M; Mann, K G

    2010-08-01

    Therapeutic agents that regulate blood coagulation are critical to the management of thrombotic disorders, with the selective targeting of factor (F) Xa emerging as a promising approach. To assess anticoagulant strategies targeting FXa. A deterministic computational model of tissue factor (Tf)-initiated thrombin generation and two empirical experimental systems (a synthetic coagulation proteome reconstruction using purified proteins and a whole blood model) were used to evaluate clinically relevant examples of the two available types of FXa-directed anticoagulants [an antithrombin (AT)-dependent agent, fondaparinux, and an AT-independent inhibitor, Rivaroxaban] in experimental regimens relevant to long-term (suppression of new Tf-initiated events) and acute (suppression of ongoing coagulation processes) clinical applications. Computational representations of each anticoagulant's efficacy in suppressing thrombin generation over a range of anticoagulant concentrations in both anticoagulation regimens were validated by results from corresponding empirical reconstructions and were consistent with those recommended for long-term and acute clinical applications, respectively. All three model systems suggested that Rivaroxaban would prove more effective in the suppression of an ongoing coagulation process than fondaparinux, reflecting its much higher reactivity toward the prothrombinase complex. The success of fondaparinux in acute settings in vivo is not explained solely by its properties as an FXa inhibitor. We have reported that FIXa contributes to the long-term capacity of clot-associated catalysts to restart a coagulation process, suggesting that the enhanced anti-FIXa activity of fondaparinux-AT may be critical to its success in acute settings in vivo. © 2010 International Society on Thrombosis and Haemostasis.

  3. Severe jaundice due to intrahepatic cholestasis after initiating anticoagulation with rivaroxaban.

    PubMed

    Aslan, Abdullah N; Sari, Cenk; Baştuğ, Serdal; Sari, Sevil Ö; Akçay, Murat; Durmaz, Tahir; Bozkurt, Engin

    2016-03-01

    Rivaroxaban, a highly selective direct factor Xa inhibitor, is a new oral anticoagulant approved by the US Food and Drug Administration in November 2011 for stroke prophylaxis in patients with nonvalvular atrial fibrillation. Because of its efficacy and once-a-day dosing, it is commonly preferred in patients with nonvalvular atrial fibrillation and intolerance to warfarin in clinical practice. However, it can result in some adverse effects such as bleeding, rashes and liver injury. Here, we described a very rare adverse reaction of rivaroxaban, jaundice due to intrahepatic cholestasis, appeared in a 71-year-old male patient after taking rivaroxaban.

  4. Differences in lupus anticoagulant final conclusion through clotting time or Rosner index for mixing test interpretation.

    PubMed

    Depreter, Barbara; Devreese, Katrien M J

    2016-09-01

    Lupus anticoagulant (LAC) testing includes a screening, mixing and confirmation step. Although recently published guidelines on LAC testing are a useful step towards standardization, a lack of consensus remains whether to express mixing tests in clotting time (CT) or index of circulating anticoagulant (ICA). The influence of anticoagulant therapy, e.g. vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) on both methods of interpretation remains to be investigated. The objective of this study was to contribute to a simplification and standardization of the LAC three-step interpretation on the level of the mixing test. Samples from 148 consecutive patients with LAC request and prolonged screening step, and 77 samples from patients non-suspicious for LAC treated with VKA (n=37) or DOAC (n=30) were retrospectively evaluated. An activated partial thromboplastin time (aPTT) and dilute Russell's viper venom time (dRVVT) were used for routine LAC testing. The supplemental anticoagulant samples were tested with dRVVT only. We focused on the interpretation differences for mixing tests expressed as CT or ICA and compared the final LAC conclusion within each distinct group of concordant and discordant mixing test results. Mixing test interpretation by CT resulted in 10 (dRVVT) and 16 (aPTT) more LAC positive patients compared to interpretation with ICA. Isolated prolonged dRVVT screen mix ICA results were exclusively observed in samples from VKA-treated patients without suspicion for LAC. We recommend using CT in respect to the 99th percentile cut-off for interpretation of mixing steps in order to reach the highest sensitivity and specificity in LAC detection.

  5. Management of anticoagulation in hip fractures: A pragmatic approach.

    PubMed

    Yassa, Rafik; Khalfaoui, Mahdi Yacine; Hujazi, Ihab; Sevenoaks, Hannah; Dunkow, Paul

    2017-09-01

    Hip fractures are common and increasing with an ageing population. In the United Kingdom, the national guidelines recommend operative intervention within 36 hours of diagnosis. However, long-term anticoagulant treatment is frequently encountered in these patients which can delay surgical intervention. Despite this, there are no set national standards for management of drug-induced coagulopathy pre-operatively in the context of hip fractures.The aim of this study was to evaluate the management protocols available in the current literature for the commonly encountered coagulopathy-inducing agents.We reviewed the current literature, identified the reversal agents used in coagulopathy management and assessed the evidence to determine the optimal timing, doses and routes of administration.Warfarin and other vitamin K antagonists (VKA) can be reversed effectively using vitamin K with a dose in the range of 2 mg to 10 mg intravenously to correct coagulopathy.The role of fresh frozen plasma is not clear from the current evidence while prothrombin complex remains a reliable and safe method for immediate reversal of VKA-induced coagulopathy in hip fracture surgery or failed vitamin K treatment reversal.The literature suggests that surgery should not be delayed in patients on classical antiplatelet medications (aspirin or clopidogrel), but spinal or regional anaesthetic methods should be avoided for the latter. However, evidence regarding the use of more novel antiplatelet medications (e.g. ticagrelor) and direct oral anticoagulants remains a largely unexplored area in the context of hip fracture surgery. We suggest treatment protocols based on best available evidence and guidance from allied specialties.Hip fracture surgery presents a common management dilemma where semi-urgent surgery is required. In this article, we advocate an evidence-based algorithm as a guide for managing these anticoagulated patients. Cite this article: EFORT Open Rev 2017;2:394-402. DOI: 10.1302/2058-5241.2.160083.

  6. Oral anticoagulant therapy in adults with congenital heart disease and atrial arrhythmias: Implementation of guidelines.

    PubMed

    Yang, H; Heidendael, J F; de Groot, J R; Konings, T C; Veen, G; van Dijk, A P J; Meijboom, F J; Sieswerda, G Tj; Post, M C; Winter, M M; Mulder, B J M; Bouma, B J

    2018-04-15

    Current guidelines on oral anticoagulation (OAC) in adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) consist of heterogeneous and divergent recommendations with limited level of evidence, possibly leading to diverse OAC management and different outcomes. Therefore, we aimed to evaluate real-world implementation and outcome of three guidelines on OAC management in ACHD patients with AA. The ESC GUCH 2010, PACES/HRS 2014 and ESC atrial fibrillation (AF) 2016 guidelines were assessed for implementation. ACHD patients with recurrent or sustained non-valvular AA from 5 tertiary centers were identified using a national ACHD registry. After two years of prospective follow-up, thromboembolism, major bleeding and death were assessed. In total, 225 adults (mean age 54±15years, 55% male) with various defects (simple 43%; moderate 37%; complex 20%) and AA were included. Following the most strict indication (OAC is recommended in all three guidelines), one should treat a mere 37% of ACHD patients with AA, whereas following the least strict indication (OAC is recommended in any one of the three guidelines), one should treat 98% of patients. The various guidelines were implemented in 54-80% of patients. From all recommendations, Fontan circulation, CHA2DS2-VASc≥1 and AF were independently associated with OAC prescription. Superiority of any guideline in identifying outcome (n=15) could not be demonstrated. The implementation of current guidelines on OAC management in ACHD patients with AA is low, probably due to substantial heterogeneity among guidelines. OAC prescription in daily practice was most consistent in patients with AF and CHA2DS2-VASc≥1 or Fontan circulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Early introduction of direct oral anticoagulants in cardioembolic stroke patients with non-valvular atrial fibrillation.

    PubMed

    Cappellari, Manuel; Carletti, Monica; Danese, Alessandra; Bovi, Paolo

    2016-10-01

    Direct oral anticoagulants (DOACs) are superior to warfarin in reduction of the intracranial bleeding risk. The aim of the present study was to assess whether early DOAC introduction (1-3 days after onset) in stroke patients with non-valvular atrial fibrillation (nVAF) may be safe and effective, compared with DOAC introduction after 4-7 days. We conducted a prospective analysis based on data collected from 147 consecutive nVAF patients who started DOAC within 7 days after stroke onset. In all patients, we performed pre-DOAC CT scan 24-36 h after onset and follow-up CT scan at 7 days after DOAC introduction. Outcome measures were post-DOAC intracranial bleeding (new any intracerebral hemorrhage (ICH) in patients with pre-DOAC infarct without hemorrhagic transformation (HT) or expansion of ICH in patients with pre-DOAC infarct with asymptomatic HT) and post-DOAC recurrent ischemic stroke (any new ischemic infarct) on follow-up CT scan. 97 patients started DOAC after 1-3 days and 50 patients started DOAC after 4-7 days. On pre-DOAC CT scan, 132 patients had an infarct without HT and 15 an infarct with asymptomatic HT. On follow-up CT scan, new any ICH was noted in seven patients (asymptomatic in 6) and asymptomatic expansion of ICH in one patient. We found no association between early DOAC introduction and intracranial bleeding. Large infarct remained the only independent predictor of post-DOAC intracranial bleeding. No patients suffered recurrent ischemic stroke after DOAC introduction. Early DOAC introduction might be safe in carefully selected patients with nVAF who experience small- and medium-sized cardioembolic ischemic strokes. Further investigation will be needed.

  8. Anticoagulation management in the ambulatory surgical setting.

    PubMed

    Eisenstein, Diana Hill

    2012-04-01

    Many people receiving maintenance anticoagulation therapy require surgery each year in ambulatory surgery centers. National safety organizations focus attention toward improving anticoagulation management, and the American College of Chest Physicians has established guidelines for appropriate anticoagulation management to balance the risk of thromboembolism when warfarin is discontinued with the risk of bleeding when anticoagulation therapy is maintained. The guidelines recommend that patients at high or moderate risk for thromboembolism should be bridged with subcutaneous low-molecular-weight heparin or IV unfractionated heparin with the interruption of warfarin, and low-risk patients may require subcutaneous low-molecular-weight heparin or no bridging with the interruption of warfarin. The guidelines recommend the continuation of warfarin for patients who are undergoing minor dermatologic or dental procedures or cataract removal. The literature reveals, however, that there is not adequate adherence to these recommendations and guidelines. Management of anticoagulation therapy by a nurse practitioner may improve compliance and safety in ambulatory surgery centers. Copyright © 2012 AORN, Inc. Published by Elsevier Inc. All rights reserved.

  9. Vitamin K for improved anticoagulation control in patients receiving warfarin.

    PubMed

    Mahtani, Kamal R; Heneghan, Carl J; Nunan, David; Roberts, Nia W

    2014-05-15

    Effective use of warfarin involves keeping the international normalised ratio (INR) within a relatively narrow therapeutic range. However, patients respond widely to their dose of warfarin. Overcoagulation can lead to an increased risk of excessive bleeding, while undercoagulation can lead to increased clot formation. There is some evidence that patients with a variable response to warfarin may benefit from a concomitant low dose of vitamin K. To assess the effects of concomitant supplementation of low-dose oral vitamin K for anticoagulation control in patients being initiated on or taking a maintenance dose of warfarin. To identify previous reviews, we searched the Database of Abstracts of Reviews of Effects (DARE via The Cochrane Library, Wiley) (Issue 2, 2011). To identify primary studies, we searched the Cochrane Central Register of Controlled Trials (CENTRAL via The Cochrane Library, Wiley) (Issue 2, 2014), Ovid MEDLINE (R) In-Process & Other Non-Indexed Citations database and Ovid MEDLINE (R) (OvidSP) (1946 to 25 February 2014), Embase (OvidSP) (1974 to week 8 of 2014), Science Citation Index Expanded™ & Conference Proceedings Citation Index - Science (Web of Science™) (1945 to 27 February 2014), and the NHS Economics Evaluations Database (NHS EED) (via The Cochrane Library, Wiley) (Issue 2, 2014). We did not apply any language or date restrictions. We used additional methods to identify grey literature and ongoing studies. Randomised controlled trials comparing the addition of vitamin K versus placebo in patients initiating warfarin or already taking warfarin. Two review authors independently selected and extracted data from included studies. When disagreement arose, a third author helped reached a consensus. We also assessed risk of bias. We identified two studies with a total of 100 participants for inclusion in the review. We found the overall risk of bias to be unclear in a number of domains. Neither study reported the time taken to the first INR in

  10. Adherence to oral anticoagulants in patients with atrial fibrillation-a population-based retrospective cohort study linking health information systems in the Valencia region, Spain: a study protocol.

    PubMed

    Sanfélix-Gimeno, G; Rodríguez-Bernal, C L; Hurtado, I; Baixáuli-Pérez, C; Librero, J; Peiró, S

    2015-10-19

    Adherence to oral anticoagulation (OAC) treatment, vitamin K antagonists or new oral anticoagulants, is an essential element for effectiveness. Information on adherence to OAC in atrial fibrillation (AF) and the impact of adherence on clinical outcomes using real-world data barely exists. We aim to describe the patterns of adherence to OAC over time in patients with AF, estimate the associated factors and their impact on clinical events, and assess the same issues with conventional measures of primary and secondary adherence-proportion of days covered (PDC) and persistence-in routine clinical practice. This is a population-based retrospective cohort study including all patients with AF treated with OAC from 2010 to date in Valencia, Spain; data will be obtained from diverse electronic records of the Valencia Health Agency. adherence trajectories. (1) primary non-adherence; (2) secondary adherence: (a) PDC, (b) persistence. Clinical outcomes: hospitalisation for haemorrhagic or thromboembolic events and death during follow-up. (1) description of baseline characteristics, adherence patterns (trajectory models or latent class growth analysis models) and conventional adherence measures; (2) logistic or Cox multivariate regression models, to assess the associations between adherence measures and the covariates, and logistic multinomial regression models, to identify characteristics associated with each trajectory; (3) Cox proportional hazard models, to assess the relationship between adherence and clinical outcomes, with propensity score adjustment applied to further control for potential confounders; (4) to estimate the importance of different healthcare levels in the variations of adherence, logistic or Cox multilevel regression models. This study has been approved by the corresponding Clinical Research Ethics Committee. We plan to disseminate the project's findings through peer-reviewed publications and presentations at relevant health conferences. Policy reports

  11. Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection.

    PubMed

    Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P; Ismail, Farooq; Im, Sun

    2016-04-01

    To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. International normalized ratio <2.0 was perceived as an ideal range for performing Botulinum toxin injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%-30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients.

  12. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis.

    PubMed

    Chai-Adisaksopha, Chatree; Crowther, Mark; Isayama, Tetsuya; Lim, Wendy

    2014-10-09

    Vitamin K antagonists (VKAs) have been the standard of care for treatment of thromboembolic diseases. Target-specific oral anticoagulants (TSOACs) have been developed and found to be at least noninferior to VKAs with regard to efficacy, but the risk of bleeding with TSOACs remains controversial. We performed a systematic review and meta-analysis of phase-3 randomized controlled trials (RCTs) to assess the bleeding side effects of TSOACs compared with VKAs in patients with venous thromboembolism or atrial fibrillation. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials; conference abstracts; and www.clinicaltrials.gov with no language restriction. Two reviewers independently performed study selection, data extraction, and study quality assessment. Twelve RCTs involving 102 607 patients were retrieved. TSOACs significantly reduced the risk of overall major bleeding (relative risk [RR] 0.72, P < .01), fatal bleeding (RR 0.53, P < .01), intracranial bleeding (RR 0.43, P < .01), clinically relevant nonmajor bleeding (RR 0.78, P < .01), and total bleeding (RR 0.76, P < .01). There was no significant difference in major gastrointestinal bleeding between TSOACs and VKAs (RR 0.94, P = .62). When compared with VKAs, TSOACs are associated with less major bleeding, fatal bleeding, intracranial bleeding, clinically relevant nonmajor bleeding, and total bleeding. Additionally, TSOACs do not increase the risk of gastrointestinal bleeding. © 2014 by The American Society of Hematology.

  13. Assessment of the efficacy of a novel tailored vitamin K dosing regimen in lowering the International Normalised Ratio in over-anticoagulated patients: a randomised clinical trial.

    PubMed

    Kampouraki, Emmanouela; Avery, Peter J; Wynne, Hilary; Biss, Tina; Hanley, John; Talks, Kate; Kamali, Farhad

    2017-09-01

    Current guidelines advocate using fixed-doses of oral vitamin K to reverse excessive anticoagulation in warfarinised patients who are either asymptomatic or have minor bleeds. Over-anticoagulated patients present with a wide range of International Normalised Ratio (INR) values and response to fixed doses of vitamin K varies. Consequently a significant proportion of patients remain outside their target INR after vitamin K administration, making them prone to either haemorrhage or thromboembolism. We compared the performance of a novel tailored vitamin K dosing regimen to that of a fixed-dose regimen with the primary measure being the proportion of over-anticoagulated patients returning to their target INR within 24 h. One hundred and eighty-one patients with an index INR > 6·0 (asymptomatic or with minor bleeding) were randomly allocated to receive oral administration of either a tailored dose (based upon index INR and body surface area) or a fixed-dose (1 or 2 mg) of vitamin K. A greater proportion of patients treated with the tailored dose returned to within target INR range compared to the fixed-dose regimen (68·9% vs. 52·8%; P = 0·026), whilst a smaller proportion of patients remained above target INR range (12·2% vs. 34·0%; P < 0·001). Individualised vitamin K dosing is more accurate than fixed-dose regimen in lowering INR to within target range in excessively anticoagulated patients. © 2017 John Wiley & Sons Ltd.

  14. Direct Oral Anticoagulants and Vitamin K Antagonists for Treatment of Deep Venous Thrombosis and Pulmonary Embolism in the Outpatient Setting: Comparative Economic Evaluation

    PubMed Central

    Al Saleh, Abdullah S; Berrigan, Patrick; Anderson, David; Shivakumar, Sudeep

    2017-01-01

    Background To date, there have been few economic evaluations, from a Canadian perspective, of direct oral anticoagulants (DOACs) for the prevention of recurrent venous thromboembolism (VTE) in patients with acute unprovoked VTE. As a result, there is a lack of consensus about which treatment strategy should be adopted in the clinical setting. Objectives To assess the cost-effectiveness of currently approved anti-coagulant options, in terms of cost per quality-adjusted life-year (QALY) gained, for the prevention of recurrent VTE in patients with unprovoked events managed on an outpatient basis. Methods Microsoft Excel was used to develop a Markov model. Model parameters were determined using published literature, local hospital data, expert opinion, and chart review. The analysis considered the costs associated with pharmaceuticals, laboratory testing, hematologist fees, and treatment of recurrent VTE and major bleeding events. Effectiveness was measured in terms of QALYs, and incremental cost-effectiveness ratios (ICERs) were calculated. Results For treatment lasting 3 months, apixaban represented the most cost-effective DOAC relative to low-molecular-weight heparin (LMWH) + vitamin K antagonist, with an ICER of $7379.66. For 6 months of treatment, apixaban again represented the most cost-effective treatment, with an ICER of $84.08 per QALY gained, and this drug dominated all the other strategies at 12 months. For lifetime treatment, DOACs were unlikely to be cost-effective, given a maximum willingness to pay of $50 000 to $100 000 per QALY. In a probabilistic sensitivity analysis at 6 months, 46.4% of iterations resulted in apixaban having lower costs and better outcomes than LMWH + vitamin K antagonist, and 78.6% of iterations resulted in an ICER below $100 000 Conclusions The findings of this study suggest that apixaban is likely cost-effective for treatment durations of 3, 6, and 12 months. However, for indefinite treatment, DOACs were unlikely to be cost

  15. Meta-analysis of safety and efficacy for direct oral anticoagulation treatment of non-valvular atrial fibrillation in relation to renal function.

    PubMed

    Zou, Rongjun; Tao, Jun; Shi, Wanting; Yang, Minglei; Li, Hongmu; Lin, Xifeng; Yang, Songran; Hua, Ping

    2017-12-01

    We performed a meta-analysis of the safety and efficacy of anticoagulation treatment for atrial fibrillation (AF) in relation to renal function. We also examined the change in estimated glomerular filtration rate (eGFR) from baseline and compared the outcomes for patients with stable and worsening renal function. We selected studies that used randomized controlled trials in which outcomes for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, or edoxaban) were compared with those for warfarin in AF patients with normal, mild or moderate renal function, except the severe one (creatinine clearance<30). We assessed five clinical trials, involving 72,608 patients. Pooled analysis indicated that the risk of stroke was lower for DOACs than for warfarin among patients with mild renal impairment (Risk ratio, 0.79; 95% confidence interval, 0.68-0.91) and moderate renal impairment (0.80, 0.69-0.92). No major differences were found in patients with normal renal function. Additionally, DOACs were associated with fewer major bleeds among patients with normal (0.77, 0.70-0.84), mild (0.86, 0.77-0.95), and moderate renal impairment (0.73, 0.65-0.82). Among those treated with DOACs, a lower dosage was associated with lower risk of major bleeding (0.75, 0.68-0.83) and higher risk of stroke or systemic embolism (1.28, 1.12-1.47). Further, DOACs tended to be associated with a lower estimated glomerular filtration rate (eGFR) than warfarin even after 30months. Finally, we found significant differences in the risk of stroke (2.09, 1.64-2.68) and major bleeding (2.01, 1.66-2.42) between patients with stable and worsening renal function. DOACs have a greater clinical benefit than warfarin with respect to renal function. They are associated with a comparatively lower risk of stroke and major bleeding, as well lower eGFR. This suggests these agents are a better choice in patients with renal disease. Copyright © 2017. Published by Elsevier Ltd.

  16. Practical aspects of treatment with target specific anticoagulants: initiation, payment and current market, transitions, and venous thromboembolism treatment.

    PubMed

    Mahan, Charles E

    2015-04-01

    Target specific anticoagulants (TSOACs) have recently been introduced to the US market for multiple indications including venous thromboembolism (VTE) prevention in total hip and knee replacement surgeries, VTE treatment and reduction in the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). Currently, three TSOACs are available including rivaroxaban, apixaban, and dabigatran with edoxaban currently under Food and Drug Administration review for VTE treatment and stroke prevention in NVAF. The introduction of these agents has created a paradigm shift in anticoagulation by considerably simplifying treatment and anticoagulant initiation for patients by giving clinicians the opportunity to use a rapid onset, rapid offset, oral agent. The availability of these rapid onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism and deep vein thrombosis which can greatly reduce healthcare costs by avoiding inpatient hospitalizations and treatment for the disease. Additionally with this practice, the complications of an inpatient hospitalization may also be avoided such as nosocomial infections. Single-agent approaches with TSOACs represent a paradigm shift in the treatment of VTE versus the complicated overlap of a parenteral agent with warfarin. Transitions between anticoagulants, including TSOACs, are a high-risk period for the patient, and clinicians must carefully consider patient characteristics such as renal function as well as the agents that are being transitioned. TSOAC use appears to be growing slowly with improved payment coverage throughout the US.

  17. Variations in Anticoagulation Practices Following the Maze Procedure.

    PubMed

    Chung, Jennifer; Sami, Magdi; Albert, Carole; Varennes, Benoit De

    2015-01-01

    The current real-world anticoagulation practices following left atrial appendectomy in the context of the Maze procedure are unknown. This is a cohort study of all patients who underwent the Maze procedure with amputation of the left atrial appendage from June 2005 to November 2012. Data was prospectively collected at regular intervals with an interview and Holter monitoring. All patients received anticoagulation for 3 months. Those then kept on anticoagulation and those for whom anticoagulation was stopped were compared in terms of death, bleeding and incidence of stroke. In total, there were 113 patients, of whom 66 were treated with anticoagulation (Group A) and 47 were not (Group B). There were no significant baseline differences between the two groups, including the presence of atrial fibrillation (A:19.7%, B:10.6%, p=0.30), CHADS2 score (A:1.41±1.05, B:1.15±1.08, p=0.19), and left atrial size (A:48.3±7.1mm, B:47.6±7.8 mm, p=0.57). There were 275 patient-years of follow-up, with an average of 2.43 years per patient. Only two patients experienced strokes, both in Group A (p=0.27). Of the 5 bleeding events, 4 occurred in the first 3 months while on anticoagulation and the remaining event occurred in Group A at 3 years post-operatively (p=0.10). No standardized approach to anticoagulation after the Maze procedure is apparent in real-world practice in an urban Canadian setting. Patients who undergo the Maze procedure with amputation of the left atrial appendage are at a low risk of stroke, but the optimal anticoagulation strategy requires further investigation.

  18. Quality of oral anticoagulation with phenprocoumon in regular medical care and its potential for improvement in a telemedicine-based coagulation service--results from the prospective, multi-center, observational cohort study thrombEVAL.

    PubMed

    Prochaska, Jürgen H; Göbel, Sebastian; Keller, Karsten; Coldewey, Meike; Ullmann, Alexander; Lamparter, Heidrun; Jünger, Claus; Al-Bayati, Zaid; Baer, Christina; Walter, Ulrich; Bickel, Christoph; ten Cate, Hugo; Münzel, Thomas; Wild, Philipp S

    2015-01-23

    The majority of studies on quality of oral anticoagulation (OAC) therapy with vitamin K-antagonists are performed with short-acting warfarin. Data on long-acting phenprocoumon, which is frequently used in Europe for OAC therapy and is considered to enable more stable therapy adjustment, are scarce. In this study, we aimed to assess quality of OAC therapy with phenprocoumon in regular medical care and to evaluate its potential for optimization in a telemedicine-based coagulation service. In the prospective observational cohort study program thrombEVAL we investigated 2,011 patients from regular medical care in a multi-center cohort study and 760 patients from a telemedicine-based coagulation service in a single-center cohort study. Data were obtained from self-reported data, computer-assisted personal interviews, and laboratory measurements according to standard operating procedures with detailed quality control. Time in therapeutic range (TTR) was calculated by linear interpolation method to assess quality of OAC therapy. Study monitoring was carried out by an independent institution. Overall, 15,377 treatment years and 48,955 international normalized ratio (INR) measurements were analyzed. Quality of anticoagulation, as measured by median TTR, was 66.3% (interquartile range (IQR) 47.8/81.9) in regular medical care and 75.5% (IQR 64.2/84.4) in the coagulation service (P <0.001). Stable anticoagulation control within therapeutic range was achieved in 63.8% of patients in regular medical care with TTR at 72.1% (IQR 58.3/84.7) as compared to 96.4% of patients in the coagulation service with TTR at 76.2% [(IQR 65.6/84.7); P = 0.001)]. Prospective follow-up of coagulation service patients with pretreatment in regular medical care showed an improvement of the TTR from 66.2% (IQR 49.0/83.6) to 74.5% (IQR 62.9/84.2; P <0.0001) in the coagulation service. Treatment in the coagulation service contributed to an optimization of the profile of time outside therapeutic range, a

  19. [Current ideas of a complex relationship between atrial fibrillation and ischemic heart disease and of optimum tactics for anticoagulant therapy to prevent embolism in systemic circulation].

    PubMed

    Golshmid, M V; Gilyarevskiy, S R; Kuzmina, I M; Sinitsina, I I

    The article discusses the issue of searching for optimum oral anticoagulants to prevent thrombosis and embolism induced by heart disease both in patients with atrial fibrillation and sinus rhythm. A complex bidirectional relationship between atrial fibrillation and coronary atherosclerosis is considered along with possible mechanisms for development of myocardial infarction in patients with atrial fibrillation. The authors provided evidence-based data which can be used in selecting an anticoagulant for prevention of heart disease induced thrombosis and embolism taking into account both the efficacy and safety established in randomized clinical studies.

  20. Direct oral anticoagulants versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease.

    PubMed

    Kimachi, Miho; Furukawa, Toshi A; Kimachi, Kimihiko; Goto, Yoshihito; Fukuma, Shingo; Fukuhara, Shunichi

    2017-11-06

    Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin. To assess the efficacy and safety of DOAC including apixaban, dabigatran, edoxaban, and rivaroxaban versus warfarin among AF patients with CKD. We searched the Cochrane Kidney and Transplant Specialised Register (up to 1 August 2017) through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. We included all randomised controlled trials (RCTs) which directly compared the efficacy and safety of direct oral anticoagulants (direct thrombin inhibitors or factor Xa inhibitors) with dose-adjusted warfarin for preventing stroke and systemic embolic events in non-valvular AF patients with CKD, defined as creatinine clearance (CrCl) or eGFR between 15 and 60 mL/min (CKD stage G3 and G4). Two review authors independently selected studies, assessed quality, and extracted data. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for the association between anticoagulant therapy and all strokes and systemic embolic events as the primary efficacy outcome and major bleeding events as the primary safety outcome. Confidence in the evidence was assessing using GRADE. Our review included 12,545 AF participants with CKD from five studies. All participants were randomised to either DOAC (apixaban, dabigatran, edoxaban

  1. What NPs need to know about anticoagulation therapy.

    PubMed

    Gay, Sarah E; Munaco, Sandra

    2012-10-10

    Venous thromboembolism (VTE) refers to pulmonary embolism and deep venous thrombosis. Anticoagulation is the cornerstone of management for patients with VTE. This review will discuss current anticoagulation guidelines.

  2. High D-dimer levels after stopping anticoagulants in pulmonary embolism with sleep apnoea.

    PubMed

    García Suquia, Angela; Alonso-Fernández, Alberto; de la Peña, Mónica; Romero, David; Piérola, Javier; Carrera, Miguel; Barceló, Antonia; Soriano, Joan B; Arque, Meritxell; Fernández-Capitán, Carmen; Lorenzo, Alicia; García-Río, Francisco

    2015-12-01

    Obstructive sleep apnoea is a risk factor for pulmonary embolism. Elevated D-dimer levels and other biomarkers are associated with recurrent pulmonary embolism. The objectives were to compare the frequency of elevated D-dimer levels (>500 ng·mL(-1)) and further coagulation biomarkers after oral anticoagulation withdrawal in pulmonary embolism patients, with and without obstructive sleep apnoea, including two control groups without pulmonary embolism.We performed home respiratory polygraphy. We also measured basic biochemical profile and haemogram, and coagulation biomarkers (D-dimer, prothrombin fragment 1+2, thrombin-antithrombin complex, plasminogen activator inhibitor 1, and soluble P-selectin).64 (74.4%) of the pulmonary embolism cases and 41 (46.11%) of the controls without pulmonary embolism had obstructive sleep apnoea. Plasmatic D-dimer was higher in PE patients with OSA than in those without obstructive sleep apnoea. D-dimer levels were significantly correlated with apnoea-hypopnoea index, and nocturnal hypoxia. There were more patients with high D-dimer after stopping anticoagulants in those with pulmonary embolism and obstructive sleep apnoea compared with PE without obstructive sleep apnoea (35.4% versus 19.0%, p=0.003). Apnoea-hypopnoea index was independently associated with high D-dimer.Pulmonary embolism patients with obstructive sleep apnoea had higher rates of elevated D-dimer levels after anticoagulation discontinuation for pulmonary embolism than in patients without obstructive sleep apnoea and, therefore, higher procoagulant state that might increase the risk of pulmonary embolism recurrence. Copyright ©ERS 2015.

  3. Assessing prescribing of NSAIDs, antiplatelets, and anticoagulants in Canadian family medicine using chart review.

    PubMed

    Hamilton, Kevin; Davis, Christine; Falk, Jamie; Singer, Alex; Bugden, Shawn

    2016-10-01

    Background Drug-related problems have been identified as a major contributor to emergency room visits, hospitalizations, and death. The most commonly implicated medications are nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelets, and anticoagulants. Considering a significant proportion of these harms are preventable, indicators to identify risky prescribing before they lead to harm have been developed. Objective To examine the prevalence and patterns of potentially inappropriate prescriptions (PIPs) in a primary care population who are using high-risk medications. Setting This study was performed within two multi-disciplinary family medicine teaching clinics in Winnipeg, Canada. Method A cross-sectional electronic/paper chart audit was conducted within two multi-disciplinary family medicine teaching clinics to evaluate the prevalence of 13 evidence-based high-risk prescriptions. Patients were included if they were prescribed an oral NSAID, antiplatelet, or an anticoagulant within the 12 month period between June 2012 and June 2013. Main outcome measure The proportion of PIPs associated with an increased bleeding risk for NSAIDs, antiplatelets, and anticoagulants. Results Of the 567 patients included in the review, 198 (35 %) patients had received at least 1 PIP in the past year. The most common PIP was the use of an oral NSAID with one or more GI risk factors without adequate gastro-protection. Only 34 (6 %) of these patients received a full medication review performed by a pharmacist. Although not statistically significant, patients who received a medication review had fewer inappropriate prescriptions (27 % with review, 35 % without). Conclusion Over one-third of the patients who were using high-risk medications were using them potentially inappropriately. Although pharmacists have been shown to reduce the amount of inappropriate prescribing, very few patients using these medications were referred to the pharmacist for a full medication review

  4. Early Transcatheter Aortic Valve Function With and Without Therapeutic Anticoagulation.

    PubMed

    Hiremath, Pranoti G; Kearney, Kathleen; Smith, Bryn; Don, Creighton; Dvir, Danny; Aldea, Gabriel; Reisman, Mark; McCabe, James M

    2017-11-01

    Prosthetic leaflet thrombosis is a growing concern in transcatheter aortic valve replacement (TAVR). Given the uncertainty of best practices for antiplatelet and anticoagulation therapies in the post-TAVR period, additional evidence regarding the impact of anticoagulation on prosthetic valve function after TAVR is needed. Patients undergoing native-valve TAVR at a single academic institution between 2012 and 2015 were analyzed based on any anticoagulant use at hospital discharge post TAVR. Changes in prosthetic valve peak velocity and mean gradient were assessed based on transthoracic echocardiograms performed immediately following valve implant and at 4-week follow-up. Multivariate regression analyses were performed to explore the impact of anticoagulation status on early TAVR valve performance. For 403 patients, there were no available data to analyze. Of those, 29.6% were discharged on anticoagulation. Following TAVR, the average mean prosthetic valve gradient was 11.8 ± 5.6 mm Hg and peak velocity was 2.33 ± 0.52 m/s. There were no significant differences between anticoagulated and non-anticoagulated groups in the mean or peak gradients or velocity immediately following implant or at 4 weeks, which remained true following multivariate adjustment (P=.80 for delta mean gradient; P=.91 for delta peak velocity). Our data suggest that the absence of anticoagulation is not associated with short-term degradation in TAVR performance and do not support the routine use of anticoagulation following native-valve TAVR.

  5. Efficacy of aprotinin with various anticoagulant agents in cardiopulmonary bypass.

    PubMed

    Terrell, M R; Walenga, J M; Koza, M J; Pifarré, R

    1996-08-01

    Aprotinin has recently been approved for clinical use in cardiopulmonary bypass. Although unfractionated heparin has been the only anticoagulant widely used for cardiopulmonary bypass, disadvantages involving heparin have led to ongoing investigations of alternative anticoagulant agents. The objective of this study was to evaluate the efficacy of aprotinin in combination with other anticoagulant agents, specifically low molecular weight heparin and recombinant hirudin, using a dog model of cardiopulmonary bypass. The blood conservation resulting from the use of aprotinin was observed only with unfractionated heparin. Efficacy of anticoagulation as measured by protein deposits in the bypass circuit filter revealed an unexpected reduction in the quantity of deposits when aprotinin was used in combination with low molecular weight heparin. As alternative anticoagulant agents are sought, the potential benefits of aprotinin in the reduction of operative blood loss must be evaluated independently for each anticoagulant agent.

  6. Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Asian Patients With Nonvalvular Atrial Fibrillation

    PubMed Central

    Wang, Kang-Ling; Lip, Gregory Y.H.; Lin, Shing-Jong

    2015-01-01

    Background and Purpose— The use of vitamin K antagonists (VKAs), the cornerstone treatment for stroke prevention in patients with atrial fibrillation, is limited by the perceived risk of serious bleeding in Asia. Non-VKA oral anticoagulants (NOACs) are safer alternatives. Here, we evaluate performance differences of NOACs between Asians and non-Asians. Methods— We compared efficacy and safety of NOACs between patients enrolled in Asian and non-Asian countries using aggregative data from phase III clinical trials. The odds ratios (ORs [95% confidence interval]) were calculated by a random effects model. Results— Comparing with VKAs, standard-dose NOACs reduced stroke or systemic embolism (OR=0.65 [0.52–0.83] versus 0.85 [0.77–0.93], P interaction= 0.045) more in Asians than in non-Asians and were safer in Asians than in non-Asians about major bleeding (OR=0.57 [0.44–0.74] versus 0.89 [0.76–1.04], P interaction=0.004), hemorrhagic stroke (OR=0.32 [0.19–0.52] versus 0.56 [0.44–0.70], P interaction=0.046) in particular, whereas gastrointestinal bleeding was significantly increased in non-Asians (OR=0.79 [0.48–1.32] versus 1.44 [1.12–1.85], P interaction=0.041). Generally, low-dose NOACs were safer than VKAs without heterogeneity in efficacy and safety between Asians and non-Asians, except for ischemic stroke, major, and gastrointestinal bleeding. Conclusions— Our findings suggest that standard-dose NOACs were more effective and safer in Asians than in non-Asians, whereas low-dose NOACs performed similarly in both populations. PMID:26304863

  7. Impact of anticoagulation therapy on valve haemodynamic deterioration following transcatheter aortic valve replacement.

    PubMed

    Del Trigo, María; Muñoz-García, Antonio J; Latib, Azeem; Auffret, Vincent; Wijeysundera, Harindra C; Nombela-Franco, Luis; Gutierrez, Enrique; Cheema, Asim N; Serra, Vicenç; Amat-Santos, Ignacio J; Kefer, Joelle; Benitez, Luis Miguel; Leclercq, Florence; Mangieri, Antonio; Le Breton, Hervé; Jiménez-Quevedo, Pilar; Garcia Del Blanco, Bruno; Dager, Antonio; Abdul-Jawad Altisent, Omar; Puri, Rishi; Pibarot, Philippe; Rodés-Cabau, Josep

    2018-05-01

    To evaluate the changes in transvalvular gradients and the incidence of valve haemodynamic deterioration (VHD) following transcatheter aortic valve replacement (TAVR), according to use of anticoagulation therapy. This multicentre study included 2466 patients (46% men; mean age 81±7 years) who underwent TAVR with echocardiography performed at 12-month follow-up. Anticoagulation therapy was used in 707 patients (28.7%) following TAVR (AC group). A total of 663 patients received vitamin K antagonists, and 44 patients received direct oral anticoagulants. A propensity score matching analysis was performed to adjust for intergroup (AC vs non-AC post-TAVR) differences. A total of 622 patients per group were included in the propensity-matched analysis. VHD was defined as a ≥10 mm Hg increase in the mean transprosthetic gradient at follow-up (vs hospital discharge). The mean clinical follow-up was 29±18 months. The mean transvalvular gradient significantly increased at follow-up in the non-AC group within the global cohort (P=0.003), whereas it remained stable over time in the AC group (P=0.323). The incidence of VHD was significantly lower in the AC group (0.6%) compared with the non-AC group (3.7%, P<0.001), and these significant differences remained within the propensity-matched populations (0.6% vs 3.9% in the AC and non-AC groups, respectively, P<0.001). The occurrence of VHD did not associate with an increased risk of all-cause death (P=0.468), cardiovascular death (P=0.539) or stroke (P=0.170) at follow-up. The lack of anticoagulation therapy post-TAVR was associated with significant increments in transvalvular gradients and a greater risk of VHD. VHD was subclinical in most cases and did not associate with major adverse clinical events. Future randomised trials are needed to determine if systematic anticoagulation therapy post-TAVR would reduce the incidence of VHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article

  8. Postpartum wound and bleeding complications in women who received peripartum anticoagulation.

    PubMed

    Limmer, Jane S; Grotegut, Chad A; Thames, Elizabeth; Dotters-Katz, Sarah K; Brancazio, Leo R; James, Andra H

    2013-07-01

    The objective of this study was to compare wound and bleeding complications between women who received anticoagulation after cesarean delivery due to history of prior venous thromboembolic disease, arterial disease, or being a thrombophilia carrier with adverse pregnancy outcome, to women not receiving anticoagulation. Women in the Duke Thrombosis Center Registry who underwent cesarean delivery during 2003-2011 and received postpartum anticoagulation (anticoagulation group, n=77), were compared with a subset of women who delivered during the same time period, but did not receive anticoagulation (no anticoagulation group, n=77). The no anticoagulation group comprised women who were matched to the anticoagulation group by age, body mass index, type of cesarean (no labor vs. labor), and date of delivery. Bleeding and wound complications were compared between the two groups. A multivariable logistic regression model was constructed to determine if anticoagulation was an independent predictor of wound complication. Women who received anticoagulation during pregnancy had a greater incidence of wound complications compared to those who did not (30% vs. 8%, p<0.001). Using multivariable logistic regression, while controlling for race, diabetes, chorioamnionitis, and aspirin use, anticoagulation predicted the development of any wound complication (OR 5.8, 95% CI 2.2, 17.6), but there were no differences in the mean estimated blood loss at delivery (782 vs. 778 ml, p=0.91), change in postpartum hematocrit (5.4 vs. 5.2%, p=0.772), or percent of women receiving blood products (6.5 vs. 1.3%, p=0.209) between the two groups. Anticoagulation following cesarean delivery is associated with an increased risk of post-cesarean wound complications, but not other postpartum bleeding complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Non-vitamin K antagonist oral anticoagulants versus warfarin for the prevention of spontaneous echo-contrast and thrombus in patients with atrial fibrillation or flutter undergoing cardioversion: A trans-esophageal echocardiography study.

    PubMed

    Kim, Yun Gi; Choi, Jong-Il; Kim, Mi-Na; Cho, Dong-Hyuk; Oh, Suk-Kyu; Kook, Hyungdon; Park, Hee-Soon; Lee, Kwang No; Baek, Yong-Soo; Roh, Seung-Young; Shim, Jaemin; Park, Seong-Mi; Shim, Wan Joo; Kim, Young-Hoon

    2018-01-01

    Spontaneous echo-contrast (SEC) and thrombus observed in trans-esophageal echocardiography (TEE) is known as a strong surrogate marker for future risk of ischemic stroke in patients with atrial fibrillation (AF) or atrial flutter (AFL). The efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin to prevent SEC or thrombus in patients with AF or AFL is currently unknown. AF or AFL patients who underwent direct current cardioversion (DCCV) and pre-DCCV TEE evaluation from January 2014 to October 2016 in a single center were analyzed. The prevalence of SEC and thrombus were compared between patients who received NOAC and those who took warfarin. NOAC included direct thrombin inhibitor and factor Xa inhibitors. Among 1,050 patients who were considered for DCCV, 424 patients anticoagulated with warfarin or NOAC underwent TEE prior to DCCV. Eighty patients who were anticoagulated for less than 21 days were excluded. Finally, 344 patients were included for the analysis (180 warfarin users vs. 164 NOAC users). No significant difference in the prevalence of SEC (44.4% vs. 43.9%; p = 0.919), dense SEC (13.9% vs. 15.2%; p = 0.722), or thrombus (2.2% vs. 4.3%; p = 0.281) was observed between the warfarin group and the NOAC group. In multivariate analysis, there was no association between NOAC and risk of SEC (odds ratio [OR]: 1.4, 95% CI: 0.796-2.297, p = 0.265) or thrombus (OR: 3.4, 95% CI: 0.726-16.039, p = 0.120). In conclusion, effectiveness of NOAC is comparable to warfarin in preventing SEC and thrombus in patients with AF or AFL undergoing DCCV. However, numerical increase in the prevalence of thrombus in NOAC group warrants further evaluation.

  10. Non-vitamin K antagonist oral anticoagulants versus warfarin for the prevention of spontaneous echo-contrast and thrombus in patients with atrial fibrillation or flutter undergoing cardioversion: A trans-esophageal echocardiography study

    PubMed Central

    Kim, Yun Gi; Kim, Mi-Na; Cho, Dong-Hyuk; Oh, Suk-Kyu; Kook, Hyungdon; Park, Hee-Soon; Lee, Kwang No; Baek, Yong-Soo; Roh, Seung-Young; Shim, Jaemin; Park, Seong-Mi; Shim, Wan Joo; Kim, Young-Hoon

    2018-01-01

    Spontaneous echo-contrast (SEC) and thrombus observed in trans-esophageal echocardiography (TEE) is known as a strong surrogate marker for future risk of ischemic stroke in patients with atrial fibrillation (AF) or atrial flutter (AFL). The efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin to prevent SEC or thrombus in patients with AF or AFL is currently unknown. AF or AFL patients who underwent direct current cardioversion (DCCV) and pre-DCCV TEE evaluation from January 2014 to October 2016 in a single center were analyzed. The prevalence of SEC and thrombus were compared between patients who received NOAC and those who took warfarin. NOAC included direct thrombin inhibitor and factor Xa inhibitors. Among 1,050 patients who were considered for DCCV, 424 patients anticoagulated with warfarin or NOAC underwent TEE prior to DCCV. Eighty patients who were anticoagulated for less than 21 days were excluded. Finally, 344 patients were included for the analysis (180 warfarin users vs. 164 NOAC users). No significant difference in the prevalence of SEC (44.4% vs. 43.9%; p = 0.919), dense SEC (13.9% vs. 15.2%; p = 0.722), or thrombus (2.2% vs. 4.3%; p = 0.281) was observed between the warfarin group and the NOAC group. In multivariate analysis, there was no association between NOAC and risk of SEC (odds ratio [OR]: 1.4, 95% CI: 0.796–2.297, p = 0.265) or thrombus (OR: 3.4, 95% CI: 0.726–16.039, p = 0.120). In conclusion, effectiveness of NOAC is comparable to warfarin in preventing SEC and thrombus in patients with AF or AFL undergoing DCCV. However, numerical increase in the prevalence of thrombus in NOAC group warrants further evaluation. PMID:29360845

  11. APOLLO I: Anticoagulation control in atrial fibrillation.

    PubMed

    Pinho-Costa, Luís; Moreira, Sónia; Azevedo, Cristiana; Azevedo, Pedro; Castro, Elisabete; Sousa, Hélder; Melo, Miguel

    2015-05-01

    Anticoagulation control as assessed by time in therapeutic range (TTR) correlates positively with the safety and efficacy of thromboprophylaxis in atrial fibrillation. We set out to assess TTR in our unit and to investigate determinants of better control. This was a case series study of atrial fibrillation patients anticoagulated with warfarin or acenocoumarol at the Family Health Unit of Fânzeres. Sociodemographic and clinical data were collected and TTR was calculated by the Rosendaal method, based on international normalized ratio tests performed in external laboratories in the preceding six months. SPSS 21.0 was used for the statistical analysis, with descriptive statistics, Spearman's correlation, and the Mann-Whitney U and Kruskal-Wallis tests. Of the 106 eligible patients, 70% participated in the study. Median TTR was 65.3% (P25=48.3%, P75=86.8%). We found a positive association between this variable and duration of atrial fibrillation (ρ=0.477, p<0.001, r(2)=0.116) and with duration of anticoagulation (ρ=0.5, p<0.001, r(2)=0.087). No association was found with age, gender, educational level or existence of a caregiver (p>0.05). Median TTR in our unit is similar to that in southern European countries and close to the good control threshold (70%) proposed by the European Society of Cardiology. The duration of atrial fibrillation and of anticoagulation explains only a small part of the measure's variability. Other determinants of anticoagulation control must be investigated in future studies and comparative studies should be carried out in family health units monitoring anticoagulation on the premises. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  12. Anticoagulants and the propagation phase of thrombin generation.

    PubMed

    Orfeo, Thomas; Gissel, Matthew; Butenas, Saulius; Undas, Anetta; Brummel-Ziedins, Kathleen E; Mann, Kenneth G

    2011-01-01

    The view that clot time-based assays do not provide a sufficient assessment of an individual's hemostatic competence, especially in the context of anticoagulant therapy, has provoked a search for new metrics, with significant focus directed at techniques that define the propagation phase of thrombin generation. Here we use our deterministic mathematical model of tissue-factor initiated thrombin generation in combination with reconstructions using purified protein components to characterize how the interplay between anticoagulant mechanisms and variable composition of the coagulation proteome result in differential regulation of the propagation phase of thrombin generation. Thrombin parameters were extracted from computationally derived thrombin generation profiles generated using coagulation proteome factor data from warfarin-treated individuals (N = 54) and matching groups of control individuals (N = 37). A computational clot time prolongation value (cINR) was devised that correlated with their actual International Normalized Ratio (INR) values, with differences between individual INR and cINR values shown to derive from the insensitivity of the INR to tissue factor pathway inhibitor (TFPI). The analysis suggests that normal range variation in TFPI levels could be an important contributor to the failure of the INR to adequately reflect the anticoagulated state in some individuals. Warfarin-induced changes in thrombin propagation phase parameters were then compared to those induced by unfractionated heparin, fondaparinux, rivaroxaban, and a reversible thrombin inhibitor. Anticoagulants were assessed at concentrations yielding equivalent cINR values, with each anticoagulant evaluated using 32 unique coagulation proteome compositions. The analyses showed that no anticoagulant recapitulated all features of warfarin propagation phase dynamics; differences in propagation phase effects suggest that anticoagulants that selectively target fXa or thrombin may

  13. Prothrombin complex concentrate administration for bleeding associated with non-vitamin K antagonist oral anticoagulants: The SAMURAI-NVAF study.

    PubMed

    Yoshimura, Sohei; Sato, Shoichiro; Todo, Kenichi; Okada, Yasushi; Furui, Eisuke; Matsuki, Takayuki; Yamagami, Hiroshi; Koga, Masatoshi; Takahashi, Jun C; Nagatsuka, Kazuyuki; Arihiro, Shoji; Toyoda, Kazunori

    2017-04-15

    Antidotes appropriate for non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are not yet in widespread clinical use. Efficacy of prothrombin complex concentrate (PCC) in NOAC-associated bleeding remains unclarified. Ten NOAC users (4 women, median 74years old) who developed major bleeding and received PCC were prospectively enrolled. Eight single-center NOAC users (0 women, median 74years old) with intracerebral hemorrhage, who over the same period did not receive PCC, were studied for comparison. Of the 10 PCC-treated patients, 8 developed intracerebral hemorrhage, 1 developed subdural hematoma, and another developed gastrointestinal bleeding. The median size of intracerebral hemorrhage was 8mL, relatively lower than the reported size for patients without NOACs. Patients received a median of 1000IU or 16IU/kg of PCC. Before and 1h after PCC administration, the median PT-INR changed from 1.41 to 1.09 (p<0.05) and median aPTT changed from 35.4 to 38.0s (p=0.39). Five patients developed intracranial hematoma expansion and 4 required surgical hematoma evacuation. No symptomatic thrombotic events occurred in either group, no participants died, and 2 participants from each group were independent. Ten NOAC users developed major bleeding and were given relatively low doses of PCC. The effect of PCC on early cessation of bleeding was unclear, while the therapy did not trigger thromboembolic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Anticoagulants for secondary prevention after acute myocardial infarction: lessons from the past decade.

    PubMed

    Atar, Dan; Bode, Christoph; Stuerzenbecher, André; Verheugt, Freek W A

    2014-08-01

    The impact of an acute coronary syndrome (ACS) event, such as an acute myocardial infarction (MI), is not limited to the acute management phase; patients face an elevated risk of residual atherothrombotic events that commonly requires chronic management for months or even years. Significant advances have been made in both the acute and chronic management of patients with acute MI over the past decade, resulting in improved prognoses. One of the hallmarks of modern treatment strategies is more aggressive antiplatelet treatment regimens. However, the risks of further ACS events, stroke and premature death remain elevated in these patients, and addressing this residual risk is challenging owing to interpatient variability, differences in management strategies between centres and countries, incomplete understanding of the specific pathophysiology of post-ACS thrombosis and limitations of current therapeutic approaches. The recent approval in Europe of the direct oral anticoagulant rivaroxaban for use in this setting in combination with clopidogrel and acetylsalicylic acid offers another strategy to consider in the management of these patients, and clinical strategies in this area continue to evolve. In this review, we chart the progress made over the past decade in reducing the burden of secondary thromboembolic events after acute MI and discuss the current position of and future perspectives on the inclusion of oral anticoagulants into care pathways in this setting. © 2014 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.

  15. Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model.

    PubMed

    Grottke, Oliver; van Ryn, Joanne; Spronk, Henri M H; Rossaint, Rolf

    2014-02-05

    New oral anticoagulants are effective alternatives to warfarin. However, no specific reversal agents are available for life-threatening bleeding or emergency surgery. Using a porcine model of trauma, this study assessed the ability of prothrombin complex concentrate (PCC), activated PCC (aPCC), recombinant FVIIa (rFVIIa) and a specific antidote to dabigatran (aDabi-Fab) to reverse the anticoagulant effects of dabigatran. Dabigatran etexilate (DE) was given orally for 3 days (30 mg/kg bid) and intravenously on day 4 to achieve consistent, supratherapeutic concentrations of dabigatran. Blood samples were collected at baseline, after oral DE, after intravenous dabigatran, and 60 minutes post-injury. PCC (30 and 60 U/kg), aPCC (30 and 60 U/kg), rFVIIa (90 and 180 μg/kg) and antidote (60 and 120 mg/kg) were added to blood samples ex-vivo. Coagulation was assessed by thromboelastometry, global coagulation assays and diluted thrombin time. Plasma concentrations of dabigatran were 380 ± 106 ng/ml and 1423 ± 432 ng/ml after oral and intravenous administration, respectively, and all coagulation parameters were affected by dabigatran. Both PCCs and aDabi-Fab, but not rFVIIa, reversed the effects of dabigatran on thromboelastometry parameters and prothrombin time. In contrast, aPTT was only normalised by aDabi-Fab. Plasma concentration (activity) of dabigatran remained elevated after PCC and rFVIIa therapy, but was not measureable after aDabi-Fab. In conclusion, PCC and aPCC were effective in reducing the anticoagulant effects of dabigatran under different conditions, while aDabi-Fab fully corrected all coagulation measures and decreased the plasma concentration of dabigatran below the limit of detection. No significant effects were observed with rFVIIa.

  16. Pathology consultation on anticoagulation monitoring: factor X-related assays.

    PubMed

    Wool, Geoffrey D; Lu, Chuanyi M

    2013-11-01

    To review various anticoagulation therapies and related laboratory monitoring issues, with a focus on factor X-related chromogenic assays. A case-based approach is used to review pertinent published literatures and product inserts of anticoagulation drugs and to look back on clinical use of factor X-related chromogenic assays. The number of anticoagulants available to clinicians has increased greatly in the past decade. Whether and how these anticoagulants should be monitored are areas of uncertainty for clinicians, which can lead to misuse of laboratory assays and suboptimal patient management. Factor X-related assays are of particular concern because of the similar and often confusing test names. Based on a common clinical case scenario and literature review regarding anticoagulant monitoring, an up-to-date discussion and review of the various factor X-related assays are provided, focusing on the differences in test designs and clinical utilities between the chromogenic anti-Xa and chromogenic factor X activity assays. Anticoagulation therapy and related laboratory monitoring are rapidly evolving areas of clinical practices. A good knowledge of relevant laboratory assays and their clinical applications is necessary to help optimize patient care.

  17. Short-Term Anticoagulant Therapy and Thrombus Location Are Independent Risk Factors for Delayed Recanalization of Deep Vein Thrombosis.

    PubMed

    Zhang, Chuanlin; Fu, Qining; Zhao, Yu; Mu, Shaoyu; Liu, Liping

    2016-01-21

    Prompt recanalization of the vein containing the thrombus is an important goal during the initial treatment of DVT, and risk factors for delayed recanalization in patients with deep vein thrombosis (DVT) in the lower extremities need to be determined. A total of 174 patients with DVT in lower extremities were recruited from June 2014 to March 2015 at our hospital. Duplex ultrasound scanning was conducted for all patients at 1 and 6 months after baseline evaluation. We divided the patients into recanalization and non-recanalization groups and analyzed risk factors for delayed recanalization. The univariate analysis revealed that an oral anticoagulant time of less than 3 months and venous thrombus location were risk factors for delayed recanalization (P<0.01). However, age, gender, hypertension, diabetes, pulmonary embolism, incidence factors, the use of catheter-directed thrombolytic (CDT) drugs, and inferior vena cava filter (IVCF) implantation had no influence on the incidence of delayed recanalization in patients with DVT (P>0.05). The multivariate analysis showed that patients with an anticoagulant time of less than 3 months had a lower incidence of recanalization than those with an anticoagulant time of more than 3 months (OR=2.358, P<0.05). The risk of delayed recanalization in patients with proximal DVT was 7 times higher than that in patients with distal DVT. Duration of anticoagulant treatment of less than 3 months and venous thrombus location are independent risk factors for delayed recanalization of DVT in the lower extremities.

  18. Effect of sodium citrate based anticoagulants on the growth activity of malaria parasites.

    PubMed

    Liu, Zhong-xiang; Wang, Xian-feng; Li, Shu-mei; Li, Xun; Xue, Cai-fang; Miao, Jun

    2004-12-01

    To study the effect of anticoagulants based on sodium citrate on the growth activity of malaria parasites. The parasites were treated with 3 anticoagulants (ACD, CD and SC), respectively, and the parasitemia was determined to measure the effect of the anticoagulants on the growth of the parasites. Unsynchronized Plasmodium falciparum was treated with the anticoagulants at different concentrations for 3 h at 37 degrees C. Treated erythrocytes were mixed with normal parasites or treated parasites with normal erythrocytes, which was followed by parasitemia determination of the two cultures to determine the cell target of the anticoagulants. Stage-synchronized parasites (ring, trophozoite and schizont) were treated as above to investigate the stage target. P. berghei was also treated with anticoagulants and inoculated in mice to detect the effect of anticoagulants on the animal malaria parasite by counting the parasitemia. All 3 anticoagulants inhibited falciparum parasite growth and ACD had the strongest potency. The treatments of the erythrocyte and the parasite with anticoagulants respectively showed that the anticoagulants targeted the parasites rather than normal erythrocytes. Stage-synchronized parasite treatment suggested anticoagulants primarily inhibited schizonts. The effect of anticoagulants on P. berghei was similar to that on P. falciparum. ACD showed the most significant inhibitive effect on the growth of malaria parasites and SC was the best anticoagulant based on sodium citrate for malarial experiments.

  19. [Analysis on long-term compliance of anticoagulation treatment and demands of disease management in patients with atrial fibrillation].

    PubMed

    Zuo, Hui-juan; Su, Jiang-lian; Lin, Yun; Zeng, Zhe-chun; Wang, Jin-wen

    2010-08-24

    To analyze the long-term compliance of oral anticoagulant therapy and the demands of disease management in patient with atrial fibrillation (AF). Inpatients with AF taking warfarin were collected from Department of Internal Medicine from January 1 to December 31, 2008. Inpatients from departments of surgery, ophthalmology, otorhinolaryngology, dermatology and pediatrics and those on a previous warfarin therapy were excluded. The data of patient profiles, medical history and anticoagulant treatment were collected from electronic medical record. And the status of anticoagulant treatment one year later and demands of disease management were inquired by telephone. A total of 268 AF patients received a telephone survey. Among them, 145 patients (54.1%) continued taking warfarin. Gender, age, type of AF, duration of AF and history of ischemic stroke was not significantly associated with the compliance of anticoagulant treatment. The odds ratio was 1.74 (95%CI: 0.67-4.47), 0.87 (95%CI: 0.30-2.53), 1.59 (95%CI: 0.35-1.09), 1.09 (95%CI: 0.61-1.93) and 0.44 (95%CI: 0.12-1.60) respectively. Among patients on warfarin, INR was monitored monthly in 88 patients (60.7%) and 70 patients (48.3%) had an INR value of 2.0-3.0. Among 123 withdrawal patients, 88 patients (71.5%) terminated treatment within 6 month. The common reasons included patient ignorance about long-term anticoagulant treatment (35.0%) and switching to aspirin because of a poor effect (24.4%). About 80% of patients wished to obtain instructions about INR monitoring and adjustment of drug dosage. Among them, 196/268 patients (73.1%) wished for a regular follow-up. And 176/196 patients (89.8%) opted for a telephone follow-up and 150/176 patients (85.2%) wanted to receive monthly instructions. The compliance of anticoagulation treatment and the target-meeting proportion of INR value are relative low. And the common reasons of withdrawal are patient ignorance about long-term anticoagulant treatment and switching to

  20. Hospital length of stay in patients initiated on direct oral anticoagulants versus warfarin for venous thromboembolism: a real-world single-center study.

    PubMed

    Badreldin, Hisham

    2018-07-01

    This study was conducted to describe the real-world hospital length of stay in patients treated with all of the U.S. Food and Drug Administration approved direct oral anticoagulants (DOACs) versus warfarin for new-onset venous thromboembolism (VTE) at a large, tertiary, academic medical center. A retrospective cohort analysis of all adult patients diagnosed with acute onset VTE was conducted. Of the 441 patients included, 261 (57%) patients received DOACs versus 180 (41%) patients received warfarin. In the DOAC group, a total of 92 (35%) patients received rivaroxaban, followed by 83 (32%) patients received apixaban, 50 (19%) patients received dabigatran, and 36 (14%) patients received edoxaban. Patients initiated on DOACs had a statistically significant shorter hospital length of stay compared to patients initiated on warfarin (median 3 days, [IQR 0-5] vs. 8 days [IQR 5-11], P < 0.05). Despite the shorter hospital length of stay in patients receiving DOACs, the overall reported differences between the DOACs group and the warfarin group in terms of recurrent VTE, major bleeding, intracranial bleeding, and gastrointestinal bleeding at 3 and 6 months were deemed to be statistically insignificant.

  1. Modelling the cost-effectiveness of pharmacist-managed anticoagulation service for older adults with atrial fibrillation in Singapore.

    PubMed

    Chua, Wen Bing Brandon; Cheen, Hua Heng McVin; Kong, Ming Chai; Chen, Li Li; Wee, Hwee Lin

    2016-10-01

    Background Oral anticoagulation with warfarin is the cornerstone therapy in atrial fibrillation (AF) for stroke prevention. Multi-disciplinary anticoagulation management services have been shown to be cost-effective in the United States, Hong Kong and Thailand, but the findings are not readily generalizable to Singapore's healthcare system. Objective This study aimed to evaluate the cost-effectiveness of pharmacist-managed anticoagulation clinic (ACC) compared with usual care (UC) for the management of older adults with AF receiving oral anticoagulation with warfarin. Setting Pharmacist-managed ACC in an academic medical centre. Method A Markov model with 3-month cycle length and 30-year time horizon compared costs and quality-adjusted life-years (QALYs) of ACC and UC from the patient's and healthcare provider's perspectives. Four pathways based on time in therapeutic range (TTR) were: ACC TTR < 70 %, ACC TTR ≥ 70 %, UC TTR < 70 % and UC TTR ≥ 70 %. A hypothetical cohort of 70-year-old Singaporean AF patients receiving warfarin was utilised. Local data from national disease registries, patient surveys and hospital databases were used. When local data was not available, published studies on Asian populations were utilized when available. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to account for uncertainties. Costs and QALYs were discounted annually by 3 %. Main outcome measure Costs and QALYs of ACC and UC. Results Pharmacist-managed ACC was found to dominate UC in all comparisons. It improved effectiveness by 0.19 and 0.13 QALYs at TTR < 70 % and TTR ≥ 70 % respectively compared with UC. From the patient's perspective, ACC reduced costs by SG$1222.67 (€1110.24) for TTR < 70 % and SG$1008.16 (€915.46) for TTR ≥ 70 %. Similar trends were observed from the healthcare provider's perspective, with ACC reducing costs by SG$1444.79 (€1311.94) for TTR < 70 % and SG$1269.17 (€1152.46) for

  2. Andexanet alfa to reverse the anticoagulant activity of factor Xa inhibitors: a review of design, development and potential place in therapy.

    PubMed

    Sartori, Michelangelo; Cosmi, Benilde

    2018-04-01

    Direct oral anticoagulants are associated with rates of major bleeding which are not negligible, albeit lower than those associated with vitamin K antagonists. No specific reversal agent for factor Xa (FXa) direct inhibitors is currently available for clinical use. A modified activated human FXa decoy protein, andexanet alfa, is being developed that binds FXa direct inhibitors in their active site, thus reversing their anticoagulant effect. The purpose of this article is to review the design, development and clinical trials of andexanet alfa. Andexanet alfa was shown to reverse FXa inhibitors anticoagulant activity both in thrombosis animal models, healthy volunteers and patients with acute major bleeding. Andexanet alfa has been studied in double-blind, placebo-controlled phase II and III studies. A preliminary report of the phase III study showed that an effective hemostasis was obtained after andexanet alfa infusion in the majority of the patients with acute major bleeding associated with FXa inhibitors. Additional studies are ongoing and andexanet alfa is expected to be launched in the market in the near future.

  3. Multinational development of a questionnaire assessing patient satisfaction with anticoagulant treatment: the 'Perception of Anticoagulant Treatment Questionnaire' (PACT-Q©)

    PubMed Central

    Prins, Martin H; Marrel, Alexia; Carita, Paulo; Anderson, David; Bousser, Marie-Germaine; Crijns, Harry; Consoli, Silla; Arnould, Benoit

    2009-01-01

    Background The side effects and burden of anticoagulant treatments may contribute to poor compliance and consequently to treatment failure. A specific questionnaire is necessary to assess patients' needs and their perceptions of anticoagulant treatment. Methods A conceptual model of expectation and satisfaction with anticoagulant treatment was designed by an advisory board and used to guide patient (n = 31) and clinician (n = 17) interviews in French, US English and Dutch. Patients had either atrial fibrillation (AF), deep venous thrombosis (DVT), or pulmonary embolism (PE). Following interviews, three PACT-Q language versions were developed simultaneously and further pilot-tested by 19 patients. Linguistic validations were performed for additional language versions. Results Initial concepts were developed to cover three areas of interest: 'Treatment', 'Disease and Complications' and 'Information about disease and anticoagulant treatment'. After clinician and patient interviews, concepts were further refined into four domains and 17 concepts; test versions of the PACT-Q were then created simultaneously in three languages, each containing 27 items grouped into four domains: "Treatment Expectations" (7 items), "Convenience" (11 items), "Burden of Disease and Treatment" (2 items) and "Anticoagulant Treatment Satisfaction" (7 items). No item was deleted or added after pilot testing as patients found the PACT-Q easy to understand and appropriate in length in all languages. The PACT-Q was divided into two parts: the first part to measure the expectations and the second to measure the convenience, burden and treatment satisfaction, for evaluation prior to and after anticoagulant treatment, respectively. Eleven additional language versions were linguistically validated. Conclusion The PACT-Q has been rigorously developed and linguistically validated. It is available in 14 languages for use with thromboembolic patients, including AF, PE and DVT patients. Its validation and

  4. Efficacy and safety of direct oral anticoagulants approved for cardiovascular indications: Systematic review and meta-analysis.

    PubMed

    Makam, Raghavendra Charan P; Hoaglin, David C; McManus, David D; Wang, Victoria; Gore, Joel M; Spencer, Frederick A; Pradhan, Richeek; Tran, Hoang; Yu, Hong; Goldberg, Robert J

    2018-01-01

    Direct oral anticoagulants (DOACs) have emerged as promising alternatives to vitamin K antagonists (VKAs) for patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Few meta-analyses have included all DOACs that have received FDA approval for these cardiovascular indications, and their overall comparisons against VKAs have shortcomings in data and methods. We provide an updated overall assessment of the efficacy and safety of those DOACs at dosages currently approved for NVAF or VTE, in comparison with VKAs. We used data from Phase 3 randomized trials that compared an FDA-approved DOAC with VKA for primary prevention of stroke in patients with NVAF or for treatment of acute VTE. Among trial participants with NVAF, DOAC recipients had a lower risk of stroke or systemic embolism [Pooled Odds Ratio (OR) 0.76, 95% Confidence Interval (CI) (0.68-0.84)], any stroke (0.80, 0.73-0.88), systemic embolism (0.56, 0.34-0.93), and total mortality (0.89, 0.84-0.95). Safety outcomes also showed a lower risk of fatal, major, and intracranial bleeding but higher risk for gastrointestinal bleeding (GIB). Patients with acute VTE randomized to DOACs had comparable risk of recurrent VTE and death (OR 0.88, 95% CI 0.75-1.03), recurrent DVT (0.83, 0.66-1.05), recurrent non-fatal PE (0.97, 0.75-1.25), and total mortality (0.94, 0.79-1.12). Safety outcomes for DOACs showed a lower risk of major, fatal, and intracranial bleeding, but similar risk of GIB. Patients receiving DOACs for NVAF had predominantly superior efficacy and safety. Patients who were treated with DOACs for acute VTE had non-inferior efficacy, but an overall superior safety profile.

  5. In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong

    2011-05-01

    Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

  6. Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study.

    PubMed

    Klok, Frederikus A; Ageno, Walter; Barco, Stefano; Binder, Harald; Brenner, Benjamin; Duerschmied, Daniel; Empen, Klaus; Faggiano, Pompilio; Ficker, Joachim H; Galiè, Nazzareno; Ghuysen, Alexandre; Held, Matthias; Heydenreich, Nadine; Huisman, Menno V; Jiménez, David; Kozak, Matija; Lang, Irene M; Lankeit, Mareike; Münzel, Thomas; Petris, Antoniu; Pruszczyk, Piotr; Quitzau, Kurt; Schellong, Sebastian; Schmidt, Kai-Helge; Stefanovic, Branislav S; Verschuren, Franck; Wolf-Puetz, Anamaria; Meyer, Guy; Konstantinides, Stavros V

    2017-12-01

    Patients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.

  7. Variation of renal function over time is associated with major bleeding in patients treated with direct oral anticoagulants for atrial fibrillation.

    PubMed

    Becattini, C; Giustozzi, M; Ranalli, M G; Bogliari, G; Cianella, F; Verso, M; Agnelli, G; Vedovati, M C

    2018-05-01

    Essential In patients on treatment with direct anticoagulants (DOACs) variation of renal function is common. The effect of variations of renal function over time on major bleeding is not well defined. Variation of renal function over time is an independent predictor of major bleeding. Identifying conditions associated with variation of renal function may increase safety of DOACs. Background Chronic kidney disease is a risk factor for major bleeding in patients with atrial fibrillation (AF) treated with warfarin. Objective To assess the effect of variations in renal function over time on the risk of major bleeding during treatment with direct oral anticoagulants (DOACs) in patients with non-valvular AF. Methods Consecutive AF patients were prospectively followed after they had received the first DOAC prescription. Estimated glomerular filtration rate (eGFR) was periodically assessed, and the incidence of major bleeding was recorded. A joint survival model was used to estimate the association between variation in eGFR and the risk of major bleeding. Results During a mean follow-up of 575 days, 44 major bleeds occurred in 449 patients (6.1% per patient-year). eGFR over time was inversely and independently associated with the risk of major bleeding; every 1 mL min -1 absolute decrease in eGFR was associated with a 2% increase in the risk of major bleeding (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.04). A similar effect of the variation in eGFR over time was observed on the risk of clinically relevant non-major bleeding (HR 1.02, 95% CI 1.01-1.03). Deterioration of renal function leading to a change in eGFR staging was associated with an increase in the risk of major bleeding (HR 2.43, 95% CI 1.33-4.45). Conclusions Variation in renal function over time is associated with the risk of major bleeding in AF patients treated with DOACs in real life. Identification of intervening clinical conditions associated with variation in renal function is

  8. Optimal duration of anticoagulation. Provoked versus unprovoked VTE and role of adjunctive thrombophilia and imaging tests.

    PubMed

    Prandoni, Paolo; Barbar, Sofia; Milan, Marta; Campello, Elena; Spiezia, Luca; Piovella, Chiara; Pesavento, Raffaele

    2015-06-01

    Once anticoagulation is stopped, the risk of recurrent venous thromboembolism (VTE) over years after a first episode is consistently around 30%. This risk is higher in patients with unprovoked than in those with (transient) provoked VTE, and among the latter in patients with medical than in those with surgical risk factors. Baseline parameters that have been found to be related to the risk of recurrent VTE are the proximal location of deep-vein thrombosis, obesity, old age, male sex and non-0 blood group, whereas the role of inherited thrombophilia is controversial. The persistence of residual vein thrombosis at ultrasound assessment has consistently been shown to increase the risk, as do persistently high values of D-dimer and the early development of the post-thrombotic syndrome. Although the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, strategies that incorporate the assessment of residual vein thrombosis and D-dimer have the potential to identify subjects in whom anticoagulation can be safely discontinued. Moreover, new opportunities are offered by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving the same effectiveness; and by low-dose aspirin, which has the potential to prevent the occurrence of both venous and arterial thrombotic events.

  9. Financial Impact of Direct-Acting Oral Anticoagulants in Medicaid: Budgetary Assessment Based on Number Needed to Treat.

    PubMed

    Fairman, Kathleen A; Davis, Lindsay E; Kruse, Courtney R; Sclar, David A

    2017-04-01

    Faced with rising healthcare costs, state Medicaid programs need short-term, easily calculated budgetary estimates for new drugs, accounting for medical cost offsets due to clinical advantages. To estimate the budgetary impact of direct-acting oral anticoagulants (DOACs) compared with warfarin, an older, lower-cost vitamin K antagonist, on 12-month Medicaid expenditures for nonvalvular atrial fibrillation (NVAF) using number needed to treat (NNT). Medicaid utilization files, 2009 through second quarter 2015, were used to estimate OAC cost accounting for generic/brand statutory minimum (13/23%) and assumed maximum (13/50%) manufacturer rebates. NNTs were calculated from clinical trial reports to estimate avoided medical events for a hypothetical population of 500,000 enrollees (approximate NVAF prevalence × Medicaid enrollment) under two DOAC market share scenarios: 2015 actual and 50% increase. Medical service costs were based on published sources. Costs were inflation-adjusted (2015 US$). From 2009-2015, OAC reimbursement per claim increased by 173 and 279% under maximum and minimum rebate scenarios, respectively, while DOAC market share increased from 0 to 21%. Compared with a warfarin-only counterfactual, counts of ischemic strokes, intracranial hemorrhages, and systemic embolisms declined by 36, 280, and 111, respectively; counts of gastrointestinal hemorrhages increased by 794. Avoided events and reduced monitoring, respectively, offset 3-5% and 15-24% of increased drug cost. Net of offsets, DOAC-related cost increases were US$258-US$464 per patient per year (PPPY) in 2015 and US$309-US$579 PPPY after market share increase. Avoided medical events offset a small portion of DOAC-related drug cost increase. NNT-based calculations provide a transparent source of budgetary-impact information for new medications.

  10. Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), warfarin, and aspirin.

    PubMed

    Lanitis, T; Cotté, F E; Gaudin, A F; Kachaner, I; Kongnakorn, T; Durand-Zaleski, I

    2014-08-01

    To conduct an economic evaluation of the currently prescribed treatments for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) including warfarin, aspirin, and novel oral anticoagulants (NOACs) from a French payer perspective. A previously published Markov model was adapted in accordance to the new French guidelines of the Commission for Economic Evaluation and Public Health (CEESP), to adopt the recommended efficiency frontier approach. A cohort of patients with NVAF eligible for stroke preventive treatment was simulated over lifetime. Clinical events modeled included strokes, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds, and myocardial infarction. Efficacy and bleeding data for warfarin, apixaban, and aspirin were obtained from ARISTOTLE and AVERROES trials, whilst efficacy data for other NOACs were from published indirect comparisons. Acute medical costs were obtained from a dedicated analysis of the French national hospitalization database (PMSI). Long-term medical costs and utility data were derived from the literature. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model projections. Warfarin and apixaban were the two optimal treatment choices, as the other five treatment strategies including aspirin, dabigatran 110 mg, dabigatran in sequential dosages, dabigatran 150 mg, and rivaroxaban were strictly dominated on the efficiency frontier. Further, apixaban was a cost-effective alternative vs warfarin with an incremental cost of €2314 and an incremental quality-adjusted life year (QALY) of 0.189, corresponding to an incremental cost-effectiveness ratio (ICER) of €12,227/QALY. Apixaban may be the most economically efficient alternative to warfarin in NVAF patients eligible for stroke prevention in France. All other strategies were dominated, yielding apixaban as a less costly yet more effective treatment alternative. As

  11. Optical sensing of anticoagulation status: Towards point-of-care coagulation testing

    PubMed Central

    Tripathi, Markandey M.; Hajjarian, Zeinab; Van Cott, Elizabeth M.; Nadkarni, Seemantini K.

    2017-01-01

    Anticoagulant overdose is associated with major bleeding complications. Rapid coagulation sensing may ensure safe and accurate anticoagulant dosing and reduce bleeding risk. Here, we report the novel use of Laser Speckle Rheology (LSR) for measuring anticoagulation and haemodilution status in whole blood. In the LSR approach, blood from 12 patients and 4 swine was placed in disposable cartridges and time-varying intensity fluctuations of laser speckle patterns were measured to quantify the viscoelastic modulus during clotting. Coagulation parameters, mainly clotting time, clot progression rate (α-angle) and maximum clot stiffness (MA) were derived from the clot viscoelasticity trace and compared with standard Thromboelastography (TEG). To demonstrate the capability for anticoagulation sensing in patients, blood samples from 12 patients treated with warfarin anticoagulant were analyzed. LSR clotting time correlated with prothrombin and activated partial thromboplastin time (r = 0.57–0.77, p<0.04) and all LSR parameters demonstrated good correlation with TEG (r = 0.61–0.87, p<0.04). To further evaluate the dose-dependent sensitivity of LSR parameters, swine blood was spiked with varying concentrations of heparin, argatroban and rivaroxaban or serially diluted with saline. We observed that anticoagulant treatments prolonged LSR clotting time in a dose-dependent manner that correlated closely with TEG (r = 0.99, p<0.01). LSR angle was unaltered by anticoagulation whereas TEG angle presented dose-dependent diminution likely linked to the mechanical manipulation of the clot. In both LSR and TEG, MA was largely unaffected by anticoagulation, and LSR presented a higher sensitivity to increased haemodilution in comparison to TEG (p<0.01). Our results establish that LSR rapidly and accurately measures the response of various anticoagulants, opening the opportunity for routine anticoagulation monitoring at the point-of-care or for patient self-testing. PMID:28771571

  12. Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Asian Patients With Nonvalvular Atrial Fibrillation: Meta-Analysis.

    PubMed

    Wang, Kang-Ling; Lip, Gregory Y H; Lin, Shing-Jong; Chiang, Chern-En

    2015-09-01

    The use of vitamin K antagonists (VKAs), the cornerstone treatment for stroke prevention in patients with atrial fibrillation, is limited by the perceived risk of serious bleeding in Asia. Non-VKA oral anticoagulants (NOACs) are safer alternatives. Here, we evaluate performance differences of NOACs between Asians and non-Asians. We compared efficacy and safety of NOACs between patients enrolled in Asian and non-Asian countries using aggregative data from phase III clinical trials. The odds ratios (ORs [95% confidence interval]) were calculated by a random effects model. Comparing with VKAs, standard-dose NOACs reduced stroke or systemic embolism (OR=0.65 [0.52-0.83] versus 0.85 [0.77-0.93], P interaction= 0.045) more in Asians than in non-Asians and were safer in Asians than in non-Asians about major bleeding (OR=0.57 [0.44-0.74] versus 0.89 [0.76-1.04], P interaction=0.004), hemorrhagic stroke (OR=0.32 [0.19-0.52] versus 0.56 [0.44-0.70], P interaction=0.046) in particular, whereas gastrointestinal bleeding was significantly increased in non-Asians (OR=0.79 [0.48-1.32] versus 1.44 [1.12-1.85], P interaction=0.041). Generally, low-dose NOACs were safer than VKAs without heterogeneity in efficacy and safety between Asians and non-Asians, except for ischemic stroke, major, and gastrointestinal bleeding. Our findings suggest that standard-dose NOACs were more effective and safer in Asians than in non-Asians, whereas low-dose NOACs performed similarly in both populations. © 2015 The Authors.

  13. Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation.

    PubMed

    Borgman, Mark P; Pendleton, Robert C; McMillin, Gwendolyn A; Reynolds, Kristen K; Vazquez, Sara; Freeman, Andrew; Wilson, Andrew; Valdes, Roland; Linder, Mark W

    2012-09-01

    We performed a randomised pilot trial of PerMIT, a novel decision support tool for genotype-based warfarin initiation and maintenance dosing, to assess its efficacy for improving warfarin management. We prospectively studied 26 subjects to compare PerMIT-guided management with routine anticoagulation service management. CYP2C9 and VKORC1 genotype results for 13 subjects randomly assigned to the PerMIT arm were recorded within 24 hours of enrolment. To aid in INR interpretation, PerMIT calculates estimated loading and maintenance doses based on a patient's genetic and clinical characteristics and displays calculated S-warfarin plasma concentrations based on planned or administered dosages. In comparison to control subjects, patients in the PerMIT study arm demonstrated a 3.6-day decrease in the time to reach a stabilised INR within the target therapeutic range (4.7 vs. 8.3 days, p = 0.015); a 12.8% increase in time spent within the therapeutic interval over the first 25 days of therapy (64.3% vs. 55.3%, p = 0.180); and a 32.9% decrease in the frequency of warfarin dose adjustments per INR measurement (38.3% vs. 57.1%, p = 0.007). Serial measurements of plasma S-warfarin concentrations were also obtained to prospectively evaluate the accuracy of the pharmacokinetic model during induction therapy. The PerMIT S-warfarin plasma concentration model estimated 62.8% of concentrations within 0.15 mg/l. These pilot data suggest that the PerMIT method and its incorporation of genotype/phenotype information may help practitioners increase the safety, efficacy, and efficiency of warfarin therapeutic management.

  14. Anticoagulant Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The Present State of the Art.

    PubMed

    Thaler, Johannes; Pabinger, Ingrid; Ay, Cihan

    2015-01-01

    Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and potentially life-threatening event. To date different agents are available for the effective treatment of acute VTE and the prevention of recurrence. For several years, the standard of care was the subcutaneous application of a low molecular weight heparin (LMWH) or fondaparinux, followed by a vitamin K antagonist (VKA). The so-called direct oral anticoagulants (DOAC) were introduced rather recently in clinical practice for the treatment of VTE. DOAC seem to have a favorable risk-benefit profile compared to VKA. Moreover, DOAC significantly simplify VTE treatment because they are administered in fixed doses and no routine monitoring is needed. Patients with objectively diagnosed DVT or PE should receive therapeutic anticoagulation for a minimum of 3 months. Whether a patient ought to receive extended treatment needs to be evaluated on an individual basis, depending mainly on risk factors determined by characteristics of the thrombotic event and patient-related factors. In specific patient groups (e.g., pregnant women, cancer patients, and elderly patients), treatment of VTE is more challenging than that in the general population and additional issues need to be considered in those patients. The aim of this review is to give an overview of the currently available treatment modalities of acute VTE and secondary prophylaxis. In particular, specific aspects regarding the initiation of VTE treatment, duration of anticoagulation, and specific patient groups will be discussed.

  15. Short-Term Anticoagulant Therapy and Thrombus Location Are Independent Risk Factors for Delayed Recanalization of Deep Vein Thrombosis

    PubMed Central

    Zhang, Chuanlin; Fu, Qining; Zhao, Yu; Mu, Shaoyu; Liu, Liping

    2016-01-01

    Background Prompt recanalization of the vein containing the thrombus is an important goal during the initial treatment of DVT, and risk factors for delayed recanalization in patients with deep vein thrombosis (DVT) in the lower extremities need to be determined. Material/Methods A total of 174 patients with DVT in lower extremities were recruited from June 2014 to March 2015 at our hospital. Duplex ultrasound scanning was conducted for all patients at 1 and 6 months after baseline evaluation. We divided the patients into recanalization and non-recanalization groups and analyzed risk factors for delayed recanalization. Results The univariate analysis revealed that an oral anticoagulant time of less than 3 months and venous thrombus location were risk factors for delayed recanalization (P<0.01). However, age, gender, hypertension, diabetes, pulmonary embolism, incidence factors, the use of catheter-directed thrombolytic (CDT) drugs, and inferior vena cava filter (IVCF) implantation had no influence on the incidence of delayed recanalization in patients with DVT (P>0.05). The multivariate analysis showed that patients with an anticoagulant time of less than 3 months had a lower incidence of recanalization than those with an anticoagulant time of more than 3 months (OR=2.358, P<0.05). The risk of delayed recanalization in patients with proximal DVT was 7 times higher than that in patients with distal DVT. Conclusions Duration of anticoagulant treatment of less than 3 months and venous thrombus location are independent risk factors for delayed recanalization of DVT in the lower extremities. PMID:26790571

  16. Triple anticoagulation therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention – real life assessment

    PubMed Central

    Kabłak-Ziembicka, Anna; Bryniarski, Krzysztof; Wrotniak, Leszek; Ostrowska-Kaim, Elżbieta; Żmudka, Krzysztof; Przewłocki, Tadeusz

    2016-01-01

    Introduction Triple anticoagulation therapy (TT), comprising dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC), is essential in atrial fibrillation (AF) patients after percutaneous coronary intervention (PCI), but it increases the bleeding risk. Aim To assess TT models, in- and out-hospital bleeding and thromboembolic complications, and TT alterations. Material and methods During 12 months, consecutive AF post-PCI patients were scheduled for TT. Alterations in TT and thromboembolic events (death, myocardial infarction, ischemic stroke, in-stent thrombosis, peripheral embolization) were recorded. Major, non-major and minor bleeding episodes were assessed. Results One hundred and thirty-six out of 3171 patients, aged 73.0 ±8.4 years (90 male), were included. Intra-hospitally, thrombotic events occurred in 9 (6.6%), while bleeding events occurred in 71 (52.2%) patients. Access-site hematoma and blood transfusions during in-hospital stay predisposed physicians to heparin administration as part of TT on discharge (p = 0.018 and p = 0.033 respectively). Eventually, DAPT plus warfarin or plus novel oral anticoagulant (NOAC) or plus low molecular weight heparin was prescribed in 72 (52.9%), 53 (39%), and 11 (8.1%) patients, respectively. HAS-BLED and CHA2DS2-VASc scores were similar between subgroups (p = 0.63 and p = 0.64 respectively). During 10.2 ±4.2 months of follow-up, 11 (8.1%) deaths, and 9 (6.6%) non-fatal thromboembolic events occurred. Bleeding events occurred in 45 (34.6%) patients, including 14 (10.3%) major. TT was the only factor associated with increased risk of major bleeding (18.6% vs. 4.2%, p = 0.008). Early termination of any TT component, which concerned 59 (45.4%) patients, did not increase the risk of thromboembolic events (p = 0.89). Conclusions Our study indicates that TT is associated with high mortality and bleeding rates in a relatively short period of time. Discontinuation of any TT drug did not increase the thromboembolic event

  17. Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy

    PubMed Central

    Labovitz, Daniel L.; Shafner, Laura; Gil, Morayma Reyes; Virmani, Deepti; Hanina, Adam

    2017-01-01

    Background and Purpose This study evaluated the use of an artificial intelligence (AI) platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants (DOACs), while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding. Methods A randomized, parallel-group, 12-week study was conducted in adults (n = 28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the AI Platform (intervention) or to no daily monitoring (control). The AI application visually identified the patient, the medication and confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups. Results For all patients (n = 28), mean (standard deviation [SD]) age was 57 (13.2) years and 53.6% were female. Mean (SD) cumulative adherence based on the AI Platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively. Conclusions Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving DOACs, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on DOAC therapy. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259. PMID:28386037

  18. Anticoagulant therapy: basic principles, classic approaches and recent developments.

    PubMed

    Sinauridze, Elena I; Panteleev, Mikhail A; Ataullakhanov, Fazoil I

    2012-09-01

    The standard multipotent anticoagulants (unfractionated and low molecular weight heparins, antagonists of vitamin K) are commonly used for treatment and/or prophylaxis of different thrombotic complications, such as deep vein thrombosis, thrombophilia, pulmonary embolism, myocardial infarction, stroke and so on. Advantages and shortcomings of these anticoagulants are considered. The modern tendencies to use small selective direct inhibitors of thrombin or factor Xa are surveyed. The search of the new targets in the coagulation cascade for development of new promising anticoagulants and improvement in antithrombotic therapy is discussed.

  19. Development of Interstitial Lung Disease after Initiation of Apixaban Anticoagulation Therapy.

    PubMed

    Tomari, Shinya; Homma, Kazunari; Noguchi, Teruo; Aiba, Takeshi; Matsuki, Takayuki; Suzuki, Rieko; Koga, Masatoshi; Takigami, Masao; Tagawa, Hiroshi; Hashimoto, Taisuke; Toyoda, Kazunori

    2016-07-01

    Nonvitamin K antagonist oral anticoagulants may cause interstitial lung disease (ILD) similar to that seen for other cardiovascular drugs. The aim of this study was to determine trends and medical conditions associated with ILD in patients taking apixaban. A single-center observational survey conducted between February 2013 and May 2015 examined patients who developed ILD after initiation of apixaban administration. Chest computed tomography showed that 4 (~.45%) out of approximately 870 apixaban users developed ILD. All patients were elderly Japanese men with decreased creatinine clearance who had nonvalvular atrial fibrillation. Three of the four were confirmed smokers, whereas three had a history of lung disease. Dyspnea occurred during the initial week after starting apixaban administration in 3 patients and at 90 days in 1 patient. All patients underwent methylprednisolone pulse therapy, with three requiring mechanical ventilation. Although 2 patients recovered, the other two died of respiratory failure. Development of ILD during anticoagulation with apixaban is not rare. When apixaban is administered in elderly high-risk patients, subjects need to be carefully monitored for respiratory symptoms. As drug-induced ILD is often reported in Japan, further studies that clarify if these types of cases are common in countries other than Japan will also need to be undertaken. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. [The study of anticoagulants selection in platelet-rich plasma preparation].

    PubMed

    Hua, Lei; Lai, Gui; Zhenjun, Liu; Guie, Ma

    2015-07-01

    To investigate the effect of the anticoagulants on PRP quality, so as to clarify the appropriate anticoagulant used in PRP production. The microstructure change of platelets collected via heparin, citrate, acid citrate dextrose (ACD) and citrate-theophylline-adenosine-dipyridamole ( CTAD) was observed by TEM following time course. The extent of spontaneous activation of platelets in four groups was detected by measuring sP-selectin in plasma. The TGF-β1 release amount of activated PRP of four groups was measured. CTAD is superior to other anticoagulants in maintaining the integrity of platelet structures for a long time and preventing platelet spontaneous activation. ACD slightly surpassed heparin and citrate in above two aspects. ACD-PRP and CTAD-PRP released significantly more TGF-β1 compared with heparin and citrate. The PRP quality and biological effects were strongly associated with the type of Anticoagulants. ACD and CTAD are optimal anticoagulants in PRP production for they can maintain platelet viability at a high level.

  1. New Anticoagulant Agents: Incidence of Adverse Drug Reactions and New Signals Thereof.

    PubMed

    Treceño-Lobato, Carlos; Jiménez-Serranía, María-Isabel; Martínez-García, Raquel; Corzo-Delibes, Francisco; Martín Arias, Luis H

    2018-06-04

    The aim of this study was to evaluate the adverse drug reaction (ADR) incidence rate and new signals thereof for classic compared with new anticoagulants in real-life ambulatory settings. The authors performed an observational cross-sectional study in two cohorts of surveyed patients treated with vitamin K antagonists (VKAs; acenocoumarol or warfarin) or nonvitamin K antagonist oral anticoagulants (NOACs; apixaban, edoxaban, rivaroxaban, dabigatran etexilate). Descriptive, clinical, and ADRs data were reported and analyzed through a bivariate analysis (odds ratio [OR]) to compare the ADRs incidence rate and an adaptation of Bayesian methodology (false discovery rate [FDR] < 0.05) to detect new signals. A total of 334 patients were surveyed-average international normalized ratio (INR) of 2.6-and 45.4% taking new anticoagulants. Note that 835 ADRs were reported; 2.5 per patient (2.8 in the VKA cohort, 2.1 in the NOAC cohort). The authors obtained higher risk of epistaxis (OR, 2.18; 95% confidence interval [CI], 1.01-4.74) and hematoma (OR, 2.43; 95% CI, 1.39-4.25) with VKAs and lower risk of global bleeding symptoms with NOACs (OR, 0.45; 95% CI, 0.28-0.71). After standardizing the data, a significant risk of diarrhea with VKAs was observed (OR, 3.37; 95% CI, 1.09-10.41). They also detected an intense positive signal regarding the use of VKAs and osteoporosis (FDR < 0.001), specifically acenocoumarol (FDR < 0.002). NOACs presented lower risk of bleeding, especially dabigatran (FDR < 0.031), and of dermatological pathologies with apixaban being the safest (FDR = 0.050). The lower risk of global bleeding and a potential protective effect against osteoporosis in patients treated with NOACs postulate them as safer than VKAs. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Low-molecular-weight heparin for the long-term treatment of symptomatic venous thromboembolism: meta-analysis of the randomized comparisons with oral anticoagulants.

    PubMed

    Iorio, A; Guercini, F; Pini, M

    2003-09-01

    The management of venous thromboembolism (VTE) requires an initial treatment with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH), followed by oral anticoagulants (OA) for at least 3 months. OA treatment however, requires laboratory monitoring of anticoagulation, carries a definite risk of bleeding, and may be contraindicated in some patients. As an alternative to vitamin K antagonists, subcutaneous LMWH has been proposed and evaluated in randomized clinical trials, but they are all small studies that lack the power to establish if these two treatment modalities are equivalent in efficacy or safety. The objective of this review was to evaluate the efficacy (VTE recurrence) and safety (bleeds and deaths) of long-term treatment of VTE with LMWH compared with OA. A secondary endpoint was to evaluate the effect of LMWH on cancer mortality. Computerized searches of MedLine and EmBase were performed. In addition, randomized clinical trials were located through personal communication with colleagues, and through the manual scanning of meeting proceedings and reference lists of relevant studies. When necessary, the authors of the selected papers were called to obtain additional information. Two reviewers (AI and FG) reviewed and extracted data independently using a standard form. The primary analysis was performed for efficacy and safety endpoints on an intention-to-treat basis for the study period of randomized treatment. A meta-regression analysis was used to investigate the relationship between daily dose and clinical outcome. Seven studies that fulfillled our predefined criteria were identified, for a total of 1379 patients. When all studies were combined, a statistically non-significant reduction in the risk of VTE (OR 0.66; 95% confidence interval [CI] 0.41, 1.07) and in the risk of major bleeding (OR 0.45; 95% CI 0.18, 1.11) in favor of LMWH treatment was found. No difference in total mortality (OR 1.19; 95% CI 0.78, 1.83) or in cancer

  3. Risk of renal failure with the non-vitamin K antagonist oral anticoagulants: systematic review and meta-analysis.

    PubMed

    Caldeira, Daniel; Gonçalves, Nilza; Pinto, Fausto J; Costa, João; Ferreira, Joaquim J

    2015-07-01

    Vitamin K antagonists (VKA)-related nephropathy is a novel entity characterized by acute kidney injury related to International Normalized Ratio supratherapeutic levels. Non-vitamin K antagonists oral anticoagulants (NOACs) have a predictable dose-response relationship and an improved safety profile. We hypothesized that these drugs do not have an increased risk of incident renal failure, which may be detrimental for the use of NOACs. Systematic review and meta-analysis of phase III randomized controlled trials (RCTs). Trials were searched through Medline, Cochrane Library and public assessment reports in August 2014. Primary outcome was renal failure. NOACs were evaluated against any comparator. Random-effects meta-analysis was performed by default, and pooled estimates were expressed as Risk Ratio (RR) and 95%CI. Heterogeneity was evaluated with I(2) test. Ten RCTs fulfilled inclusion criteria (one apixaban RCT, three dabigatran RCTs, and six rivaroxaban RCTs), enrolling 75 100 patients. Overall NOACs did not increase the risk of renal failure with an RR 0.96, 95%CI 0.88-1.05 compared with VKA or Low-molecular weight heparin (LMWH), without significant statistical heterogeneity (I(2)  = 3.5%). Compared with VKA, NOACs did not increase the risk of renal failure (RR 0.96, 95%CI 0.87-1.07; I(2)  = 17.8%; six RCTs). Rivaroxaban did not show differences in the incidence of renal failure compared with LMWH (RR 1.20, 95%CI 0.37-3.94; four trials), but there was an increased risk of creatinine elevation RR 1.25, 95%CI 1.08-1.45; I(2)  = 0%. NOACs had a similar risk of renal failure compared with VKA/LMWH in phase III RCTs. Post-marketing surveillance should be warranted. Copyright © 2015 John Wiley & Sons, Ltd.

  4. VKORC1 and VKORC1L1 have distinctly different oral anticoagulant dose-response characteristics and binding sites

    PubMed Central

    Czogalla, Katrin J.; Liphardt, Kerstin; Höning, Klara; Hornung, Veit; Biswas, Arijit; Watzka, Matthias

    2018-01-01

    Vitamin K reduction is catalyzed by 2 enzymes in vitro: the vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) and its isozyme VKORC1-like1 (VKORC1L1). In vivo, VKORC1 reduces vitamin K to sustain γ-carboxylation of vitamin K-dependent proteins, including coagulation factors. Inhibition of VKORC1 by oral anticoagulants (OACs) is clinically used in therapy and in prevention of thrombosis. However, OACs also inhibit VKORC1L1, which was previously shown to play a role in intracellular redox homeostasis in vitro. Here, we report data for the first time on specific inhibition of both VKOR enzymes for various OACs and rodenticides examined in a cell-based assay. Effects on endogenous VKORC1 and VKORC1L1 were independently investigated in genetically engineered HEK 293T cells that were knocked out for the respective genes by CRISPR/Cas9 technology. In general, dose-responses for 4-hydroxycoumarins and 1,3-indandiones were enzyme-dependent, with lower susceptibility for VKORC1L1 compared with VKORC1. In contrast, rodenticides exhibited nearly identical dose-responses for both enzymes. To explain the distinct inhibition pattern, we performed in silico modeling suggesting different warfarin binding sites for VKORC1 and VKORC1L1. We identified arginine residues at positions 38, 42, and 68 in the endoplasmatic reticulum luminal loop of VKORC1L1 responsible for charge-stabilized warfarin binding, resulting in a binding pocket that is diametrically opposite to that of VKORC1. In conclusion, our findings provide insight into structural and molecular drug binding on VKORC1, and especially on VKORC1L1. PMID:29581108

  5. Effects of Marine Fish Oils on the Anticoagulation Status of Patients Receiving Chronic Warfarin Therapy.

    PubMed

    Bender; Kraynak; Chiquette; Linn; Clark; Bussey

    1998-07-01

    The purpose of this placebo-controlled, randomized, double-blinded, parallel study was to determine the existence and magnitude of effect of various doses of fish oil supplements on International Normalized Ratio (INR) determinations in patients receiving chronic warfarin therapy. Patients from anticoagulation clinics from both the Brady Green Community Health Center and Audie L. Murphy Veterans Administration in San Antonio, Texas were enrolled in the study. The enrolled subjects included 5 males and 11 females, all of whom were receiving chronic warfarin therapy for indications requiring oral anticoagulation. All enrolled patients underwent a 4-week placebo monitoring period in which INRs were determined on a weekly basis. If the INRs were found to be stable, patients were randomized to receive a 4-week treatment period of either placebo capsules (n = 6), 3 grams of fish oil daily (n = 5), or 6 grams of fish oil daily (n = 5). Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. Five patients were discontinued from the study due to noncompliance (2) and unstable INRs (3). There was no statistically significant difference in INRs between the placebo lead-in and treatment period within each group (P = 0.82). There was also no difference in INRs found between groups (P= 0.41). One bruising episode was reported, yet no major bleeding episodes were observed during the study. Fish oil supplementation in doses of 3-6 grams per day does not seem to create a statistically significant effect on the anticoagulation status of patients receiving chronic warfarin therapy.

  6. Symptoms of depression and anxiety predict mortality in patients undergoing oral anticoagulation: Results from the thrombEVAL study program.

    PubMed

    Michal, Matthias; Prochaska, Jürgen H; Keller, Karsten; Göbel, Sebastian; Coldewey, Meike; Ullmann, Alexander; Schulz, Andreas; Lamparter, Heidrun; Münzel, Thomas; Reiner, Iris; Beutel, Manfred E; Wild, Philipp S

    2015-01-01

    Depression and anxiety are highly prevalent in cardiovascular patients. Therefore, we examined whether the 4-item Patient Health Questionnaire (PHQ-4, measuring symptoms of depression and anxiety) predicts all-cause mortality in outpatients with long-term oral anticoagulation (OAC). The sample comprised n=1384 outpatients from a regular medical care setting receiving long-term OAC with vitamin K antagonists. At baseline, symptoms of anxiety and depression were assessed with the PHQ-4 and the past medical history was taken. The outcome was all-cause mortality in the 24 month observation period. The median follow-up time was 13.3 months. N=191 patients from n=1384 died (death rate 13.8%). Each point increase in the PHQ-4 score was associated with a 10% increase in mortality (hazard ratio [HR] 1.10, 95% confidence interval [95% CI] 1.05-1.16) after adjustment for age, sex, high school graduation, partnership, smoking, obesity, frailty according to the Barthel Index, Charlson Comorbidity Index and CHA2DS2-VASc score. The depression component (PHQ-2) increased mortality by 22% and anxiety (GAD-2) by 11% respectively. Neither medical history of any mental disorder, nor intake of antidepressants, anxiolytics or hypnotics predicted excess mortality. Elevated symptoms of depression and, to a lesser degree, symptoms of anxiety are independently associated with all-cause mortality in OAC outpatients. The PHQ-4 questionnaire provides valuable prognostic information. These findings emphasize the need for implementing regular screening procedures and the development and evaluation of appropriate psychosocial treatment approaches for OAC patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Evaluation of the anticoagulant potential of polysaccharide-rich fractions extracted from macroalgae.

    PubMed

    Adrien, Amandine; Dufour, Delphine; Baudouin, Stanislas; Maugard, Thierry; Bridiau, Nicolas

    2017-09-01

    The aim of this study was to evaluate the potential anticoagulant activity of sulphated polysaccharide-containing extracts of six french edible marine macroalgae. Aqueous extracts of brown (Himanthalia elongata, Laminaria digitata, Ascophyllum nodosum, Fucus vesiculosus), green (Ulva lactuca) and red (Chondrus crispus) macroalgae were prepared and their biochemical properties were determined, including major biomolecules, sulphate and ash contents. The anticoagulant activity of each extract was investigated using different scales from the specific antithrombin-dependent pathway (anti-Xa and anti-IIa) to the intrinsic and/or common (Activated Partial Thromboplastin Time, APTT), extrinsic (Prothrombin Time, PT) or common (Thrombin Time, TT) anticoagulant pathways, and compared with those of commercial anticoagulants, heparin and Lovenox®. Laminaria digitata, Fucus vesiculosus and Chondrus crispus extracts showed a significant APTT anticoagulant capacity, only 5-fold lower than that of Lovenox®, which is a pure low molecular weight heparin used as an anticoagulant agent to prevent pulmonary embolism in patients undergoing surgery.

  8. Relations of Anticoagulant Therapy with Cognitive Impairment among Patients with Atrial Fibrillation: A Meta-Analysis and Systematic Review.

    PubMed

    Cheng, Wenke; Liu, Weijun; Li, Bin; Li, Dongfang

    2018-03-02

    Currently, it is considered that atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia, which is independent of stroke. However, the relationship between anticoagulant drugs and cognitive function in patients with atrial fibrillation is unknown. This study aimed to complete a meta-analysis, and investigate the association between Anticoagulant therapy and cognitive impairment in patients undergoing AF. Two investigators systematically searched the Cochrane Library, PubMed, Embase databases and Web of Science for all studies showing associations. Hazard ratios (HRs) were extracted and pooled. 8 studies included 471057 participants; TTR < 25% vs TTR> 75%; (HR 3.02, 95% CI 1.12-8.91; P=0.03); TTR 25-50% vs TTR> 75% (HR 2.44, 95% CI 0.95-6.22; P=0.06); TTR 50-75% vs TTR> 75% (HR 1.75, 95% CI 0.90-3.99; P=0.1); OAC vs No OAC (HR 0.71, 95% CI.69-0.74; P<0.00001) NOAC vs warfarin (HR0.51, 95% CI0.37-0.71; P<0.00001). Oral anticoagulants (OAC) significantly reduce the occurrence of cognitive impairment in patients with atrial fibrillation. Compared with warfarin, NOAC has an efficiently protective effect on cognition. In the range of INR2-3, with the increase of TTR, the incidence of cognitive impairment is lower.

  9. Patient Factors But Not the Use of Novel Anticoagulants or Warfarin Are Associated With Internal Jugular Vein Access-Site Hematoma After Right Heart Catheterization.

    PubMed

    Dasa, Osama; Shafiq, Qaiser; Ruzieh, Mohammed; Alhazmi, Luai; Al-Dabbas, Maen; Ammari, Zaid; Khouri, Samer; Moukarbel, George

    2017-12-01

    Right heart catheterization (RHC) is routinely performed to assess hemodynamics. Generally, anticoagulants are held prior to the procedure. At our center, anticoagulants are continued and ultrasound guidance is always used for internal jugular vein access. A micropuncture access kit is used to place a 5 or 6 Fr sheath using the modified Seldinger technique. Manual compression is applied for 10-15 min and the patient is observed for at least 2 hours after the procedure. In a retrospective analysis, we investigated the risk of bleeding complications associated with RHC via the internal jugular vein in patients with and without full anticoagulation. Our catheterization laboratory database was searched for adult patients who underwent RHC by a single operator between January 2012 and December 2015. A total of 571 patients were included in the analysis. Baseline characteristics, labs, relevant invasive hemodynamics, co-morbid conditions, and incidence of access-site hematoma are presented. Multivariable binary logistic regression was performed using IBM SPSS v. 23.0 software. Statistically significant associations with access-site hematoma were observed with body mass index (P=.02; 95% confidence interval [CI], 1.0-1.1), right atrial pressure (P=.03; 95% CI, 0.7-0.9), and dialysis dependence (P<.01; 95% CI, 0.1-0.6). There was no association of access-site hematoma with the use of anticoagulants (P>.99). The incidence of internal jugular vein access-site hematoma is small when using careful access techniques for RHC even with the continued use of novel oral anticoagulants and warfarin. Patient characteristics and co-morbid conditions are related to bleeding complications.

  10. Design of anticoagulant surfaces based on cellulose nanocrystals.

    PubMed

    Ehmann, Heike M A; Mohan, Tamilselvan; Koshanskaya, Maria; Scheicher, Sylvia; Breitwieser, Doris; Ribitsch, Volker; Stana-Kleinschek, Karin; Spirk, Stefan

    2014-11-07

    The anticoagulant activity of surfaces decorated with cellulose nanocrystals (CNCs) prepared via sulfuric acid hydrolysis, is explored. Such surfaces bear a high amount of negatively charged sulfate groups, which mimic the naturally occurring anticoagulant heparin in terms of charge density. It is demonstrated that CNC decorated surfaces significantly enhance the coagulation times of blood plasma and whole blood as proven by QCM-D and simple clotting tests.

  11. Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study.

    PubMed

    Jun, Min; Lix, Lisa M; Durand, Madeleine; Dahl, Matt; Paterson, J Michael; Dormuth, Colin R; Ernst, Pierre; Yao, Shenzhen; Renoux, Christel; Tamim, Hala; Wu, Cynthia; Mahmud, Salaheddin M; Hemmelgarn, Brenda R

    2017-10-17

    Objective  To determine the safety of direct oral anticoagulant (DOAC) use compared with warfarin use for the treatment of venous thromboembolism. Design  Retrospective matched cohort study conducted between 1 January 2009 and 31 March 2016. Setting  Community based, using healthcare data from six jurisdictions in Canada and the United States. Participants  59 525 adults (12 489 DOAC users; 47 036 warfarin users) with a new diagnosis of venous thromboembolism and a prescription for a DOAC or warfarin within 30 days of diagnosis. Main outcome measures  Outcomes included hospital admission or emergency department visit for major bleeding and all cause mortality within 90 days after starting treatment. Propensity score matching and shared frailty models were used to estimate adjusted hazard ratios of the outcomes comparing DOACs with warfarin. Analyses were conducted independently at each site, with meta-analytical methods used to estimate pooled hazard ratios across sites. Results  Of the 59 525 participants, 1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2 days. The risk of major bleeding was similar for DOAC compared with warfarin use (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the overall direction of the association favouring DOAC use. No difference was found in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared with warfarin use. There was no evidence of heterogeneity across centres, between patients with and without chronic kidney disease, across age groups, or between male and female patients. Conclusions  In this analysis of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with an increased risk of major bleeding or all cause mortality in the first 90 days of treatment. Trial registration  Clinical trials NCT02833987. Published by the BMJ Publishing Group Limited. For permission to use (where not

  12. Primary Nonadherence to Oral Anticoagulants in Patients with Atrial Fibrillation: Real-World Data from a Population-Based Cohort.

    PubMed

    Rodriguez-Bernal, Clara L; Peiró, Salvador; Hurtado, Isabel; García-Sempere, Aníbal; Sanfélix-Gimeno, Gabriel

    2018-05-01

    Primary nonadherence (not filling a first prescription) is an important yet unstudied aspect of adherence to oral anticoagulant (OAC) therapy. To estimate the rates of primary nonadherence to OACs and determine associated factors in real-world practice. This population-based retrospective cohort study set in the Valencia region of Spain (about 5 million inhabitants) included all patients with atrial fibrillation who were newly prescribed OACs during 2011-2014 (N = 18,715). Primary nonadherence was obtained by linking electronic prescription and dispensing data and assessed by type of OAC-vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs). Covariates were obtained from diverse databases, including electronic medical records. Multivariate logistic regression models were used to assess characteristics associated with primary nonadherence, adjusting for a propensity score to minimize confounding by indication. Primary nonadherence to OACs was 5.62% (VKA 4.29% vs. NOAC 10.81%; P < 0.001), with varying rates among specific drugs (acenocoumarol 4.2%, warfarin 10.9%, apixaban 5.0%, dabigatran 7.9%, and rivaroxaban 15.5%). After adjusting for potential confounders, the likelihood of not filling the first prescription was higher for NOAC patients than for VKA patients (OR = 2.76, 95% CI = 2.41-3.15). High coinsurance in the older groups (OR = 2.63, 95% CI = 1.47-4.69 for patients aged 66-75 years and OR = 3.02, 95% CI = 1.58-5.76 for patients aged > 75 years); being a non-Spanish European (OR = 1.49, 95% CI = 1.12-1.99); and having dementia (OR = 1.72, 95% CI = 1.37-2.16) were positively associated with primary nonadherence. Electronic transmission of prescriptions (OR = 0.85, 95% CI = 0.74-0.96); liver disease (OR = 0.73, 95% CI = 0.54-0.99); and polypharmacy (OR = 0.59, 95% CI = 0.50-0.70) were inversely associated with primary nonadherence. Overall, primary nonadherence to OACs was relatively low (5%). However, important differences were found between

  13. Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding.

    PubMed

    Parks, Anna L; Fang, Margaret C

    2017-07-01

    Anticoagulant medications are frequently used to prevent and treat thromboembolic disease. However, the benefits of anticoagulants must be balanced with a careful assessment of the risk of bleeding complications that can ensue from their use. Several bleeding risk scores are available, including the Outpatient Bleeding Risk Index, HAS-BLED, ATRIA, and HEMORR 2 HAGES risk assessment tools, and can be used to help estimate patients' risk for bleeding on anticoagulants. These tools vary by their individual risk components and in how they define and weigh clinical factors. However, it is not yet clear how best to integrate bleeding risk tools into clinical practice. Current bleeding risk scores generally have modest predictive ability and limited ability to predict the most devastating complication of anticoagulation, intracranial hemorrhage. In clinical practice, bleeding risk tools should be paired with a formal determination of thrombosis risk, as their results may be most influential for patients at the lower end of thrombosis risk, as well as for highlighting potentially modifiable risk factors for bleeding. Use of bleeding risk scores may assist clinicians and patients in making informed and individualized anticoagulation decisions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial.

    PubMed

    Pol, Tymon; Held, Claes; Westerbergh, Johan; Lindbäck, Johan; Alexander, John H; Alings, Marco; Erol, Cetin; Goto, Shinya; Halvorsen, Sigrun; Huber, Kurt; Hanna, Michael; Lopes, Renato D; Ruzyllo, Witold; Granger, Christopher B; Hijazi, Ziad

    2018-02-01

    Dyslipidemia is a major risk factor for cardiovascular events. The prognostic importance of lipoproteins in patients with atrial fibrillation is not well understood. We aimed to explore the association between apolipoprotein A1 (ApoA1) and B (ApoB) and cardiovascular events in patients with atrial fibrillation receiving oral anticoagulation. Using data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, ApoA1 and ApoB plasma levels were measured at baseline in 14 884 atrial fibrillation patients. Median length of follow-up was 1.9 years. Relationships between continuous levels of ApoA1 and ApoB and clinical outcomes were evaluated using Cox models adjusted for cardiovascular risk factors, medication including statins, and cardiovascular biomarkers. A composite ischemic outcome (ischemic stroke, systemic embolism, myocardial infarction, and cardiovascular death) was used as the primary end point. Median (25th, 75th) ApoA1 and ApoB levels were 1.10 (0.93, 1.30) and 0.70 g/L (0.55, 0.85), respectively. In adjusted analyses, higher levels of ApoA1 were independently associated with a lower risk of the composite ischemic outcome (hazard ratio, 0.81; P <0.0001). Similar results were observed for the individual components of the composite outcome. ApoB was not significantly associated with the composite ischemic outcome ( P =0.8240). Neither apolipoprotein was significantly associated with major bleeding. There was no interaction between lipoproteins and randomized treatment for the primary outcome (both P values ≥0.2448). In patients with atrial fibrillation on oral anticoagulation, higher levels of ApoA1 were independently associated with lower risk of ischemic cardiovascular outcomes. Investigating therapies targeting dyslipidemia may thus be useful to improve cardiovascular outcomes in patients with atrial fibrillation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984. © 2018 The

  15. Quality of anticoagulation control: do race and language matter?

    PubMed

    Bhandari, Vijay Kumar; Wang, Frances; Bindman, Andrew B; Schillinger, Dean

    2008-02-01

    No studies have evaluated the quality of anticoagulation control among populations characterized by low socioeconomic status, diverse racial and ethnic backgrounds, or limited English proficiency. We conducted a retrospective cohort study to evaluate the effects of race/ethnicity and language on anticoagulation outcomes among patients (N=864) receiving continuous anticoagulation services at a university-affiliated public hospital. White/non-Hispanic patients made up 24%, Asian/Pacific Islanders 33%, Hispanics 22%, African Americans 18%. English (63%), Spanish, (14%), and Cantonese (13%) were the most common languages. Mean time in therapeutic range (TTR) was 43%. After adjustment, TTR was lower for African Americans than for Whites (absolute difference, -8.7%, p< .001) and for Spanish-speaking than for English-speaking Hispanics (absolute difference, -7.2%, p< .05). There were no differences between Asian/Pacific Islanders and Whites, nor between Cantonese-speaking and English-speaking Asian/Pacific Islanders. Future research should examine mechanisms by which race/ethnicity and language affect quality of anticoagulation and evaluate programs to improve treatment in diverse communities.

  16. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature.

    PubMed

    Chan, W S; Anand, S; Ginsberg, J S

    2000-01-24

    The management of women with prosthetic heart valves during pregnancy poses a particular challenge as there are no available controlled clinical trials to provide guidelines for effective antithrombotic therapy. Oral anticoagulants such as warfarin sodium cause fetal embryopathy; subcutaneous administration of heparin sodium has been reported to be ineffective in preventing thromboembolic complications. To identify the risks of maternal and fetal complications in women with mechanical heart valves treated with different anticoagulation regimens during pregnancy. We performed a systematic review of the literature to determine pooled estimates of maternal and fetal risks associated with the 3 commonly used approaches: (1) oral anticoagulants (OA) throughout pregnancy, (2) replacing OA with heparin in the first trimester (from 6-12 weeks' gestation), and (3) heparin use throughout pregnancy. Fetal outcomes included spontaneous abortions and fetopathic effects, and maternal outcomes were major bleeding, thromboembolic complications, and death. The use of OA throughout pregnancy is associated with warfarin embryopathy in 6.4% (95% confidence interval [CI], 4.6%-8.9%) of livebirths. The substitution of heparin at or prior to 6 weeks, and continued until 12 weeks, eliminated this risk. Overall risks for fetal wastage (spontaneous abortion, stillbirths, and neonatal deaths) were similar in women treated with OA throughout, compared with women treated with heparin in the first trimester. Maternal mortality was 2.9% (95% CI, 1.9%-4.2%). Maj or bleeding events occurred in 2.5% (95% CI, 1.7%-3.5%) of all pregnancies, most at the time of delivery. The regimen associated with the lowest risk of valve thrombosis (3.9%; 95% CI, 2.9-5.9%) was the use of OA throughout; using heparin only between 6 and 12 weeks' gestation was associated with an increased risk of valve thrombosis (9.2%; 95% CI, 5.9%-13.9%). Thromboembolic prophylaxis of women with mechanical heart valves during

  17. The effect anticoagulation status on geriatric fall trauma patients.

    PubMed

    Coleman, Julia; Baldawi, Mustafa; Heidt, David

    2016-12-01

    This research study aims to identify the effect of anticoagulation status on hospital course, complications, and outcomes among geriatric fall trauma patients. The study design is a retrospective cohort study, looking at fall trauma among patients aged 60 to 80 years from 2009 to 2013 at a university hospital in the United States. The statistical analysis, conducted with SPSS software with a threshold for statistical significance of P < .05, was stratified by anticoagulation status and then further by type of anticoagulation (aspirin, warfarin, clopidogrel, enoxaparin, and dipyridamole). Outcomes variables include mortality, length of stay (LOS), intensive care unit (ICU) admission, and complications. The total number of patients included in this study was 1,121. Compared with patients not on anticoagulation, there was a higher LOS among patients on anticoagulation (6.3 ± 6.2 vs 4.9 ± 5.2, P = .001). A higher LOS (7.2 ± 6.8 vs 5.0 ± 5.3, P = .001) and days in the ICU (2.1 ± 5.4 vs 1.1 ± 3.8, P = .010) was observed in patients on warfarin. A higher mortality (7.1% vs 2.8%, P = .013), LOS (6.3 ± 6.2 vs 5.1 ± 5.396, P = .036), and complication rate (49.1 vs 36.7, P = .010) was observed among patients on clopidogrel. In this study, a higher mortality and complication rate were seen among clopidogrel, and a greater LOS and number of days in the ICU were seen in patients on warfarin. These differences are important, as they can serve as a screening tool for triaging the severity of a geriatric trauma patient's condition and complication risk. For patients on clopidogrel, it is essential that these patients are recognized early as high-risk patients who will need to be monitored more closely. For patients on clopidogrel or warfarin, bridging a patient's anticoagulation should be initiated as soon as possible to prevent unnecessary increased LOS. At last, these data also provide support against prescribing patients clopidogrel when other anticoagulation options

  18. Use and Outcomes of Antiarrhythmic Therapy in Patients with Atrial Fibrillation Receiving Oral Anticoagulation: Results from the ROCKET AF Trial

    PubMed Central

    Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Halperin, Jonathan L.; Breithardt, Günter; Passman, Rod; Hankey, Graeme J.; Patel, Manesh R.; Becker, Richard C.; Singer, Daniel E.; Hacke, Werner; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

    2014-01-01

    Background Antiarrhythmic drugs (AAD) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. Objective We aimed to study the use and outcomes of AAD therapy in anticoagulated AF patients. Methods Patients in the ROCKET AF trial (n=14,264) were grouped by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across groups, as well as across treatment assignment (rivaroxaban or warfarin). Results Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone, 537 [3.8%] with other AADs). Amiodarone-treated patients were less-often female (38% vs. 48%), had more persistent AF (64% vs. 40%), and more concomitant heart failure (71% vs. 41%) than patients receiving other AADs. Patients receiving no AAD more closely-resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone versus no AAD (50% vs. 58%, p<0.0001). Compared with no AAD, neither amiodarone (adjusted HR 0.98, 95% CI 0.74–1.31, p=0.9) nor other AADs (adjusted HR 0.66, 95% CI 0.37–1.17, p=0.15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Rivaroxaban treatment effects in patients not on an AAD were consistent with the overall trial (primary endpoint adjusted HR 0.82, 95% CI 0.68–0.98, pinteraction=0.06; safety endpoint adjusted HR 1.12, 95% CI 0.90–1.24, pinteraction=0.33). Conclusion Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The influence of amiodarone on outcomes in patients receiving rivaroxaban requires further study. PMID:24833235

  19. In-hospital mortality after pre-treatment with antiplatelet agents or oral anticoagulants and hematoma evacuation of intracerebral hematomas.

    PubMed

    Stein, Marco; Misselwitz, Björn; Hamann, Gerhard F; Kolodziej, Malgorzata; Reinges, Marcus H T; Uhl, Eberhard

    2016-04-01

    Pre-treatment with antiplatelet agents is described to be a risk factor for mortality after spontaneous intracerebral hemorrhage (ICH). However, the impact of antithrombotic agents on mortality in patients who undergo hematoma evacuation compared to conservatively treated patients with ICH remains controversial. This analysis is based on a prospective registry for quality assurance in stroke care in the State of Hesse, Germany. Patients' data were collected between January 2008 and December 2012. Only patients with the diagnosis of spontaneous ICH were included (International Classification of Diseases 10th Revision codes I61.0-I61.9). Predictors of in-hospital mortality were determined by univariate analysis. Predictors with P<0.1 were included in a binary logistic regression model. The binary logistic regression model was adjusted for age, initial Glasgow Coma Score (GCS), the presence of intraventricular hemorrhage (IVH), and pre-ICH disability prior to ictus. In 8,421 patients with spontaneous ICH, pre-treatment with oral anticoagulants or antiplatelet agents was documented in 16.3% and 25.1%, respectively. Overall in-hospital mortality was 23.2%. In-hospital mortality was decreased in operatively treated patients compared to conservatively treated patients (11.6% versus 24.0%; P<0.001). Patients with antiplatelet pre-treatment had a significantly higher risk of death during the hospital stay after hematoma evacuation (odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.24-4.97; P=0.010) compared to patients without antiplatelet pre-treatment treatment (OR: 0.9; 95% CI: 0.79-1.09; P=0.376). In conclusion a higher rate of in-hospital mortality after pre-treatment with antiplatelet agents in combination with hematoma evacuation after spontaneous ICH was observed in the presented cohort. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Anticoagulant rodenticides and wildlife: Introduction

    USGS Publications Warehouse

    van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.; van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.

    2018-01-01

    Rodents have interacted with people since the beginning of systematic food storage by humans in the early Neolithic era. Such interactions have had adverse outcomes such as threats to human health, spoiling and consumption of food sources, damage to human infrastructure and detrimental effects on indigenous island wildlife (through inadvertent anthropogenic assisted introductions). These socio/economic and environmental impacts illustrate the clear need to control populations of commensal rodents. Different methods have been applied historically but the main means of control in the last decades is through the application of rodenticides, mainly anticoagulant rodenticides (ARs) that inhibit blood clotting. The so-called First Generation Anticoagulant Rodenticides (FGARs) proved highly effective but rodents increasingly developed resistance. This led to a demand for more effective alternative compounds and paved the way to the development of Second Generation Anticoagulant Rodenticides (SGARs). These were more acutely toxic and persistent, making them more effective but also increasing the risks of exposure of non-target species and secondary poisoning of predatory species. SGARs often fail the environmental thresholds of different regulatory frameworks because of these negative side-effects, but their use is still permitted because of the overwhelming societal needs for rodent control and the lack of effective alternatives. This book provides a state-of-the-art overview of the scientific advancements in assessment of environmental exposure, effects and risks of currently used ARs. This is discussed in relation to the societal needs for rodent control, including risk mitigation and development of alternatives.

  1. Does sex affect anticoagulant use for stroke prevention in nonvalvular atrial fibrillation? The prospective global anticoagulant registry in the FIELD-Atrial Fibrillation.

    PubMed

    Lip, Gregory Y H; Rushton-Smith, Sophie K; Goldhaber, Samuel Z; Fitzmaurice, David A; Mantovani, Lorenzo G; Goto, Shinya; Haas, Sylvia; Bassand, Jean-Pierre; Camm, Alan John; Ambrosio, Giuseppe; Janský, Petr; Al Mahmeed, Wael; Oh, Seil; van Eickels, Martin; Raatikainen, Pekka; Steffel, Jan; Oto, Ali; Kayani, Gloria; Accetta, Gabriele; Kakkar, Ajay K

    2015-03-01

    Among patients with atrial fibrillation (AF), women are at higher risk of stroke than men. Using prospective cohort data from a large global population of patients with nonvalvular AF, we sought to identify any differences in the use of anticoagulants for stroke prevention in women and men. This was a prospective multicenter observational registry with 858 randomly selected sites in 30 countries. A total of 17 184 patients with newly diagnosed (≤6 weeks) nonvalvular AF and ≥1 additional investigator-defined stroke risk factor(s) were recruited (March 2010 to June 2013). The main outcome measure was the use of anticoagulants (vitamin K antagonists, factor Xa inhibitors, and direct thrombin inhibitors) for stroke prevention at AF diagnosis. Of 17 184 patients enrolled, 43.8% were women. More women than men were at moderate-to-high risk of stroke (CHADS2 score ≥2: 65.1% versus 54.7%). Rates of anticoagulant use were not different overall (60.9% of men versus 60.8% of women) and in patients with a CHADS2 score ≥2 (adjusted odds ratio for women versus men, 1.00; 95% confidence interval, 0.92-1.09). In patients at low risk (CHA2DS2-VASc of 0 in men and 1 in women), 41.8% of men and 41.1% of women received an anticoagulant. In patients at high risk (CHA2DS2-VASc score ≥2), 35.4% of men and 38.4% of women did not receive an anticoagulant. These contemporary global data show that anticoagulant use for stroke prevention is no different in men and women with nonvalvular AF. Thromboprophylaxis was, however, suboptimal in substantial proportions of men and women, with underuse in those at moderate-to-high risk of stroke and overuse in those at low risk. http://www.clinicaltrials.gov. Unique identifier: NCT01090362. © 2015 American Heart Association, Inc.

  2. Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon

    PubMed Central

    Verhoef, Talitha I; Redekop, William K; Daly, Ann K; van Schie, Rianne M F; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse

    2014-01-01

    Coumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon are frequently prescribed oral anticoagulants to treat and prevent thromboembolism. Because there is a large inter-individual and intra-individual variability in dose–response and a small therapeutic window, treatment with coumarin derivatives is challenging. Certain polymorphisms in CYP2C9 and VKORC1 are associated with lower dose requirements and a higher risk of bleeding. In this review we describe the use of different coumarin derivatives, pharmacokinetic characteristics of these drugs and differences amongst the coumarins. We also describe the current clinical challenges and the role of pharmacogenetic factors. These genetic factors are used to develop dosing algorithms and can be used to predict the right coumarin dose. The effectiveness of this new dosing strategy is currently being investigated in clinical trials. PMID:23919835

  3. The effect of the amiodarone-warfarin interaction on anticoagulation quality in a single, high-quality anticoagulation center.

    PubMed

    White, Ryan D; Riggs, Kyle W; Ege, Ed J; Petroski, Gregory F; Koerber, Scott M; Flaker, Greg

    2016-03-01

    Clinical trials have reported a low time in therapeutic range (TTR) in patients with atrial fibrillation treated with both warfarin andamiodarone. These trials included centers and countries with both high and low TTRs. What is the impact of amiodarone on the TTR in a single, high-quality anticoagulation clinic? TTR was assessed in amiodarone and nonamiodarone-treated patients from a University anticoagulation clinic. Baseline characteristics between patients ever-taking or never-taking amiodarone were similar, except more amiodarone patients were smokers (19.5 vs. 6.1%, P = 0.0031). The TTR calculated from 8901international normalized ratios (INRs) in 249 nonamiodarone patients with a mean follow-up of 34 ± 20 months (mean INR 36 ± 18) was 66 ± 16.6% compared with 61.3 ± 16.2% (P = 0.111) from 1455 INRs in 41 amiodarone-treated patients with a mean follow-up of 28 ± 20 months (mean INR 35 ± 22). Factors associated with a low TTR were male sex (P = 0.0013), smoker (P = 0.0048), and amiodarone use (P = 0.0374). A second on-treatment analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar findings; however, amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the TTR prior to amiodarone (54.5 ± 22.2%) was not significantly different in the first 3 months (54.6 ± 33.4%) or after 3 months (67.2 ± 33.7%) of amiodarone. In a single high-quality anticoagulation center, anticoagulation quality, as measured by the TTR, can be comparable in amiodarone and nonamiodarone-treated patients.

  4. Scintigraphic detection of occult hemorrhage in a patient receiving anticoagulants

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rosenbaum, R.C.; Johnston, G.S.; Whitley, N.O.

    1986-02-01

    The exact location of hemorrhage complicating anticoagulant therapy is sometimes difficult to establish. We present a case in which imaging with 99mTc-labeled red cells had a significant role in the diagnosis of soft-tissue bleeding in a paraplegic patient receiving long-term anticoagulation.

  5. Practicability of patient self-testing of oral anticoagulant therapy by the international normalized ratio (INR) using a portable whole blood monitor. A pilot investigation.

    PubMed

    Hasenkam, J M; Knudsen, L; Kimose, H H; Grønnesby, H; Attermann, J; Andersen, N T; Pilegaard, H K

    1997-01-01

    The prophylactic efficacy of long-term oral anticoagulant treatment (OAT) has been demonstrated in a number of clinical conditions with increased tendency to thromboembolism, and the number of individuals subjected to OAT in the industrialised world has increased substantially in recent years. Since this therapy requires considerable resources from both the health care system and the patients, the feasibility of patients' self-monitoring and self-management of OAT has been investigated (1,2,3). The anticipated advantages of this approach include improved convenience and compliance for the patient, who may increase his apprehension for managing the treatment. In addition, self-testing allows for more frequent control compared to the conventional out-patient approach. Importantly, a prerequisite for conceiving a safe and operational concept for patient self-management (PSM) is the availability of a portable INR monitoring system with an accuracy, precision, reproducibility, and long-term reliability comparable to standard coagulometric equipment. The purpose of the present study was to evaluate the feasibility of a commercially available INR-monitor. CoaguChek, for patient self-testing, through a step-wise investigation of the performance characteristics of the equipment in the laboratory, in command of the patient, and during self-testing and self-adjustment of treatment at home. Laboratory INR values were used as reference.

  6. Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

    PubMed

    Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

    2015-01-01

    Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.

  7. Effect of lysine clonixinate on the pharmacokinetics and anticoagulant activity of phenprocoumon.

    PubMed

    Russmann, S; Dilger, K; Trenk, D; Nagyivanyi, P; Jähnchen, E

    2001-11-01

    The effect of the non-steroidal anti-inflammatory drug lysine clonixinate ([2-(3-chloro-o-toluidino)nicotinic acid]-L-lysinate, CAS 55837-30-4) on the pharmacokinetics and anticoagulant activity of phenprocoumon (4-hydroxy-3-(1-phenylpropyl)-coumarin, CAS 435-97-2) was investigated in an open, randomised, two-fold, cross-over study in 12 healthy male volunteers. These subjects received a single dose of 18 mg phenprocoumon without or with concomitant treatment with lysine clonixinate (125 mg five times a day for 3 days before and 13 days after ingestion of a single dose of phenprocoumon). Pharmacokinetic parameters of phenprocoumon following oral administration were: CL/f: 0.779 +/- 0.157 ml/min, half-life of elimination: 147.2 +/- 19.9 h; free fraction in serum: 0.51 +/- 0.20%. These parameters were not significantly altered by concomitant treatment with lysine clonixinate. Prothrombin time increased from 13.3 +/- 1.3 s (at time 0) to 17.7 +/- 2.7 s following phenprocoumon and from 13.3 +/- 1.2 s to 18.0 +/- 2.2 s following combined administration. Prothrombin time returned to the pretreatment values 240 h after administration of phenprocoumon. The integrated effect (AUEC0-288 h) was identical following both treatments (4.303 +/- 461 and 4.303 +/- 312 s x h for phenprocoumon alone and phenprocoumon with lysine clonixinate, respectively). Thus, lysine clonixinate administered in therapeutic doses does not affect the pharmacokinetics and anticoagulant activity of phenproxoumon.

  8. Review of economics and cost-effectiveness analyses of anticoagulant therapy for stroke prevention in atrial fibrillation in the US.

    PubMed

    von Schéele, Birgitta; Fernandez, Maria; Hogue, Susan Lynn; Kwong, Winghan Jacqueline

    2013-05-01

    To summarize the available evidence on the issues in health economics related to oral anticoagulation for stroke prevention in atrial fibrillation (AF) in the US. A literature review was performed using PubMed, EMBASE, Cochrane Library, and International Pharmaceutical Abstracts, as well as the websites of professional organizations. The search was conducted according to a prespecified protocol, limiting articles to those published in English from 2001 to October 2012 and focused on the economics associated with AF and AF-related stroke in the US. Data from 27 studies were extracted and included in the review. Strokes in patients with AF are more debilitating and have higher recurrence rates and mortality compared with strokes unrelated to AF. However, data describing the long-term cost of AF-related stroke and stroke subtypes remain limited. The costs of major gastrointestinal (GI) bleeding and intracranial bleeding related to warfarin are significant, whereas the costs of the more frequent minor GI bleeding are relatively low. Overall, the cost-effectiveness of warfarin versus aspirin or no treatment in patients with at least 1 risk factor for stroke is well established. Economic evaluations based on results from randomized controlled clinical trials generally found that new anticoagulants were a cost-effective alternative to warfarin for stroke prevention in AF. However, these cost-effectiveness results are highly sensitive to how well optimal international normalized ratio control is maintained (within target of 2.0-3.0) for warfarin and the time horizon used for analysis. Time in therapeutic range for warfarin in routine clinical practice was lower than in clinical trials, as shown by previous studies. This review identified several areas of uncertainty regarding the economic benefit of anticoagulants. The generalizability of cost-effectiveness results of anticoagulant therapy in AF based on clinical trial data must be confirmed by comparative effectiveness

  9. Intravenous lipid emulsion does not reverse dabigatran-induced anticoagulation in a rat model.

    PubMed

    Blum, Jared; Carreiro, Stephanie; Hack, Jason B

    2013-10-01

    The anticoagulant dabigatran has no reversal agent and may cause life-threatening bleeding in patients with trauma or closed-space hemorrhage. Intravenous lipid emulsion (ILE) is thought to create a lipid compartment in serum that sequesters lipophilic drugs. Dabigatran is lipophilic, and its anticoagulant effects are concentration dependent. The study objective was to determine if ILE therapy reverses dabigatran's anticoagulant effects. Twenty rats were selected at random, 10 in the ILE group and 10 in a normal saline (NS) control group. Animals had a baseline tail bleeding time (T0), followed by oral dabigatran administration (15 mg/kg). At 45 minutes (T45), a second tail bleed time measurement was performed, followed by a 7-minute infusion of 15 mL/kg ILE or NS. A final 60-minute (T60) bleed time measurement was obtained. An ILE-only group of five animals had bleeding times assessed prior to (T0) and 15 minutes after (T15) ILE therapy. A mixed-effect repeated-measures analysis of variance modeling the effect of time, group, and the interaction of group and time on bleed times was conducted. There was a significant within-subject change in bleeding time across the assessment points (F(2,36) = 33; p < 0.001), but there were no effect of group (F(1,18) = 1.42, p = 0.25) or an interaction between group and assessment point on mean bleeding time (F(2,36) = 0.59, p = 56). Between T0 and T45, average bleeding times increased from 109.5 seconds (95% confidence interval [CI] = 94 to 125 seconds) to 231.8 seconds (95% CI = 193 to 271 seconds; p < 0.0001) for both the ILE group and the NS control group. Between T45 and T60, bleeding times in the ILE group decreased by 31.5 seconds (95% CI = -77 to 14 seconds) and by 6 seconds (95% CI = -67 to 55 seconds) in the NS group (p = 0.46). In the five ILE-only animals, the average bleeding time at T0 was 114 seconds (95% CI = 62 to 166 seconds), which increased significantly at T15 to 237

  10. Suboptimal Anticoagulant Management in Japanese Patients with Nonvalvular Atrial Fibrillation Receiving Warfarin for Stroke Prevention.

    PubMed

    Hirano, Teruyuki; Kaneko, Hirokazu; Mishina, Sari; Wang, Feng; Morita, Satoshi

    2017-10-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia, with increasing prevalence in Japan. Although prothrombin time-international normalized ratio (PT-INR) targets for monitoring warfarin therapy in patients with nonvalvular AF (NVAF) are well defined, real-world patient characteristics and PT-INR levels remain unknown among Japanese patients with NVAF who initiate and continue warfarin (warfarin maintainers) versus those who switch from warfarin to direct oral anticoagulants (DOACs; warfarin switchers). Patients with NVAF receiving oral anticoagulants between February 2013 and June 2015 were identified using a nationwide electronic medical record (EMR) database from 69 hospitals in Japan. Demographics and characteristics of patients, PT-INR, time in therapeutic range (TTR), and frequency in range (FIR) of PT-INR between warfarin maintainers and warfarin switchers were assessed. A total of 1705 patients met inclusion criteria and were examined (1501 warfarin maintainers versus 204 warfarin switchers). CHADS 2 , CHA 2 DS 2 -VASc, and HAS-BLED scores were comparable between groups. However, these scores were significantly higher among warfarin switchers at the time of switching than at the time of warfarin initiation. Furthermore, TTR and FIR of PT-INR were lower in warfarin switchers than in maintainers. Nevertheless, TTR and FIR were below 50% (PT-INR, 1.6-2.6) in both patient groups. In this EMR-based clinical study, patients who switched to DOACs had both poor or inadequate PT-INR control and higher risk factors of stroke. Many patients receiving warfarin did not achieve sufficient PT-INR therapeutic range. DOACs could be recommended in Japanese patients with NVAF with inadequate PT-INR control and increased risk of stroke. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. All-Cause, Stroke/Systemic Embolism-, and Major Bleeding-Related Health-Care Costs Among Elderly Patients With Nonvalvular Atrial Fibrillation Treated With Oral Anticoagulants.

    PubMed

    Deitelzweig, Steve; Luo, Xuemei; Gupta, Kiran; Trocio, Jeffrey; Mardekian, Jack; Curtice, Tammy; Hlavacek, Patrick; Lingohr-Smith, Melissa; Menges, Brandy; Lin, Jay

    2018-05-01

    In this study, all-cause, stroke/systemic embolism (SE)-related, and major bleeding (MB)-related health-care costs among elderly patients with nonvalvular atrial fibrillation (NVAF) initiating treatment with different oral anticoagulants (OACs) were compared. Patients ≥65 years of age initiating OACs, including apixaban, rivaroxaban, dabigatran, and warfarin, were identified from the Humana Research Database between January 1, 2013, and September 30, 2015. Propensity score matching was used to separately match the different OAC cohorts with the apixaban cohort. All-cause health-care costs and stroke/SE-related and MB-related medical costs per patient per month (PPPM) were compared using generalized linear or 2-part regression models. Compared to apixaban, rivaroxaban was associated with significantly higher all-cause health-care costs (US$2234 vs US$1846 PPPM, P < .001) and MB-related medical costs (US$106 vs US$47 PPPM, P < .001), dabigatran was associated with significantly higher all-cause health-care costs (US$1980 vs US$1801 PPPM, P = .007), and warfarin was associated with significantly higher all-cause health-care costs (US$2386 vs US$1929 PPPM, P < .001), stroke/SE-related medical costs (US$42 vs US$18 PPPM, P < .001), and MB-related medical costs (US$132 vs US$51 PPPM, P < .001). Among elderly patients with NVAF, other OACs were associated with higher all-cause health-care costs than apixaban.

  12. Patterns of direct oral anticoagulant drug prescription in France in 2010-2013: a study in the Midi-Pyrénées area.

    PubMed

    Diaz, Hugo; Bagheri, Haleh; Palmaro, Aurore; Rousseau, Vanessa; Bourrel, Robert; Montastruc, Jean-Louis; Birebent, Jordan

    2018-03-27

    The aim of our study was to study the pattern of prescription of direct-acting oral anticoagulants (DOACs) according to the French recommendations. We performed a cross-sectional study using anonymous data of patients covered by the French National Health Insurance information system (SNIIRAM) from 1 January 2010 to 31 December 2013 in the area of Midi-Pyrénées (southwest of France). Of the 355,608 patients identified, 325,216 (91.5%) were included, of whom 22,142 received at least one DOAC. About 39.1% (8,652 patients) had DOAC in an orthopedic indication, 46.5% (10,303 patients) in a cardiac indication, and 16.1% (3568 patients) in an indeterminate indication. Overall, guidelines were largely followed as for renal function monitoring, prescribing in orthopedic indications, in cardiac indications in patients aged 80 years and older, and in the case of concomitant use of verapamil. However, inappropriate prescriptions were observed for cardiac indications, and for dosage adjustments in orthopedic indications, with respect to both the age of patients (75 years and older) and those taking verapamil or amiodarone concomitantly. Guidelines were more followed in women and patients aged 80 or more. Among patients receiving DOACs, 58% were exposed to a prescription falling outside the guidelines. This study on DOAC prescription patterns revealed insufficiencies in the compliance with the French guidelines in certain indications.

  13. Health care expenditures and therapeutic outcomes of a pharmacist-managed anticoagulation service versus usual medical care.

    PubMed

    Hall, Deanne; Buchanan, Julianne; Helms, Bethany; Eberts, Matthew; Mark, Scott; Manolis, Chronis; Peele, Pamela; Docimo, Anne

    2011-07-01

    To evaluate the differences in health care expenditures and therapeutic outcomes of patients receiving warfarin therapy management by a pharmacist-managed anticoagulation service compared with those receiving warfarin management by usual medical care. Retrospective, matched-cohort study. University of Pittsburgh Medical Center (UPMC) and UPMC Health Plan. Three hundred fifty adults who received warfarin therapy; 175 were managed by the pharmacist-managed anticoagulation service for at least 2 months between October 1, 2007, and September 30, 2008, (case patients) and 175 received usual care (matched comparison group). Medical claims data compared were direct anticoagulation cost and overall medical care costs, anticoagulation-related adverse events, hospitalizations and emergency department visits, frequency of international normalized ratio (INR) testing, and quantity of warfarin refills. Operational costs of the anticoagulation service were also calculated. The INR values and time within therapeutic range were assessed through anticoagulation service reports and laboratory results. The direct anticoagulation care cost was $35,465 versus $111,586 and the overall medical care cost was $754,191 versus $1,480,661 for the anticoagulation service group versus the usual care group. Accounting for operational and drug expenditure costs, the cost savings was $647,024 for the anticoagulation service group. The anticoagulation service group had significantly fewer anticoagulation-related adverse events (14 vs 41, p<0.0001), hospital admissions (3 vs 14, p<0.00001), and emergency department visits (58 vs 134, p<0.00001). The percentage of INR values in range and the percentage of time the INR values were in range were significantly higher in the anticoagulation service group (67.2% vs 54.6%, p<0.0001, and 73.7% vs 61.3%, p<0.0001, respectively). Compared with the usual care group, the anticoagulation service group had significantly more INR tests performed but demonstrated

  14. Rivaroxaban in the cardiovascular world: a direct anticoagulant useful to prevent stroke and venous and arterial thromboembolism.

    PubMed

    Seoane, Leonardo; Cortés, Marcia; Aris Cancela, María Esther; Furmento, Juan; Baranchuk, Adrián; Conde, Diego

    2018-06-14

    Until recently, vitamin K antagonists (VKA) were the only drugs available for long-term anticoagulation. The use of these drugs is laborious due to their variable pharmacokinetics and pharmacodynamics. The advent of direct oral anticoagulants has produced a paradigm shift due to their low incidence of drug interactions, their stable plasma levels, and their lack of monitoring. Rivaroxaban, a factor Xa inhibitor, has been tested in different clinical scenarios and has proved to be effective and safe, even increasing the scope of the old VKA. Areas covered: A non-systematic review of the literature was conducted using the PubMed and Cochrane databases, focusing on randomized clinical trials and real-world observational studies that evaluated rivaroxaban in patients with atrial fibrillation, venous thromboembolism, and atherosclerotic coronary and peripheral vascular disease. Expert commentary: The role of rivaroxaban keeps expanding into areas that were unimaginable few years ago, in the light of solid evidence that has eliminated old strict paradigms. Nonetheless, it will be necessary to adjust costs and better understand the perceived barriers to its widespread implementation, to get fully acceptation of rivaroxaban for the different clinical conditions that have been suggested.

  15. Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation.

    PubMed

    Clarkesmith, Danielle E; Pattison, Helen M; Khaing, Phyo H; Lane, Deirdre A

    2017-04-05

    Current guidelines recommend oral anticoagulation therapy for patients with atrial fibrillation (AF) with one or more risk factors for stroke; however, anticoagulation control (time in therapeutic range (TTR)) with vitamin K antagonists (VKAs) is dependent on many factors. Educational and behavioural interventions may impact patients' ability to maintain their international normalised ratio (INR) control. This is an updated version of the original review first published in 2013. To evaluate the effects of educational and behavioural interventions for oral anticoagulation therapy (OAT) on TTR in patients with AF. We updated searches from the previous review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (January 2016, Issue 1), MEDLINE Ovid (1949 to February week 1 2016), EMBASE Classic + EMBASE Ovid (1980 to Week 7 2016), PsycINFO Ovid (1806 to Week 1 February 2016) and CINAHL Plus with Full Text EBSCO (1937 to 16/02/2016). We applied no language restrictions. We included randomised controlled trials evaluating the effect of any educational and behavioural intervention compared with usual care, no intervention, or intervention in combination with other self-management techniques among adults with AF who were eligible for, or currently receiving, OAT. Two of the review authors independently selected studies and extracted data. Risk of bias was assessed using the Cochrane 'Risk of bias' tool. We included outcome data on TTR, decision conflict (patient's uncertainty in making health-related decisions), percentage of INRs in the therapeutic range, major bleeding, stroke and thromboembolic events, patient knowledge, patient satisfaction, quality of life (QoL), beliefs about medication, illness perceptions, and anxiety and depression. We pooled data for three outcomes - TTR, anxiety and depression, and decision conflict - and reported mean differences (MD). Where

  16. Adherence to non-vitamin-K-antagonist oral anticoagulant medications based on the Pharmacy Quality Alliance measure.

    PubMed

    McHorney, Colleen A; Crivera, Concetta; Laliberté, François; Nelson, Winnie W; Germain, Guillaume; Bookhart, Brahim; Martin, Silas; Schein, Jeffrey; Lefebvre, Patrick; Deitelzweig, Steven

    2015-12-01

    CMS Star Ratings help inform beneficiaries about the performance of health and drug plans. Medication adherence is currently weighted at nearly half of a Part D plan's Star Ratings. Including the adherence to non-vitamin-K-antagonist oral anticoagulants (NOACs) as a measure in the Star Ratings program may increase a plan's incentives to improve patient adherence. To assess the adherence to medication of patients who used the NOACs rivaroxaban, dabigatran, or apixaban in 2014 based on the Pharmacy Quality Alliance (PQA) adherence measure. Healthcare claims from the Humana database between July 2013 and December 2014 were analyzed. Adult patients with ≥2 dispensings of NOAC agents in 2014, at least 180 days apart, with >60 days of supply, and ≥180 days of continuous enrollment prior to the index NOAC were identified. The PQA measure was calculated as the percentage of patients who had a proportion of days covered (PDC) ≥0.8. Multivariate logistic regression analyses were also conducted adjusting for baseline confounders. A total of 11,095 rivaroxaban, 6548 dabigatran, and 3532 apixaban users were identified. Based on the PQA adherence measure (PDC ≥0.8), a significantly higher proportion of rivaroxaban users (72.7%) was found to be adherent compared to dabigatran (67.2%: p < 0.001) and apixaban (69.5%: p < 0.001) users. Compared to apixaban users, the adjusted likelihood of being adherent was significantly higher for rivaroxaban users (unadjusted OR [95% CI]: 1.17 [1.08-1.27], p < 0.001; adjusted OR [95% CI]: 1.20 (1.10-1.31), p < 0.001) and significantly lower for dabigatran users (unadjusted OR [95% CI]: 0.90 [0.82-0.98], p = 0.019; adjusted OR [95% CI]: 0.85 [0.77-0.93], p < 0.001). Limitations of the study are potential inaccuracies in claims data, possible change in patterns over time, and the impossibility of knowing whether all supplied tablets were taken. Using the PQA's adherence measure, rivaroxaban users were found to have

  17. Antioxidant and anticoagulant activity of polyphenol and polysaccharides from fermented Sargassum sp.

    PubMed

    Shobharani, P; Nanishankar, V H; Halami, P M; Sachindra, N M

    2014-04-01

    The current investigation was carried out with an objective of determining the structural characteristic of polysaccharides extracted from fermented Sargassum sp. to be used as potent natural heparin substitute anticoagulant compound. Sargassum sp. fermented with marine lactic acid bacteria was initially subjected to ethanol precipitation for the recovery of bioactive compounds. Antioxidant activity was maximum in the soluble fraction whereas anticoagulant activity was observed to be high in the precipitate which correlated with the increased polyphenols and total sugars respectively. The precipitate was purified by anion exchange chromatography and the fractions collected were analyzed for total sugars and anticoagulant activity. There was 2.6-3.9-folds increase in anticoagulant activity in the final purified fractions, with a maximum activity in case of sample fermented with Enterococcus faecium (6.7±0.22 IU/mg). Structural elucidation of potential anticoagulant polysaccharide by Fourier Transform Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance (NMR) analysis indicated the presence of alginate rich in mannuronic acid. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Comparison of effectiveness and safety of treatment with apixaban vs. other oral anticoagulants among elderly nonvalvular atrial fibrillation patients.

    PubMed

    Deitelzweig, Steven; Luo, Xuemei; Gupta, Kiran; Trocio, Jeffrey; Mardekian, Jack; Curtice, Tammy; Lingohr-Smith, Melissa; Menges, Brandy; Lin, Jay

    2017-10-01

    To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) of elderly (≥65 years of age) nonvalvular atrial fibrillation (NVAF) patients initiating apixaban vs. rivaroxaban, dabigatran, or warfarin. NVAF patients with Medicare Advantage coverage in the US initiating oral anticoagulants (OACs, index event) were identified from the Humana database (1 January 2013-30 September 2015) and grouped into cohorts depending on OAC initiated. Propensity score matching (PSM), 1:1, was conducted among patients treated with apixaban vs. each other OAC, separately. Rates of S/SE and MB were evaluated in the follow-up. Cox regressions were used to compare the risk of S/SE and MB between apixaban and each of the other OACs during the follow-up. The matched pairs of apixaban vs. rivaroxaban (n = 13,620), apixaban vs. dabigatran (n = 4654), and apixaban vs. warfarin (n = 14,214) were well balanced for key patient characteristics. Adjusted risks for S/SE (hazard ratio [HR] vs. rivaroxaban: 0.72, p = .003; vs. warfarin: 0.65, p < .001) and MB (HR vs. rivaroxaban: 0.49, p < .001; vs. warfarin: 0.53, p < .001) were significantly lower during the follow-up for patients treated with apixaban vs. rivaroxaban and warfarin. Adjusted risks for S/SE (HR: 0.78, p = .27) and MB (HR: 0.82, p = .23) of NVAF patients treated with apixaban vs. dabigatran trended to be lower, but did not reach statistical significance. In the real-world setting after controlling for differences in patient characteristics, apixaban is associated with significantly lower risk of S/SE and MB than rivaroxaban and warfarin, and a trend towards better outcomes vs. dabigatran among elderly NVAF patients in the US.

  19. Comparative risks of bleeding, ischemic stroke and mortality with direct oral anticoagulants versus phenprocoumon in patients with atrial fibrillation.

    PubMed

    Ujeyl, Mariam; Köster, Ingrid; Wille, Hans; Stammschulte, Thomas; Hein, Rebecca; Harder, Sebastian; Gundert-Remy, Ursula; Bleek, Julian; Ihle, Peter; Schröder, Helmut; Schillinger, Gerhard; Zawinell, Anette; Schubert, Ingrid

    2018-06-16

    The pivotal trials for stroke prevention in non-valvular atrial fibrillation (NVAF) compared rivaroxaban, dabigatran, and apixaban with warfarin, as did most claims-based studies. Comparisons with phenprocoumon, the most frequently used vitamin K antagonist (VKA) in Germany, are scarce. Risk of bleeding, ischemic stroke, and all-cause mortality in patients with NVAF were analyzed using data for 2010 to 2014 from a large German claims database. New users of oral anticoagulants from January 2012 to December 2013 were included and observed over 1 year. Baseline characteristics were adjusted using propensity score matching and logistic regression. Several sensitivity analyses were carried out. Fifty-nine thousand four hundred forty-nine rivaroxaban, 23,654 dabigatran, 4894 apixaban, and 87,997 matched phenprocoumon users were included. Adjusted hazard ratios (95% confidence intervals) compared with phenprocoumon were as follows: hospitalized bleedings: rivaroxaban 1.04 (0.97; 1.11), dabigatran 0.87 (0.77; 0.98), and apixaban 0.65 (0.50; 0.86); ischemic stroke: rivaroxaban 1.05 (0.94; 1.17), dabigatran 1.14 (0.96; 1.35), and apixaban 1.84 (1.20; 2.84); all-cause mortality: rivaroxaban 1.17 (1.11; 1.22), dabigatran 1.04 (0.95; 1.13), and apixaban 1.14 (0.97; 1.34). With rivaroxaban, no significant differences were observed compared to phenprocoumon with regard to hospitalized bleedings or ischemic strokes. Dabigatran was associated with fewer bleedings and a similar risk of ischemic strokes compared to phenprocoumon. Apixaban was also associated with fewer bleedings but was unexpectedly associated with more ischemic strokes, possibly reflecting selective prescribing. The association of rivaroxaban with higher all-cause mortality unrelated to bleedings or strokes has been described previously but remains to be explained.

  20. Recurrent hemorrhage from corpus luteum during anticoagulant therapy.

    PubMed Central

    Wong, K. P.; Gillett, P. G.

    1977-01-01

    A 43-year old woman had recurrent massive intraperitoneal hemorrhage from rupture of a hemorrhagic corpus luteum in two successive menstrual cycles while receiving anticoagulant therapy. Left oophorectomy was performed on the first occasion and right salpingo-oophorectomy with left salpingectomy on the second. While the precise incidence cannot be determined, rupture from a hemorrhagic corpus luteum appears to be a rare but potentially catastrophic complication of anticoagulant therapy. Hence possible ovarian hemorrhage should be considered in women of reproductive age receiving heparin or sodium warfarin therapy. PMID:844024

  1. Lupus anticoagulant, anticardiolipin antibodies, and human immunodeficiency virus in haemophilia.

    PubMed Central

    Cohen, H; Mackie, I J; Anagnostopoulos, N; Savage, G F; Machin, S J

    1989-01-01

    The prevalence of lupus anticoagulant, using the dilute Russell's viper venom time (DRVT), was determined in 22 patients with mild to severe haemophilia A to see if there was any association with the presence of viral disease. Twelve haemophiliacs (58%) were lupus anticoagulant positive, with a mean patient:control ratio of 1.24 (range 1.15-1.52, normal range 0.84-1.06 which partially corrected with lysed, washed platelets). Nine of these patients were IgG or IgM, or both, anticardiolipin antibody positive and nine were human immunodeficiency virus (HIV) antibody positive, but associations between lupus anticoagulant, anticardiolipin antibodies, and HIV antibody positivity were not significant. Mixing studies of normal plasma and immune depleted factor VIII deficient plasma showed that the DRVT ratio increased when the factor VIII concentration fell below 0.15 IU/ml. There was no significant association between plasma factor VIII concentration and positive DRVT results in haemophiliacs. The addition of porcine factor VIII concentrate produced no correction in eight of the 12 with DRVTs indicative of lupus anticoagulant, suggesting that these were prolonged by antiphospholipid activity. It is concluded that the presence of lupus anticoagulant and anticardiolipin antibodies in haemophiliacs may represent an antiphospholipid response to viraemic challenge, not only to HIV but also to other viral antigens, and that a very low factor VIII concentration may produce a false positive DRVT result. PMID:2500459

  2. Fall risk and anticoagulation for atrial fibrillation in the elderly: A delicate balance.

    PubMed

    Hagerty, Tracy; Rich, Michael W

    2017-01-01

    Guidelines for managing atrial fibrillation recommend systemic anticoagulation for almost all patients age 65 and older, but in practice up to 50% of older patients do not receive maintenance anticoagulation therapy. The most common reason physicians cite for withholding anticoagulation in older patients with atrial fibrillation is a perception of a high risk of falling and associated bleeding, especially intracranial hemorrhage. Copyright © 2017 Cleveland Clinic.

  3. Relation of psychological distress to the international normalized ratio in patients with venous thromboembolism with and without oral anticoagulant therapy.

    PubMed

    Von Känel, R; Vökt, F; Biasiutti, F Demarmels; Stauber, S; Wuillemin, W A; Lukas, P S

    2012-08-01

    Psychological distress might affect the international normalized ratio (INR), but effects might vary depending on oral anticoagulant (OAC) therapy. To investigate the association of psychological distress with INR and clotting factors of the extrinsic pathway in patients with and without OAC therapy. We studied 190 patients with a previous venous thromboembolism (VTE); 148 had discontinued OAC therapy and 42 had ongoing OAC therapy. To assess psychological distress, all patients completed validated questionnaires to measure symptoms of depression, anxiety, worrying, anger and hostility. INR, fibrinogen, factor (F)II:C, FV:C, FVII:C and FX:C were measured as part of outpatient thrombophilia work-up. In VTE patients without OAC therapy, the odds of a reduced INR (< 1.00) were significantly increased from 1.5 to 1.8 times for an increase of 1 standard deviation (SD) in symptoms of depression, anxiety, worrying and anger, respectively, after adjusting for gender, age, body mass index, socioeconomic status, hematocrit and C-reactive protein. Worrying, anger and hostility also showed significant direct associations with FVII:C. In patients with OAC therapy, INR was unrelated to a negative affect; however, lower FVII:C related to anxiety and worrying as well as lower FX:C related to anger and hostility were observed in patients with OAC therapy compared with those without OAC therapy. Psychological distress was associated with a reduced INR in VTE patients without OAC therapy. The direction of the association between psychological distress and activity in some clotting factors of the extrinsic coagulation pathway might differ depending on whether VTE patients are under OAC therapy or not. © 2012 International Society on Thrombosis and Haemostasis.

  4. A randomized trial comparing INR monitoring devices in patients with anticoagulation self-management: evaluation of a novel error-grid approach.

    PubMed

    Hemkens, Lars G; Hilden, Kristian M; Hartschen, Stephan; Kaiser, Thomas; Didjurgeit, Ulrike; Hansen, Roland; Bender, Ralf; Sawicki, Peter T

    2008-08-01

    In addition to the metrological quality of international normalized ratio (INR) monitoring devices used in patients' self-management of long-term anticoagulation, the effectiveness of self-monitoring with such devices has to be evaluated under real-life conditions with a focus on clinical implications. An approach to evaluate the clinical significance of inaccuracies is the error-grid analysis as already established in self-monitoring of blood glucose. Two anticoagulation monitors were compared in a real-life setting and a novel error-grid instrument for oral anticoagulation has been evaluated. In a randomized crossover study 16 patients performed self-management of anticoagulation using the INRatio and the CoaguChek S system. Main outcome measures were clinically relevant INR differences according to established criteria and to the error-grid approach. A lower rate of clinically relevant disagreements according to Anderson's criteria was found with CoaguChek S than with INRatio without statistical significance (10.77% vs. 12.90%; P = 0.787). Using the error-grid we found principally consistent results: More measurement pairs with discrepancies of no or low clinical relevance were found with CoaguChek S, whereas with INRatio we found more differences with a moderate clinical relevance. A high rate of patients' satisfaction with both of the point of care devices was found with only marginal differences. A principal appropriateness of the investigated point-of-care devices to adequately monitor the INR is shown. The error-grid is useful for comparing monitoring methods with a focus on clinical relevance under real-life conditions beyond assessing the pure metrological quality, but we emphasize that additional trials using this instrument with larger patient populations are needed to detect differences in clinically relevant disagreements.

  5. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

    PubMed

    Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

    2015-06-25

    Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

  6. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles

    PubMed Central

    Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F.; Hamaoka, Takafumi

    2015-01-01

    Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously. PMID:26109079

  7. Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass.

    PubMed

    Gunaratne, Ruwan; Kumar, Shekhar; Frederiksen, James W; Stayrook, Steven; Lohrmann, Jens L; Perry, Kay; Bompiani, Kristin M; Chabata, Charlene V; Thalji, Nabil K; Ho, Michelle D; Arepally, Gowthami; Camire, Rodney M; Krishnaswamy, Sriram; Sullenger, Bruce A

    2018-06-04

    Unfractionated heparin (UFH), the standard anticoagulant for cardiopulmonary bypass (CPB) surgery, carries a risk of post-operative bleeding and is potentially harmful in patients with heparin-induced thrombocytopenia-associated antibodies. To improve the activity of an alternative anticoagulant, the RNA aptamer 11F7t, we solved X-ray crystal structures of the aptamer bound to factor Xa (FXa). The finding that 11F7t did not bind the catalytic site suggested that it could complement small-molecule FXa inhibitors. We demonstrate that combinations of 11F7t and catalytic-site FXa inhibitors enhance anticoagulation in purified reaction mixtures and plasma. Aptamer-drug combinations prevented clot formation as effectively as UFH in human blood circulated in an extracorporeal oxygenator circuit that mimicked CPB, while avoiding side effects of UFH. An antidote could promptly neutralize the anticoagulant effects of both FXa inhibitors. Our results suggest that drugs and aptamers with shared targets can be combined to exert more specific and potent effects than either agent alone.

  8. Anticoagulant and antithrombotic drugs in pregnancy: what are the anesthetic implications for labor and cesarean delivery?

    PubMed

    Butwick, A J; Carvalho, B

    2011-02-01

    Neuraxial anesthetic techniques are commonly used during the peripartum period to provide effective pain relief for labor and anesthesia during cesarean delivery. Major neurologic complications are rare after neuraxial anesthesia; however, spinal hematoma is associated with catastrophic neurologic outcomes (including lower-limb paralysis). Anticoagulant and antithrombotic drugs can increase the risk of spinal hematoma after neuraxial anesthesia, and better understanding of the pharmacokinetics and pharmacodynamics of anticoagulants has led to greater appreciation for withholding anticoagulation before and after neuraxial anesthesia. A number of national anesthetic societies have produced guidelines for performing neuraxial anesthesia in patients receiving anticoagulation. However, there is limited information about anesthetic implications of anticoagulation during the peripartum period. This article will review the risks of spinal hematoma after neuraxial anesthesia in pregnant patients; current guidelines for neuraxial anesthesia for anticoagulated patients; and relevant pharmacological data of specific anticoagulant and antithrombotic drugs in pregnancy.

  9. Non-vitamin K antagonist oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation

    PubMed Central

    Camm, A. John; Pinto, Fausto J.; Hankey, Graeme J.; Andreotti, Felicita; Hobbs, F.D. Richard

    2015-01-01

    Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers. PMID:26116685

  10. Catheter-related thrombosis: biological and clinical evidence for risk with currently available anticoagulants.

    PubMed

    Montalescot, Gilles; Walenga, Jeanine M

    2009-01-01

    Anticoagulants used during percutaneous coronary intervention (PCI) should not only prevent coronary events, but also minimize the risk of periprocedural complications. Current anticoagulation therapies for PCI include unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin. UFH and enoxaparin have good efficacy and safety profiles in PCI; furthermore, associated periprocedural complications such as catheter thrombosis are rare. Although newer anticoagulants seem safe and effective in patients with acute coronary syndrome, clinical trial data suggest that some pure factor Xa (FXa) inhibitors are associated with increased rates of catheter thrombosis, compared with heparin-based agents. Experimental systems show that polytherapeutic agents, including UFH and enoxaparin, are more effective anticoagulants than certain single-target agents. More studies are needed to assess whether catheter thrombosis is a class-, drug-, or dose-related effect, and how best to prevent it. Future trials should report the rates of periprocedural complications when assessing the safety of novel anticoagulation therapies in PCI.

  11. Utilization of Anticoagulation Therapy in Medicare Patients with Nonvalvular Atrial Fibrillation

    PubMed Central

    Fitch, Kate; Broulette, Jonah; Pyenson, Bruce; Iwasaki, Kosuke; Kwong, Winghan Jacqueline

    2012-01-01

    Background Clinical guidelines recommend oral anticoagulation for stroke prevention in patients with atrial fibrillation (AF) at moderate or high risk for stroke but not at high risk for bleeding; however, studies consistently report suboptimal use of such therapy. This study used Medicare Part D claims data to assess the use of warfarin in the Medicare population. Objectives To compare real-world warfarin utilization with current treatment guideline recommendations, and to assess the effect of warfarin exposure level on patient outcomes in Medicare beneficiaries with nonvalvular AF (NVAF). Methods Patients who were recently diagnosed with NVAF were identified using a random 5% sample of Research Identifiable Files of Medicare beneficiaries in 2006 or 2007. Individuals with moderate-to-high stroke risk per CHADS2 but not at high bleeding risk per ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score were evaluated for warfarin use, as identified by the presence of ≥1 warfarin prescription claims within 12 months after the index diagnosis. Warfarin exposure level was assessed by the proportion of days covered during the 12-month follow-up period. The effect of warfarin exposure on ischemic stroke and major bleeding event rates during the 12-month follow-up period were assessed using multivariate logistic regression. Results Data from 14,149 newly diagnosed patients with NVAF (mean age, 79 years; 58.7% female) were analyzed, and of these, 7524 (53.2%) patients were identified as having moderate-to-high stroke risk and not being at high bleeding risk. Of these patients, 3110 (41.3%) did not receive warfarin within 12 months of the index diagnosis. The risk for ischemic stroke was significantly lower in those with warfarin exposure versus no warfarin exposure (adjusted odds ratio [OR], 0.51; confidence interval [CI], 0.43–0.61; P <.001) and in patients with warfarin proportion of days covered ≥80% versus those with proportion of days

  12. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study.

    PubMed

    Wilson, Duncan; Ambler, Gareth; Shakeshaft, Clare; Brown, Martin M; Charidimou, Andreas; Al-Shahi Salman, Rustam; Lip, Gregory Y H; Cohen, Hannah; Banerjee, Gargi; Houlden, Henry; White, Mark J; Yousry, Tarek A; Harkness, Kirsty; Flossmann, Enrico; Smyth, Nigel; Shaw, Louise J; Warburton, Elizabeth; Muir, Keith W; Jäger, Hans Rolf; Werring, David J

    2018-06-01

    Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0-20·3

  13. What Are Anticoagulants and Antiplatelet Agents?

    MedlinePlus

    ... activated partial thromboplastin time (aPTT) test. • Never take aspirin with anticoagulants unless your doctor tells you to. • ... before taking other medicines or supplements, such as aspirin, vitamins, cold medicine, pain medicine, sleeping pills or ...

  14. Preemptive Anticoagulation in Patients With a High Pretest Probability of Pulmonary Embolism: Are Guidelines Followed?

    PubMed

    Willoughby, Laura; Adams, Daniel M; Evans, R Scott; Lloyd, James F; Stevens, Scott M; Woller, Scott C; Bledsoe, Joseph R; Aston, Valerie T; Wilson, Emily L; Elliott, C Gregory

    2018-05-01

    Guidelines suggest anticoagulation of patients with high pretest probability of pulmonary embolism (PE) while awaiting diagnostic test results (preemptive anticoagulation). Data relevant to the practice of preemptive anticoagulation are not available. We reviewed 3,500 consecutive patients who underwent CT pulmonary angiography (CTPA) at two EDs. We classified the pretest probability for PE using the revised Geneva Score (RGS) as low (RGS 0-3), intermediate (RGS 4-10), or high (RGS 11-18). We classified patients with a high pretest probability of PE as receiving preemptive anticoagulation if therapeutic anticoagulation was given before CTPA completion. Patients with a high bleeding risk and those receiving treatment for DVT before CTPA were excluded from the preemptive anticoagulation analysis. We compared the time elapsed between ED registration and CTPA completion for patients with a low, intermediate, and high pretest probability for PE. We excluded three of 3,500 patients because CTPA preceded ED registration. Of the remaining 3,497 patients, 167 (4.8%) had a high pretest probability for PE. After excluding 29 patients for high bleeding risk and 21 patients who were treated for DVT prior to CTPA, only two of 117 patients (1.7%) with a high pretest probability for PE received preemptive anticoagulation. Furthermore, 37 of the remaining 115 patients (32%) with a high pretest probability for PE had a preexisting indication for anticoagulation but did not receive preemptive anticoagulation. The time from ED registration to CTPA completion did not differ based on the pretest probability of PE. Physicians rarely use preemptive anticoagulation in patients with a high pretest probability for PE. Clinicians do not expedite CTPA examinations for patients with a high pretest probability for PE. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  15. Anticoagulation Use and Clinical Outcomes Following Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation

    PubMed Central

    Hernandez, Inmaculada; Zhang, Yuting; Brooks, Maria M.; Chin, Paul K.L.; Saba, Samir

    2016-01-01

    Background and Purpose Little is known about the clinical outcomes associated with post-hemorrhage anticoagulation resumption for atrial fibrillation. This study had two objectives: first, to evaluate anticoagulation use after a first major bleed on warfarin or dabigatran; and second, to compare effectiveness and safety outcomes between patients discontinuing anticoagulation after a major bleed and patients restarting warfarin or dabigatran. Methods Using 2010-2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding event while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their post-hemorrhage use of anticoagulation. We followed them until an ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors impacting anticoagulation resumption, and Cox Proportional Hazard models to compare the combined risk of ischemic stroke and all-cause mortality, and the risk of recurrent bleeding between treatment groups. Results Resumption of anticoagulation with warfarin (hazard ratio (HR) 0.76; 95%CI, 0.59-0.97) or dabigatran (HR0.66; 95%CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients prescribed warfarin after the event than for those prescribed dabigatran (HR2.31; 95%CI, 1.19-4.76) or whose anticoagulation ceased (HR1.56; 95%CI, 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation (HR0.66; 95% CI, 0.32-1.33). Conclusions Dabigatran was associated with a superior benefit/risk ratio than warfarin and anticoagulation discontinuation in the treatment of atrial fibrillation patients who have survived a major bleed. PMID:27909200

  16. STS/SCA/AmSECT Clinical Practice Guidelines: Anticoagulation during Cardiopulmonary Bypass.

    PubMed

    Shore-Lesserson, Linda; Baker, Robert A; Ferraris, Victor; Greilich, Philip E; Fitzgerald, David; Roman, Philip; Hammon, John

    2018-03-01

    Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, the Society of Thoracic Surgeons (STS), the Society of Cardiovascular Anesthesiologists (SCA), and the American Society of Extracorporeal Technology (AmSECT) developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered together to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation for CPB using the available evidence. To identify relevant evidence a systematic review was outlined and literature searches were conducted in PubMed® using standardized MeSH terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published prior to 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved more than

  17. Anticoagulation therapy is harmful to large-sized cerebellar infarction.

    PubMed

    Zhang, She-Qing; Wang, Wei; Ma, Xiao-Long; Xia, Yu-Ye; Liu, Ai-Jun

    2014-09-01

    Anticoagulants are commonly used to treat ischemic stroke. Its impact on cerebellar infarction has not been fully understood. In the clinical study, we reviewed a consecutive series of patients with large-sized cerebellar infarction (diameter > 3 cm, n = 30) treated with or without anticoagulation. In animal study, cerebellar infarction operation was performed in 12 Cynomolgus monkeys. Then the animals were administrated with low molecular weight heparin (LMWH) or vehicle for 14 days. Six patients died during the following treatment. All the subjects that died received anticoagulation therapy, while nobody in the survival group received such a therapy. Compared with sham-operated animals, all monkeys with cerebellar infarction have obvious neurological deficits. The number and size of the Purkinje cells in the cerebellar area were also reduced. Two animals in the LMWH group (33%) died, while all animals in the vehicle control group survived. Compared with the vehicle group, the neurological score in the LMWH group was significantly increased (P < 0.05). The water content in the cerebella was also significantly higher (P < 0.05). Edema, hemorrhage, and subarachnoid hemorrhage occurred in the cerebella as well as brainstem of all the LMWH treated animals. These results indicated the harmful effects of anticoagulation therapy on large-sized cerebellar infarction. © 2014 John Wiley & Sons Ltd.

  18. Contact laser prostatectomy in a patient on chronic anticoagulation

    NASA Astrophysics Data System (ADS)

    Mueller, Edward J.

    1995-05-01

    The `gold standard' therapy for patients with symptomatic bladder outlet obstruction secondary to benign prostatic hyperplasia has always been electrocautery TURP. However, in patients with medical problems requiring chronic anticoagulation, this procedure is contraindicated due to the extreme risk of hemorrhage, both during the procedure and the immediate post operative period. With the recent development of contact laser prostatectomy the patient on chronic anticoagulation can safely undergo the procedure. Herein, I present a case of a 60 year old with significant bladder outlet obstruction yielding an AUA symptom score of 18. The patient had a history of multiple episodes of deep venous thrombosis of the left leg with three prior pulmonary emboli. He was maintained on chronic anticoagulation with alternating days of 3.5 mg. and 5.0 mg. of warfarin sodium (coumadin). Preoperative cystoscopy showed a 4 cm prostatic fossa obstructed by tri-lobar hypertrophy, with large kissing lateral lobes and visual obstruction from the verumontanum. The patient underwent a contact laser prostatectomy with the SLT Nd:YAG laser at 50 watts. There was minimal bleeding both during the procedure and in the immediate postoperative period. At three months post-op the AUA symptom score had decreased to 2. This case demonstrated that contact laser prostatectomy can be safely and effectively performed in patients on chronic anticoagulation.

  19. Cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation in the primary prevention of ischemic stroke.

    PubMed

    Lightowlers, S; McGuire, A

    1998-09-01

    A number of clinical trials have shown the value of anticoagulating patients with nonrheumatic atrial fibrillation to prevent ischemic stroke. The purpose of this study was to assess the cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation with particular reference to the very elderly (aged >75 years) who have a higher incidence of bleeding events while undergoing anticoagulation. We calculated the incremental costs per life-year gained for 4 base cases using efficacy data from the Boston Area Anticoagulation Trial for Atrial Fibrillation, the meta-analysis of the 5 nonrheumatic atrial fibrillation trials, cost data from a district general hospital, and review of the literature. The cost per life-year gained free from stroke over 10 years ranged from -pound sterling 400.45 (ie, a resource saving achieved for each life-year gained free from stroke) to pound sterling 13,221.29. The results were most sensitive to alteration in the frequency of anticoagulation monitoring. For medical and economic reasons, anticoagulation treatment in the prevention of ischemic stroke is justified. Although older patients are more at risk of adverse events, anticoagulation is more cost-effective in this group.

  20. Left Atrial Appendage Closure Device With Delivery System: A Health Technology Assessment

    PubMed Central

    Nevis, Immaculate; Falk, Lindsey; Wells, David; Higgins, Caroline

    2017-01-01

    Background Atrial fibrillation is a common cardiac arrhythmia, and 15% to 20% of those who have experienced stroke have atrial fibrillation. Treatment options to prevent stroke in people with atrial fibrillation include pharmacological agents such as novel oral anticoagulants or nonpharmacological devices such as the left atrial appendage closure device with delivery system (LAAC device). The objectives of this health technology assessment were to assess the clinical effectiveness and cost-effectiveness of the LAAC device versus novel oral anticoagulants in patients without contraindications to oral anticoagulants and versus antiplatelet agents in patients with contraindications to oral anticoagulants. Methods We performed a systematic review and network meta-analysis. We also conducted an economic literature review, economic evaluation, and budget impact analysis to assess the cost-effectiveness and budget impact of the LAAC device compared with novel oral anticoagulants and oral antiplatelet agents (e.g., aspirin). We also spoke with patients to better understand their preferences, perspectives, and values. Results Seven randomized controlled studies met the inclusion criteria for indirect comparison. Five studies assessed the effectiveness of novel oral anticoagulants versus warfarin, and two studies compared the LAAC device with warfarin. No studies were identified that compared the LAAC device with aspirin in patients in whom oral anticoagulants were contraindicated. Using the random effects model, we found that the LAAC device was comparable to novel oral anticoagulants in reducing stroke (odds ratio [OR] 0.85; credible interval [Cr.I] 0.63–1.05). Similarly, the reduction in the risk of all-cause mortality was comparable between the LAAC device and novel oral anticoagulants (OR 0.71; Cr.I 0.49–1.22). The LAAC device was found to be superior to novel oral anticoagulants in preventing hemorrhagic stroke (OR 0.45; Cr.I 0.29–0.79), whereas novel oral