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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. The novel oral anticoagulants.

    PubMed

    Rojas-Hernandez, Cristhiam M; Garcia, David A

    2013-03-01

    After the introduction of warfarin, long-term oral anticoagulation treatment remained unchanged for more than 50 years. Most recently, with the development and approval of new oral anticoagulants, the treatment of medical conditions that require thrombosis prophylaxis and long-term anticoagulation has become more complex. In the case of venous thromboembolism (VTE) prevention after orthopedic surgery, the new oral agents will be less costly than the parenteral alternative. In other settings (such as atrial fibrillation or treatment of acute VTE), the new agents will offer additional convenience at higher cost, but the degree to which they will reduce clinically important events such as thrombosis or bleeding will be limited, especially for patients on optimally controlled warfarin. As the use of the new oral anticoagulants becomes more widespread, it will be important for all clinicians to have a basic understanding of their pharmacology, advantages, and limitations. Although the need to measure or reverse the effect of these drugs will arise infrequently, clinicians--especially hematologists--will desire evidence-based recommendations about how to manage such scenarios, which will require research studies.

  3. The Monitoring of Oral Anticoagulants

    PubMed Central

    Carter, Cedric J.

    1988-01-01

    The author briefly reviews the use of anticoagulants, describing the specific tests their use requires. These tests are usually performed in a specialized laboratory. The clinical implication of the laboratory's use of different prothrombin time systems is explained. Implications of the use of oral anticoagulants in family practice are discussed. PMID:21253057

  4. Reimagining Anticoagulation Clinics in the Era of Direct Oral Anticoagulants

    PubMed Central

    Barnes, Geoffrey D.; Nallamothu, Brahmajee K.; Sales, Anne E.; Froehlich, James B.

    2016-01-01

    Anticoagulation clinics were initially developed to provide safe and effective care for warfarin-treated patients with atrial fibrillation, venous thromboembolism and mechanical valve replacement. Traditionally, these patients required ongoing laboratory monitoring and warfarin dose adjustment by expert providers. With the introduction of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban), many have questioned the need for anticoagulation clinic. However, we believe the growing number of oral anticoagulant choices creates an urgent need for expanding the traditional role of the anticoagulation clinic. We outline three key purposes that a “re-imagined” anticoagulation clinic would serve: 1) to assist patients and clinicians with selecting the most appropriate drug and dose from a growing list of anticoagulant options (including warfarin), 2) to help patients minimize the risk of serious bleeding complications with careful long-term monitoring and peri-procedural management, and 3) to encourage ongoing adherence to these life-saving medications. We also describe how re-purposing anticoagulation clinics as broader “medication safety clinics” would promoting safe and effective care across a range of cardiovascular conditions for high-risk medications (e.g. spironolactone, amiodarone). Finally, we highlight a few existing health systems that are overcoming key challenges to implementing a re-imagined anticoagulation or medication safety clinic structure. PMID:26933047

  5. Reimagining Anticoagulation Clinics in the Era of Direct Oral Anticoagulants.

    PubMed

    Barnes, Geoffrey D; Nallamothu, Brahmajee K; Sales, Anne E; Froehlich, James B

    2016-03-01

    Anticoagulation clinics were initially developed to provide safe and effective care for warfarin-treated patients with atrial fibrillation, venous thromboembolism, and mechanical valve replacement. Traditionally, these patients required ongoing laboratory monitoring and warfarin dose adjustment by expert providers. With the introduction of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban), many have questioned the need for anticoagulation clinic. However, we think that the growing number of oral anticoagulant choices creates an urgent need for expanding the traditional role of the anticoagulation clinic. We outline 3 key purposes that a reimagined anticoagulation clinic would serve: (1) to assist patients and clinicians with selecting the most appropriate drug and dose from a growing list of anticoagulant options (including warfarin), (2) to help patients minimize the risk of serious bleeding complications with careful long-term monitoring and peri-procedural management, and (3) to encourage ongoing adherence to these life-saving medications. We also describe how repurposing anticoagulation clinics as broader medication safety clinics would promote safe and effective care across a range of cardiovascular conditions for high-risk medications (eg, spironolactone, amiodarone). Finally, we highlight a few existing health systems that are overcoming key challenges to implementing a reimagined anticoagulation or medication safety clinic structure.

  6. [New oral anticoagulants. Regional anaesthesia and new oral anticoagulants].

    PubMed

    Standl, Thomas

    2014-03-01

    New oral anticoagulants (NOAC) are increasingly applied after hip and knee replacement and in patients with non-vavular atrial fibrillation. Patients with cardiac disease benefit from regional anaesthesia, especially catheter-provided postoperative pain relief, but are at higher risk for puncture-related haematoma when NOAC are applied simultaneously. Therefore recommended time intervals between drug application and performance of RA including catheter removal of 22-34 h must be respected. The next dose of NOAC must not be given before 6 h have been elapsed; after bloody tap a delay of 24 h is recommended. The respective time intervals are prolonged in patients with renal insufficiency, especially when Dabigatran is applied, until 36 to 72 h. In general, high risk patients with NOAC undergoing surgery benefit from an interdicsciplinary approach and from less traumatic techniques such as spinal anaesthesia or superficial peripheral nerve blocks. © Georg Thieme Verlag Stuttgart · New York.

  7. The debate concerning oral anticoagulation: whether to suspend oral anticoagulants during dental treatment.

    PubMed

    António, Natália; Castro, Graça; Ramos, Domingos; Machado, António; Gonçalves, Lino; Macedo, Tice; Providência, Luís A

    2008-04-01

    The management of patients taking long-term oral anticoagulants who require dental surgery is still highly controversial. The risk of bleeding associated with dental treatment under oral anticoagulants must be weighed against the risk of thromboembolism associated with suspension of antithrombotic therapy. Mortality and morbidity associated with thromboembolic events are higher than those associated with hemorrhagic events after minor oral surgery procedures. Evidence-based information does not support oral anticoagulant suspension before minor oral surgery. The authors propose a management protocol for chronically anticoagulated patients who require a dental procedure, to reduce both thromboembolic risk and the risk of bleeding.

  8. Monitoring anticoagulant therapy with new oral agents

    PubMed Central

    Ramos-Esquivel, Allan

    2015-01-01

    Thromboembolic disease is a major leading cause of mortality and morbidity in industrialized countries. Currently, the management of these patients is challenging due to the availability of new drugs with proven efficacy and security compared to traditional oral vitamin K antagonists. These compounds are characterized by a predictable pharmacokinetic profile for which blood monitoring is not routinely needed. Nevertheless, some data have suggested inter-patient variability in the anticoagulant effect of these drugs, raising concerns about their effectiveness and safety. Although mass-spectrometry is the gold standard to determine drug plasma concentrations, this method is not widely available in every-day practice and some coagulation assays are commonly used to determine the anticoagulant effect of these drugs. The present review aims to summarize the current knowledge regarding the clinical question of how and when to monitor patients with new anticoagulant oral agents. PMID:26713281

  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. Newer Oral Anticoagulants: Stroke Prevention and Pitfalls

    PubMed Central

    Patel, Anand; Goddeau Jr, Richard P.; Henninger, Nils

    2016-01-01

    Warfarin is very effective in preventing stroke in patients with atrial fibrillation. However, its use is limited due to fear of hemorrhagic complications, unpredictable anticoagulant effects related to multiple drug interactions and dietary restrictions, a narrow therapeutic window, frequent difficulty maintaining the anticoagulant effect within a narrow therapeutic window, and the need for inconvenient monitoring. Several newer oral anticoagulants have been approved for primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation. These agents have several advantages relative to warfarin therapy. As a group, these direct oral anticoagulants (DOAC), which include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), are more effective than dose adjusted warfarin for prevention of all-cause stroke (including both ischemic and hemorrhagic stroke), and have an overall more favorable safety profile. Nevertheless, an increased risk of gastrointestinal bleeding (with the exception of apixaban), increased risk for thrombotic complication with sudden discontinuation, and inability to accurately assess and reverse anticoagulant effect require consideration prior to therapy initiation, and pose a challenge for decision making in acute stroke therapy. PMID:27347226

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

    PubMed

    Serrano-Sánchez, V; Ripollés-de Ramón, J; Collado-Yurrita, L; Vaello-Checa, I; Colmenero-Ruiz, C; Helm, A; Ciudad-Cabañas, M-J; Serrano-Cuenca, V

    2017-09-01

    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. 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. 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. 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.

  12. Oral anticoagulant treatment with and without aspirin.

    PubMed

    Altman, R; Rouvier, J; Gurfinkel, E

    1995-07-01

    For preventing thromboembolic events, the concurrent use of oral anticoagulant and antiplatelet drugs has been proposed. In prosthetic heart valves the use of moderate intensity anticoagulants [International Normalized Ratio (INR) 2-3] plus aspirin (100 mg/day) decreases the amount and severity of embolic episodes. The possibility that the same regimen could provide benefit in the prevention of thrombotic events in other arterial diseases is also indicated by the ATACS trial in unstable angina. The ongoing studies in ischemic heart diseases will also give the answer to this possibility.

  13. Novel oral anticoagulants in atrial fibrillation: which novel oral anticoagulant for which patient?

    PubMed

    Prisco, Domenico; Cenci, Caterina; Silvestri, Elena; Ciucciarelli, Lucia; Di Minno, Giovanni

    2015-07-01

    Atrial fibrillation is the most common rhythm disorder and represents a major public health problem because it carries an increased risk of arterial thromboembolism and ischemic stroke. Current european society of cardiology guidelines recommend to stratify atrial fibrillation patients according to the CHA2DS2-VASc score and to administer anticoagulation, preferably with novel oral anticoagulants, that is, dabigatran, rivaroxaban, or apixaban, if the CHA2DS2-VASc score is at least 1. All novel anticoagulants have shown the same, if not greater, efficacy and safety as warfarin, with some advantages. The choice among the novel oral anticoagulants depends on their different pharmacokinetic profile, patients' stroke and bleeding risk, comorbidities, drug tolerability and costs and, finally, patients' preferences.

  14. [Therapeutic equivalence of the new oral anticoagulants].

    PubMed

    Moreno Villar, A; Nacle López, I; Barbero Hernández, M J; Lizan Tudela, L

    2015-10-01

    In an attempt to minimize the economic impact due to the incorporation of innovative drugs, health authorities have promoted and supported the evaluation and market positioning of drugs, as equivalent therapeutic alternatives. This issue has recently gained importance, possibly due to the current economic crisis. The equivalent therapeutic alternatives are justified by the need to compete on price, and by the authorities recommendation to establish therapeutic equivalence, price and financing of medicinal products at the same time. The establishment of the new oral anticoagulants and the equivalent therapeutic alternatives is a problematic issue if it is based on the absence of direct comparisons between different drugs and the questionable methodology used in the current indirect comparisons. Currently, it is difficult to determine when a new oral anticoagulant is more recommendable than others, but efforts are being made in order to propose alternatives for the decision based on patient characteristics.

  15. [New oral anticoagulants in atrial fibrillation].

    PubMed

    Veltkamp, R; Hacke, W

    2011-02-01

    Atrial fibrillation (AF) causes at least 20% of all ischemic strokes. In large randomized trials of primary and secondary stroke prevention, anticoagulation with vitamin K antagonists (VKA) protected much more efficiently than antiplatelet agents against stroke. Because of the problematic pharmacological properties of VKA only part of the AF patients are currently being treated with oral anticoagulants (OAK). The targeted development of specific oral inhibitors of the central coagulation factors thrombin and factor Xa allows reliable anticoagulation without regular coagulation monitoring. In the present review, pharmacological properties of the different agents are compared. Of the four large randomized phase 3 studies in AF (RELY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) with the primary efficacy endpoint stroke and systemic embolism, the published data from the RELY trial indicate a superior efficacy of dabigatran etexilate (2 × 150 mg/day) and a lower risk of intracranial hemorrhage compared to warfarin. Favorable preliminary results have been demonstrated for the factor Xa inhibitor rivaroxaban. Apixaban was more efficacious than ASA and had a similar risk of hemorrhage in the AVERROES study. Thus, the available data suggest a favorable benefit-risk ratio for the new substances in addition to improved patient comfort. Currently unresolved issues relate to the verification of patient adherence by suitable coagulation tests and to the emergency coagulation diagnostics and therapy in acute ischemic or hemorrhagic strokes under the new OAC.

  16. Dental management of patients taking novel oral anticoagulants (NOAs): Dabigatran

    PubMed Central

    Albaladejo, Alberto; Alvarado, Alfonso

    2017-01-01

    Background A new group of oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban) with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. Patients being treated with oral anticoagulants are at higher risk for bleeding when undergoing dental treatments. Material and Methods A literature search was conducted through April 2016 for publications in the ISI Web of Knowledge, PubMed and Cochrane Library using the keywords “dabigatran”, “rivaroxaban”, “apixaban”, “edoxaban”, “new oral anticoagulants”, “novel oral anticoagulants”, “bleeding” and “dental treatment”. Results There is no need for regular coagulation monitoring of patients on dabigatran therapy. Whether or not to temporarily discontinue dabigatran must be assessed according to the bleeding risk involved in the dental procedure to be performed. Conclusions The number of patients under treatment with new oral anticoagulants will increase in the coming years. It is essential to know about the pharmacokinetics and pharmacodynamics of new oral anticoagulants and about their interactions with other drugs. It is necessary to develop clinical guidelines for the perioperative and postoperative management of these new oral anticoagulants in oral surgical procedures, and to carefully evaluate the bleeding risk of dental treatment, as well as the thrombotic risk of suppressing the new oral anticoagulant. Key words:Dabigatran, rivaroxaban, apixaban, edoxaban, novel oral anticoagulants, bleeding. PMID:28210451

  17. Novel oral anticoagulants in plastic surgery.

    PubMed

    Munson, C F; Reid, A J

    2016-05-01

    Novel oral anticoagulants (NOACs) have emerged as a good alternative to warfarin in the prevention of stroke for patients with atrial fibrillation. NOAC use is increasing rapidly; therefore, greater understanding of their use in the perioperative period is important for optimal care. Studies and reviews that reported on the use of NOACs were identified, with particular focus on the perioperative period. PubMed was searched for relevant articles published between January 2000 and August 2015. The inevitable rise in the use of NOACs such as rivaroxaban (Xarelto™), apixaban (Eliquis™), edoxaban (Lixiana™) and dabigatran (Pradaxa™) may present a simplified approach to perioperative anticoagulant management due to fewer drug interactions, rapidity of onset of action and relatively short half-lives. Coagulation status, however, cannot reliably be monitored and no antidotes are currently available. When planning for discontinuation of NOACs, special consideration of renal function is required. Advice regarding the management of bleeding complications is provided for consideration in emergency surgery. In extreme circumstances, haemodialysis may be considered for bleeding with the use of dabigatran. NOACs will increasingly affect operative planning in plastic surgery. In order to reduce the incidence of complications associated with anticoagulation, the management of NOACs in the perioperative period requires knowledge of the time of last dose, renal function and the bleeding risk of the planned procedure. Consideration of these factors will allow appropriate interpretation of the current guidelines.

  18. [The role of new oral anticoagulants].

    PubMed

    Pierard, Luc; Sprynger, Muriel

    2014-08-27

    New oral anticoagulants (NOACs) are going to deeply modify the treatment of non valvular atrial fibrillation and thromboembolic disease. They are non-inferior to warfarin and trials show a similar bleeding rate (even lower for some NOACs). Nevertheless one must be cautious when dealing with patients at risk (elderly patients, frail ones, renal or liver impairment...) and practicians must be well aware of doses and contraindications. NOACs' long- term tolerance is not yet well-known. In cancer, their benefit-risk ratio compared to low molecular weight heparin remains to be determined.

  19. Self management of oral anticoagulation: randomised trial

    PubMed Central

    Fitzmaurice, D A; Murray, E T; McCahon, D; Holder, R; Raftery, J P; Hussain, S; Sandhar, H; Hobbs, F D R

    2005-01-01

    Objective To determine the clinical effectiveness of self management compared with routine care in patients on long term oral anticoagulants. Design Multicentre open randomised controlled trial. Setting Midlands region of the UK. Participants 617 patients aged over 18 and receiving warfarin randomised to intervention (n = 337) and routine care (n = from 2470 invited; 193/337 (57%) completed the 12 month intervention. Intervention Intervention patients used a point of care device to measure international normalised ratio twice a week and a simple dosing chart to interpret their dose of warfarin. Main outcome measure Percentage of time spent within the therapeutic range of international normalised ratio. Results No significant differences were found in percentage of time in the therapeutic range between self managment and routine care (70% v 68%). Self managed patients with poor control before the study showed an improvement in control that was not seen in the routine care group. Nine patients (2.8/100 patient years) had serious adverse events in the self managed group, compared with seven (2.7/100 patient years) in the routine care arm (χ2(df = 1) = 0.02, P = 0.89). Conclusion With appropriate training, self management is safe and reliable for a sizeable proportion of patients receiving oral anticoagulation treatment. It may improve the time spent the therapeutic range for patients with initially poor control. Trial registration ISRCTN 19313375. PMID:16216821

  20. Direct oral anticoagulant medications in calciphylaxis.

    PubMed

    King, Brian J; El-Azhary, Rokea A; McEvoy, Marian T; Shields, Raymond C; McBane, Robert D; McCarthy, James T; Davis, Mark D P

    2017-10-01

    Recent studies suggest that calciphylaxis is a thrombotic condition in which arteriolar thrombosis leads to painful skin infarcts and consequent morbidity and mortality. Paradoxically, warfarin is implicated as a risk factor for calciphylaxis. Our objective is to report the use of oral direct thrombin and factor Xa inhibitors (termed direct oral anticoagulants [DOACs]) in patients with calciphylaxis. We retrospectively reviewed records of 16 patients with calciphylaxis who received concomitant administration of novel anticoagulants. Patient data, including demographics, comorbidities, other treatments, and adverse events, were abstracted from the health records. Eleven patients (69%) had chronic kidney disease (stage ≥3A), and eight (50%) received dialysis. Apixaban was the most frequently used agent (n = 11 [69%]). Dabigatran (n = 4 [25%]) and rivaroxaban (n = 2 [13%]) were reserved for patients with mild renal impairment (stage ≤2). One clinically relevant but nonmajor bleeding event occurred. There were no major bleeding events. Nine patients (56%) were alive at last follow-up, and five (31%) had complete resolution of their calciphylaxis (mean follow-up, 523 days; range, 26-1884 days). DOACs were safe and well tolerated in patients with calciphylaxis, in this initial experience. Several patients had improvement or resolution of calciphylaxis in response to therapy that included DOACs. The degree of renal impairment should guide DOAC choice. Randomized trials are required to determine treatment efficacy. © 2017 The International Society of Dermatology.

  1. Interpretation of coagulation test results under direct oral anticoagulants.

    PubMed

    Mani, H

    2014-06-01

    Diagnostic of global coagulation parameters is part of the daily clinical routine practice in conservative as well in operative disciplines. The correct interpretation of in vitro test results in context to the ex vivo influence of anticoagulant drugs and the in vivo hemostatic system of the individual patient is dependent on the doctors clinical and laboratory experience. This article shortly reviews the laboratory interference of oral anticoagulants including the target-specific inhibitors dabigatran, rivaroxaban and apixaban on coagulation parameters and discusses the potential of several methods for measuring the anticoagulant effect of the direct oral anticoagulants.

  2. [Antidotes to novel direct oral anticoagulants].

    PubMed

    Khorev, N G; Momot, A P; Kon'kova, V O

    During the last 10 years, several novel direct oral anticoagulants (NOACs) have entered the clinical arena and were registered in the Russian Federation for use in patients presenting with atrial fibrillation, venous thrombosis, and pulmonary artery thromboembolism. NOACs are classified into two groups: direct thrombin inhibitor (notably dabigatran) and factor Xa inhibitors (including rivaroxaban, apixaban, and edoxaban). Their disadvantage is lack of specific antidotes in case of an emergency situation (injury, infarction, stroke requiring thrombolysis, urgent operation). The review contains the data on the existing therapeutic regimens of treating haemorrhage on the background of taking these coagulants. This is followed by analysing the present-day results of clinical trials aimed at working out pharmaceutical agents (andexanet alpha, idarucizumab, aripazine) being antidotes to direct thrombin inhibitor and the factor Xa inhibitors. Administration of these agents makes it possible to reverse coagulation and minimize the aftermaths of haemorrhage in patients taking these drugs, in emergency situations.

  3. Novel oral anticoagulants in acute coronary syndrome.

    PubMed

    Costopoulos, Charis; Niespialowska-Steuden, Maria; Kukreja, Neville; Gorog, Diana A

    2013-09-10

    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide with a prevalence that has now reached pandemic levels as a consequence of the rapid modernization of the developing world. Its presentation as an acute coronary syndrome (ACS) is a frequent reason for hospital admission and of profound implications for personal, societal and global health. Despite improvements in the management of ACS with anti-platelet and anticoagulant therapy and revascularization techniques, many patients continue to suffer recurrent ischemic events. The need to reduce future cardiovascular events has led to the development of novel therapies to prevent coronary thrombosis, targeting thrombin-mediated pathways. These include direct Xa inhibitors (apixaban, rivaroxaban and darexaban), direct thrombin inhibitors (dabigatran) and PAR 1 antagonists (vorapaxar and atopaxar). This article critically reviews the comparative mechanisms of action, the risks and benefits, together with the clinical evidence base for the use of these novel oral agents in the management of ACS patients.

  4. Suboptimal Use of Oral Anticoagulants in Atrial Fibrillation: Has the Introduction of Direct Oral Anticoagulants Improved Prescribing Practices?

    PubMed

    Alamneh, Endalkachew A; Chalmers, Leanne; Bereznicki, Luke R

    2016-06-01

    Atrial fibrillation (AF) and the associated risk of stroke are emerging epidemics throughout the world. Suboptimal use of oral anticoagulants for stroke prevention has been widely reported from observational studies. In recent years, direct oral anticoagulants (DOACs) have been introduced for thromboprophylaxis. We conducted a systematic literature review to evaluate current practices of anticoagulation in AF, pharmacologic features and adoption patterns of DOACs, their impacts on proportion of eligible patients with AF who receive oral anticoagulants, persisting challenges and future prospects for optimal anticoagulation. In conducting this review, we considered the results of relevant prospective and retrospective observational studies from real-world practice settings. PubMed (MEDLINE), Scopus (RIS), Google Scholar, EMBASE and Web of Science were used to source relevant literature. There were no date limitations, while language was limited to English. Selection was limited to articles from peer reviewed journals and related to our topic. Most studies identified in this review indicated suboptimal use of anticoagulants is a persisting challenge despite the availability of DOACs. Underuse of oral anticoagulants is apparent particularly in patients with a high risk of stroke. DOAC adoption trends are quite variable, with slow integration into clinical practice reported in most countries; there has been limited impact to date on prescribing practice. Available data from clinical practice suggest that suboptimal oral anticoagulant use in patients with AF and poor compliance with guidelines still remain commonplace despite transition to a new era of anticoagulation featuring DOACs.

  5. Oral anticoagulant therapy in patients undergoing dental surgery.

    PubMed

    Weibert, R T

    1992-10-01

    The literature on dental surgery in patients receiving oral anticoagulants is reviewed, and methods of managing anticoagulant therapy to minimize the risk of complications are discussed. Although blood loss during and after oral surgery in patients receiving oral anticoagulant drugs can be substantial, research indicates that most bleeding incidents are not serious and can be controlled by local measures. Studies of 241 anticoagulant-treated patients undergoing more than 500 dental extractions during the 1950s and 1960s showed that only 9 had postoperative bleeding. More recent studies indicate that continued anticoagulation can increase the frequency of prolonged bleeding and delay wound healing. An antifibrinolytic mouthwash containing tranexamic acid can effectively suppress postoperative bleeding. Gelatin sponges, oxidized cellulose, and microcrystalline collagen are other useful hemostatic agents. A reduction in the intensity of anticoagulation therapy has been recommended; the prothrombin time should be measured shortly before the procedure in such patients. In many patients the duration of subtherapeutic anticoagulation must be minimized to reduce the possibility of thromboembolism. An option for high-risk patients is to switch them to heparin. Each patient must be evaluated individually, and the level of risk of the dental procedure and the risk of thromboembolism should be taken into account. In patients taking oral anticoagulants who must undergo dental surgery, careful control of the intensity of anticoagulation and improved methods of local hemostasis can minimize the risk of hemorrhagic complications and thromboembolism.

  6. Personalizing oral anticoagulant treatment in patients with atrial fibrillation.

    PubMed

    Capranzano, Piera; Miccichè, Eligio; D'Urso, Lucia; Privitera, Fiorella; Tamburino, Corrado

    2013-08-01

    For decades, warfarin has remained the standard oral anticoagulation for stroke prevention in atrial fibrillation (AF). Three novel oral anticoagulants (NOACs) have been recently approved for stroke prevention in non-valvular AF: dabigatran, rivaroxaban and apixaban. Better pharmacological and clinical profiles make these newcomers a preferable alternative over warfarin. Current AF guidelines do not endorse NOACs over warfarin, or one NOAC over another. Indeed, choice of the anticoagulation regimen should be personalized based on the relative efficacy and safety of different agents across subgroups stratified by thrombotic and bleeding risk, as well as on other clinical factors, including anticoagulation control on warfarin, drug interactions, compliance and need for coagulation monitoring. This review appraises i) the randomized evidence on approved NOACs versus warfarin in AF across subgroups stratified by risk factors of stroke and bleeding and by the anticoagulation level reached on warfarin; and ii) clinical factors impacting on the anticoagulation regimen selection.

  7. Managing dentoalveolar surgical procedures in patients taking new oral anticoagulants.

    PubMed

    Sivolella, Stefano; De Biagi, Marleen; Brunello, Giulia; Berengo, Mario; Pengo, Vittorio

    2015-09-01

    The development of new orally administered anticoagulants, such as dabigatran, rivaroxaban, and apixaban, in the past few years has focused on avoiding some of the drawbacks associated with warfarin. This work aims to illustrate the main features of the most commonly used new oral anticoagulants, reviewing the current literature on the management of patients taking these drugs and needing oral and implant surgery, and discussing the currently proposed related guidelines.

  8. Management of acute stroke in patients taking novel oral anticoagulants

    PubMed Central

    Hankey, Graeme J; Norrving, Bo; Hacke, Werner; Steiner, Thorsten

    2014-01-01

    Each year, 1·0–2·0% of individuals with atrial fibrillation and 0·1–0·2% of those with venous thromboembolism who are receiving one of the novel oral anticoagulants (dabigatran, rivaroxaban, or apixaban) can be expected to experience an acute ischemic stroke. Additionally, 0·2–0·5% of individuals with atrial fibrillation who are receiving one of the novel oral anticoagulants can be expected to experience an intracranial hemorrhage. This opinion piece addresses the current literature and offers practical approaches to the management of patients receiving novel oral anticoagulants who present with an ischemic or hemorrhagic stroke. Specifically, we discuss the role of thrombolysis in anticoagulated patients with acute ischemic stroke and factors to consider concerning restarting anticoagulation after acute ischemic and hemorrhagic stroke. PMID:24891030

  9. Direct Oral Anticoagulants in the Treatment of Venous Thromboembolic Disease.

    PubMed

    Salmerón Febres, Luis Miguel; Cuenca Manteca, Jorge

    2017-07-01

    Anticoagulation is the treatment of choice in the management of venous thromboembolic disease. This approach is applied to reduce mortality and the risk of recurrences and associated complications. Standard therapy for non-oncologic patients has traditionally been based on parenteral anticoagulation followed by vitamin K antagonists. However, this approach has many limitations. The aim of this manuscript was to critically review current evidence on the use of direct oral anticoagulants in the treatment of venous thromboembolic disease by analyzing the specific characteristics of each drug. Direct oral anticoagulants have many advantages over standard therapy. While they are equally effective as standard therapy for reducing the possibility of recurrence of venous thromboembolic disease, they carry a lower risk of major bleeding. Direct oral anticoagulants are an attractive alternative to standard therapy for the treatment of venous thromboembolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Peri-procedural management of patients taking oral anticoagulants.

    PubMed

    Daniels, Paul R

    2015-07-14

    The use of oral anticoagulants is becoming increasingly common. For many years warfarin was the main oral anticoagulant available, but therapeutic options have expanded with the introduction of oral direct thrombin (dabigatran) and factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban). Management of patients taking any oral anticoagulant in the peri-procedural period poses a challenge to medical and surgical providers because of the competing risks of thrombosis and hemorrhage. Bridging therapy has been used to minimize time without anticoagulation when warfarin is interrupted for invasive procedures, but validated strategies based on high quality data are lacking. Existing data suggest that the use of bridging therapy may increase the risk of bleeding for some patients without reducing the risk of thrombosis. Clinical trials are currently under way to answer these questions. Because the half lives and time to anticoagulant activity of newer oral anticoagulants are shorter than for warfarin, bridging therapy is not thought to be necessary with these agents. Peri-procedural management of patients taking these agents is complicated by the lack of demonstrated reversal agents in emergency situations, although specific antidotes are being developed and tested. Existing guidelines for peri-procedural management of patients on oral anticoagulants highlight the importance of individualized patient decision making and suggest strategies to minimize complications. From a patient's perspective, given the uncertainties surrounding optimal management, explicit discussions regarding risks and benefits of treatment options and demonstration of effective communication among medical and surgical providers are essential.

  11. [Role of new oral anticoagulants in interventional cardiology].

    PubMed

    Brasselet, C; Duval, S

    2012-12-01

    New oral anticoagulants constitute an important breakthrough for cardiologists and their patients. After reviewing their mechanism of action, their role in the context of interventional cardiology, particularly for patients with acute coronary syndromes, is discussed.

  12. New Oral Anticoagulants and Their Reversal.

    PubMed

    Pinto, Ian; Giri, Anshu; Arshad, Umbreen; Gajra, Ajeet

    2015-01-01

    The advent of new oral anticoagulants (NOAC) has increased the armamentarium against thromboembolic diseases but has given rise to a conundrum on their reversal. NOAC's have comparable efficacy to traditional vitamin K antagonists with similar rates of major bleeding. However there is no standardized method for reversal of these agents and no specific antidote. This is of concern not only in acute bleeding episodes but also in clinical scenarios where emergency surgery is required. Recent studies have investigated reversal of dabigatran, rivaroxaban, and apixaban using prothrombin complex concentrates (PCC), recombinant factor VIIa, and in the case of dabigatran, a monoclonal antibody. These studies have been encouraging in showing improvement of bleeding times and blood loss in most models, especially with the use of PCCs and the dabigatran antibody. Of note the majority of common currently used coagulation assays may not correlate with clinical reversal. The management of overt bleeding with NOACs is difficult due to the lack of clinical trials. Current animal trials, case reports and hemostatic testing on human blood have shown some promise; provide guidance but warrant further investigation.

  13. New oral anticoagulants: are coagulation units still required?

    PubMed Central

    2014-01-01

    Chronic antithrombotic therapy involves the use of anticoagulants, antiplatelets given either as monotherapy or in combination for the prevention of thrombotic complications. The most feared and sometimes fatal complication with this therapy is bleeding. It should be considered a “golden rule” that a drug or combination of drugs that maximizes efficiency (decreased thromboembolic risk) will probably be less safe (increased risk of bleeding), and this holds true either for single therapy or during combined therapy. The chances of bleeding indicated by risk tables can be useful but show only a snapshot, and the biological, social, environmental, and drug changes and therapeutic adherence also determine changes in the risk of thrombosis and bleeding. Bleeding is an eventuality that occurs in places of “locus minoris resistentiae,” and the results of careful phase 3 studies thus cannot be completely predictive of outcomes when a medication is introduced on the pharmaceutical market. With the use of warfarin, the International Normalized Ratio (INR) that has been established to indicate adequately balanced therapy is between 2.0 and 3.0. With the new oral anticoagulants, the pharmaceutical companies emphasize that it is not necessary to monitor anticoagulant effects. In studies with different doses of new oral anticoagulants, however, incidence of clinically significant bleeding complications have been directly related to the doses. Therefore, therapeutic excesses can condition bleeding risk and therapeutic limitation can increase thrombotic risk, especially when short-acting drugs such as the new oral anticoagulants are used. Hence, it is imperative to establish an appropriate method for monitoring new oral anticoagulants, setting levels of safety and effectiveness through periodic dosage and monitoring of their anticoagulant effects. Therefore, we still recommend the use of anticoagulation units for monitoring during treatment with the new oral anticoagulants

  14. Management of oral anticoagulation in patients undergoing minor dental procedures.

    PubMed

    Alaali, Yathreb; Barnes, Geoffrey D; Froehlich, James B; Kaatz, Scott

    2012-08-01

    Approximately 4.2 million patients in the United States are taking warfarin, making it the 11th most prescribed drug. Warfarin is primarily used for treatment of venous thromboembolic disease and stroke prevention in patients with atrial fibrillation and mechanical heart valves. Dentists frequently encounter anticoagulated patients and are faced with management decisions in these patients who require dental procedures. Observational studies suggest the risk of thrombosis if anticoagulation is suspended during dental procedures is higher than the risk of bleeding if anticoagulation is not suspended. Several groups now offer guidelines that recommend most minor dental procedures should be performed while on therapeutic warfarin. The recent approval of several new oral anticoagulants has introduced greater complexity to the management of the anticoagulated patient, and this narrative review will discuss current guidelines, the scientific underpinnings of the guidelines, and offer some practical suggestions for patients that are receiving the new agents.

  15. New antiplatelet drugs and new oral anticoagulants.

    PubMed

    Koenig-Oberhuber, V; Filipovic, M

    2016-09-01

    In our daily anaesthetic practice, we are confronted with an increasing number of patients treated with either antiplatelet or anticoagulant agents. During the last decade, changes have occurred that make the handling of antithrombotic medication a challenging part of anaesthetic perioperative management. In this review, the authors discuss the most important antiplatelet and anticoagulant drugs, the perioperative management, the handling of bleeding complications, and the interpretation of some laboratory analyses related to these agents.

  16. The management of dental patients taking new generation oral anticoagulants.

    PubMed

    Scott, Alun; Gibson, John; Crighton, Alexander

    2014-11-01

    Recently, new oral anticoagulants have been introduced as alternatives to warfarin. While national guidelines for treatment of dental patients taking warfarin as an anticoagulant are well-established, no such information is available for these novel therapeutic agents. At present, the local guidance available is contradictory between different health boards/health planning units, and liaison with the medical practitioner managing the individual patient's anticoagulation is imperative if any invasive procedure is proposed. This paper examines the available evidence regarding these drugs and sets out proposals for clinical guidance of dental practitioners treating these patients in primary dental care.

  17. New oral anticoagulants in patients with chronic kidney disease.

    PubMed

    Belmar Vega, Lara; de Francisco, A L M; Bada da Silva, Jairo; Galván Espinoza, Luis; Fernández Fresnedo, Gema

    2016-12-08

    Patients with chronic kidney disease (CKD) develop bleeding and thrombotic tendencies, so the indication of anticoagulation at the onset of atrial fibrillation (AF) is complex. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are major complications. In recent years, new oral anticoagulant drugs have been developed, and they have shown superiority over the classical AVK in preventing stroke, systemic embolism and bleeding risk, constituting an effective alternative to those resources.

  18. Alternative to oral dicoumarin anticoagulants: Considerations in dental care.

    PubMed

    Mingarro-de-León, Ana; Chaveli-López, Begonya

    2013-12-01

    For over 50 years, vitamin K antagonists such as warfarin (Aldocumar®) and acenocoumarol (Sintrom®) have been the gold standard for reducing the risk of cerebrovascular events. In the last 5 years alternative anticoagulants have been evaluated that act directly upon a concrete target within the coagulation cascade, thereby affording a more predictable anticoagulant effect. The present study offers an update on the new oral anticoagulants and reviews the implications referred to the dental care of patients administered these substances. An exhaustive PubMed-Medline and Cochrane Library search was made of the main alternatives to conventional oral anticoagulation, covering those studies published in English and Spanish over the last 10 years. Specialized textbooks and pharmaceutical catalogs were also consulted. A total of 184 articles were identified, of which 76 met the inclusion criteria. The new oral anticoagulants dabigatran, rivaroxaban and apixaban are safe and effective, and offer a series of advantages, including rapid action, no need for constant monitoring, few drug and food interactions, and a broad therapeutic margin. These drugs are expensive, however, and some lack a specific antidote, while others must be administered twice a day. Regarding the dental treatment of patients receiving these drugs, suspension or modification of the background medication is not required when performing invasive dental procedures, except where indicated by the prescribing physician. The new oral anticoagulants do not pose significantly greater risks than conventional oral anticoagulants when providing invasive dental treatment, and their suspension is not strictly required in such situations. Key words:Dabigatran, rivaroxaban, apixaban, dental, hemostasis.

  19. Alternative to oral dicoumarin anticoagulants: Considerations in dental care

    PubMed Central

    Mingarro-de-León, Ana

    2013-01-01

    Introduction: For over 50 years, vitamin K antagonists such as warfarin (Aldocumar®) and acenocoumarol (Sintrom®) have been the gold standard for reducing the risk of cerebrovascular events. In the last 5 years alternative anticoagulants have been evaluated that act directly upon a concrete target within the coagulation cascade, thereby affording a more predictable anticoagulant effect. The present study offers an update on the new oral anticoagulants and reviews the implications referred to the dental care of patients administered these substances. Material and methods: An exhaustive PubMed-Medline and Cochrane Library search was made of the main alternatives to conventional oral anticoagulation, covering those studies published in English and Spanish over the last 10 years. Specialized textbooks and pharmaceutical catalogs were also consulted. A total of 184 articles were identified, of which 76 met the inclusion criteria. Results: The new oral anticoagulants dabigatran, rivaroxaban and apixaban are safe and effective, and offer a series of advantages, including rapid action, no need for constant monitoring, few drug and food interactions, and a broad therapeutic margin. These drugs are expensive, however, and some lack a specific antidote, while others must be administered twice a day. Regarding the dental treatment of patients receiving these drugs, suspension or modification of the background medication is not required when performing invasive dental procedures, except where indicated by the prescribing physician. Conclusions: The new oral anticoagulants do not pose significantly greater risks than conventional oral anticoagulants when providing invasive dental treatment, and their suspension is not strictly required in such situations. Key words:Dabigatran, rivaroxaban, apixaban, dental, hemostasis. PMID:24455094

  20. Development and Validation of an Oral Anticoagulation Knowledge Tool (AKT)

    PubMed Central

    Obamiro, Kehinde O.; Chalmers, Leanne; Bereznicki, Luke R. E.

    2016-01-01

    Background Assessing and improving patients’ anticoagulation knowledge can lead to better treatment outcomes. While validated knowledge instruments exist for use in people taking warfarin, these tools are not necessarily applicable to patients taking direct-acting oral anticoagulants. Objective To develop and validate an oral anticoagulation knowledge instrument that is applicable to all oral anticoagulant medications. Methods Ten anticoagulation experts participated in the development of the Anticoagulation Knowledge Tool to ensure content validity. The knowledge instrument was administered to three groups of participants comprising of 44 pharmacists, 50 patients and 50 members of the general public. A subgroup of participants in the patient and pharmacist group were retested approximately 2–3 months after the initial testing. Statistical tests were conducted to determine the validity and reliability of the scale, and item analysis was used to determine the performance of individual questions. Results The 28-item instrument developed had a scale content validity index of 0.92, supporting content validity. The pharmacist group’s mean score was significantly higher than that of the patient group, and the patient group scored significantly higher than the general public group (94% vs 62% vs 20%, respectively; p<0.001), supporting construct validity. Internal consistency reliability was acceptable with a Cronbach’s α value of > 0.7 across the three groups, and the test–retest reliability was confirmed with a Pearson’s correlation coefficient of 0.72 and 0.78 for the pharmacist and patient groups, respectively. Conclusion The Anticoagulation Knowledge Tool is a valid and reliable instrument that can be used in routine clinical practice to assess patients’ anticoagulation knowledge. PMID:27351746

  1. [Tranexamic acid gel in patients treated with oral anticoagulants].

    PubMed

    Ripollés-de Ramón, Jorge; Muñoz-Corcuera, Marta; Bravo-Llatas, Carmen; Bascones-Martínez, Antonio

    2014-12-09

    Patients treated with oral anticoagulants have increased susceptibility to bleeding, and therefore any surgical medical procedure and especially oral surgery requires a therapeutic approach that minimizes bleeding effects in these patients. The working hypothesis was based on studies of local application of tranexamic acid after maxillofacial interventions as effective therapeutic alternative for the prevention and control of bleeding. The aim was to assess the effectiveness of the application of a gel solution tranexamic acid after tooth extraction in anticoagulated patients in terms of healing time and degree of healing. The results indicate that application of tranexamic acid gel is very effective for consistency and maintenance in the place of action and shows its efficacy as a procoagulant material. The application of a gel solution of tranexamic acid in oral anticoagulants patients ameliorates healing time and the bleeding time within the first 48-72 h. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  2. [Improvements in oral anticoagulant therapy for atrial fibrillation].

    PubMed

    Briongos Figuero, Sem; García Santos-Gallego, Carlos; Badimón, Juan José

    2013-12-07

    For the last decades vitamin K antagonists have been the most effective anticoagulant treatment of atrial fibrillation. New molecules are being designed, mainly due to the great amount of disadvantages in the management of conventional anticoagulation. Dabigatran, rivaroxaban and apixaban will soon be available as an alternative to warfarin/acenocumarol. All of them have demonstrated to be non-inferior to warfarin in preventing stroke and systemic embolism, with even dabigatran 150 mg bid and apixaban being superior. They have also a lower risk of bleeding, especially regarding severe/fatal and intracranial hemorrhages. This is a real revolution. The advance of these new anticoagulants will be limited only by the higher cost, and will progressively become the protagonists of oral anticoagulation in patients with nonvalvular atrial fibrillation.

  3. [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.

  4. Oral surgery in patients undergoing oral anticoagulant therapy.

    PubMed

    Vicente Barrero, Mario; Knezevic, Milan; Tapia Martín, Manuel; Viejo Llorente, Aurora; Orengo Valverde, Juan Carlos; García Jiménez, Francisco; López Pérez, Omar; Domínguez Sarmiento, Sergio; Díaz Cremades, Jose Manuel; Castellano Reyes, Juan

    2002-01-01

    There is an evident need for procedural protocol for oral surgery patients who undergo oral anticoagulant treatment (OAT) because of: 1) the possible severity of complications and 2) the growing demand for OAT, which in some cases may be as much as 8% of the oral surgery patients that are referred to the hospital from primary care centers. In this study, the authors define the parameters for creating a proto- col applicable to this group of patients. The conclusion is that it is not necessary to suspend OAT before surgery; rather, these procedures should be performed under multidisciplinary medical control. The authors demonstrate that it is possible to perform oral surgery on OAT patients, without having to sus- pend treatment beforehand. A longitudinal study was performed in OAT patients that required some type of oral surgical procedures. After an INR control, the patient underwent surgery and afterwards the patient was given tranexamic acid as a mouth rinse. Postoperative hemorrhage was classified as slight when it lasted less than 5 minutes, moderate when it lasted longer than five minutes, and severe when it required blood transfusion. The study was performed over a 5-year period (1996-2000), by the maxillofacial surgery department. In that time period, 125 patients with OAT were treated; 90 of them were males and 35 were females. Tooth extraction was per- formed in 229 sessions and a total of 367 teeth were extracted, with an average of 1.6% per session. With regards to postoperative hemorrahage, it was slight in 210 cases (91.7%), moderate in 18 (7.9%) and severe only in one case (0.4%). All the variables were compared and no statistically significant differences were found. We believe that OAT should not be suspended before oral surgery, but it surgery should be performed under multidisciplinary control-especially in the case of the elderly (over 65) or with those patients that have other concomitant illnesses such as renal insufficiency or anemia or other

  5. New oral anticoagulants and their implications for dental patients.

    PubMed

    O'Connell, John Edward; Stassen, Leo F A

    2014-01-01

    Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. Over the last 40 years, warfarin has been the oral anticoagulant of choice and has been considered the mainstay of treatment. However, its use is limited by a narrow therapeutic index and complex pharmacodynamics, necessitating regular monitoring and dose adjustments. Recently, two new oral anticoagulants--dabigatran etexilate (a direct thrombin inhibitor) and rivaroxiban (a factor Xa inhibitor)--have been approved for use in North America and Europe. Unlike warfarin, dabigatran and rivaroxiban are relatively small molecules that work as anticoagulants by targeting specific single steps of the coagulation cascade. Their advantages, relative to warfarin, include: predictable pharmacokinetics; limited food and drug interactions; rapid onset of action; and, short half-life. They require no monitoring. However, they lack a specific reversal agent. The number of patients taking dabigatran and rivaroxaban is increasing. Therefore, it is inevitable that dentists will be required to perform invasive procedures on this cohort of patients. This paper outlines the various properties of the new oral anticoagulants and the most recent guidelines regarding the management of these dental patients taking these medications.

  6. Improvement of oral anticoagulation therapy by INR self-management.

    PubMed

    Horstkotte, Dieter; Piper, Cornelia

    2004-05-01

    Thromboembolic complications after valve replacement are significantly reduced if the INR is increased from 1.0 to 2.0. Hemorrhagic events increase exponentially with more intensive oral anticoagulation. In INR (patient) self-testing (PST), patients self-check their INR after being appropriately educated and supplied with a coagulometer. Patients contact their home physician if the actual INR tends to run outside an individually defined target INR corridor for correction. For patient self-management (PSM), subjects are trained to self-test their INR and to adjust the anticoagulant dose according to their anticoagulation state. The median difference between self-tested and laboratory-tested INRs was < 5.0%, indicating no significant differences between the two methods. PSM resulted in a significantly more stable oral anticoagulation therapy (OAT), which was the strongest predictor for a low complication rate after valve replacement surgery. Lower rates of thromboembolism (0.9 versus 3.6% per patient-year; pt-yr) and bleeding (4.5 versus 10.9% per pt-yr) (p < 0.001) were seen in PSM subjects than with conventional INR management. A switch from conventional to PSM resulted in a 30% reduction in complication rates in the German Experience with Low Intensity Anticoagulation (GELIA) study. After appropriate education and provision with a handy coagulometer, the vast majority of patients after valve replacement can self-check INRs and adjust the anticoagulant dosage accordingly. PSM results in a significantly more stable oral anticoagulation treatment and consequently in lower incidences of thromboembolic and bleeding events.

  7. 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.

  8. Traditional Anticoagulants and Hair Loss: A Role for Direct Oral Anticoagulants? A Review of the Literature.

    PubMed

    Watras, Magdalena M; Patel, Jignesh P; Arya, Roopen

    2016-03-01

    Hair loss is associated with the anticoagulants heparin and warfarin. With the recent availability of direct oral anticoagulants (DOACs) it is of clinical interest to know if they are implicated with hair loss and/or whether they could be successfully prescribed for patients who suffer from coumarin- or heparin-related alopecia. Initially reports of heparin- and coumarin-associated alopecia available through PubMed and Medline were explored in order to establish the cause of this side effect. Currently there is a lack of unanimity on why anticoagulants cause alopecia. However, timing and presentation strongly suggest that telogen effluvium is part of the process. The observation that both heparins and coumarins cause a similar pattern of hair loss suggests a shared mechanism related to anticoagulant activity. To date, the World Health Organization has received 405 reports of DOAC-associated alopecia through their pharmacovigilance database VigiBase(®). Additionally, real world registry data describes an alopecia incidence of 4.4 per 100 patient years in patients prescribed rivaroxaban and dabigatran. Further widespread clinical experience is required to ascertain if this is true, but early indications suggest that DOACs are implicated in hair loss and will not provide a suitable alternative for patients suffering from alopecia related to traditional anticoagulants.

  9. Traditional Anticoagulants and Hair Loss: A Role for Direct Oral Anticoagulants? A Review of the Literature.

    PubMed

    Watras, Magdalena M; Patel, Jignesh P; Arya, Roopen

    Hair loss is associated with the anticoagulants heparin and warfarin. With the recent availability of direct oral anticoagulants (DOACs) it is of clinical interest to know if they are implicated with hair loss and/or whether they could be successfully prescribed for patients who suffer from coumarin- or heparin-related alopecia. Initially reports of heparin- and coumarin-associated alopecia available through PubMed and Medline were explored in order to establish the cause of this side effect. Currently there is a lack of unanimity on why anticoagulants cause alopecia. However, timing and presentation strongly suggest that telogen effluvium is part of the process. The observation that both heparins and coumarins cause a similar pattern of hair loss suggests a shared mechanism related to anticoagulant activity. To date, the World Health Organization has received 405 reports of DOAC-associated alopecia through their pharmacovigilance database VigiBase(®). Additionally, real world registry data describes an alopecia incidence of 4.4 per 100 patient years in patients prescribed rivaroxaban and dabigatran. Further widespread clinical experience is required to ascertain if this is true, but early indications suggest that DOACs are implicated in hair loss and will not provide a suitable alternative for patients suffering from alopecia related to traditional anticoagulants.

  10. Dental procedures in patients receiving oral anticoagulation therapy.

    PubMed

    Saour, J N; Ali, H A; Mammo, L A; Sieck, J O

    1994-05-01

    Over a 10-year period a uniform management plan for patients receiving long term oral anticoagulation therapy for prosthetic heart valves and needing dental procedures was instituted. Those undergoing dental extraction or gum hygiene in the presence of gross gum pathology (Group A) had their oral anticoagulation discontinued two days prior to the procedure which was carried out only if the INR was 1.5 or less on the day of the procedure. Patients who needed dental fillings or gum hygiene in the absence of gross gum pathology (Group B) continued their anticoagulation therapy and had these procedures completed provided the INR was 3.0 or less. The main outcome measured were valve thrombosis, thromboembolism and excessive bleeding requiring hospitalization and/or blood transfusion. In Group A, 240 procedures were carried out; 212 dental extractions and 28 dental hygiene in the presence of gross gum pathology. They had a brief period of under-anticoagulation (3-7 days) to an INR of 1.5 or less. In Group B, 156 procedures were performed. No patient developed valve thrombosis or thromboembolism. Two patients, both in Group A needed hospitalization for observation but no blood transfusion. This management plan was easy to implement. Patients needed one extra visit to the anticoagulation clinic within one week of the procedure. It was both safe and effective.

  11. Perioperative Management of Direct Oral Anticoagulants (DOACs): A Systemic Review

    PubMed Central

    Sunkara, Tagore; Ofori, Emmanuel; Zarubin, Vadim; Caughey, Megan E.; Gaduputi, Vinaya; Reddy, Madhavi

    2016-01-01

    Direct oral anticoagulants (DOACs) are in wide use among patients requiring both short- and long-term anticoagulation, mainly due to their ease of use and the lack of monitoring requirements. With growing use of DOACs, it is imperative that physicians be able to manage patients on these medications, especially in the perioperative period. We aim to provide guidance on the management of DOACs in the perioperative period. In this review, we performed an extensive literature search summarizing the management of patients on direct-acting anticoagulants in the perioperative period. A total of four direct-acting oral anticoagulants were considered appropriate for inclusion in this review. The drugs were dabigatran etexilate mesylate (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa). Management of patients on DOACs in the perioperative period involves an assessment of thromboembolic event risk while off anticoagulation compared to the relative risk of bleeding if such drug is continued. DOACs may not need to be discontinued in minor surgeries or procedures, and in major surgeries, they may be discontinued hours prior depending on drug pharmacokinetics and renal function of the patients. PMID:28008269

  12. Novel oral anticoagulants in secondary prevention of stroke.

    PubMed

    Diener, H C; Easton, J D; Hankey, G J; Hart, R G

    2013-06-01

    In patients with atrial fibrillation (AF) oral anticoagulation with vitamin-K antagonists (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention yielding a 60-70% relative reduction in stroke risk compared with placebo, as well as a mortality reduction of 26 percent. Vitamin-K antagonists have a number of well documented shortcomings. Recently the results of randomised trials for three new oral anticoagulants that do not exhibit the limitations of vitamin-K antagonists have been published. These include direct factor Xa inhibitors (rivaroxaban and apixaban) and a direct thrombin inhibitor (dabigatran). The studies (RE-LY, ROCKET-AF, ARISTOTLE, AVERROES) provide promising results for the new agents, including higher efficacy and a significantly lower incidence of intracranial bleeds compared with warfarin or aspirin. The new drugs show similar results in secondary as well as in primary stroke prevention in patients with AF. Apixaban was demonstrated to be clearly superior to aspirin and had the same rate of major bleeding complications. Meta-analyses show that the novel anticoagulants are superior to warfarin for the reduction of stroke, major bleeding and intracranial bleeds. New anticoagulants add to the therapeutic options for patients with AF, and offer a number of advantages over warfarin, for both the clinician and patient, including a favorable bleeding profile and convenience of use. Aspirin is no longer an option in secondary stroke prevention in patients with atrial fibrillation. Consideration of these new anticoagulants will improve clinical decision making.

  13. Comparison of Prescribing Practices with Direct Acting Oral Anticoagulant Protocols.

    PubMed

    Draper, Evan; Parkhurst, Brandon; Carley, Blake; Krueger, Kori; Larson, Tonja; Griesbach, Sara

    2017-09-08

    The goal of anticoagulation management programs is to prevent thrombosis while minimizing the risks of hemorrhage. Direct acting oral anticoagulants (DOACs) selectively inhibit coagulation proteins to inhibit thrombosis. Previous studies suggest patient monitoring and education provided through anticoagulation services enhance adherence and decrease adverse outcomes in patients receiving DOAC therapy. The objectives of this study were to describe DOAC prescribing adherence to anticoagulation service protocols and to observe whether enrollment in an anticoagulation service resulted in greater prescribing adherence to DOAC protocols. A retrospective cohort study evaluated all initial prescriptions of apixaban, dabigatran, and rivaroxaban at Marshfield Clinic from 19 October 2010 to 21 August 2014. Three algorithms analyzed patient and prescription data extracted from the organization's electronic health record and classified prescriptions as per protocol or not per protocol. The algorithms classified not per protocol prescriptions as off-label indication, renal impairment [estimated glomerular filtration rate (eGFR) <30 ml/min], hepatic impairment (rivaroxaban and apixaban), advanced age >74 years (dabigatran), dose too low, or dose too high. The analysis assessed whether enrollment in the Marshfield Clinic Anticoagulation Service DOAC monitoring process was associated with increased adherence to protocols. In aggregate, 72% of apixaban prescriptions, 52% of dabigatran prescriptions, and 70% of rivaroxaban prescriptions were per protocol. Off-label indications and dosage too low were the most common not per protocol reasons for apixaban and rivaroxaban prescriptions. Age ≥75 years and off-label indication were the most common not per protocol reasons for dabigatran prescriptions. Enrollment in the anticoagulation service process was not associated with increased adherence to protocols. A significant proportion of DOAC prescriptions did not adhere to protocol

  14. [State of the art: Direct oral anticoagulants and transfusion].

    PubMed

    Martin, A-C; Godier, A; Smadja, D M; Mauge, L; Fischer, A-M

    2017-09-01

    Direct oral anticoagulants (DOAC) are indicated for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism. As any anticoagulant, they are associated with a bleeding risk. Management of DOAC-induced bleeding is challenging. Idarucizumab, antidote for dabigatran, is currently available and is part of the therapeutic strategy, whereas antidotes for anti-Xa agents are under development. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. We propose an update on DOAC-associated bleeding management, integrating the availability of idarucizumab and the critical place of DOAC concentration measurements. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. [Vitamin K antagonist, direct oral anticoagulants: Where is the truth?

    PubMed

    Laroche, J-P; Schved, J-F

    2016-12-01

    Vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs) are now in competition. The companies are trying to replace VKA by DOACs, totally or at least greatly VKA should VKA disappear in favor of DOACs? There are still many questions about DOACs. The purpose of this article is to make a well-considered decision in this area. The aim is not to denigrate one or the other but to share things between these two families of anticoagulants. Physicians using these drugs must have a full knowledge about compared efficacy and safety. We feel necessary to increase distance between effective results of the clinical trials and industrial communication around DOACs.

  16. How we treat bleeding associated with direct oral anticoagulants

    PubMed Central

    Marano, Giuseppe; Vaglio, Stefania; Pupella, Simonetta; Liumbruno, Giancarlo M.; Franchini, Massimo

    2016-01-01

    Direct oral anticoagulants are at least as effective as vitamin K antagonists for the prevention and treatment of thromboembolism. Unfortunately, differently from vitamin K antagonists, they have the great drawback of lacking specific antidotes in the case of bleeding or emergency situations such as trauma, stroke requiring thrombolysis, and urgent surgery. The progressive development of antidotes for these new drugs, which, it is hoped, will become available in the near future, will allow better and safer management of the rapid reversal of their anticoagulant effect. PMID:27136433

  17. 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

  18. Measurement and reversal of the direct oral anticoagulants.

    PubMed

    Samuelson, Bethany T; Cuker, Adam

    2017-01-01

    Direct oral anticoagulants (DOACs) offer noninferior efficacy and improved safety compared to vitamin K antagonists (VKAs) for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Unlike VKAs, DOACs do not require routine laboratory monitoring of anticoagulant effect and dose adjustment. In certain situations, however, laboratory assessment of anticoagulant effect may be desirable. Here we review the utility of currently available assays for assessment of DOAC effect and recommend an optimal assessment strategy for each drug, including calibrated dilute thrombin time or ecarin-based assays for dabigatran and calibrated anti-Xa activity assays for the factor Xa inhibitors. We also discuss reversal strategies, both specific and nonspecific, for each drug, including the preferential use of idarucizumab for the reversal of dabigatran and two agents, andexanet and ciraparantag, currently under development for the reversal of rivaroxaban, apixaban, and edoxaban. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. 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

  20. Intracranial hemorrhage during administration of a novel oral anticoagulant

    PubMed Central

    Tempaku, Akira

    2016-01-01

    Objective: Oral anticoagulants are widely administered to patients with atrial fibrillation in order to prevent the onset of cardiogenic embolisms. However, intracranial bleeding during anticoagulant therapy often leads to fatal outcomes. Accordingly, the use of novel oral anticoagulants (NOACs), which less frequently have intracranial bleeding as a complication, is expanding. A nationwide survey of intracranial bleeding and its prognosis in Japan reported that intracranial bleeding of advanced severity was not common after NOAC administration. In this report, two cases from our institute are presented. Patients: Case 1 was an 85-year-old man with a right frontal lobe hemorrhage while under dabigatran therapy. Case 2 was an 81-year-old man who had cerebellar hemorrhage while under rivaroxaban therapy. Result: In both patients, the clinical course progressed without aggravation of bleeding or neurological abnormalities once anticoagulant therapy was discontinued. Conclusion: These observations suggest that intracranial hemorrhage during NOAC therapy is easily controlled by discontinuation of the drug. NOAC administration may therefore be appropriate despite the risk of such severe complications. Further case studies that include a subgroup analysis with respect to each NOAC or patient background will be required to establish appropriate guidelines for the prevention of cardiogenic embolisms in patients with atrial fibrillation. PMID:27928459

  1. Management of antiplatelet and anticoagulant therapy for endoscopic procedures: Introduction to novel oral anticoagulants.

    PubMed

    González Bárcenas, Martha L; Pérez Aisa, Ángeles

    2016-02-01

    The development of novel antithrombotic therapy in the past few years and its prescription in patients with cardiovascular and circulatory disease has widened the spectrum of drugs that need to be considered when performing an endoscopic procedure. The balance between the thrombotic risk patients carry due to their medical history and the bleeding risk involved in endoscopic procedures should be thoroughly analyzed by Gastroenterologists. New oral anticoagulants (NOACs) impose an additional task. These agents, that specifically target factor IIa or Xa, do not dispose of an anticoagulation monitoring method nor have an antidote to revert their effect, just as with antiplatelet agents. Understanding the fundamental aspects of these drugs provides the necessary knowledge to determine the ideal period the antithrombotic therapy should be interrupted in order to perform the endoscopic procedure, offering maximum safety for patients and optimal results.

  2. Use of novel oral anticoagulant agents in venous thromboembolism

    PubMed Central

    Madan, Shivanshu; Shah, Shenil; Dale, Patrick; Partovi, Sasan

    2016-01-01

    New oral anticoagulants (NOAC) serve as alternatives for patients currently using warfarin for the prevention and treatment of venous thromboembolic (VTE) disease. This article provides a brief summary of the clinical use of these drugs as well as a review of the landmark clinical trials which evaluated described their safety and efficacy. As more data becomes available, a fundamental understanding of these medications will be vital to cardiovascular practitioners managing patients with VTE. PMID:28123977

  3. Control of oral anticoagulant treatment by chromogenic prothrombin assay.

    PubMed Central

    O'Donnell, J R; Walker, I D; Davidson, J F

    1987-01-01

    Doses of oral anticoagulants in 50 patients on long term treatment were easily and satisfactorily monitored over six months by an automated chromogenic assay of prothrombin (CPA). It is suggested that chromogenic assay of one or more of the vitamin K dependent coagulation factors would provide a readily standardised alternative to those conventional tests which depend on human brain derived reagents, now regarded as a biohazard. PMID:3108332

  4. 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.

  5. Bridging of oral anticoagulation therapy for invasive procedures.

    PubMed

    Spyropoulos, Alex C

    2005-09-01

    The management of patients who need temporary interruption of chronic oral anticoagulant (OAC) therapy for an elective surgical or invasive procedure is problematic and complex. Patient and procedural risk factors for thrombosis and bleeding, anticoagulant-related risks of bleeding, and clinical consequences of a thrombotic or bleeding event need to be assessed and properly risk-stratified in the perioperative period. Certain procedures, such as dental, endoscopic, and cutaneous procedures, can be completed without discontinuing OAC, but most procedures with a high bleeding risk (including major surgeries) will necessitate temporary discontinuation of OAC. Bridging therapy with shorter-acting anticoagulants, such as heparin, for patients at intermediate to high risk of thromboembolism represents one strategy to maintain functional anticoagulation during this period. Large, prospective cohort studies and registries of patients on chronic OAC who underwent bridging therapy mostly with low-molecular-weight heparin have been completed recently. This paper reviews these clinical data on bridging therapy and provides an evidence-based perioperative management strategy for the at-risk patient on chronic OAC.

  6. [Novel oral anticoagulants and atrial fibrillation in the elderly].

    PubMed

    Hanon, Olivier

    2013-12-01

    Atrial fibrillation treatment relies on anticoagulation therapy that reduces the risk of stroke. Vitamin K antagonists (VKA) were the only oral anticoagulant drugs for more than 50 years, but they are difficult to manage especially in the elderly. In France, VKA are the main cause of iatrogenic hospitalizations with about 17,000 hospitalizations per year and around 4,000 to 5,000 deaths per year. Pharmacologic properties of VKA, especially the narrow therapeutic margin explain the complexity of their management. Several studies have shown that patients treated with VKA were on average only 50% of the time with an INR in the therapeutic range. In other words, patients are, half of the time, either-under treated or over-treated. Within this framework, development of new oral anticoagulant drugs appeared necessary, in order to obtain drugs with larger therapeutic margin and a better risk/benefit profile than VKA. Three large randomized clinical trials including almost 50,000 patients with 20,000 subjects over 75 years old and 8,000 over 80 years old, show a better risk/benefit profile of the new oral anticoagulants (NOAC) than VKA, characterized by a 50% reduction of cerebral hemorrhages, 22% reduction of stroke and 12% reduction of total mortality. Meanwhile, their renal elimination and the lack of control of the biological efficacy need to be taken into account for their prescription. Renal failure (estimated glomerular filtration rate according to Cockcroft formula < 30 mL/min) contraindicates their use. Their half-life is shorter than that of VKA and the biological monitoring is not available, thus a good adherence to the treatment is important. Studies specifically conducted among geriatric older population with poly-pathologies and frail are therefore needed to evaluate tolerance of NOAC in real life conditions.

  7. [Secondary anticoagulant prophylaxis with low molecular heparins or oral anticoagulants and bone mineral density].

    PubMed

    Wawrzyńska, L; Przedlacki, J; Hajduk, B; Tomkowski, W; Fijałkowska, A; Ostrowski, K; Torbicki, A

    2000-11-01

    A broad spectrum of indications for low molecular weight heparin (LMWH) requires an assessment of side effects especially during prolonged administration. There are common risk factors for venous thromboembolism (VTE) and osteoporosis; heparin is "the drug of choice" for VTE treatment. The aim of our study was to assess the effect of treatment and prophylaxis with LMWH (enoxaparine sodium) and oral anticoagulant (acenocoumarol) for bone structure. Material consists of in- and outpatients. 49 densitometries were performed in 31 patients (in 15 cases double examination). We observed a decrease of bone mineral density in comparison to the initial examination in most cases: mean change of bone mass for examined areas was 3.05%.

  8. Novel oral Anticoagulants in Non-Valvular Atrial Fibrillation

    PubMed Central

    da Silva, Rose M.F.L.

    2014-01-01

    Atrial fibrillation is the most frequent arrhythmia in clinical practice, reaching 2% of the people in the world and is associated with systemic embolism. Thus, the use of anticoagulants is indicated if CHA2DS2-VASc score ≥2 or in patients with previous transient ischemic attack or stroke. For decades, warfarin, a vitamin K antagonist, was the only choice for chronic oral anticoagulation. Recently, novel oral anticoagulants (NOACs) have been introduced, offering similar (or better) effectiveness, safety, and convenience to the vitamin K antagonists. Dabigatran was the first NOAC approved and is a direct thrombin inhibitor. Rivaroxaban and apixaban are factor Xa inhibitors. They display rapid onset of action, more predictable of pharmacological profile, less interactions with other drugs, lack of significant effects in the diet, and less risk of intracranial hemorrhage than warfarin. Despite that dose adjustment is necessary for patients with chronic kidney disease or according to body weight, these new drugs do not require regular monitoring. There are recommendations for the start and follow-up therapy with NOACs, planning for cardioversion, ablation and surgical interventions and the management of bleeding. This article is a review of the major studies of the NOACs. The clinical use of these drugs in patients with non-valvular atrial fibrillation is presented. PMID:25470147

  9. The target-specific oral anticoagulants: practical considerations.

    PubMed

    Garcia, David A

    2014-12-05

    More than 4 years have passed since the first approval of a target-specific oral anticoagulant (TSOAC) in the United States, and the number of clinicians who have prescribed (or considered prescribing) one or more of these medications is increasing. Although these agents may, in properly selected patients, offer advantages over more traditional therapies, their lack of familiarity can be intimidating. Clinicians who are prescribing the TSOACs face a number of management questions not definitively answered by the registration trials. This chapter reviews some of these situations, including updated information on the periprocedural management of TSOACs and the latest evidence about how to best measure TSOAC effect. The lack of an antidote and other considerations that may be relevant when deciding between newer and more traditional anticoagulant medications are also discussed.

  10. Antidotes for novel oral anticoagulants: current status and future potential.

    PubMed

    Crowther, Mark; Crowther, Mark A

    2015-08-01

    The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies.

  11. Comparing the quality of oral anticoagulant management by anticoagulation clinics and by family physicians: a randomized controlled trial

    PubMed Central

    Wilson, S. Jo-Anne; Wells, Philip S.; Kovacs, Michael J.; Lewis, Geoffrey M.; Martin, Janet; Burton, Erica; Anderson, David R.

    2003-01-01

    Background There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians. We carried out a randomized controlled trial to evaluate these 2 models of anticoagulant care. Methods We randomly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practices. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio (INR) of patients receiving warfarin sodium was within the target therapeutic range ± 0.2 INR units (expanded therapeutic range) while they were managed in anticoagulation clinics as opposed to family physicians' care over 3 months. We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups. Results Of the 221 patients enrolled, 112 were randomly assigned to anticoagulation clinics and 109 to family physicians. The INR values of patients who were managed by anticoagulation clinics were within the expanded therapeutic range 82% of the time versus 76% of the time for those managed by family physicians (p = 0.034). High-risk INR values (defined as being < 1.5 or > 5.0) were more commonly observed in patients managed by family physicians (40%) than in patients managed by anticoagulation clinics (30%, p = 0.005). More INR measurements were performed by family physicians than by anticoagulation clinics (13 v. 11, p = 0.001). Major bleeding events (2 [2%] v. 1 [1%]), thromboembolic events (1 [1%] v. 2 [2%]) and deaths (5 [4%] v. 6 [6%]) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively. Of the 170 (77%) patients who completed the patient satisfaction questionnaire, more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by

  12. Upper gastrointestinal endoscopy in emergency setting for patients receiving oral anticoagulants – practice updates

    PubMed Central

    Oprita, R; Oprita, B; Diaconescu, B; Bratu, MR; Berceanu, D

    2017-01-01

    Anticoagulants are frequently used medications in diverse cardiovascular diseases. Their uses highly increase the risk of bleeding from upper and lower gastrointestinal sources, whether there is a classic vitamin K antagonist or a novel oral anticoagulant. Their interruption can promote procoagulation status with different thromboembolic accidents. Discontinuation of oral anticoagulants before the elective procedures is standardized but there are no guidelines for managing bleeding lesions of upper gastrointestinal tract concomitant with anticoagulation. Also, because some of the anticoagulants are new comers, there is no specific antidote, and so their anticoagulation effect cannot be antagonized fast in order to reduce the bleeding. Therefore, the endoscopic hemostasis must be definitive and efficient. This is a short review of the current management for the bleeding lesions of the upper gastrointestinal tract in patients taking oral anticoagulants. PMID:28255372

  13. Evaluating the Initiation of Novel Oral Anticoagulants in Medicare Beneficiaries

    PubMed Central

    Baik, Seo Hyon; Hernandez, Inmaculada; Zhang, Yuting

    2016-01-01

    BACKGROUND As alternatives to warfarin, 2 novel oral anticoagulants (NOACs), dabigatran and rivaroxaban, were approved in 2010 and 2011 to prevent stroke and other thromboembolic events in patients with atrial fibrillation. It is unclear how patient characteristics are associated with the initiation of anticoagulants. OBJECTIVE To evaluate how patient demographics, clinical characteristics, types of insurance, and patient out-of-pocket spending affect the initiation of warfarin and 2 NOACs—dabigatran and rivaroxaban. METHODS We used pharmacy claims data from a 5% random sample of Medicare beneficiaries to identify patients who were newly diagnosed with atrial fibrillation between October 1, 2010, and October 31, 2012, and who were prescribed an oral anticoagulant within 60 days of diagnosis. We identified key predictors of initiation of NOACs using a multinomial logistic regression model with generalized logit link. RESULTS Patients who were black and who had a history of acute myocardial infarction, stroke or transient ischemic attack, chronic kidney disease, or congestive heart failure were significantly associated with lower odds of receiving NOACs compared with warfarin. Age greater than 65 years, a history of hypertension, and use of nonsteroidal anti-inflammatory drugs were positively associated with the initiation of NOACs. Rivaroxaban was most likely to be initiated among women, followed by warfarin and dabigatran. Individuals receiving a low-income subsidy were more likely to initiate warfarin than NOACs, even though they paid little copayment. Individuals with supplemental Part D drug coverage, such as national Programs for All-Inclusive Care for the Elderly or employer-sponsored plans, were more likely to initiate NOACs compared with warfarin. CONCLUSIONS We found that race, sex, type of Part D plans, and some clinical conditions were associated with the initiation of NOACs relative to warfarin. But patient demographic and clinical characteristics did

  14. New oral anticoagulants and dual antiplatelet therapy: Focus on apixaban.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J; Rosano, Giuseppe

    2016-12-15

    The combination of AF and coronary artery disease not only is a common clinical setting, it is also a complex setting to deal with anticoagulation and antiplatelet therapy, and it is associated with significantly higher mortality rates. Unfortunately, there are no sufficient data available to optimally guide clinical practice in such settings. This review focuses specifically on newer oral anticoagulants (NOACs) associated with dual antiplatelet therapy (DAPT) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). There are no randomized studies comparing vitamin K antagonists and NOACs in patients with AF undergoing PCI either for acute coronary syndromes or for stable patients, i.e. those patients who have an indication to receive DAPT. Moreover, new antiplatelet agents such as ticagrelor and prasugrel have entered the market for acute coronary syndromes. So far, there are no large-scale randomized studies published evaluating these newer antiplatelet agents in patients with AF receiving either vitamin K antagonists or NOACs, adding to the uncertainty on how to use these antithrombotics in combination when both coronary artery disease (unstable or stable patients) and AF converge in a given patient. The lack of large outcome trials and the large number of possible combinations are reflected in the wide variety of practices in the real world. To date, given the lack of data, watchfulness when using NOACs as component of DAPT or triple oral antithrombotic therapy is warranted.

  15. Self-monitoring and self-management of oral anticoagulation.

    PubMed

    Heneghan, Carl J; Garcia-Alamino, Josep M; Spencer, Elizabeth A; Ward, Alison M; Perera, Rafael; Bankhead, Clare; Alonso-Coello, Pablo; Fitzmaurice, David; Mahtani, Kamal R; Onakpoya, Igho J

    2016-07-05

    The introduction of point-of-care devices for the management of patients on oral anticoagulation allows self-testing by the patient at home. Patients who self-test can either adjust their medication according to a pre-determined dose-INR (international normalized ratio) schedule (self-management), or they can call a clinic to be told the appropriate dose adjustment (self-monitoring). Increasing evidence suggests self-testing of oral anticoagulant therapy is equal to or better than standard monitoring. This is an updated version of the original review published in 2010. To evaluate the effects on thrombotic events, major haemorrhages, and all-cause mortality of self-monitoring or self-management of oral anticoagulant therapy compared to standard monitoring. For this review update, we re-ran the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), 2015, Issue 6, the Cochrane Library, MEDLINE (Ovid, 1946 to June week 4 2015), Embase (Ovid, 1980 to 2015 week 27) on 1 July 2015. We checked bibliographies and contacted manufacturers and authors of relevant studies. We did not apply any language restrictions . Outcomes analysed were thromboembolic events, mortality, major haemorrhage, minor haemorrhage, tests in therapeutic range, frequency of testing, and feasibility of self-monitoring and self-management. Review authors independently extracted data and we used a fixed-effect model with the Mantzel-Haenzel method to calculate the pooled risk ratio (RR) and Peto's method to verify the results for uncommon outcomes. We examined heterogeneity amongst studies with the Chi(2) and I(2) statistics and used GRADE methodology to assess the quality of evidence. We identified 28 randomised trials including 8950 participants (newly incorporated in this update: 10 trials including 4227 participants). The overall quality of the evidence was generally low to moderate. Pooled estimates showed a reduction in thromboembolic events (RR 0.58, 95% CI 0.45 to 0

  16. 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...

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

    PubMed Central

    Toth, Peter P

    2016-01-01

    Background 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. Methods 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. Conclusion 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. PMID:26929637

  18. 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.

  19. Novel oral anticoagulants and reversal agents: Considerations for clinical development.

    PubMed

    Sarich, Troy C; Seltzer, Jonathan H; Berkowitz, Scott D; Costin', James; Curnutte, John T; Gibson, C Michael; Hoffman, Maureane; Kaminskas, Edvardas; Krucoff, Mitchell W; Levy, Jerrold H; Mintz, Paul D; Reilly, Paul A; Sager, Philip T; Singer, Daniel E; Stockbridge, Norman; Weitz, Jeffrey I; Kowey, Peter R

    2015-06-01

    This white paper provides a summary of presentations and discussions that were held at an Anticoagulant-Induced Bleeding and Reversal Agents Think Tank co-sponsored by the Cardiac Safety Research Consortium and the US Food and Drug Administration (FDA) at the FDA's White Oak Headquarters on April 22, 2014. Attention focused on a development pathway for reversal agents for the novel oral anticoagulants (NOACs). This is important because anticoagulation is still widely underused for stroke prevention in patients with atrial fibrillation. Undertreatment persists, although NOACs, in general, overcome some of the difficulties associated with anticoagulation provided by vitamin K antagonists. One reason for the lack of a wider uptake is the absence of NOAC reversal agents. As there are neither widely accepted academic and industry standards nor a definitive regulatory policy on the development of such reversal agents, this meeting provided a forum for leaders in the fields of cardiovascular clinical trials and cardiovascular safety to discuss the issues and develop recommendations. Attendees included representatives from pharmaceutical companies; regulatory agencies; end point adjudication specialist groups; contract research organizations; and active, academically based physicians. There was wide and solid consensus that NOACs overall offer improvements in convenience, efficacy, and safety compared with warfarin, even without reversal agents. Still, it was broadly accepted that it would be helpful to have reversal agents available for clinicians to use. Because it is not feasible to do definitive outcomes studies demonstrating a reversal agent's clinical benefits, it was felt that these agents could be approved for use in life-threatening bleeding situations if the molecules were well characterized preclinically, their pharmacodynamic and pharmacokinetic profiles were well understood, and showed no harmful adverse events in early human testing. There was also consensus

  20. [Oral anticoagulation in chronic kidney disease with atrial fibrillation].

    PubMed

    Expósito, Víctor; Seras, Miguel; Fernández-Fresnedo, Gema

    2015-05-21

    Atrial fibrillation is a common finding in patients with chronic kidney disease (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED scales, used in the general population to assess the risk/benefit of oral anticoagulation (OAC), underestimate respectively the risk of embolism and haemorrhage in CKD, making it difficult to decide whether to use OAC or not. Based on the available evidence, it seems indicated to use OAC in stage 3 CKD, while it is controversial in advanced stages. New OAC such as dabigatran and rivaroxaban have been approved in stage 3 CKD but their role is still somewhat uncertain. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  1. Clinical pearls: Laboratory assessments of direct oral anticoagulants (DOACS).

    PubMed

    Gosselin, Robert C; Gosselin, Robert; Douxfils, Jonathan; Adcock, Dorothy

    2017-07-05

    Direct oral anticoagulants (DOACS) are being used for stroke prevention in patients with atrial fibrillation as well as for prophylaxis and treatment of venous thromboembolism. Clinicians who treat, or may encounter, patients with DOAC exposure, should be aware of the limitations of coagulation testing in this setting, and seek counsel from their laboratory to understand the effects of DOACS on coagulation results. Generally, assays that employ clot based principles, or methods that require thrombin or Factor Xa activation or substrates may be affected by the presence of DOACS. The clinical laboratory should have an algorithmic testing plan for adequately assessing the presence of all DOACS and readily provide this information to clinicians. We describe Clinical Pearls for DOAC assessment using common and esoteric coagulation testing.

  2. [Anticoagulation in atrial fibrillation in the elderly: the geriatrician point of view with a focus on the direct oral anticoagulants].

    PubMed

    Vogel, T; Geny, B; Kaltenbach, G; Lang, P-O

    2015-01-01

    Prescribing anticoagulant therapy when the CHA₂DS₂-VASc score is ≥ 1 prevents strokes secondary to non-valvular atrial fibrillation (AF). However, it is important to remember that whether the aged population has the highest risk of stroke in case of AF, under anticoagulant therapy this population is also at the highest risk of bleeding. Vitamin K antagonists were for decades the molecules of reference with benefits even after 75 years of age. The direct oral anticoagulants have overcome the biological constraints inherent to monitoring vitamin K antagonists and provide a more stable pharmacological action with a limited number of drug-drug interactions. However, the widespread use of these molecules in the older population remains controversial. In this review article, indications and modalities of administration of anticoagulant therapy in the elderly will be detailed and discussed on the basis of the most recent recommendations proposed in particular by the European Society of Cardiology. Particular attention will be paid to new oral anticoagulant therapies compared with vitamin K antagonists and antiplatelet agents.

  3. Influence of Direct Oral Anticoagulants on Rates of Oral Anticoagulation for Atrial Fibrillation.

    PubMed

    Marzec, Lucas N; Wang, Jingyan; Shah, Nilay D; Chan, Paul S; Ting, Henry H; Gosch, Kensey L; Hsu, Jonathan C; Maddox, Thomas M

    2017-05-23

    Oral anticoagulation (OAC) with warfarin is underused for atrial fibrillation (AF). The availability of direct oral anticoagulants (DOACs) may improve overall OAC rates in AF patients, but a large-scale evaluation of their effects has not been conducted. This study assessed the effect of DOAC availability on overall OAC rates for nonvalvular AF. Between April 1, 2008 and September 30, 2014, we identified 655,000 patients with nonvalvular AF and a CHA2DS2-VASc score of >1 in the National Cardiovascular Data Registry PINNACLE registry. Temporal trends in overall OAC and individual warfarin and DOAC use were analyzed. Multivariable hierarchical logistic regression identified patient factors associated with OAC and DOAC use. Practice variation of OAC and DOAC use was also assessed. Overall OAC rates increased from 52.4% to 60.7% among eligible AF patients (p for trend <0.01). Warfarin use decreased from 52.4% to 34.8% (p for trend <0.01), and DOAC use increased from 0% to 25.8% (p for trend <0.01). An increasing CHA2DS2-VASc score was associated with higher OAC use (odds ratio [OR]: 1.06; 95% confidence interval [CI]: 1.05 to 1.07), but with lower DOAC use (OR: 0.97; 95% CI: 0.96 to 0.98). Significant practice variation was present in OAC use (median odds ratio [MOR]: 1.52; 95% CI: 1.45 to 1.57) and in DOAC use (MOR: 3.58; 95% CI: 3.05 to 4.13). Introduction of DOACs in routine practice was associated with improved rates of overall OAC use for AF, but significant gaps remain. In addition, there is significant practice-level variation in OAC and DOAC use. Copyright © 2017 American College of Cardiology Foundation. All rights reserved.

  4. Use of direct oral anticoagulants with regional anesthesia in orthopedic patients.

    PubMed

    Cappelleri, Gianluca; Fanelli, Andrea

    2016-08-01

    The use of direct oral anticoagulants including apixaban, rivaroxaban, and dabigatran, which are approved for several therapeutic indications, can simplify perioperative and postoperative management of anticoagulation. Utilization of regional neuraxial anesthesia in patients receiving anticoagulants carries a relatively small risk of hematoma, the serious complications of which must be acknowledged. Given the extensive use of regional anesthesia in surgery and the increasing number of patients receiving direct oral anticoagulants, it is crucial to understand the current clinical data on the risk of hemorrhagic complications in this setting, particularly for anesthesiologists. We discuss current data, guideline recommendations, and best practice advice on effective management of the direct oral anticoagulants and regional anesthesia, including in specific clinical situations, such as patients undergoing major orthopedic surgery at high risk of a thromboembolic event, or patients with renal impairment at an increased risk of bleeding. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. [Major thromboembolic complications during oral anticoagulant therapy. Importance of level of anticoagulation].

    PubMed

    de Vicente Cámara, M P; Lucía Cuesta, J F; Aguilar Franco, C; Solano Bernad, V; Serrano González, C; García-Erce, J A

    1999-12-01

    The incidence of major thromboembolic complications in patients on oral anticoagulant therapy (OAT) and the correlation of this with the intensity of the OAT and the INR level at the time of the episode have been assessed in our study. We have carried out a retrospective study including 1350 patients with an overall follow-up period of 6432 patient-years. The mean INR level throughout OAT and at the time of the mayor thromboembolic event were considered. The statistical analysis was performed by means of a survival analysis test. The incidence of major thromboembolic complications found in our study was 1.18/100 patient-years. Those patients with a mean INR below the therapeutic range showed significantly a higher risk (3.31 times higher) of suffering from some sort of major thromboembolic complication. Mean INR level at the time of the event was 1.9 and 47% of those patients had an INR level < 2 at the time of the thromboembolic complication. The probability of suffering a major thromboembolic complication for those subjects on OAT increases as the INR falls below the therapeutic range; therefore we must pay special attention to this factor in order to avoid any further recurrences.

  6. Non-vitamin K antagonist oral anticoagulants and heart failure.

    PubMed

    Isnard, Richard; Bauer, Fabrice; Cohen-Solal, Alain; Damy, Thibaud; Donal, Erwan; Galinier, Michel; Hagège, Albert; Jourdain, Patrick; Leclercq, Christophe; Sabatier, Rémi; Trochu, Jean-Noël; Cohen, Ariel

    2016-11-01

    Thromboembolism contributes to morbidity and mortality in patients with heart failure (HF), and atrial fibrillation (AF) is one of the main factors promoting this complication. As they share many risk factors, HF and AF frequently coexist, and patients with both conditions are at a particularly high risk of thromboembolism. Non-vitamin K antagonist oral anticoagulants (NOACs) are direct antagonists of thrombin (dabigatran) and factor Xa (rivaroxaban, apixaban and edoxaban), and were designed to overcome the limitations of vitamin K antagonists. Compared with warfarin in non-valvular AF, NOACs demonstrated non-inferiority with better safety, most particularly for intracranial haemorrhages. Therefore, the European Society of Cardiology guidelines recommend NOACs for most patients with non-valvular AF. Subgroups of patients with both AF and HF from the pivotal studies investigating the safety and efficacy of NOACs have been analysed and, for each NOAC, results were similar to those of the total analysis population. A recent meta-analysis of these subgroups has confirmed the better efficacy and safety of NOACs in patients with AF and HF - particularly the 41% decrease in the incidence of intracranial haemorrhages. The prothrombotic state associated with HF suggests that patients with HF in sinus rhythm could also benefit from treatment with NOACs. However, in the absence of clinical trial data supporting this indication, current guidelines do not recommend anticoagulant treatment of patients with HF in sinus rhythm. In conclusion, recent analyses of pivotal studies support the use of NOACs in accordance with their indications in HF patients with non-valvular AF.

  7. Ischaemic stroke in patients treated with oral anticoagulants.

    PubMed

    Cano, L M; Cardona, P; Quesada, H; Lara, B; Rubio, F

    2016-01-01

    Cardioembolic stroke is associated with poorer outcomes. Prevention is based on oral anticoagulant (OAC) therapy. Haemorrhage is the main complication of OACs, which are sometimes ineffective. We retrospectively reviewed 1014 consecutive patients who suffered an ischaemic stroke between 2011 and 2013, analysing those who were receiving OAC treatment at stroke onset (107 patients in total) with special attention to aetiology, outcomes, and INR value in the acute phase. The mean age (SD) was 71.9 (10) years. Patients had been treated with OACs for 5.9 (5.5) years; 98.1% of them were being treated for heart disease. INR was <2 in 77 patients (72%), and 30 patients (28%) had an INR≥2. Nine patients (8.4%) had INR values within the therapeutic range. According to TOAST classification criteria, 88.8% of strokes were cardioembolic and 1.9% were atherothrombotic. Anticoagulation therapy was discontinued in 48 patients (44.9%) due to haemorrhagic transformation (24 patients), extensive infarction (23), or endarterectomy (1). Therapy was resumed in 24 patients (50%) after a mean lapse of 36 days. This was not possible in the remaining patients because of death or severe sequelae. New OACs (NOACs) were prescribed to 9 patients (18.7% of all potential candidates). At 3 months, patients with INR>1.7 in the acute phase exhibited better outcomes than patients with INR≤1.7 (mRS 0-2 in 62% vs 30.8%; death in 10% vs 38.4%; P=.0004). Some patients taking OACs suffer ischaemic strokes that are usually cardioembolic, especially if INR is below the therapeutic range. OACs can be resumed without complications, and NOACs are still underused. Despite cases in which treatment is ineffective, outcomes are better when INR is above 1.7 at stroke onset. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Factors Affecting Patients' Perception On, and Adherence To, Anticoagulant Therapy: Anticipating the Role of Direct Oral Anticoagulants.

    PubMed

    Pandya, Ekta Y; Bajorek, Beata

    2017-04-01

    The role of the direct oral anticoagulants (DOACs) in practice has been given extensive consideration recently, albeit largely from the clinician's perspective. However, the effectiveness and safety of using anticoagulants is highly dependent on the patient's ability to manage and take these complex, high-risk medicines. This structured narrative review explores the published literature to identify the factors underpinning patients' non-adherence to anticoagulants in atrial fibrillation (AF), and subsequently contemplates to what extent the DOACs might overcome the known challenges with traditional warfarin therapy. This review comprised a two-tier search of various databases and search platforms (CINAHL, Cochrane, Current Contents Connect, EMBASE, MEDLINE Ovid, EBSCO, PubMed, Google, Google Scholar) to yield 47 articles reporting patients perspectives on, and patients adherence to, anticoagulant therapy. The findings from the literature were synthesised under five interacting dimensions of adherence: therapy-related factors, patient-related factors, condition-related factors, social-economic factors and health system factors. Factors negatively affecting patients' day-to-day lives (especially regular therapeutic drug monitoring, dose adjustments, dietary considerations) predominantly underpin a patient's reluctance to take warfarin therapy, leading to non-adherence. Other patient-related factors underpinning non-adherence include patients' perceptions and knowledge about the purpose of anticoagulation; understanding of the risks and benefits of therapy; socioeconomic status; and expectations of care from health professionals. In considering these findings, it is apparent that the DOACs may overcome some of the barriers to traditional warfarin therapy at least to an extent, particularly the need for regular monitoring, frequent dose adjustment and dietary considerations. However, their high cost, twice-daily dosing and gastrointestinal adverse effects may present

  9. Congenital Malformations Associated with the Administration of Oral Anticoagulants During Pregnancy

    ERIC Educational Resources Information Center

    Pettifor, J. M.; Benson, R.

    1975-01-01

    Reported are case histories of three infants with congenital malformations (including defective formation of the nose and hands) associated with ingestion of oral anticoagulants during the first trimester of pregnancy. (CL)

  10. Oral Anticoagulants and Atrial Fibrillation: An Update for the Clinical Nurse.

    PubMed

    Spivak, Inna E

    2015-01-01

    Anticoagulation is an important strategy for the prevention of stroke associated with atrial fibrillation. Development of new oral agents has created a need to educate nurses to administer these medications and provide patient education.

  11. A cost-effectiveness analysis of aspirin versus oral anticoagulants after acute myocardial infarction in Italy -- equivalence of costs as a possible case for oral anticoagulants.

    PubMed

    Gianetti, J; Gensini, G; De Caterina, R

    1998-12-01

    The recent publication of two large trials of secondary prevention of coronary artery disease with oral anticoagulants (WARIS and ASPECT) has caused a revival of the interest for this antithrombotic therapy in a clinical setting where the use of aspirin is common medical practice. Despite this, the preferential use of aspirin has been supported by an American cost-effectiveness analysis (JAMA 1995; 273: 965). Using the same parameters used in that analysis and incidence of events from the Antiplatelet Trialists Collaboration and the ASPECT study, we re-evaluated the economic odds in favor of aspirin or oral anticoagulants in the Italian Health System, which differs significantly in cost allocation from the United States system and is, conversely, similar to other European settings. Recalculated costs associated with each therapy were 2,150 ECU/ patient/year for oral anticoagulants and 2,187 ECU/patient/year for aspirin. In our analysis, the higher costs of oral anticoagulants versus aspirin due to a moderate excess of bleeding (about 10 ECU/ patient/year) and the monitoring of therapy (168 ECU/ patient/year) are more than offset by an alleged savings for recurrent ischemic syndromes and interventional procedures (249 ECU/ patient/year). Preference of aspirin vs. oral anticoagulants in a pharmaco-economical perspective is highly dependent on the geographical situation whereupon calculations are based. On a pure cost-effectiveness basis, and in the absence of data of direct comparisons between aspirin alone versus I.N.R.-adjusted oral anticoagulants, the latter are not more expensive than aspirin in Italy and, by cost comparisons, in other European countries in the setting of post-myocardial infarction.

  12. Clinical strategies for selecting oral anticoagulants in patients with atrial fibrillation

    PubMed Central

    Sherwood, Matthew W.; Becker, Richard C.

    2014-01-01

    Atrial fibrillation is a common arrhythmia. One of the important aspects of the management of atrial fibrillation is stroke prevention. Warfarin has been the longstanding anticoagulant used for stroke prevention in patients with atrial fibrillation. There are now three novel oral anticoagulants, which have been studied in randomized controlled trials and subsequently approved by the Federal Drug Administration for stroke prevention in patients with atrial fibrillation. Special patient populations, including renal insufficiency, elderly, prior stroke, and extreme body weights, were represented to varying degrees in the clinical trials of the novel oral anticoagulants. Furthermore, there is variation in the pharmacokinetics and pharmacodynamics of each anticoagulant, which affect the patient populations differently. Patients and clinicians are faced with the task of selecting among the available anticoagulants, and this review is designed to be a tool for clinical decision-making. PMID:23846737

  13. Differences between warfarin and new oral anticoagulants in dental clinical practice

    PubMed Central

    MIRANDA, M.; MARTINEZ, L.S.; FRANCO, R.; FORTE, V.; BARLATTANI, A.; BOLLERO, P.

    2016-01-01

    SUMMARY The oral anticoagulant therapy is used for the cure and the prevention of thromboembolic diseases. In the last fifty years the warfarin has been considered the oral anticoagulant of choice. However, its use is limited by a narrow therapeutic index and by a complex pharmacodynamics, which requires regular adjustments and monitoring of the dose. Recently, three new oral anticoagulant – dabigatran etexilato (direct thrombin inhibitor), rivaroxaban and apixaban (Xa factor direct inhibitor) – have been approved for use in europe. Increasing the number of patients taking these drugs, it is important that the dentist knows these new oral anticoagulants, their indications and methods of action, in particular for the management of patients, who require invasive treatments. With regard to the management of the patient threated with the new oral anticoagulants (NAO), there have been new significant changes in the procedure compared to the one followed by patients treated with warfarin. This led to the development of new guidelines that the dentist has to follow in order to ensure a safe and appropriate dental treatment and reduce any postoperative complications. The aim of this work is to evaluate the effectiveness of the new oral anticoagulants compared to warfarin, especially in terms of risks of bleeding events and intra and postoperative complications, in patients requiring multiple dental extractions. PMID:28042443

  14. Differences between warfarin and new oral anticoagulants in dental clinical practice.

    PubMed

    Miranda, M; Martinez, L S; Franco, R; Forte, V; Barlattani, A; Bollero, P

    2016-01-01

    The oral anticoagulant therapy is used for the cure and the prevention of thromboembolic diseases. In the last fifty years the warfarin has been considered the oral anticoagulant of choice. However, its use is limited by a narrow therapeutic index and by a complex pharmacodynamics, which requires regular adjustments and monitoring of the dose. Recently, three new oral anticoagulant - dabigatran etexilato (direct thrombin inhibitor), rivaroxaban and apixaban (Xa factor direct inhibitor) - have been approved for use in europe. Increasing the number of patients taking these drugs, it is important that the dentist knows these new oral anticoagulants, their indications and methods of action, in particular for the management of patients, who require invasive treatments. With regard to the management of the patient threated with the new oral anticoagulants (NAO), there have been new significant changes in the procedure compared to the one followed by patients treated with warfarin. This led to the development of new guidelines that the dentist has to follow in order to ensure a safe and appropriate dental treatment and reduce any postoperative complications. The aim of this work is to evaluate the effectiveness of the new oral anticoagulants compared to warfarin, especially in terms of risks of bleeding events and intra and postoperative complications, in patients requiring multiple dental extractions.

  15. A review of traditional and novel oral anticoagulant and antiplatelet therapy for dermatologists and dermatologic surgeons.

    PubMed

    Brown, Deanna G; Wilkerson, Eric C; Love, W Elliot

    2015-03-01

    Dermatologic surgeons will increasingly encounter patients on novel oral antiplatelet and anticoagulant medications. We conducted a complete overview of the pharmacokinetics, pharmacodynamics, and side effects of traditional and novel oral anticoagulant and antiplatelet therapies along with dietary supplements with anticoagulant or antiplatelet properties. A PubMed search was completed for "aspirin," "warfarin," "clopidogrel," "dabigatran," "rivaroxaban," "apixaban," "prasugrel," and "ticagrelor." Review articles and publications emphasizing perioperative management of oral anticoagulant or antiplatelet medications were selected. An additional PubMed search was completed for "hemorrhage," "bleeding," and "thrombosis" in conjunction with "dermatology," "dermatologic surgery," and "cutaneous surgery." Aspirin, clopidogrel, and warfarin have shortfalls in dosing, monitoring, and efficacy. Several trials show superior efficacy with dabigatran, rivaroxaban, and apixaban, with equal or reduced risk of bleeding compared with warfarin. Prasugrel and ticagrelor may be associated with an increased bleeding risk. Many over-the-counter medications also have anticoagulant properties with associated bleeding risks that cannot be overlooked. There are few publications evaluating the novel oral anticoagulants' effects on outpatient surgical procedures. Novel anticoagulant and antiplatelet drugs are revolutionizing therapy for cardiovascular diseases. As these medications become more prevalent, dermatologists and dermatologic surgeons must be mindful of the bleeding risk that will apply in our everyday practices. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  16. Oral anticoagulant therapy during and after coronary angioplasty the intensity and duration of anticoagulation are essential to reduce thrombotic complications.

    PubMed

    ten Berg, J M; Hutten, B A; Kelder, J C; Verheugt, F W; Plokker, H W

    2001-04-24

    In the randomized Balloon Angioplasty and Anticoagulation Study (BAAS), the addition of oral anticoagulants to aspirin significantly reduced early and late events after coronary angioplasty. However, bleeding episodes were increased. The present report studied the intensity and the duration of anticoagulation as predictors of thrombotic and bleeding events. A total of 530 patients, 34% of whom received a stent, were treated with aspirin plus coumarins. Half of the patients were randomized to angiographic follow-up. The target international normalized ratio (INR) was 2.1 to 4.8 during angioplasty and 6-month follow-up. Thrombotic events were death, myocardial infarction, target lesion revascularization, and thrombotic stroke. Bleeding complications were hemorrhagic stroke, major extracranial bleeding, and false aneurysm. "Optimal" anticoagulation was defined as an INR in the target range for at least 70% of the follow-up time. There were 17 early thrombotic events (3.2%), 7 early bleeding episodes (1.3%), and 10 false aneurysms (1.9%). The incidence rate for both early thrombotic and bleeding events was lowest in patients in the target range. A total of 61 late thrombotic events occurred (11.6%). Optimal anticoagulation was an independent predictor of late thrombotic events (relative risk, 0.33; 95% CI, 0.19 to 0.57) and was associated with a 0.21 mm (95% CI, 0.17 to 0.42) larger vessel lumen at 6 months. Late bleeding episodes (1.4%) were lowest in patients in the target range. Coumarins started before coronary angioplasty with a target INR of 2.1 to 4.8 led to the lowest procedural event rate, without an increase in bleeding episodes. During follow-up, optimal anticoagulation was associated with a decrease in the incidence of late events by 67% and a significant improvement in 6-month angiographic outcome.

  17. 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.

  18. Patterns of initiation of oral anticoagulants in patients with atrial fibrillation- quality and cost implications.

    PubMed

    Desai, Nihar R; Krumme, Alexis A; Schneeweiss, Sebastian; Shrank, William H; Brill, Gregory; Pezalla, Edmund J; Spettell, Claire M; Brennan, Troyen A; Matlin, Olga S; Avorn, Jerry; Choudhry, Niteesh K

    2014-11-01

    Dabigatran, rivaroxaban, and apixaban have been approved for use in patients with atrial fibrillation based upon randomized trials demonstrating their comparable or superior efficacy and safety relative to warfarin. Little is known about their adoption into clinical practice, whether utilization is consistent with the controlled trials on which their approval was based, and how their use has affected health spending for patients and insurers. We used medical and prescription claims data from a large insurer to identify patients with nonvalvular atrial fibrillation who were prescribed an oral anticoagulant in 2010-2013. We plotted trends in medication initiation over time, assessed corresponding insurer and patient out-of-pocket spending, and evaluated the cumulative number and cost of anticoagulants. We identified predictors of novel anticoagulant initiation using multivariable logistic models. Finally, we estimated the difference in total drug expenditures over 6 months for patients initiating warfarin versus a novel anticoagulant. There were 6893 patients with atrial fibrillation that initiated an oral anticoagulant during the study period. By the end of the study period, novel anticoagulants accounted for 62% of new prescriptions and 98% of anticoagulant-related drug costs. Female sex, lower household income, and higher CHADS2, CHA2DS2-VASC, and HAS-BLED scores were significantly associated with lower odds of receiving a novel anticoagulant (P <.001 for each). Average combined patient and insurer anticoagulant spending in the first 6 months after initiation was more than $900 greater for patients initiating a novel anticoagulant. This study demonstrates rapid adoption of novel anticoagulants into clinical practice, particularly among patients with lower CHADS2 and HAS-BLED scores, and high health care cost consequences. These findings provide important directions for future comparative and cost-effectiveness research. Copyright © 2014 Elsevier Inc. All rights

  19. [Face-to-face education to optimize knowledge in patients initiating oral anticoagulant treatment (OAT)].

    PubMed

    Izazola-Conde, Consuelo; Majluf-Cruz, Abraham; Reyes-Lagunes, Isabel; Mandoki, Juan José; Molina-Guarneros, Juan

    2016-01-01

    Insufficient knowledge of patients about oral anticoagulants that they have been prescribed is recognized as a risk factor for adverse effects. Education of patients under oral anticoagulation may improve quality and control of anticoagulant treatment; limitations of educational interventions include lack of assessment of patients' knowledge. Our goal was to determine the effect of an individualized educational intervention on knowledge of patients who recently started treatment with oral anticoagulants, to assess patients' knowledge, and to analyze factors associated with knowledge acquisition. In 49 consecutive patients attending a thrombosis clinic who initiated or re-initiated oral anticoagulant treatment, knowledge about the treatment was assessed by means of a validated questionnaire, before an individualized, face-to-face educational intervention, and at least four weeks after. Educational intervention started after the questionnaire had been answered by patients for the first time. Knowledge level increased by about 50%; the improvement was higher in patients with more years in school. Timely acquisition of knowledge about oral anticoagulant drugs is optimized with interventions provided earlier during the patients' treatment. Assessment of knowledge should be performed and instruction should be adapted to patient characteristics such as level of education and availability to receive education.

  20. Safety and efficacy of bone wax in patients on oral anticoagulant therapy.

    PubMed

    Krasny, Marta; Krasny, Kornel; Fiedor, Piotr

    2014-01-01

    Cardiovascular conditions, apart from neoplastic diseases, remain the major cause of death in developed countries; therefore, the number of patients receiving oral anticoagulants is constantly increasing. Anticoagulant therapy considerably reduced mortality in patients with history of myocardial infarction among others. Although many interventions may be performed without withdrawal of the anticoagulant and tooth extraction was qualified as a procedure of low hemorrhage risk, a majority of dentists refer the patient to a cardiologist several days before the elective tooth extraction to withdraw anticoagulants. The aim of the study was to evaluate the efficacy and safety of bone wax used to stop bleeding after dental procedures in a group of patients on chronic anticoagulant therapy and find an answer to a question, whether it is justified to temporarily withdraw anticoagulants for this type of procedures. The study involved 176 patients on chronic anticoagulant therapy undergoing tooth extraction (154 subjects) or surgical extraction of a retained tooth (48 subjects). After the procedure, in each case the alveolus was filled with bone wax to stop bleeding. In all patients involved in the study bleeding from the alveolus was successfully stopped during the procedure. None of the subjects reported increased bleeding from the operational site after coming back home. Bone wax is a good, efficient, and safe material to block bleeding from the alveolus following tooth extractions, also in patients on chronic anticoagulant therapy. The study demonstrated that withdrawal or adjustment of anticoagulant therapy is not necessary before an elective tooth extraction.

  1. Drug and dietary interactions of warfarin and novel oral anticoagulants: an update.

    PubMed

    Nutescu, Edith; Chuatrisorn, Ittiporn; Hellenbart, Erika

    2011-04-01

    Clinicians and patients around the world have been intrigued by the concept of developing an oral anticoagulant with a broad therapeutic window and few drug and dietary interactions that can be administered at fixed doses with no or minimal monitoring. The recently approved oral direct thrombin inhibitor dabigatran, along with the emerging oral anti-factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, have been developed to address many of the shortcomings of warfarin therapy. As warfarin is associated with extensive food and drug interactions, there is also a need to consider such interactions with the new oral anticoagulants. While to date few drug and dietary interactions have been reported with the new oral anticoagulants, it is still early in their development and clinical use cycle. Pharmacokinetic and pharmacodynamic profiles will have to be closely accounted for when determining the likelihood of a potential drug interaction prior to therapy initiation. As the list of drugs and supplements that interact with warfarin is continuously expanding, and the knowledge on drug interactions with the novel oral anticoagulants is still in its infancy, clinicians need to be vigilant when initiating any of these agents or when any changes in the patient's medication profile occur and perform a close screening for potential drug and dietary interactions. The objective of this paper is to give an update on drug and dietary interactions with warfarin and the novel oral anticoagulants, dabigatran, rivaroxaban, apixaban, and edoxaban.

  2. Suboptimal use of non-vitamin K antagonist oral anticoagulants

    PubMed Central

    Başaran, Özcan; Dogan, Volkan; Beton, Osman; Tekinalp, Mehmet; Aykan, Ahmet Cağri; Kalaycioğlu, Ezgi; Bolat, Ismail; Taşar, Onur; Şafak, Özgen; Kalcik, Macit; Yaman, Mehmet; İnci, Sinan; Altintaş, Bernas; Kalkan, Sedat; Kirma, Cevat; Biteker, Murat

    2016-01-01

    Abstract This study aimed to investigate the potential misuse of novel oral anticoagulants (NOACs) and the physicians’ adherence to current European guideline recommendations in real-world using a large dataset from Real-life Multicenter Survey Evaluating Stroke Prevention Strategies in Turkey (RAMSES Study). RAMSES study is a prospective, multicenter, nationwide registry (ClinicalTrials.gov identifier NCT02344901). In this subgroup analysis of RAMSES study, patients who were on NOACs were classified as appropriately treated (AT), undertreated (UT), and overtreated (OT) according to the European Society of Cardiology (ESC) guidelines. The independent predictors of UT and OT were determined by multivariate logistic regression. Of the 2086 eligible patients, 1247 (59.8%) received adequate treatment. However, off-label use was detected in 839 (40.2%) patients; 634 (30.4%) patients received UT and 205 (9.8%) received OT. Independent predictors of UT included >65 years of age, creatinine clearance ≥50 mL/min, urban living, existing dabigatran treatment, and HAS-BLED score of <3, whereas that of OT were creatinine clearance <50 mL/min, ongoing rivaroxaban treatment, and HAS-BLED score of ≥3. The suboptimal use of NOACs is common because of physicians’ poor compliance to the guideline recommendations in patients with nonvalvular atrial fibrillation (NVAF). Older patients who were on dabigatran treatment with good renal functions and low risk of bleeding were at risk of UT, whereas patients who were on rivaroxaban treatment with renal impairment and high risk of bleeding were at risk of OT. Therefore, a greater emphasis should be given to prescribe the recommended dose for the specified patients. PMID:27583892

  3. Utilization and prescribing patterns of direct oral anticoagulants

    PubMed Central

    Whitworth, Maegan M; Haase, Krystal K; Fike, David S; Bharadwaj, Ravindra M; Young, Rodney B; MacLaughlin, Eric J

    2017-01-01

    Background Scant literature exists evaluating utilization patterns for direct oral anticoagulants (DOACs). Objectives The primary objective was to assess DOAC prescribing in patients with venous thromboembolism (VTE) and nonvalvular atrial fibrillation (NVAF) in outpatient clinics. Secondary objectives were to compare utilization between family medicine (FM) and internal medicine (IM) clinics, characterize potentially inappropriate use, and identify factors associated with adverse events (AEs). Methods This was a retrospective cohort study of adults with NVAF or VTE who received a DOAC at FM or IM clinics between 10/19/2010 and 10/23/2014. Descriptive statistics were utilized for the primary aim. Fisher’s exact test was used to evaluate differences in prescribing using an adapted medication appropriateness index. Logistic regression evaluated factors associated with inappropriate use and AEs. Results One-hundred twenty patients were evaluated. At least 1 inappropriate criterion was met in 72 patients (60.0%). The most frequent inappropriate criteria were dosage (33.0%), duration of therapy (18.4%), and correct administration (18.0%). Apixaban was dosed inappropriately most frequently. There was no difference in dosing appropriateness between FM and IM clinics. The odds of inappropriate choice were lower with apixaban compared to other DOACs (odds ratio [OR]=0.088; 95% confidence interval [CI] 0.008–0.964; p=0.047). Twenty-seven patients (22.5%) experienced an AE while on a DOAC, and the odds of bleeding doubled with each inappropriate criterion met (OR=1.949; 95% CI 1.190–3.190; p=0.008). Conclusion Potentially inappropriate prescribing of DOACs is frequent with the most common errors being dosing, administration, and duration of therapy. These results underscore the importance of prescriber education regarding the appropriate use and management of DOACs. PMID:28331354

  4. Anticoagulation

    MedlinePlus

    ... gums or nosebleeds. Oral Medications These mainly include aspirin or clopidogrel (Plavix) and warfarin (Coumadin). These medications ... will decide which one is right for you. Aspirin tends to cause fewer bleeding complications than clopidogrel ...

  5. Old and new oral anticoagulants: Food, herbal medicines and drug interactions.

    PubMed

    Di Minno, Alessandro; Frigerio, Beatrice; Spadarella, Gaia; Ravani, Alessio; Sansaro, Daniela; Amato, Mauro; Kitzmiller, Joseph P; Pepi, Mauro; Tremoli, Elena; Baldassarre, Damiano

    2017-02-05

    The most commonly prescribed oral anticoagulants worldwide are the vitamin K antagonists (VKAs) such as warfarin. Factors affecting the pharmacokinetics of VKAs are important because deviations from their narrow therapeutic window can result in bleedings due to over-anticoagulation or thrombosis because of under-anticoagulation. In addition to pharmacodynamic interactions (e.g., augmented bleeding risk for concomitant use of NSAIDs), interactions with drugs, foods, herbs, and over-the-counter medications may affect the risk/benefit ratio of VKAs. Direct oral anticoagulants (DOACs) including Factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and thrombin inhibitor (dabigatran) are poised to replace warfarin. Phase-3 studies and real-world evaluations have established that the safety profile of DOACs is superior to those of VKAs. However, some pharmacokinetic and pharmacodynamic interactions are expected. Herein we present a critical review of VKAs and DOACs with focus on their potential for interactions with drugs, foods, herbs and over-the-counter medications.

  6. New oral anticoagulants in severe trauma patients: enemy at the gates?

    PubMed

    Egea-Guerrero, J J; Quintana Díaz, M

    2015-04-01

    The high incidence of trauma, especially in elderly people anticoagulated with new oral anticoagulants (NOAs), has become a major challenge, particularly in critical situations with life-threatening bleeding. Under these circumstances, urgent NOA reversion becomes mandatory. Prothrombin complex has become a frequent indication in critical situations in which rapid reversal of anticoagulation is needed and where the use of fresh frozen plasma is limited. This study offers our point of view regarding the usefulness of NOAs, not only in the prevention of cardioembolic events but also as regards their emergent reversion in cases of severe bleeding associated to trauma.

  7. [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

    2016-10-28

    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.

  8. Trends in Prescribing Oral Anticoagulants in Canada, 2008-2014.

    PubMed

    Weitz, Jeffrey I; Semchuk, William; Turpie, Alexander G G; Fisher, William D; Kong, Cindy; Ciaccia, Antonio; Cairns, John A

    2015-11-01

    The non-vitamin K antagonist oral anticoagulants (NOACs), dabigatran, rivaroxaban, and apixaban, provide several advantages over vitamin K antagonists, such as warfarin. Little is known about the trends of prescribing OACs in Canada. In this study we analyzed changes in prescription volumes for OAC drugs since the introduction of the NOACs in Canada overall, by province and by physician specialty. Canadian prescription volumes for warfarin, dabigatran, rivaroxaban, and apixaban from January 2008 to June 2014 were obtained from the Canadian Compuscript Audit of IMS Health Canada Inc and were analyzed by physician specialty at the national and provincial levels. Total prescriptions by indication were calculated based on data from the Canadian Disease and Therapeutic Index for all OAC indications and for each commonly prescribed dose of dabigatran (75, 110, and 150 mg), rivaroxaban (10, 15, and 20 mg), and apixaban (2.5 and 5 mg). The overall number of OAC prescriptions in Canada has increased annually since 2008. With the availability of the NOACs, the proportion of total OAC prescriptions attributable to warfarin has steadily decreased, from 99% in 2010 to 67% by June 2014, and the absolute number of warfarin prescriptions has been decreasing since February 2011. The greatest decline in proportionate warfarin prescriptions was in Ontario. In general, the increase of NOAC prescriptions coincided with the introduction of provinces' reimbursement of NOAC prescription costs. The proportion of total OAC prescriptions represented by the NOACs varied by specialty, with the greatest proportionate prescribing found among orthopedic surgeons, cardiologists, and neurologists. Since their approval, the NOACs have represented a growing share of total OAC prescriptions in Canada. This trend is expected to continue because the NOACs are given preference over warfarin in guidelines on stroke prevention in patients with atrial fibrillation, because of growing physician experience

  9. [Efficacy and safety of oral anticoagulants in frail elderly patients with atrial fibrillation: an unsolved problem].

    PubMed

    Alboni, Paolo; Stucci, Nicola; Cojocaru, Elena; Ungar, Andrea

    2017-03-01

    At present, the efficacy and safety of anticoagulants, warfarin, or new oral anticoagulants in frail patients remain unknown, as these patients have largely been excluded from both randomized trials and "real-world" studies; as a result, the guidelines do not provide guidance for the management of this population. Frail patients with atrial fibrillation (AF) are significantly less likely to receive oral anticoagulants compared to their nonfrail counterparts; is that an expression of reasonable prudence or malpractice? In this regard, some aspects of physical frailty should be considered: (i) increased vulnerability to stressors, including pharmacological agents with potential severe adverse effects; (ii) frail elderly patients are at high risk of falls and, therefore, of severe traumatic hemorrhages on oral anticoagulation; (iii) frail patients are more likely to have complications during intercurrent affections, potentially responsible for hemorrhages. Prospective "real-world" studies including frail AF patients are necessary. Waiting for more evidence, the doubt whether to prescribe or not an oral anticoagulant to frail AF patients remains legitimate.

  10. Point-of-care coagulation testing for assessment of the pharmacodynamic anticoagulant effect of direct oral anticoagulant.

    PubMed

    Mani, Helen; Herth, Natalie; Kasper, Alexander; Wendt, Thomas; Schuettfort, Gundolf; Weil, Yvonne; Pfeilschifter, Waltraud; Linnemann, Birgit; Herrmann, Eva; Lindhoff-Last, Edelgard

    2014-10-01

    This investigation was carried out with already available point-of-care testing (POCT) systems for coagulation parameters to evaluate the qualitative and semiquantitative determination of the time- and concentration-dependent anticoagulant effects of the direct oral anticoagulants rivaroxaban and dabigatran. The whole blood prothrombin time (PT), activated partial thromboplastin time (aPTT), and activated clotting time (ACT) were determined using the GEM PCL Plus coagulation system. Whole blood PT was also measured on the CoaguCheck XS instrument. In addition, PT and aPTT values were obtained in citrated plasma using the PT reagent Neoplastin Plus and the STA APTT reagent. Drug concentrations of rivaroxaban and dabigatran were determined with a chromogenic anti-Xa assay and the hemoclot assay, which are reported to have good agreement with liquid chromatography coupled with tandem mass spectrometry measurements. POCT was performed in 27 consecutive patients who received rivaroxaban 10, 15, or 20 mg once daily and in 15 patients receiving dabigatran 110 or 150 mg twice daily. Blood samples were collected predose and 2 hours after observed drug intake at steady state. Two hours after observed rivaroxaban administration, the whole blood PT measured on the GEM PCL Plus was prolonged by an average of 64.5% in comparison with predose levels. Less differentiation was observed for rivaroxaban when the PT was measured on the CoaguCheck XS instrument or in plasma (prolongation of 24.1% and 36.8%, respectively). After 2 hours observed dabigatran administration, the whole blood aPTT was comparable with plasma values and was prolonged by 23.5% in comparison with trough values. Significant concentration-dependent prolongations of the activated clotting time were observed to different extents for both direct anticoagulants. Direct oral anticoagulants display variable ex vivo effects on different POCT-assays. POCT for aPTT is sensitive to increased concentrations of dabigatran

  11. Beyond warfarin: the new generation of oral anticoagulants and their implications for the management of dental patients.

    PubMed

    Firriolo, F John; Hupp, Wendy S

    2012-04-01

    Warfarin has been the primary anticoagulant drug used in the USA for more than 50 years. However, 2 novel types of oral anticoagulants have recently been approved for use in the USA. These are direct thrombin inhibitors (e.g., dabigatran etexilate) and factor Xa inhibitors (e.g., rivaroxaban). Dental health care providers may soon encounter patients who are being prescribed these medications. This article describes the pharmacologic properties and medical uses of these new oral anticoagulants. Also discussed are implications for the management of dental patients being treated with these new oral anticoagulants, including potential interactions with drugs commonly used or prescribed in the course of dental treatment.

  12. 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.

  13. [Cerebral haemorrhage in patients treated with oral anticoagulation].

    PubMed

    Rodríguez-Campello, A; Roquer-González, J; Gomis-Cortina, M; Munteis-Olivas, E; Ois-Santiago, A; Herraiz-Rocamora, J

    Intracranial haemorrhage (ICH) during dicumarinic treatment is a complication related to anticoagulation intensity with a high level of mortality. The aim of our study is to analize etiology, location and outcome of intracerebral haemorrhages related with anticoagulant therapy. Over 401 spontaneous intracranial haemorrhages consecutively admitted in the neurological ward, we analyzed the acenocumarol ICH by location, anticoagulation range and factors that conditioned the outcome. We identified 26 patients, 6.5% of total ICH. Mean age was 75.2 +/- 7.9 years-old, over the rest of ICH. International Normalized Ratio (INR) was less than 2 in 10 patients, between 2 and 3 in six and greater than 3 in ten patients. 8 patients (31%) died, three of them had multiple ICH, but none of them had a INR greater than 2. Dicumarinic haemorrhages were of lobar location in 14 cases (three of them multiples) and deep in 12 cases. In our study, dicumarinic ICH are responsible of 6.5% total intracranial haemorrhages and they are not in clear relation with excessive anticoagulation. Mortality is slightly greater than the other ICH. Relatively benignity of these patients, the age and lobar location suggest that the etiology of these haemorrhages can be related to a subjacent amyloid angiopathy.

  14. 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

  15. Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: the SAMURAI-NVAF study.

    PubMed

    Toyoda, Kazunori; 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

    2015-08-01

    Large clinical trials are lack of data on non-vitamin K antagonist oral anticoagulants for acute stroke patients. 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). 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. 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 CHADS2 , CHA2 DS2 -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 shorter hospitalization (OR 2·46, 95% CI 1·87-3·24

  16. Antithrombotic management in patients with percutaneous coronary intervention requiring oral anticoagulation

    PubMed Central

    Undas, Anetta

    2016-01-01

    The dynamic evolution of therapeutic options including the use of vitamin K antagonists (VKA), non-vitamin K oral anticoagulants (NOAC), more potent antiplatelet drugs as well as new generation drug-eluting stents could lead to the view that the current recommendations on the management of patients with percutaneous coronary intervention (PCI) requiring oral anticoagulation do not keep up with the results of several clinical studies published within the last 5 years. In the present overview, we summarize the recent advances in antithrombotic management used in atrial fibrillation patients undergoing PCI for stable coronary artery disease or acute coronary syndrome (ACS). The safety and efficacy of prasugrel and ticagrelor taken with oral anticoagulants also remain to be established in randomized trials; therefore the P2Y12 inhibitor clopidogrel on top of aspirin or without is now recommended to be used together with a VKA or NOAC. It is still unclear which dose of a NOAC in combination with antiplatelet agents and different stents should be used in this clinical setting and whether indeed NOAC are safer compared with VKA in such cardiovascular patients. Moreover, we discuss the use of anticoagulation in addition to antiplatelet therapy for secondary prevention in patients with ACS. To minimize bleeding risk in anticoagulated patients following PCI or ACS, the right agent should be prescribed to the right patient at the right dose and supported by regular clinical evaluation and laboratory testing, especially assessment of renal function when a NOAC is used. PMID:27980542

  17. Direct oral anticoagulants: key considerations for use to prevent stroke in patients with nonvalvular atrial fibrillation

    PubMed Central

    Ment, Jerome

    2015-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Strokes that occur as a complication of AF are usually more severe and associated with a higher disability or morbidity and mortality rate compared with non-AF-related strokes. The risk of stroke in AF is dependent on several risk factors; AF itself acts as an independent risk factor for stroke. The combination of effective anticoagulation therapy, risk stratification (based on stroke risk scores, such as CHADS2 and CHA2DS2-VASc), and recommendations provided by guidelines is essential for decreasing the risk of stroke in patients with AF. Although effective in preventing the occurrence of stroke, vitamin K antagonists (VKAs; eg, warfarin) are associated with several limitations. Therefore, direct oral anticoagulants, such as apixaban, dabigatran etexilate, edoxaban, and rivaroxaban, have emerged as an alternative to the VKAs for stroke prevention in patients with nonvalvular AF. Compared with the VKAs, these agents have more favorable pharmacological characteristics and, unlike the VKAs, they are given at fixed doses without the need for routine coagulation monitoring. It remains important that physicians use these direct oral anticoagulants responsibly to ensure optimal safety and effectiveness. This article provides an overview of the existing data on the direct oral anticoagulants, focusing on management protocols for aiding physicians to optimize anticoagulant therapy in patients with nonvalvular AF, particularly in special patient populations (eg, those with renal impairment) and other specific clinical situations. PMID:26089678

  18. Direct oral anticoagulants: key considerations for use to prevent stroke in patients with nonvalvular atrial fibrillation.

    PubMed

    Ment, Jerome

    2015-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Strokes that occur as a complication of AF are usually more severe and associated with a higher disability or morbidity and mortality rate compared with non-AF-related strokes. The risk of stroke in AF is dependent on several risk factors; AF itself acts as an independent risk factor for stroke. The combination of effective anticoagulation therapy, risk stratification (based on stroke risk scores, such as CHADS2 and CHA2DS2-VASc), and recommendations provided by guidelines is essential for decreasing the risk of stroke in patients with AF. Although effective in preventing the occurrence of stroke, vitamin K antagonists (VKAs; e.g., warfarin) are associated with several limitations. Therefore, direct oral anticoagulants, such as apixaban, dabigatran etexilate, edoxaban, and rivaroxaban, have emerged as an alternative to the VKAs for stroke prevention in patients with nonvalvular AF. Compared with the VKAs, these agents have more favorable pharmacological characteristics and, unlike the VKAs, they are given at fixed doses without the need for routine coagulation monitoring. It remains important that physicians use these direct oral anticoagulants responsibly to ensure optimal safety and effectiveness. This article provides an overview of the existing data on the direct oral anticoagulants, focusing on management protocols for aiding physicians to optimize anticoagulant therapy in patients with nonvalvular AF, particularly in special patient populations (e.g., those with renal impairment) and other specific clinical situations.

  19. [Perioperative management of direct oral anticoagulant in emergency surgery and bleeding. Haemostasis monitoring and treatment].

    PubMed

    Hidalgo, F; Gómez-Luque, A; Ferrandis, R; Llau, J V; de Andrés, J; Gomar, C; Sierra, P; Castillo, J; Torres, L M

    2015-10-01

    There is an almost unanimous consensus on the management of the direct new oral anticoagulants, dabigatran, rivaroxaban, and apixaban in elective surgery. However, this general consensus does not exist in relation with the direct new oral anticoagulants use in emergency surgery, especially in the bleeding patient. For this reason, a literature review was performed using the MEDLINE-PubMed. An analysis was made of the journal articles, reviews, systematic reviews, and practices guidelines published between 2000 and 2014 using the terms "monitoring" and "reversal". From this review, it was shown that the routine tests of blood coagulation, such as the prothrombin time and activated partial thromboplastin time, have a limited efficacy in the perioperative control of blood coagulation in these patients. There is currently no antidote to reverse the effects of these drugs, although the possibility of using concentrated prothrombin complex and recombinant activated factor vii has been suggested for the urgent reversal of the anticoagulant effect.

  20. Trials of novel oral anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation.

    PubMed

    Halperin, Jonathan L; Dorian, Paul

    2014-11-01

    Patients with non-valvular atrial fibrillation (AF) face an increased risk of stroke compared with those in normal sinus rhythm. The vitamin K antagonist warfarin, available for over half a century, is highly effective in reducing the risk of stroke in patients with AF, but it is a difficult drug to use properly. As a result, it is challenging to keep the anticoagulant effect of warfarin in the desired range. Newer oral anticoagulants (NOACs) that directly inhibit Factor IIa (thrombin) or Factor Xa provide reliable anticoagulation when administer in fixed oral doses without routine coagulation monitoring. This manuscript will review in detail the pivotal trials of these NOACs that led to their approval as well as comment on the factors that should influence their selection.

  1. Trials of Novel Oral Anticoagulants for Stroke Prevention In Patients with Non-valvular Atrial Fibrillation

    PubMed Central

    Halperin, Jonathan L; Dorian, Paul

    2014-01-01

    Patients with non-valvular atrial fibrillation (AF) face an increased risk of stroke compared with those in normal sinus rhythm. The vitamin K antagonist warfarin, available for over half a century, is highly effective in reducing the risk of stroke in patients with AF, but it is a difficult drug to use properly. As a result, it is challenging to keep the anticoagulant effect of warfarin in the desired range. Newer oral anticoagulants (NOACs) that directly inhibit Factor IIa (thrombin) or Factor Xa provide reliable anticoagulation when administer in fixed oral doses without routine coagulation monitoring. This manuscript will review in detail the pivotal trials of these NOACs that led to their approval as well as comment on the factors that should influence their selection. PMID:24821657

  2. Treatment Changes among Users of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation.

    PubMed

    Hellfritzsch, Maja; Husted, Steen Elkjaer; Grove, Erik Lerkevang; Rasmussen, Lotte; Poulsen, Birgitte Klindt; Johnsen, Søren Paaske; Hallas, Jesper; Pottegård, Anton

    2017-02-01

    Patients with atrial fibrillation discontinuing anticoagulant therapy are left unprotected against ischaemic stroke. Further, switching between oral anticoagulants may be associated with a transiently increased risk of bleeding or thromboembolism. However, there is a paucity of real-life data on pattern of switching and discontinuation of oral anticoagulants. To address this, we conducted a nationwide drug utilization study including all registered Danish atrial fibrillation patients initiating a non-VKA oral anticoagulant (NOAC) between August 2011 and February 2016. We assessed changes in anticoagulant treatment, including switching between oral anticoagulants and discontinuation of NOACs, and explored patient characteristics predicting these changes. We identified 50,632 patients with atrial fibrillation initiating NOAC therapy within the study period. The majority initiated dabigatran (49.9%) and one-third had previously used VKA. Within 1 year, 10.1% switched to VKA, 4.8% switched to another NOAC and 14.4% discontinued treatment. The frequencies of switching to VKA and discontinuation were highest among NOAC users of young age (<55 years) and with low CHA2 DS2 -VASc score (=0). However, the majority of patients (87.3%) stopping NOAC treatment had a CHA2 DS2 -VASc score ≥1. We conclude that switching from VKA to NOAC, and to a lesser extent from NOAC to VKA, is common, as is early treatment discontinuation. The majority of treatment changes are observed in patients at increased risk of stroke. More research is warranted on the risks of bleeding and thromboembolism associated with switching and discontinuation of NOACs as well as the underlying reasons why these treatment changes occur.

  3. 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

  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.

  5. Guidelines for the management of patients on oral anticoagulants requiring dental surgery.

    PubMed

    Perry, D J; Noakes, T J C; Helliwell, P S

    2007-10-13

    The objective of these guidelines is to provide healthcare professionals, including primary care dental practitioners, with clear guidance on the management of patients on oral anticoagulants requiring dental surgery. The guidance may not be appropriate in all cases and individual patient circumstances may dictate an alternative approach.

  6. Non-Vitamin K Oral Anticoagulants for Stroke Prevention in Special Populations with Atrial Fibrillation.

    PubMed

    Bisson, Arnaud; Angoulvant, Denis; Philippart, Raphael; Clementy, Nicolas; Babuty, Dominique; Fauchier, Laurent

    2017-06-01

    Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke or systemic embolism compared with normal sinus rhythm. These strokes may efficiently be prevented in patients with risk factors using oral anticoagulant therapy, with either vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) (i.e., direct thrombin inhibitors or direct factor Xa inhibitors). Owing to their specific risk profiles, some AF populations may have increased risks of both thromboembolic and bleeding events. These AF patients may be denied oral anticoagulants, whilst evidence shows that the absolute benefits of oral anticoagulants are greatest in patients at highest risk. NOACs are an alternative to VKAs to prevent stroke in patients with "non-valvular AF", and NOACs may offer a greater net clinical benefit compared with VKAs, particularly in these high-risk patients. Physicians have to learn how to use these drugs optimally in specific settings. We review concrete clinical scenarios for which practical answers are currently proposed for use of NOACs based on available evidence for patients with kidney disease, elderly patients, women, patients with diabetes, patients with low or high body weight, and those with valve disease.

  7. A multicentre randomised assessment of the DAWN AC computer-assisted oral anticoagulant dosage program.

    PubMed

    Poller, Leon; Keown, Michelle; Ibrahim, Saied; Lowe, Gordon; Moia, Marco; Turpie, Alexander G; Roberts, Christopher; van den Besselaar, Anton M H P; van der Meer, Felix J M; Tripodi, Armando; Palareti, Gualtiero; Shiach, Caroline; Bryan, Stirling; Samama, Meyer; Burgess-Wilson, Michael; Heagerty, Anthony; Maccallum, Peter; Wright, David; Jespersen, Jørgen

    2009-03-01

    Computer-assisted oral anticoagulant dosage is being increasingly used to meet growing demands for oral anticoagulation. The DAWN AC is one of the most widely used computer-dosage programs. Evidence of its value and that of other computer programs has been based previously only on laboratory evidence of "time in target INR range" (TIR) not on clinical safety in practice. A five-year international randomised clinical study of computer assistance with the DAWN AC program compared with manual dosage in 2,631 patients has been performed at 13 centres with established expertise in oral anticoagulation mainly in the EU. Safety assessment have been based on the comparison of bleeding or thrombotic events with DAWN AC compared with manual dosage in a randomised study. Safety of the DAWN AC program has been demonstrated. Clinical events of bleeding and thrombosis were almost identical with the experienced manual dosage group. Therapeutic control improved with DAWN AC to 66.8% from 63.4% TIR. The program failed to provide a dosage recommendation on only 5.7% of occasions. At a group of experienced centres with a special interest in oral anticoagulation, the DAWN AC computer-dosage program proved as safe clinically as manual dosage by experienced medical staff. With DAWN AC, laboratory control was improved, the difference being highly significant. The results should reassure hospitals and community clinics that the DAWN AC program is safe and facilitate greater and longer provision of warfarin treatment where required.

  8. 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.

  9. [Oral anticoagulation control in a cardiac surgery ward].

    PubMed

    Melis Tormos, Eloida

    2008-09-01

    In patients who undergo cardiac surgery, particularly valvular surgery it is essential to carry out frequent anticoagulation controls during their hospital stay The author questions if it is viable to carry out these controls by means of a portable coagulation meter which, in principle, can provide advantages in patient care. To determine this viability the author evaluates the concordance between the measurements obtained with this device and measurements taken in a laboratory The author compared the INR (prothrombin time, Normalized International Ratio) in 106 pairs of simultaneous blood samples, from both veins and capillaries, taken from 60 patients receiving anticoagulation medicine hospitalized in the cardiac surgery ward at the La Fe Hospital after each underwent surgery The samples taken from veins were processed in a hemostasia laboratory while the capillary samples were processed with a portable coagulation meter, a Roche CoaguChek"S. The statistical analyses applied were Pearson coefficient, intraclass correlation coefficient (CCI) and the method for mean differences (MMD). Numbers for hemocytes and therapy combined with heparine were taken into account. The results showed, in the overall analysis of data, a very good degree of concordance, CCI = 0.939 (confidence interval, IC=95%, 0.902-0.961) and MMD numbers <10%. For hemocytes <32, the concordance decreases, CCI = 0.876 (IC 95% = 0.787-0.930). The author concludes that this coagulation meter is trustworthy therefore using it would improve care for a patient needing anti-coagulation treatment during his/her stay in the ward since using this meter helps to obtain immediate results and reduces the trauma when extracting blood samples, etc. Nonetheless, when dealing with patients having a low hemocyte level, it is more prudent to make use of laboratory results.

  10. 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

  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. New oral anticoagulants: discussion on monitoring and adherence should start now!

    PubMed

    Ten Cate, Hugo

    2013-06-28

    New oral anticoagulants (NOACs) have been introduced to improve anticoagulant therapy worldwide, but safe implementation may require additional measures. First, optimization of dose adjustment based on therapeutic levels of the drug may be more appropriate than fixed dose therapy. The development and implementation in quantitative laboratory assays will enable further dose optimization. Second, non-adherence to medication is a potential threat to the safe use of NOACs. Since cardiovascular medication may not be optimally used in about 50% of patients, procedures to improve adherence are imperative, also for NOAC therapy and in particular in elderly patients.

  13. Recent advances in the treatment of venous thromboembolism in the era of the direct oral anticoagulants.

    PubMed

    Weitz, Jeffrey I; Jaffer, Iqbal H; Fredenburgh, James C

    2017-01-01

    The direct oral anticoagulants (DOACs) have now supplanted vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE). The DOACs include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. The DOACs are as effective for the prevention of recurrence as conventional VTE treatment, consisting of a parenteral anticoagulant followed by a VKA, and are associated with less bleeding. Because of these properties and the convenience of fixed dosing without the need for routine coagulation monitoring, guidelines now recommend DOACs over VKAs for VTE treatment in patients without active cancer. This paper examines the increasing role of the DOACs for VTE treatment.

  14. Oral surgery for patients on anticoagulant therapy: current thoughts on patient management.

    PubMed

    Doonquah, Ladi; Mitchell, Anika D

    2012-01-01

    Minor oral surgical procedures make up a significant part of the daily practice of dentistry. With the increased sophistication of medical technology and medications there is increased likelihood of performing surgery on patients who are being treated for conditions that require some type of anticoagulant therapy. These patients are at an increased risk for perioperative bleeding or thrombotic complications if anticoagulation is discontinued or the dosage is adjusted. Therefore, a fine balance needs to be obtained and adequate preparation of these patients is the key to establishing this balance. This article reviews suggested approaches to the management of such patients.

  15. Use of novel oral anticoagulant agents in atrial fibrillation: current evidence and future perspective

    PubMed Central

    Madan, Shivanshu; Shah, Shenil; Partovi, Sasan

    2014-01-01

    The increasing availability of novel oral anticoagulants (NOAC) for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) offers alternatives for patients currently prescribed warfarin. This article provides a brief overview on the mechanism and clinical use of these drugs as well as a review of the pivotal clinical trials providing the basis for each agent’s safety and efficacy. While these agents are currently Food and Drug Administration (FDA) approved for anticoagulation of patients with nonvalvular AF, additional studies continually emerge offering further insight into the application of these agents in other areas. PMID:25276617

  16. 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.

  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. Novel oral anticoagulants for stroke prevention in atrial fibrillation: focus on apixaban.

    PubMed

    Potpara, Tatjana S; Polovina, Marija M; Licina, Marina M; Stojanovic, Radan M; Prostran, Milica S; Lip, Gregory Y H

    2012-06-01

    Stroke prevention in atrial fibrillation (AF) has been challenging over decades, mostly due to a number of difficulties associated with oral vitamin K antagonists (VKAs), which have been the most effective stroke prevention treatment for a long time. The oral direct thrombin inhibitors (e.g., dabigatran) and oral direct inhibitors of factor Xa (e.g., rivaroxaban, apixaban) have emerged recently as an alternative to VKAs for stroke prevention in AF. These drugs act rapidly, and have a predictable and stable dose-related anticoagulant effect with a few clinically relevant drug-drug interactions. The novel oral anticoagulants are used in fixed doses with no need for regular laboratory monitoring of anticoagulation intensity. However, each of these drugs has distinct pharmacological properties that could influence optimal use in clinical practice. The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban. Moreover, the Apixaban Versus Acetylsalicylic Acid to prevent Strokes (AVERROES) trial included patients with AF who have failed or were unsuitable for warfarin, and compared apixaban versus aspirin for stroke prevention in AF. Overall, apixaban has two large trials for stroke prevention in AF showing benefits not only over warfarin, but also over aspirin among those patients who have failed or refused warfarin. In the ARISTOTLE trial, apixaban was superior to warfarin in the reduction of stroke or systemic embolism, major bleeding, intracranial hemorrhage, and all-cause mortality

  19. Prescribing trends of atrial fibrillation patients who switched from warfarin to a direct oral anticoagulant.

    PubMed

    Hale, Zachary D; Kong, Xiowen; Haymart, Brian; Gu, Xiaokui; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Krol, Gregory D; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

    2017-02-01

    Direct oral anticoagulant (DOAC) agents offer several lifestyle and therapeutic advantages for patients relative to warfarin in the treatment of atrial fibrillation (AF). These alternative agents are increasingly used in the treatment of AF, however the adoption practices, patient profiles, and reasons for switching to a DOAC from warfarin have not been well studied. Through the Michigan Anticoagulation Quality Improvement Initiative, abstracted data from 3873 AF patients, enrolled between 2010 and 2015, were collected on demographics and comorbid conditions, stroke and bleeding risk scores, and reasons for anticoagulant switching. Over the study period, patients who switched from warfarin to a DOAC had similar baseline characteristics, risk scores, and insurance status but differed in baseline CrCl. The most common reasons for switching were patient related ease of use concerns (37.5%) as opposed to clinical reasons (16.5% of patients). Only 13% of patients that switched to a DOAC switched back to warfarin by the end of the study period.

  20. Prevention of postoperative bleeding in anticoagulated patients undergoing oral surgery: use of platelet-rich plasma gel.

    PubMed

    Della Valle, Antonio; Sammartino, Gilberto; Marenzi, Gaetano; Tia, Mariano; Espedito di Lauro, Alessandro; Ferrari, Francesca; Lo Muzio, Lorenzo

    2003-11-01

    This study evaluated the effectiveness of a protocol using platelet-rich plasma (PRP) to prevent bleeding after dental extraction in patients treated with anticoagulant oral therapy. Forty patients with mechanical heart-value replacement who were treated with anticoagulant oral therapy were selected for the study. Each patient was treated with PRP gel placed into residual alveolar bone after extraction without heparin administration after suspension of oral anticoagulant drugs (36 hours). Only 2 patients reported hemorrhagic complications (5%). Sixteen patients (40%) had mild bleeding that was easy to control with hemostatic topical agents; this mild bleeding terminated completely 1 to 3 days after the surgical procedures. The remaining 22 patients (55%) presented with adequate hemostasis. Oral surgery in heart surgical patients under oral anticoagulant therapy may be facilitated with PRP gel. Its use is an advanced and safe procedure. This biological and therapeutical improvement can simplify systemic management and help avoid hemorrhagic and/or thromboembolic complications.

  1. [Assessment of the quality of oral anticoagulation management in patients admitted to Amiens University Hospital].

    PubMed

    Gras-Champel, Valérie; Voyer, Annelise; Lematte, Céline; Pakula, Pauline; Roussel, Bertrand; Lefrère, Jean-Jacques; Andréjak, Michel

    2005-01-01

    Excessive or insufficient anticoagulation therapy and its associated risks are of major concern in patients receiving oral anticoagulants. Such complications can be avoided by more rigorous management. The aim of our study was to evaluate those patients receiving oral anticoagulant therapy on the day of hospitalisation among all patients admitted to the Amiens University Hospital during 14 days. We evaluated the quality of management of the treatment in these patients, taking into account the international normalised ratio (INR), as well as important parameters such as the summary of the product characteristics (SPCs), drug interactions, and the level of knowledge of anticoagulant treatment by the patients themselves (questionnaire). Of the 2498 adult patients hospitalised, 86 patients (30 female and 56 male aged between 26 and 95 years [mean 70 years]) treated with oral anticoagulants were evaluated. At admission, seven cases of haemorrhage and two of thrombosis were registered. One drug-related death occurred and one patient had sequelae. In 17.5% of the cases, the prescription was not fully in agreement with the SPCs. This percentage increased to 67% for patients with adverse effects. In 41% of the patients, the INR was outside the therapeutic zone. The dosage regimen was too complex in 11% of cases. Six drug combinations were labelled as not recommended in the SPCs: four with aspirin <3 g/day and two with nonsteroidal anti-inflammatory drugs. The analysis of questionnaires showed that patients had insufficient knowledge of their treatment: only 16 of 66 knew the risks resulting from overdose or an insufficient dose of the anticoagulant drug, 25 of 66 knew that anticoagulation induced by the treatment can be influenced by food, 10 of 66 knew the therapeutic range of the INR appropriate for them, and 8 of 66 knew that intramuscular injections were prohibited. These data confirm that anticoagulant treatment needs to be more strictly controlled in order to avoid

  2. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors.

    PubMed

    van der Meer, F J; Rosendaal, F R; Vandenbroucke, J P; Briët, E

    1993-07-12

    Insufficient data are available about the safety of oral anticoagulant therapy. The specialized organization of thrombosis services in the Netherlands can provide important information on the bleeding risk and various risk factors for bleeding in patients receiving oral anticoagulant therapy. In a follow-up study over a 12-month period beginning in January 1988 on all patients treated by the Leiden Thrombosis Service, the frequency of bleeding complications was assessed. A Poisson regression model was used to assess the relative contribution to the bleeding risk of age, sex, target zone (intensity of anticoagulant effect aimed at), achieved intensity of anticoagulant therapy (International Normalized Ratio), and the type of coumarin derivative used. Six thousand eight hundred fourteen patients experienced 1003 bleeding complications (16.5 per 100 treatment-years), 162 of which were major bleeds (2.7 per 100 treatment-years). Bleeding increased significantly with age (32% increase for all bleeding, 46% for major bleeding for every 10-year increase in age in comparison with age < 40 years). Women had more minor bleeding complications than men, whereas both sexes experienced major bleeding in an equal frequency. There was no influence of target zone, while every one-point increase in International Normalized Ratio gave 42% more major bleeding (54% more regarding all bleeding). Use of acenocoumarol resulted in fewer bleeds (26% less regarding all bleeding and 46% less regarding major bleeding) than use of phenprocoumon. The risk of anticoagulant therapy in a routine, real-life situation is similar as in the setting of several well-organized clinical trials. The risk of bleeding complications rises significantly with age and with the achieved intensity of anticoagulation, and is dependent on the type of coumarin derivative that is used.

  3. Minimizing bleeding risk in patients receiving direct oral anticoagulants for stroke prevention

    PubMed Central

    Habert, Jeffrey Steven

    2016-01-01

    Many primary care physicians are wary about using direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AF). Factors such as comorbidities, concomitant medications, and alcohol misuse increase concerns over bleeding risk, especially in elderly and frail patients with AF. This article discusses strategies to minimize the risk of major bleeding events in patients with AF who may benefit from oral anticoagulant therapy for stroke prevention. The potential benefits of the DOACs compared with vitamin K antagonists, in terms of a lower risk of intracranial hemorrhage, are discussed, together with the identification of reversible risk factors for bleeding and correct dose selection of the DOACs based on a patient’s characteristics and concomitant medications. Current bleeding management strategies, including the new reversal agents for the DOACs and the prevention of bleeding during preoperative anticoagulation treatment, in addition to health care resource use associated with anticoagulation treatment and bleeding, are also discussed. Implementing a structured approach at an individual patient level will minimize the overall risk of bleeding and should increase physician confidence in using the DOACs for stroke prevention in their patients with nonvalvular AF. PMID:27785089

  4. Tooth Extraction in Patients on Oral Anticoagulants: Prospective Study Conducted in 108 Brazilian Patients

    PubMed Central

    Pereira, Claudio Maranhão; Gasparetto, Patrícia Freire; Carneiro, Danilo Santos; Corrêa, Maria Elvira P.; Souza, Cármino Antônio

    2011-01-01

    Introduction. Dental treatment performed in patients receiving continuous oral anticoagulant drug therapy is becoming increasingly common in dental offices. For these patients it is imperative to carry out careful anamnesis, as well as a multiprofessional clinical evaluation with regard to the risk and control of hemorrhagic or thromboembolic episodes. Objectives and Material and Methods. The aim is to evaluate postextraction hemorrhagic or thromboembolic episodes in patients who have been on anticoagulant medications for an uninterrupted period of 48 months. Results. Among the 108 patients evaluated, 215 extractions were performed in which there was only one case of postoperative bleeding. Warfarin was used by 98 patients; Warfarin associated with salicylic acetic acid by 9 patients and salicylic acetic acid in only 1 patient. As regards the serologic tests performed, International Normalized Ratio (INR) ranged from 0.8 to 4.9, with a mean of 3.15. Conclusion. Extractions in patients on oral anticoagulants must be performed in the least traumatic manner possible. It is not necessary to stop anticoagulant therapy to perform extractions. Local hemostasis techniques, such as obliterative sutures alone are sufficient to prevent hemorrhagic complications. PMID:21991458

  5. [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

  6. High antiangiogenic and low anticoagulant efficacy of orally active low molecular weight heparin derivatives.

    PubMed

    Park, Jin Woo; Jeon, Ok Cheol; Kim, Sang Kyoon; Al-Hilal, Taslim Ahmed; Jin, Shun Ji; Moon, Hyun Tae; Yang, Victor C; Kim, Sang Yoon; Byun, Youngro

    2010-12-20

    Heparin, an anticoagulant that is widely used clinically, is also known to bind to several kinds of proteins through electrostatic interactions because of its polyanionic character. These interactions are mediated by the physicochemical properties of heparin such as sequence composition, sulfation patterns, charge distribution, overall charge density, and molecular size. Although this electrostatic character mediates its binding to many proteins related with tumor progression, thereby providing its antiangiogenic property, the administration of heparin for treating cancer is limited in clinical applications due to several drawbacks, such as its low oral absorption, unsatisfactory therapeutic effects, and strong anticoagulant activity which induces hemorrhaging. Here, we evaluated novel, orally active, low molecular weight heparin (LMWH) derivatives (LHD) conjugated with deoxycholic acid (DOCA) that show reduced anticoagulant activity and enhanced antiangiogenic activity. The chemical conjugate of LMWH and DOCA was synthesized by conjugating the amine group of N-deoxycholylethylamine (EtDOCA) with the carboxylic groups of heparin at various DOCA conjugation ratios. The LMWH-DOCA conjugate series (LHD1, LHD1.5, LHD2, and LHD4) were further formulated with poloxamer 407 as a solubilizer for oral administration. An in vitro endothelial tubular formation and in vivo Matrigel plug assay were performed to verify the antiangiogenic potential of LHD. Finally, we evaluated tumor growth inhibition of oral LHD administration in a SCC7 model as well as in A549 human cancer cell lines in a mouse xenograft model. Increasing DOCA conjugation ratios showed decreased anticoagulant activity, eventually to zero. LHD could block angiogenesis in the tubular formation assay and the Matrigel plug assay. In particular, oral administration of LHD4, which has 4 molecules of DOCA per mole of LMWH, inhibited tumor growth in SCC7 mice model as well as A549 mice xenograft model. LHD4 was orally

  7. Oral anticoagulation to reduce risk of stroke in patients with atrial fibrillation: current and future therapies.

    PubMed

    Amin, Alpesh

    2013-01-01

    Atrial fibrillation (AF) is associated with an increased incidence and severity of strokes. The burden of AF-related stroke is expected to increase in parallel with the aging of the population. Oral anticoagulation with warfarin has been the pharmacologic standard for stroke risk reduction in patients with AF. When used with close attention to dosing and monitoring, warfarin is effective prophylactic therapy against thromboembolic stroke. However, it is underused by physicians, in part because of the known risks of adverse events with warfarin. Consequently, many patients with AF live with an avoidably elevated risk of stroke. New options, ie, oral anticoagulants with novel mechanisms of action, have recently been approved to reduce the risk of stroke in AF, and others are in development. These newer agents may address some of the complexities of warfarin use while providing similar or better efficacy and safety.

  8. [New oral anticoagulants and prostate biopsy: Which usual precaution should we use?].

    PubMed

    Coscarella, M; Viart, L; Nguyen, P; Saint, F

    2015-07-01

    In 2013, more than 30,000 prostate biopsies have been performed in France. Bleeding complications are not rare. It imposes meticulous perioperative management in order to avoid them. In a close future, new oral anticoagulants (NOAC) will probably substitute vitamin K antagonist in many indications. The management of these new drugs is not really familiar in urology. The authors have specified it by using a systematic literature search in association to guidelines analysis edited by learned society. This article is based on a systematic literature search by using Pubmed database and by consulting international learned society of urology, anesthesiology or cardiology and the French National Agency of Drugs Security. There was no guidelines edited by urological learned society. A standardized protocol adapted to prostate biopsies has been suggested using French Anesthesiologist and Hemostasian guidelines. The authors recommended stopping the oral anticoagulant treatment 5 days prior the biopsy. A bridge, by using a curative dose of heparin, was required during the preoperative period in order to manage the bleeding risk. It must be stopped 12 hours or 24 hours before biopsy (standard or low molecular weight heparin). Contrary to vitamin K antagonist, the re-initiation of the oral should begin 6-8 hours after procedure. The treatment should not overlap with heparin. The NOAC anticoagulant effect is quickly effective after 2 to 4 hours. The treatment should be re-initiated directly after the biopsy, in the absence of bleeding complications. The perioperative management of new oral anticoagulants seems to be more simple than vitamin K antagonist (VKA) during prostate biopsy. A standardized protocol should be recommended. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. [Non-vitamin K dependent oral anticoagulants : What is important in intensive care medicine].

    PubMed

    Gulba, D C; Broscaru, L

    2017-03-01

    Since first used in 2009, non-vitamin K oral anticoagulants (NOAC) have gained world-wide acceptance. Two groups of NOAC are currently used: the direct thrombin antagonist dabigatran and three direct factor  Xa antagonists apixaban, edoxaban, and ricaroxaban. With their increasing use for prevention of thromboembolism, the probability increases that NOAC-pretreated patients are admitted to emergency departments or intensive care units.The clinical challenge in NOAC preanticoagulated patients is to adequately cope with the given anticoagulated status of such patients. Because of their short half-life, many patients will be adequately treated with a "wait and see" approach, and surgeries and interventions are postponed until anticoagulant activities have totally subsided. In the few cases where immediate action is mandated, based on appropriate risk assessments it can be decided either to take the increased hemorrhagic risk of early intervention or to transfuse factor concentrates like PPSB or FEIBA which can safely reverse the anticoagulant activities of the three factor Xa antagonists (and potentially also of dabigatran). Recently a humanized Fab antibody fragment for dabigatran, idarucizumab, has been introduced onto the market, that can immediately reverse the anticoagulant effects of dabigatran. For the reversal of dabigatran, idarucizumab is therefore the drug of choice.In addition, in some specific indications of emergency and intensive care medicine, the primary use of a NOAC can be considered advantageous. Such indications are early cardioversion in patients admitted for new episodes of atrial fibrillation and patients with acute pulmonary embolism. For the widespread use of low-molecular-weight heparins in such indications, however, the decision to use a NOAC for anticoagulant therapy is frequently postponed to the treatment phase when the stabilized patient is already treated on the general ward.

  10. Impact of Non-Vitamin K Antagonist Oral Anticoagulants From a Basic Science Perspective.

    PubMed

    Hoffman, Maureane; Monroe, Dougald M

    2017-10-01

    The biochemical properties of the non-vitamin K antagonist oral anticoagulants (NOACs) and their differences from the mechanism of action of vitamin K antagonists contribute to their properties as anticoagulants. These properties include as follows: (1) Inhibiting a single protease is much less effective at inhibiting coagulation than is inhibiting at multiple steps. Thus, the dose-response relationship between NOAC level and intensity of anticoagulation is shallower and more linear than that of vitamin K antagonists. This partially accounts for the greater safety of NOACs than vitamin K antagonists reported in some studies. (2) Because they are small molecules, NOACs can reach their target proteases in locations that plasma protease inhibitors, such as antithrombin, cannot. (3) NOACs compete with substrates for binding at the active site of the target protease and that binding is reversible. When the drug level falls, the drug dissociates from its target, and protease activity is restored. Thus, there is the possibility of a rebound in procoagulant activity if the drug is abruptly terminated. (4) The effects of a NOAC can be overcome by increasing the amount of substrate available for the target protease or the amount of protease produced. This property may contribute to the safety of NOACs and their potential reversibility by coagulation factor concentrates. The biochemical properties of NOACs contribute to their suitability for use in conditions that require a predictable moderate degree of anticoagulation when administered orally at a consistent dose. Their effects can be overcome by a sufficiently strong procoagulant stimulus. This characteristic likely contributes to their generally reduced risk of serious bleeding. However, they are not well suited for use in settings that require a profound degree of anticoagulation. © 2017 American Heart Association, Inc.

  11. Periodontal and biochemical bone metabolism assessment on a chronic oral anticoagulation population treated with dicoumarins.

    PubMed

    López-Lacomba, D; Roa-López, A; González-Jaranay, M; Gómez-Moreno, G; Moreu, G

    2017-03-01

    The aim is to evaluate periodontal alteration and biochemical markers associated with bone turnover in chronic oral with dicoumarins anticoagulant treatment patients. 80 patients treated with oral anticoagulants were divided into 2 cohort: Group A (n=36) 6 month to 1 year with anticoagulant treatment and Group B (n=44) > 2 years with anticoagulant treatment. Clinical evaluation included: Clinical attachment level (CAL), plaque index (PI) and gingival index (GI). Analytically biochemical parameters of bone remodeling (calcium and phosphorus), formation (total acid phosphatase, alkaline phosphatase and osteocalcin) and resorption (tartrate-resistant acid phosphatase and beta-crosslaps) were evaluated. High values of PI (67-100%) especially in men and in Group B were observed. Men with anticoagulation treatment length showed an increased GI (49.167 vs 78.083) while Group B women showed a decreased GI in comparison with Group A (59.389 vs 42.120). Women presented a greater average CAL than men as well as Group B vs Group A but without statistical significance. All biochemical markers were decreased respect to values of general population. Osteocalcin in GroupB women showed a statistically significant outcome vs GroupA (p=0.004). Acid phosphatase (total and tartrate-resistant) has a slight increase in Group B women versus Group A, and Beta-crosslap showed lower values in Group A men than Group B and slightly lower in Group A women versus Group B, without statistical significance. Patients showed a slight to moderate degree of periodontal affectation, especially gingivitis related to bacterial plaque. Periodontal disorders tended to be more severe in Group B. While bone remodeling showed an overall decrease with greater affectation of bone neoformation phenomena, bone destruction tended to recover and normalize in time.

  12. Periodontal and biochemical bone metabolism assessment on a chronic oral anticoagulation population treated with dicoumarins

    PubMed Central

    López-Lacomba, Daniel; Roa-López, Antonio; González-Jaranay, Maximino; Gómez-Moreno, Gerardo

    2017-01-01

    Background The aim is to evaluate periodontal alteration and biochemical markers associated with bone turnover in chronic oral with dicoumarins anticoagulant treatment patients. Material and Methods 80 patients treated with oral anticoagulants were divided into 2 cohort: Group A (n=36) 6 month to 1 year with anticoagulant treatment and Group B (n=44) > 2 years with anticoagulant treatment. Clinical evaluation included: Clinical attachment level (CAL), plaque index (PI) and gingival index (GI). Analytically biochemical parameters of bone remodeling (calcium and phosphorus), formation (total acid phosphatase, alkaline phosphatase and osteocalcin) and resorption (tartrate-resistant acid phosphatase and beta-crosslaps) were evaluated. Results High values of PI (67-100%) especially in men and in Group B were observed. Men with anticoagulation treatment length showed an increased GI (49.167 vs 78.083) while Group B women showed a decreased GI in comparison with Group A (59.389 vs 42.120). Women presented a greater average CAL than men as well as Group B vs Group A but without statistical significance. All biochemical markers were decreased respect to values of general population. Osteocalcin in GroupB women showed a statistically significant outcome vs GroupA (p=0.004). Acid phosphatase (total and tartrate-resistant) has a slight increase in Group B women versus Group A, and Beta-crosslap showed lower values in Group A men than Group B and slightly lower in Group A women versus Group B, without statistical significance. Conclusions Patients showed a slight to moderate degree of periodontal affectation, especially gingivitis related to bacterial plaque. Periodontal disorders tended to be more severe in Group B. While bone remodeling showed an overall decrease with greater affectation of bone neoformation phenomena, bone destruction tended to recover and normalize in time. Key words:Periodontal disease, dicoumarin, biochemical markers, bone remodeling. PMID:28160591

  13. [Restraints to anticoagulation prescription in atrial fibrillation and attitude towards the new oral anticoagulants].

    PubMed

    Pereira-Da-Silva, Tiago; Souto Moura, Teresa; Azevedo, Luísa; Sá Pereira, Margarida; Virella, Daniel; Alves, Marta; Borges, Luís

    2013-01-01

    Introdução e Objetivos: Avaliar a taxa de prescrição de anticoagulantes orais na fibrilhação auricular, os fatores associados à não prescrição, os motivos referidos pelos clínicos para não prescrição de anticoagulantes incluindo os de nova geração e realizar estudo evolutivo a médio prazo. Material e Métodos: Estudo prospetivo sobre casos consecutivos de doentes com fibrilhação auricular com alta hospitalar. Registaram- se os scores CHA2DS2VASc e HASBLED, comorbilidades associadas e a medicação prévia e à data de alta. Na alta hospitalar, o médico assistente indicou em questionário o motivo de não prescrição de anticoagulantes orais e dos novos anticoagulantes orais. Exclusão: contra-indicação absoluta para anticoagulação, CHA2DS2VASc ≤ 1 e doença valvular. Os doentes foram reavaliados um ano após o recrutamento do primeiro doente. Resultados: Identificaram-se 103 candidatos a anticoagulação oral (79,6 ± 8,0 anos; CHA2DS2VASc 5,8 ± 1,4; HASBLED 2,6 ± 1,0; HASBLED ≥ 3 em 55,3%); os anticoagulantes foram prescritos em 34,0%. Fatores associados à não prescrição por ordem decrescente de relevância: uso prévio de antiagregantes, doente acamado e/ou demente, ausência de insuficiência cardíaca e número de fatores de risco hemorrágico. Razões invocadas para não prescrição por ordem decrescente de frequência: risco hemorrágico elevado, pequeno benefício, incapacidade de seguir o esquema terapêutico e dificuldade na monitorização da razão normalizada internacional (INR). Os novos anticoagulantes não foram prescritos e as razões invocadas foram, por ordem decrescente de frequência: informação insuficiente sobre estes fármacos, risco hemorrágico elevado, custo elevado e pequeno benefício. Aos 8,2 ± 2,5 meses de estudo evolutivo 33,3% dos doentes encontravam-se sob anticoagulação sem que os novos anticoagulantes tivessem sido prescritos. Conclusões: Nesta amostra, a taxa de prescrição de

  14. [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.

  15. Bosentan and oral anticoagulants in HIV patients: what we can learn of cases reported so far

    PubMed Central

    Morales-Molina, José Antonio; Martínez-de la Plata, Juan Enrique; Urquízar-Rodríguez, Olivia; Molina-Arrebola, María Angustias

    2011-01-01

    Pulmonary arterial hypertension is an infrequent but nevertheless serious life-threatening severe complication of HIV infection. It can be treated with bosentan and oral anticoagulants. Bosentan could induce the acenocoumarol metabolism and it increases the INR values. Until now, no study of interaction between bosentan and oral anticoagulants in HIV patients has reported. So we present a case of this interaction between these drugs and we reviewed MEDLINE to identify all the papers published so far. In our case, several weeks after increasing dose of bosentan acenocoumarol dose had to be progressively increased to 70 mg/week (+33%) without obtaining an adequate INR level (2.0–3.0). Forty-nine days later, we achieved a therapeutic INR with 90 mg/week of warfarin. The use of bosentan and oral anticoagulants together in these patients require a closer monitoring during first weeks of treatment, after increasing the bosentan dose and even during longer periods of time. PMID:22184537

  16. 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.

  17. [Acute coronary syndrome: Is there a place for direct oral anticoagulants?

    PubMed

    Cayla, Guillaume; Leclercq, Florence; Schmutz, Laurent; Cornillet, Luc; Ledermann, Bertrand; Messner, Patrick; Lattuca, Benoit

    2016-10-01

    Venous thromboembolism and atrial fibrillation are two important indications of direct oral anticoagulants. Acute coronary syndrome is another potential indication of prolonged antithrombotic therapy in addition to antiplatelet therapy. Phase 2 and 3 studies were conducted with different molecules at different doses in acute coronary syndrome in addition to dual antiplatelet therapy. Studies have not shown a reduction of ischemic events for dabigatran and apixaban, but an excess of bleeding complications was observed. A reduction of ischemic events and stent thrombosis was observed with low dose of rivaroxaban taken twice a day but with an increased risk of major bleeding complications. This data was used to obtain a European marketing authorization but the positioning of the molecule remains difficult. A new study is currently being conducted to test rivaroxaban in association with a P2Y12 inhibitor without aspirin. Direct oral anticoagulants can also be used after percutaneous coronary intervention in patients requiring long-term oral anticoagulants. Dedicated studies are currently being conducted to confirm the optimal doses and the ideal association of antithrombotic drugs.

  18. Implementing evidence-based patient and family education on oral anticoagulation therapy: a community-based participatory project.

    PubMed

    Shaha, Maya; Wüthrich, Erika; Stauffer, Yvonne; Herczeg, Franziska; Fattinger, Karin; Hirter, Kathrin; Papalini, Marianne; Herrmann, Luzia

    2015-06-01

    This study aimed at developing and implementing evidence-based patient and family education on oral anticoagulation therapy. The number of persons with chronic diseases who live at home is increasing. They have to manage multiple diseases and complex treatments. One such treatment is oral anticoagulation therapy, a high risk variable dose medication. Adherence to oral anticoagulation therapy is jeopardised by limited information about the medications, their risk and complications, the impact of individual daily routine and the limited inclusion of family members in education. Hence, improved and tailored education is essential for patients and families to manage oral anticoagulation therapy at home. A community-based participatory research design combined with the Precede-Proceed model was used including a systematic literature review, posteducation analysis, an online nurse survey, a documentation analysis and patient/family interviews. The study was conducted between April 2010-December 2012 at a department of general internal medicine in a teaching hospital in Switzerland. Participants were the department's nursing and medical professionals including the patients and their families. The evidence-based patient and family education on oral anticoagulation therapy emerged comprising a learning assessment, teaching units, clarification of responsibilities of nurse professionals and documentation guidelines. The inclusion of the whole department has contributed to the development and implementation of this evidence-based patient family education on oral anticoagulation therapy, which encompasses local characteristics and patient preferences. This education is now being used throughout the department. © 2015 John Wiley & Sons Ltd.

  19. Dabigatran: A new oral anticoagulant. Guidelines to follow in oral surgery procedures. A systematic review of the literature

    PubMed Central

    Ramírez-Martínez-Acitores, Lucía; López-Pintor, Rosa Mª; Casañas-Gil, Elisabeth; Hernández-Vallejo, Gonzalo

    2016-01-01

    Background Dabigatran is a newly commercialized drug that is replacing other anticoagulants in the prevention of venous thromboembolism, stroke and systemic arterial valve embolism. It acts directly on thrombin presenting in a dynamic and predictable way, which does not require monitoring these patients. Therefore, we consider the need to assess whether their use increases the risk of bleeding involved before any dental treatment. Material and Methods We performed a systematic review with a bibliographic search in PubMed/Medline along with the Cochrane Library. We excluded articles dealing with all anticoagulants other than dabigatran, and works about surgical treatments in anatomical locations other than the oral cavity. Results We included a total of 13 papers of which 1 was a randomized clinical trial, 9 narrative literature reviews, 1 case series, 2 clinical cases and 1 expert opinion. Because we did not obtain any properly designed clinical trials, we were unable to conduct a meta-analysis. Conclusions Currently, there is no consensus on the procedure to be followed in patients taking dabigatran. However, all authors agree to treat each case individually in accordance to the risk of embolism, postoperative bleeding and renal function. Also, it is necessary to perform minimally invasive interventions, and take the appropriate local anti-hemolytic measures. Key words:Oral anticoagulants, dabigatran, risk of bleeding, oral surgery, dentistry. PMID:27694780

  20. An Audit of Management of Patients on Oral Anticoagulant Therapy With International Normalized Ratio (INR) Five or Above.

    PubMed

    Chopra, Sandeep; Kakkar, Naveen

    2013-03-01

    Maintaining the international normalized ratio (INR) within the therapeutic range in patients on oral anticoagulant treatment is a challenge for the physician. Excessive anticoagulation poses the risk of bleeding in patients. Management strategies vary among clinicians although standard guidelines exist for the same. We conducted an audit in patients on oral anticoagulant therapy in our hospital with excessive anticoagulation. This retrospective study was carried out among patients on oral anticoagulant therapy for various thrombotic conditions with at least a single INR recording of 5 or more. Other than demographic details, the type of oral anticoagulant used, indication, duration of treatment, dosage and concomitant use of interacting drugs or alcohol were also recorded. Detail of the nature and site of bleed and management for the same was also noted. Data were analyzed using descriptive statistics. Fifty episodes with INR ≥ 5 (5.0-10.75) were noted in 44 patients (M:F = 1:1). Their age ranged from 20 to 88 years (mean 50.3 ± 16.4 years). The duration of anticoagulant therapy varied from 3 days to 180 months. Of the 43 episodes in patients who had no bleeding, the anticoagulant was stopped on 32 occasions for variable periods with dose reduction in the rest of the patients. Spontaneous bleeding was seen in seven patients (6 major and 1 minor). Among the seven patients with bleeding, other than stopping he oral anticoagulant drug, other measures taken were vitamin K therapy, fresh frozen plasma or packed red cell transfusion. Overall management strategy of patients with high INR was in compliance with standard recommendations.

  1. Pharmacology of antithrombotic drugs: an assessment of oral antiplatelet and anticoagulant treatments.

    PubMed

    Mega, Jessica L; Simon, Tabassome

    2015-07-18

    Antithrombotic drugs, which include antiplatelet and anticoagulant therapies, prevent and treat many cardiovascular disorders and, as such, are some of the most commonly prescribed drugs worldwide. The first drugs designed to inhibit platelets or coagulation factors, such as the antiplatelet clopidogrel and the anticoagulant warfarin, significantly reduced the risk of thrombotic events at the cost of increased bleeding in patients. However, both clopidogrel and warfarin have some pharmacological limitations including interpatient variability in antithrombotic effects in part due to the metabolism, interactions (eg, drug, environment, and genetic), or targets of the drugs. Increased knowledge of the pharmacology of antithrombotic drugs and the mechanisms underlying thrombosis has led to the development of newer drugs with faster onset of action, fewer interactions, and less interpatient variability in their antithrombotic effects than previous antithrombotic drugs. Treatment options now include the next-generation antiplatelet drugs prasugrel and ticagrelor, and, in terms of anticoagulants, inhibitors that directly target factor IIa (dabigatran) or Xa (rivaroxaban, apixaban, edoxaban) are available. In this Series paper we review the pharmacological properties of these most commonly used oral antithrombotic drugs, and explore the development of antiplatelet and anticoagulant therapies.

  2. 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

  3. Recent advances in the development of specific antidotes for target-specific oral anticoagulants.

    PubMed

    Mo, Yoonsun; Yam, Felix K

    2015-02-01

    Warfarin, a vitamin K antagonist, has been the only orally available anticoagulant for > 60 years. During the past decade, the U.S. Food and Drug Administration has approved several target-specific oral anticoagulants (TSOACs) for the prophylaxis and treatment of arterial and venous thromboembolism and stroke prevention in patients with nonvalvular atrial fibrillation. These new agents have several advantages over warfarin including more predictable pharmacokinetics and pharmacodynamics, fewer food and drug interactions, and lack of need for routine coagulation monitoring. However, unlike warfarin, currently no antidotes are available to reverse the anticoagulant effect of TSOACs. Specific antidotes for TSOACs may not be needed in most situations due to their short half-life, yet the absence of antidotes for these agents is a concern, especially in emergent situations such as life-threatening major bleeding or nonelective major surgery. Several specific antidotes for TSOACs including idarucizumab, andexanet alfa, and aripazine have been developed and have shown promise in early clinical trials evaluating their efficacy and safety. In this narrative review, the progress made in developing specific antidotes for TSOACs is summarized based on the latest available preclinical and clinical data.

  4. Management of bleeding with oral anticoagulants in patients with atrial fibrillation.

    PubMed

    Bosch, J; Eikelboom, J W

    2015-01-01

    Fear of bleeding is a common barrier to the use of anticoagulants. Warfarin has been the only oral anticoagulant for more than 60 years and warfarin-related bleeding is reported to be the most common drug-related cause of emergency hospitalization in elderly Americans. Non-vitamin K oral antagonists were introduced five years ago and compared with warfarin are associated with lower risk of intracranial bleeding, and similar or lower case fatality after major bleeding. Despite their superior safety profile, serious bleeding can occur. Most bleeding can be managed with holding the drug, local measures to control the bleeding and transfusion support as required because the NOACs have a relatively short half life and their anticoagulant effect rapidly dissipates. In patients with ongoing bleeding despite supportive measures and in those with life-threatening bleeding, consideration may be given to the use of general hemostatic agents. Experimental and animal evidence suggests that 3 and 4 factor prothrombin complex concentrates can improve hemostasis in the presence of a NOAC and this is reinforced by anecdotal evidence in humans. Specific antidotes are currently in phase 3 trials and could become available in the near future.

  5. Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration.

    PubMed

    Vandenbroucke, V; Bousquet-Melou, A; De Backer, P; Croubels, S

    2008-10-01

    The first aim of the study was to investigate the pharmacokinetics of eight anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen and warfarin) in plasma and liver of the mouse after single oral administration. Eight groups of mice dosed orally with a different anticoagulant rodenticide in a dose equal to one-half the lethal dose 50 (LD(50)), were killed at various times up to 21 days after administration. The eight anticoagulant rodenticides were assayed in plasma and liver by an LC-ESI-MS/MS method. Depending on the compound, the limit of quantification was set at 1 or 5 ng/mL in plasma. In liver, the limit of quantification was set at 250 ng/g for coumatetralyl and warfarin and at 100 ng/g for the other compounds. The elimination half-lives in plasma for first-generation rodenticides were shorter than those for second-generation rodenticides. Coumatetralyl, a first-generation product, had a plasma elimination half-life of 0.52 days. Brodifacoum, a second-generation product, showed a plasma elimination half-life of 91.7 days. The elimination half-lives in liver varied from 15.8 days for coumatetralyl to 307.4 days for brodifacoum. The second aim of the study was to illustrate the applicability of the developed method in a clinical case of a dog suspected of rodenticide poisoning.

  6. Effective management of venous thromboembolism in the community: non-vitamin K antagonist oral anticoagulants

    PubMed Central

    Patel, Raj

    2016-01-01

    Anticoagulation therapy is essential for the effective treatment and secondary prevention of venous thromboembolism (VTE). For many years, anticoagulation for acute VTE was limited to the use of initial parenteral heparin, overlapping with and followed by a vitamin K antagonist. Although highly effective, this regimen has several limitations and is particularly challenging when given in an ambulatory setting. Current treatment pathways for most patients with deep-vein thrombosis typically involve initial hospital or community-based ambulatory care with subsequent follow-up in a secondary care setting. With the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into routine clinical practice, it is now possible for the initial acute management of patients with deep-vein thrombosis to be undertaken by primary care. As hospital admissions associated with VTE become shorter, primary care will play an increasingly important role in the long-term management of these patients. Although the NOACs can potentially simplify patient management and improve clinical outcomes, primary care physicians may be less familiar with these new treatments compared with traditional therapy. To assist primary care physicians in further understanding the role of the NOACs, this article outlines the main differences between NOACs and traditional anticoagulation therapy and discusses the benefit–risk profile of the different NOACs in the treatment and secondary prevention of recurrent VTE. Key considerations for the use of NOACs in the primary care setting are highlighted, including dose transition, risk assessment and follow-up, duration of anticoagulant therapy, how to minimize bleeding risks, and the importance of patient education and counseling. PMID:27217793

  7. 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

  8. Changes in Oral Anticoagulant Prescribing for Stroke Prevention in Patients With Atrial Fibrillation.

    PubMed

    Admassie, Endalkachew; Chalmers, Leanne; Bereznicki, Luke R

    2017-10-01

    Suboptimal guideline adherence and underuse of anticoagulants in patients with atrial fibrillation (AF) have been reported worldwide. This study aimed to compare anticoagulation practice in Australia during the pre- and postdirect oral anticoagulant (DOAC) eras. Between January 2011 and July 2015, patients with nonvalvular AF (NVAF) admitted to the Royal Hobart Hospital, Tasmania, Australia, were retrospectively reviewed. The pre- and post-DOAC era cohorts included admissions from January 2011 to July 2013 and August 2013 to July 2015, respectively. Overall, 2,118 patients met our inclusion criteria. The overall rate of anticoagulation increased from 52.5% in the pre-DOAC era to 60.7% in the post-DOAC era (p <0.001). Moreover, prescribing of OACs among high-risk patients improved significantly (63.1% vs 55.2%, p = 0.001). OAC overprescribing in low-risk patients did not change significantly between the 2 cohorts (35.0% vs 42.9% in the pre- and post-DOAC eras, respectively, p = 0.59). In multivariate analysis, DOAC era (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.17 to 1.68 and CHA2DS2-VASc ≥2 (OR 1.95, 95% CI 1.36 to 2.80) were independent predictors of OAC prescribing in both eras and the whole study period. Conversely, aging and previous bleeding were inversely associated with OAC prescribing. In conclusion, there has been a significant increase in OAC prescribing in the post-DOAC era, potentially driven by the widespread availability of DOACs. However, OAC underuse in high-risk patients and overuse in low-risk patients was apparent throughout our study. These findings highlight the need to identify the drivers of anticoagulant underuse and overuse and address them accordingly. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Why develop antidotes and reversal agents for non-vitamin K oral anticoagulants?

    PubMed

    Washam, Jeffrey B; Piccini, Jonathan P

    2016-02-01

    Over the past several years, non-vitamin K oral anticoagulants (NOACs) have been introduced into clinical practice for the treatment of venous thromboembolism and prevention of stroke in patients with nonvalvular atrial fibrillation. Clinical trials have shown these agents to have similar or less risk of major bleeding as compared to warfarin therapy. Moreover, when patients do experience a major bleeding event administration of advanced factor products is rare, and post-bleed outcomes are similar in those receiving a NOAC compared to those receiving warfarin. However, there are situations where urgent reversal of NOAC anticoagulation would be desirable. The following review focuses on the outcomes and management strategies for patients experiencing a major bleed with warfarin or NOAC agents and describes the rationale for the development of therapies capable of targeted NOAC-reversal.

  10. Non-vitamin K antagonist oral anticoagulants: new choices for patient management in atrial fibrillation.

    PubMed

    Saliba, Walid

    2015-10-01

    Atrial fibrillation (AF) is a significant problem for the aging population and remains a major factor underlying stroke risk. Warfarin anticoagulation has been proven effective for stroke prevention in AF, but can be difficult to manage and requires frequent monitoring. The non-vitamin K antagonist oral anticoagulants (NOACs) have been shown to be as effective as warfarin for stroke prevention in nonvalvular AF (NVAF) and are associated with a reduced risk of bleeding compared with warfarin. Dabigatran, rivaroxaban, apixaban, and edoxaban have been approved in the USA for reducing the risk of stroke in patients with NVAF. In this article, AF risk assessment is discussed and NOAC phase III clinical trials for the prevention of stroke and systemic embolic events are reviewed. Further, differences in stroke and bleeding outcomes between NOACs are highlighted, the use of NOACs for cardioversion and special patient populations is discussed, and management considerations for patients with AF are reviewed.

  11. Oral anticoagulants and status of antidotes for the reversal of bleeding risk.

    PubMed

    Ebright, Joseph; Mousa, Shaker A

    2015-03-01

    Anticoagulants have been used in clinical practice for more than 50 years. Their indications expand, as more people are diagnosed each year with atrial fibrillation and venous thromboembolism. Vitamin K antagonists have been the most popular choice due to their effectiveness and their ability to reverse bleeding using a known antidote; oral and intravenous vitamin K have long been known to reverse the effects of warfarin. With new classes of anticoagulants making their way onto the market, such as factor Xa inhibitors (rivaroxaban, apixaban) and direct thrombin inhibitors (dabigatran), the need for new reversal agents is paramount. Patients tend to be more receptive to these medications because they do not require routine blood monitoring, can be used at fixed doses, and do not have major drug or food interactions. Antidotes for these medications have shown promise in animal models and are currently in clinical trials.

  12. Ischemic stroke in cancer patients treated with direct oral anticoagulants for venous thromboembolism.

    PubMed

    Gon, Yasufumi; Sakaguchi, Manabu; Takasugi, Junji; Mochizuki, Hideki

    2017-06-01

    Direct oral anticoagulants (DOACs) are at least as efficacious as conventional anticoagulation therapy for the initial and long-term treatment of cancer patients with venous thromboembolism (VTE). Whether DOACs are non-inferior to low-molecular-weight heparin for the management of cancer patients with VTE is under investigation. In addition, the efficacy of DOACs for the treatment of cancer patients with arterial thrombosis (e.g., ischemic stroke) remains unclear. Herein, we report on two cancer patients admitted to our hospital with Stage IV gastric adenocarcinoma who were being treated with DOACs due to a history of VTE and had developed their first ever ischemic stroke, which was diagnosed due to cancer-related hypercoagulation. Notably, neither patient had recurrence of VTE during the course of their disease. In cancer-related thrombosis, DOACs effectively reduce VTE, but may be insufficient for preventing ischemic stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    1996-01-01

    BACKGROUND: 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. AIM: 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). METHOD: 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. RESULTS: 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. CONCLUSION: 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. PMID

  14. 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

  15. Management of dental extraction in patients undergoing anticoagulant oral direct treatment: a pilot study.

    PubMed

    Mauprivez, Cédric; Khonsari, Roman Hossein; Razouk, Omar; Goudot, Patrick; Lesclous, Philippe; Descroix, Vianney

    2016-11-01

    The main goal of this study was to compare the incidence of postoperative bleeding events after dental extractions between patients treated with direct oral anticoagulants (DOACs) and those treated with vitamin K antagonists (VKAs) without withdrawal of oral anticoagulant therapy (OAT). Our second objective was to evaluate the risk factors affecting postoperative hemorrhage after tooth extraction in patients taking DOACs. This prospective observational study included 51 patients who were being treated with oral anticoagulants and required dental extractions. They were divided into two groups: 31 patients receiving a DOAC and 20 control patients taking VKA with an international normalized ratio between 2.0 and 3.0. In both groups, extractions were performed under continued OAT, and the same local hemostatic measures were applied. All procedures were performed in an outpatient facility. A bleeding event was defined as persistent oozing or marked hemorrhage over 20 minutes after tooth extraction despite local hemostasis procedures or all bleeding episode occurring during the first postoperative week. Five patients taking DOACs had seven bleeding episodes, and four patients receiving VKAs had five bleeding episodes during the postoperative follow-up period. The difference in the number of bleeding events between the two groups was not statistically significant (adjusted odds ratio = 0.77; 95% confidence interval 0.19-3.19; P = .723). Eleven (91.67%) bleeding events were mild and controlled by mechanical compression with gauzes, and one (8.33 %) was managed with a revision of the wound, application of fibrin glue, and resuturing. No bleeding required hospitalization or blood transfusion. All bleeding episodes occurred during the first 3 postoperative days. According to our preliminary outcome data, dental extractions can be performed safely in an outpatient facility in patients treated with DOAC by applying local hemostatic measures, without interrupting or

  16. Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives.

    PubMed

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

    2015-11-01

    In recent years, several direct-acting oral anticoagulants (DOAC) have become available for use in Europe and other regions in indications related to prophylaxis and treatment of venous and arterial thromboembolism. They include the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa, Boehringer Ingelheim) and the oral direct FXa inhibitors rivaroxaban (Xarelto, Bayer HealthCare), apixaban (Eliquis, Bristol-Myers Squibb), and edoxaban (Lixiana/Savaysa, Daiichi-Sankyo). The new compounds have a predictable dose response and few drug-drug interactions (unlike vitamin k antagonists), and they do not require parenteral administration (unlike heparins). However, they accumulate in patients with renal impairment, lack widely available monitoring tests for measuring its anticoagulant activity, and no specific antidotes for neutralization in case of overdose and/or severe bleeding are currently available. In this review, we describe the pharmacology of the DOAC, the efficacy, and safety data from pivotal studies that support their currently approved indications and discuss the postmarketing experience available. We also summarize practical recommendations to ensure an appropriate use of the DOAC according to existing data. Finally, we discuss relevant ongoing studies and future perspectives. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. [New oral anticoagulants: emerging clinical data and role of the primary care physician].

    PubMed

    Motte, S

    2011-09-01

    New oral anticoagulants offer several potential advantages including oral administration, fixed doses, no regular coagulation monitoring and dose adjustment and wide therapeutic index. The results from clinical studies for prevention and treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation show that these agents are at least as effective as or superior to currently available therapies depending on the molecules and dose regimen. Physicians will have to make choices among available new agents taking into account their pharmacokinetic properties, half-life, route of elimination and patient comorbidities. But the use of these new agents in daily practice raises some issues such as temporary discontinuation in patients undergoing invasive procedures and management of patients with bleeding in the absence of specific antidote. New oral anticoagulants should be used with caution in daily practice in special populations such as elderly patients, patients with renal impairment and patients with cancer. Primary care physicians will have to play a role in monitoring and evaluating the long-term efficacy and safety of these agents in daily practice.

  18. 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.

  19. Cost-effectiveness of oral anticoagulants for treatment of atrial fibrillation.

    PubMed

    Canestaro, William J; Patrick, Amanda R; Avorn, Jerry; Ito, Kouta; Matlin, Olga S; Brennan, Troyen A; Shrank, William H; Choudhry, Niteesh K

    2013-11-01

    New anticoagulants may improve health outcomes in patients with atrial fibrillation, but it is unclear whether their use is cost-effective. A Markov state transition was created to compare 4 therapies: dabigatran 150 mg BID, apixaban 5 mg BID, rivaroxaban 20 mg QD, and warfarin therapy. The population included those with newly diagnosed atrial fibrillation who were eligible for treatment with warfarin. Compared with warfarin, apixaban, rivaroxaban, and dabigatran, costs were $93 063, $111 465, and $140 557 per additional quality-adjusted life year gained, respectively. At a threshold of $100 000 per quality-adjusted life year, apixaban provided the greatest absolute benefit while still being cost-effective, although warfarin would be superior if apixaban was 2% less effective than expected. Although apixaban was the optimal strategy in our base case, in probabilistic sensitivity analysis, warfarin was optimal in an equal number of iterations at a cost-effectiveness threshold of $100 000 per quality-adjusted life year. While at a standard cost-effectiveness threshold of $100 000 per quality-adjusted life year, apixaban seems to be the optimal anticoagulation strategy; this finding is sensitive to assumptions about its efficacy and cost. In sensitivity analysis, warfarin seems to be the optimal choice in an equal number of simulations. As a result, although all the novel oral anticoagulants produce greater quality-adjusted life expectancy than warfarin, they may not represent good value for money.

  20. Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests.

    PubMed

    Halbmayer, Walter-Michael; Weigel, Guenter; Quehenberger, Peter; Tomasits, Josef; Haushofer, Alexander C; Aspoeck, Gerold; Loacker, Lorin; Schnapka-Koepf, Mirjam; Goebel, Georg; Griesmacher, Andrea

    2012-01-01

    Dabigatran etexilate is a new oral anticoagulant for the therapy and prophylaxis of venous thromboembolism and stroke prevention in patients with atrial fibrillation. To investigate the extent of interactions of this new anticoagulant with frequently used coagulation assays, we completed a multicenter in vitro trial with Conformité Européenne(CE)-labeled dabigatran-spiked plasma samples. Lyophilized plasma samples with dabigatran concentrations ranging from 0.00 to 0.48 μg/mL were sent to the coagulation laboratories of six major Austrian hospitals for evaluation. Coagulation assays were performed under routine conditions using standard reagents and analyzer. Dabigatran led to a dose-dependent prolongation of the clotting times in coagulometric tests and influenced the majority of the parameters measured. Statistically significant interference could be observed with the prothrombin time (PT), activated partial thromboplastin time (aPTT) and PT/aPTT-based assays (extrinsic/intrinsic factors, APC-resistance test) as well as lupus anticoagulant testing. Even non-clotting tests, such as the colorimetric factor XIII activity assay and to a minor extent the amidolytic antithrombin activity assay (via factor IIa) were affected. This multicenter trial confirms and also adds to existing data, demonstrating that laboratories should expect to observe strong interferences of coagulation tests with increasing concentrations of dabigatran. This finding might become particularly important in the elderly and in patients with renal impairment as well as patients whose blood is drawn at peak levels of dabigatran.

  1. Non-VKA Oral Anticoagulants: Accurate Measurement of Plasma Drug Concentrations.

    PubMed

    Douxfils, Jonathan; Mani, Helen; Minet, Valentine; Devalet, Bérangère; Chatelain, Bernard; Dogné, Jean-Michel; Mullier, François

    2015-01-01

    Non-VKA oral anticoagulants (NOACs) have now widely reached the lucrative market of anticoagulation. While the marketing authorization holders claimed that no routine monitoring is required and that these compounds can be given at fixed doses, several evidences arisen from the literature tend to demonstrate the opposite. New data suggests that an assessment of the response at the individual level could improve the benefit-risk ratio of at least dabigatran. Information regarding the association of rivaroxaban and apixaban exposure and the bleeding risk is available in the drug approval package on the FDA website. These reviews suggest that accumulation of these compounds increases the risk of experiencing a bleeding complication. Therefore, in certain patient populations such as patients with acute or chronic renal impairment or with multiple drug interactions, measurement of drug exposure may be useful to ensure an optimal treatment response. More specific circumstances such as patients experiencing a haemorrhagic or thromboembolic event during the treatment duration, patients who require urgent surgery or an invasive procedure, or patient with a suspected overdose could benefit from such a measurement. This paper aims at providing guidance on how to best estimate the intensity of anticoagulation using laboratory assays in daily practice.

  2. The case against using hypertension as the only criterion for oral anticoagulation in atrial fibrillation.

    PubMed

    Rabkin, Simon W; Moe, Gordon

    2015-05-01

    According to recent guidelines for atrial fibrillation (AF) management, the presence of hypertension warrants anticoagulation, often involving the use of newer oral anticoagulants (NOACs). To discuss this idea, we posited the case against this proposition. We note that the data on hypertension that formulated the most commonly used Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack (CHADS2) risk algorithm were not clearly defined and that there are insufficient data that hypertension in the presence of AF produces a meaningful incremental increase in stroke risk over and above the stroke risk increase for hypertension alone. Data exist that persons younger than 65 years of age with only 1 stroke risk factor such as hypertension, have a very small stroke risk. We further note that there are no quantitative data to allow clinicians to decide the level of blood pressure that meaningfully increases stroke risk in AF. Furthermore, there are insufficient data on the blood pressure level at which the risk of cerebral hemorrhage outweighs the risk of cardioembolic events. Clinical trials of NOACs in AF did not usually include hypertension as the only entry criteria. Another issue is the recent changes in the level of blood pressure for the diagnosis of hypertension based on home and ambulatory blood pressure measurement, which were not used to construct either stroke risk algorithms or entry criteria for NOAC clinical trials. These considerations highlight some of the complexities of using hypertension as a sole criterion for decision-making for anticoagulation in AF.

  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. Non-vitamin-K oral anticoagulants and laboratory testing: now and in the future

    PubMed Central

    Salmonson, Tomas; Dogné, Jean-Michel; Janssen, Heidi; Garcia Burgos, Juan; Blake, Paul

    2017-01-01

    In contrast to vitamin K antagonists, no routine coagulation monitoring is required in patients taking non-vitamin-K oral anticoagulants (NOACs). However, dosing must take into account factors such as patient age, renal function, and accompanying haemorrhagic risk. There has been considerable debate about when laboratory measurement might be appropriate and which tests should be used. A workshop at the European Medicines Agency recently discussed the evidence about laboratory measurement from formal studies, clinical experience, and the multiple perspectives on NOAC treatment, and considered how our knowledge might be further enhanced. PMID:28025213

  5. [Laboratory coagulation tests in patients treated by direct oral anticoagulants (DOACs)].

    PubMed

    Sié, Pierre

    2015-01-01

    Routine clotting time assays (Prothrombin Time/INR, activated Partial Thromboplastin Time [aPTT]) are prolonged at variable extent by direct oral anticoagulants (DOAC), according to the assay, the reagent and the type of DOAC. These assays are not reliable for monitoring the intensity of treatment and the measurement of the plasma level of the DOAC is usually not required. At high concentrations, DOAC interfere with the routine clotting assays, making them difficult to interpret. In critical situations such as major bleeding or urgent invasive procedure, the measurement of DOAC level and its kinetics are simple and useful to manage the patient. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. 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

  7. Choice of New Oral Anticoagulant Agents Versus Vitamin K Antagonists in Atrial Fibrillation: FANTASIIA Study.

    PubMed

    Moreno-Arribas, José; Bertomeu-González, Vicente; Anguita-Sanchez, Manuel; Cequier, Ángel; Muñiz, Javier; Castillo, Jesús; Sanchis, Juan; Roldán, Inmaculada; Marín, Francisco; Bertomeu-Martínez, Vicente

    2016-03-01

    Atrial fibrillation (AF) is associated with an increased risk of thromboembolic events. Many patients with AF receive chronic anticoagulation, either with vitamin K antagonists (VKAs) or with non-VKA oral anticoagulants (NOACs). We sought to analyze variables associated with prescription of NOAC. Patients with AF under anticoagulation treatment were prospectively recruited in this observational registry. The sample comprised 1290 patients under chronic anticoagulation for AF, 994 received VKA (77.1%) and 296 NOAC (22.9%). Univariate and multivariate analyses were performed to identify variables associated with use of NOAC. Mean age was 73.8 ± 9.4 years, and 42.5% of the patients were women. The CHA2DS2-VASc score was 0 in 4.9% of the population, 1 in 24.1%, and ≥2 in 71% (median = 4, interquartile range = 2). Variables associated with NOAC treatment were major bleeding (odds ratio [OR] = 3.36; confidence interval [CI] 95%: 1.73-6.51; P < .001), hemorrhagic stroke (OR = 3.19; CI 95% 1.00-10.15, P = .049), university education (OR = 2.44; CI 95%: 1.55-3.84; P < .001), high diastolic blood pressure (OR = 1.02; CI 95%: 1.00-1.03; P = .006), and higher glomerular filtration rate (OR 1.01, CI 95% 1.00-1.01; P = .01). And variables associated with VKA use were history of cancer (OR = 0.46; CI 95%: 0.25-0.85; P = .013) and bradyarrhythmia (OR = 0.40; CI 95% 0.19-0.85; P = .020). Medical and social variables were associated with prescription of NOAC. Major bleeding, hemorrhagic stroke, university education, and higher glomerular filtration rate were more frequent among patients under NOAC. On the contrary, patients with history of cancer or bradyarrhythmias more frequently received VKA. © The Author(s) 2015.

  8. Dabigatran etexilate: the first oral anticoagulant available in the United States since warfarin.

    PubMed

    Tran, Arlene; Cheng-Lai, Angela

    2011-01-01

    For more than 5 decades, warfarin has been the mainstay of therapy when oral anticoagulation is required. It has been shown to be effective in the prevention as well as treatment of various thromboembolic disorders. However, drawbacks of warfarin, such as time-consuming requirements for frequent international normalized ratio monitoring, as well as drug and food interactions, have encouraged the development of alternative oral agents. One such agent, dabigatran, has risen up to the challenge. Due to its predictable anticoagulation response, dabigatran does not require routine anticoagulation monitoring. Another advantage dabigatran has over warfarin is its more favorable drug and food interaction profiles. Dabigatran was shown to be noninferior to warfarin in studies evaluating the prevention of stroke and systemic embolism in patients with atrial fibrillation, thus leading to the US Food and Drug Administration approval for this indication. Dabigatran has also demonstrated efficacy in the prevention of venous thromboembolism in patients undergoing total hip or knee replacement surgery as well as the prevention of recurrent venous thromboembolism, although these are not current Food and Drug Administration-approved indications. The safety profile appears to be similar to warfarin with regards to overall bleeding risk, though the risk for gastrointestinal bleeds was higher in patients on dabigatran 150 mg twice daily. Disadvantages of dabigatran may include a higher frequency of dyspepsia compared with warfarin, lack of dosing information in severe renal impairment, possible missed opportunities for periodic health examinations and interventions due to elimination of regular physician's visit for international normalized ratio monitoring, and drug costs. This article provides an overview of the clinical studies, pharmacokinetic profile, adverse effects, drug interactions as well as advantages and disadvantages associated with dabigatran.

  9. 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.

  10. Decision-making about the use of non-vitamin K oral anticoagulant therapies for patients with atrial fibrillation.

    PubMed

    Eckman, Mark H

    2016-02-01

    Until recently, vitamin K antagonists, warfarin being the most commonly used agent in the United States, have been the only oral anticoagulant therapies available to prevent stroke in patients with atrial fibrillation (AF). In the last 5 years four new, non-vitamin K oral anticoagulants, the so-called NOACs or novel oral anticoagulants, have come to market and been approved by the Federal Drug Administration. Despite comparable if not superior efficacy in preventing AF-related stroke, and generally lower risks of major hemorrhage, particularly intracranial bleeding, the uptake of these agents has been slow. A number of barriers stand in the way of the more widespread use of these novel agents. Chief among them is concern about the lack of antidotes or reversal agents. Other concerns include the need for strict medication adherence, since missing even a single dose can lead to a non-anticoagulated state; out-of-pocket costs for patients; the lack of easily available laboratory tests to quantitatively assess the level of anticoagulant activity when these agents are being used; contraindications to use in patients with severe chronic kidney disease; and black-box warnings about the increased risk of thromboembolic events if these agents are discontinued prematurely. Fortunately, a number of reversal agents are in the pipeline. Three reversal agents, idarucizumab, andexanet alfa, and aripazine, have already progressed to human studies and show great promise as either antidotes for specific drugs or as universal reversal agents. The availability of these reversal agents will likely increase the clinical use of the non-vitamin K oral anticoagulants. In light of the many complex and nuanced issues surrounding the choice of an optimal anticoagulant for any AF patient, a patient-centered/shared decision-making approach will be useful.

  11. Direct oral anticoagulants and antiplatelet agents. Clinical relevance and options for laboratory testing.

    PubMed

    Sibbing, D; Spannagl, M

    2014-01-01

    Oral anticoagulants and platelet receptor blockers are widely used in clinical practice with the aim of reducing the risk of thrombotic complications in patients with cardiovascular diseases. Their regular intake and adequate antithrombotic action is vital and this is way numerous assays have been developed for laboratory testing and monitoring of these agents. Available assays can be stratified into pharmacokinetic and pharmacodynamic assays. Such assays are increasingly used in clinical routine and their daily use is triggered by the advent of the novel direct oral anticoagulants (DOACs) as an alternative for vitamin K antagonist (VKA) treatment, which are dabigatran, rivaroxaban and apixaban, and by the advent of prasugrel or ticagrelor as an alternative for clopidogrel with regard to platelet P2Y12 receptor inhibition. In this review the most important and most commonly used laboratory assays are summarized as well as their clinical implications with the focus on DOACs as an alternative for VKAs and the different P2Y12 receptor blockers for antiplatelet treatment.

  12. 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

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

    PubMed

    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.

  14. Sailing between Scylla and Charybdis: oral long-term anticoagulation in dialysis patients.

    PubMed

    Krüger, Thilo; Brandenburg, Vincent; Schlieper, Georg; Marx, Nikolaus; Floege, Jürgen

    2013-03-01

    End-stage renal disease (ESRD) patients exhibit an increased risk of bleeding compared with non-chronic kidney disease (CKD) patients due to uraemic platelet dysfunction, altered vessel architecture and other factors. This renders any long-term oral anticoagulation potentially difficult. While there is little doubt that ESRD patients with recurrent thromboembolism or a mechanical cardiac valve should receive vitamin K antagonists (coumarins), the use of coumarins in ESRD patients with atrial fibrillation is a matter of debate. In non-CKD patients, current guidelines strongly recommend the use of oral anticoagulants for stroke prophylaxis in atrial fibrillation if certain risk factors are present (CHA2DS2-VASc score). This recommendation is often extrapolated to patients with advanced CKD or ESRD but data supporting this practice are weak to absent. Besides an increased bleeding risk in ESRD patients, coumarins will also accelerate cardiovascular calcification and are potent risk factors for the development of calcific uraemic arteriolopathy (calciphylaxis). Novel coumarin alternatives such as direct thrombin inhibitors are promising but none is currently approved for use in ESRD patients. Whether interventional treatment strategies such as atrial appendage occlusion are safe and effective options in advanced CKD is also as yet unresolved. This review attempts to balance the potential risks and benefits of coumarin usage in ESRD patients and to give the best possible recommendations for everyday patient care.

  15. Non-Vitamin K Oral Anticoagulants in Stroke Patients: Practical Issues

    PubMed Central

    Diener, Hans-Christoph; Kleinschnitz, Christoph

    2016-01-01

    Non-vitamin-K oral anticoagulants (NOACs) represent a major advance in the prevention of stroke in patients with atrial fibrillation (AF), offering a similar, if not superior, efficacy and safety profile and several practical advantages over oral vitamin K antagonists (VKAs). The rapid onset of action of the NOACs, their relatively short half-live, and the availability of specific reversal agents may be advantageous when managing acute ischemic strokes, and in the post-stroke, post-transient ischemic attack, and post-intracranial hemorrhage settings. In this review article, we offer practical guidance on the use of NOACs in these settings, focusing on managing the acute event and on initiating or resuming anticoagulation for secondary prevention. We also assess the use of NOACs to prevent stroke and bleeding in patients with AF who have chronic kidney disease, are elderly, or cognitively impaired, and we offer guidance on optimizing the use of NOACs and VKAs in these patient groups in the absence of evidence-based guidelines. PMID:27165264

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

    PubMed

    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

    2014-03-04

    We aimed to evaluate whether oral anticoagulants (OACs) alter faecal immunochemical test (FIT) performance in average-risk colorectal cancer (CRC) screening. Individuals aged 50-69 years were invited to receive one FIT sample (cutoff 75 ng ml(-1)) between November 2008 and June 2011. 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). 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.

  17. [Spontaneous intraocular hemorrhage under oral anticoagulation : Apixaban in comparison to phenprocoumon].

    PubMed

    Treder, M; Alnawaiseh, M; Wirths, G; Rosentreter, A; Eter, N

    2017-06-08

    To determine and compare the frequency of intraocular hemorrhage in patients who underwent oral anticoagulation with apixaban or phenprocoumon. A retrospective analysis of patients under oral anticoagulant medication (apixaban or phenprocoumon) seen between January 2015 and June 2015 at the department of ophthalmology, University of Muenster Medical Center was performed. Vitreal or retinal hemorrhage in addition to clinical information including age, gender, best corrected visual acuity, concomitant diseases, concomitant medication and therapy were obtained. Bleeding frequency in both groups was compared using Fisher's exact test. A total of 172 patients were included with a mean age = 74.0 ± 10.6 years, 57.0% (n = 98) male and 43.0% (n = 74) female. In the phenprocoumon group 147 patients (3.4%, n = 5) developed a retinal or vitreal hemorrhage. In the apxiban group 25 patients (36%, n = 9) developed a retinal or vitreal hemorrhage. There was a significant correlation between the group and bleeding risk (p < 0.001). There was a significant correlation between medication (apixaban vs. phenprocoumon) and bleeding risk in this study population. Further studies with more patients especially in patients with a high risk of hemorhage, age-related macular degeneration (AMD) and proliferative diabetic retinopathy are needed.

  18. Net clinical benefit of oral anticoagulants: a multiple criteria decision analysis.

    PubMed

    Hsu, Jason C; Hsieh, Cheng-Yang; Yang, Yea-Huei Kao; Lu, Christine Y

    2015-01-01

    This study quantitatively evaluated the comparative efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, and apizaban) and warfarin for treatment of nonvalvular atrial fibrillation. We also compared these agents under different scenarios, including population with high risk of stroke and for primary vs. secondary stroke prevention. We used multiple criteria decision analysis (MCDA) to assess the benefit-risk of these medications. Our MCDA models contained criteria for benefits (prevention of ischemic stroke and systemic embolism) and risks (intracranial and extracranial bleeding). We calculated a performance score for each drug accounting for benefits and risks in comparison to treatment alternatives. Overall, new agents had higher performance scores than warfarin; in order of performance scores: dabigatran 150 mg (0.529), rivaroxaban (0.462), apixaban (0.426), and warfarin (0.191). For patients at a higher risk of stroke (CHADS2 score≥3), apixaban had the highest performance score (0.686); performance scores for other drugs were 0.462 for dabigatran 150 mg, 0.392 for dabigatran 110 mg, 0.271 for rivaroxaban, and 0.116 for warfarin. Dabigatran 150 mg had the highest performance score for primary stroke prevention, while dabigatran 110 mg had the highest performance score for secondary prevention. Our results suggest that new oral anticoagulants might be preferred over warfarin. Selecting appropriate medicines according to the patient's condition based on information from an integrated benefit-risk assessment of treatment options is crucial to achieve optimal clinical outcomes.

  19. Computer-aided dosage in oral anticoagulation therapy using phenprocoumon. Problems and approaches.

    PubMed

    Cromme, L; Völler, H; Gäbler, F; Salzwedel, A; Taborski, U

    2010-11-01

    Oral anticoagulation using vitamin K antagonists has been established for over 50 years. Although it is highly effective in preventing thromboembolic incidents, its therapeutic control still remains problematic. Therefore, a computer-aided approach is recommended for deriving dosages. Up to now, the dosage is often based on the visual inspection of previous INR measurements, average weekly doses, and the INR target range. Statistical variations of measurement results and time-delayed effects of dosages, however, frequently result in the misinterpretation of data and suggest pseudo-trends. Treating physicians are not only responsible for determining the patient-specific maintenance dose, but must also respond to deviating INR values, overdosage or underdosage, initiate the oral anticoagulation therapy, and control the INR level in case of a new target range (bridging). Instructive examples are provided to illustrate the described difficulties. A computer-aided expert system is currently developed to ensure the therapeutic safety under the specified conditions. We present preliminary results from a study designed to validate mathematical models underlying such expert systems.

  20. 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

  1. Review of atrial fibrillation outcome trials of oral anticoagulant and antiplatelet agents.

    PubMed

    Bassand, Jean-Pierre

    2012-03-01

    Atrial fibrillation (AF) is strongly associated with cardioembolic stroke, and thromboprophylaxis is an established means of reducing stroke risk in patients with AF. Oral vitamin K antagonists such as warfarin have been the mainstay of therapy for stroke prevention in patients with AF. However, they are associated with a number of limitations, including excessive bleeding when not adequately controlled. Antiplatelet agents do not match vitamin K antagonists in terms of their preventive efficacy. Dual-antiplatelet therapy (clopidogrel and acetylsalicylic acid) or combined antiplatelet-vitamin K antagonist therapy in AF has also failed to provide convincing evidence of their additional benefit over vitamin K antagonists alone. Novel oral anticoagulants, including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban, have now been approved or are currently in late-stage clinical development in AF. These newer agents may provide a breakthrough in the optimal management of stroke risk.

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

    PubMed

    Inchingolo, Francesco; Tatullo, Marco; Abenavoli, Fabio M; Marrelli, Massimo; Inchingolo, Alessio D; Scacco, Salvatore; Papa, Francesco; Inchingolo, Angelo M; Dipalma, Gianna

    2011-07-19

    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. 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. Among the 193 patients, only 2 had postoperative complications. We think that the protocol used in the present study can be used for complete safety in the treatment of this type of patients.

  3. 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

  4. Review of atrial fibrillation outcome trials of oral anticoagulant and antiplatelet agents

    PubMed Central

    Bassand, Jean-Pierre

    2012-01-01

    Atrial fibrillation (AF) is strongly associated with cardioembolic stroke, and thromboprophylaxis is an established means of reducing stroke risk in patients with AF. Oral vitamin K antagonists such as warfarin have been the mainstay of therapy for stroke prevention in patients with AF. However, they are associated with a number of limitations, including excessive bleeding when not adequately controlled. Antiplatelet agents do not match vitamin K antagonists in terms of their preventive efficacy. Dual-antiplatelet therapy (clopidogrel and acetylsalicylic acid) or combined antiplatelet–vitamin K antagonist therapy in AF has also failed to provide convincing evidence of their additional benefit over vitamin K antagonists alone. Novel oral anticoagulants, including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban, have now been approved or are currently in late-stage clinical development in AF. These newer agents may provide a breakthrough in the optimal management of stroke risk. PMID:22355190

  5. New Oral Anticoagulants vs Vitamin K Antagonists: Benefits for Health-Related Quality of Life in Patients with Atrial Fibrillation

    PubMed Central

    Alegret, Josep M.; Viñolas, Xavier; Arias, Miguel A.; Martínez-Rubio, Antoni; Rebollo, Pablo; Ràfols, Carles; Martínez-Sande, José L.

    2014-01-01

    New oral anticoagulants (NOAC) have demonstrated their efficacy as an alternative to vitamin K antagonists (VKA) in the prophylaxis of cardioembolic events in patients with atrial fibrillation (AF). However, evidence on the benefits of NOAC in health-related quality of life (HRQoL) is lacking.We evaluated changes in HRQoL related to oral anticoagulation therapy employing a specific questionnaire in a cohort of 416 patients with AF undergoing electrical cardioversion. In terms of HRQoL, we observed a progressive adaptation to treatment with VKA; satisfaction with NOAC remained constant. Older age, higher left ventricular ejection fraction and NOAC were associated with better HRQoL. PMID:24843316

  6. A clinician’s perspective: novel oral anticoagulants to reduce the risk of stroke in nonvalvular atrial fibrillation – full speed ahead or proceed with caution?

    PubMed Central

    Yang, Eugene

    2014-01-01

    Over the past few years, three novel oral anticoagulants, dabigatran, rivaroxaban, and apixaban, have been approved in the USA and Europe to reduce the risk of stroke or systemic embolism in patients with nonvalvular atrial fibrillation, and the results of a Phase III trial for a fourth novel oral anticoagulant, edoxaban, have recently been published. The aim of this review is to examine this indication from a clinician’s perspective, highlighting efficacy and safety results from the major trials with these novel oral agents. Clinical issues regarding bleeding, monitoring, and reversal are discussed, along with requirements to consider when interrupting treatment with a novel oral anticoagulant for the purpose of transitioning to another anticoagulant and prior to cardioversion, ablation, percutaneous coronary intervention, or emergency surgery. The cost-effectiveness of each of the approved novel oral anticoagulants is reviewed, and the author provides recommendations for selecting appropriate patients for these agents. PMID:25187724

  7. 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 CHA2DS2-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 CHA2DS2-VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA2DS2-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 CHA2DS2-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-led intervention re

  8. Haemorrhagic Transformation after Ischaemic Stroke in Patients Taking Non-vitamin K Antagonist Oral Anticoagulants

    PubMed Central

    Purrucker, Jan C.; Haas, Kirsten; Wolf, Marcel; Rizos, Timolaos; Khan, Shujah; Kraft, Peter; Poli, Sven; Dziewas, Rainer; Meyne, Johannes; Palm, Frederick; Jander, Sebastian; Möhlenbruch, Markus; Heuschmann, Peter U.; Veltkamp, Roland

    2017-01-01

    Background and Purpose To evaluate the frequency and outcome of haemorrhagic transformation (HT) after ischaemic stroke in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). Methods Patients with stroke on treatment with a NOAC were prospectively enrolled in this multicentre observational study between February 2012 and 2015. Brain imaging at admission and follow-up imaging until day 7 were reviewed for HT. Functional outcome was assessed by the modified Rankin scale (mRS) before the index event, at discharge, and at 3-months. Results 231 patients without recanalisation therapy (no-RT), and 32 patients with RT were eligible for analysis. Any HT was present at admission in 9/231 no-RT patients (3.9%, 95% CI 2.0 to 7.3) and in none of the patients with RT. In patients with follow-up imaging (no-RT, n=129, and RT, n=32), HT was present in 14.0% (no-RT; 95% CI, 8.9 to 21.1), and 40.6% (RT, 95% CI, 25.5 to 57.8), respectively. After adjustment for stroke severity, this difference between the no-RT and RT groups became non-significant. Symptomatic ICH was observed in 1 patient per group. HT was not associated with unfavourable outcome (mRS 3-6) at 3-months in multivariable analysis. Resumption of OAC after stroke was delayed in patients with HT compared to those without (15 d [IQR, 5–26] vs. 1 d [0–4], P<0.001). Conclusions The frequency and severity of HT after stroke on NOAC appears similar to previous reports for vitamin K antagonists and no anticoagulation. Whether asymptomatic HT should delay resumption of preventive anticoagulation requires further investigation. PMID:28178406

  9. 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.

  10. Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data.

    PubMed

    Heneghan, Carl; Ward, Alison; Perera, Rafael; Bankhead, Clare; Fuller, Alice; Stevens, Richard; Bradford, Kairen; Tyndel, Sally; Alonso-Coello, Pablo; Ansell, Jack; Beyth, Rebecca; Bernardo, Artur; Christensen, Thomas Decker; Cromheecke, M E; Edson, Robert G; Fitzmaurice, David; Gadisseur, Alain P A; Garcia-Alamino, Josep M; Gardiner, Chris; Hasenkam, J Michael; Jacobson, Alan; Kaatz, Scott; Kamali, Farhad; Khan, Tayyaba Irfan; Knight, Eve; Körtke, Heinrich; Levi, Marcel; Matchar, David; Menéndez-Jándula, Bárbara; Rakovac, Ivo; Schaefer, Christian; Siebenhofer, Andrea; Souto, Juan Carlos; Sunderji, Rubina; Gin, Kenneth; Shalansky, Karen; Völler, Heinz; Wagner, Otto; Zittermann, Armin

    2012-01-28

    Uptake of self-testing and self-management of oral anticoagulation [corrected] has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism. We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat. Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12,800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0·51; 95% CI 0·31-0·85) but not for major haemorrhagic events (0·88, 0·74-1·06) or death (0·82, 0·62-1·09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0·33, 95% CI 0·17-0·66), as did participants with mechanical heart valve (0·52, 0·35-0·77). Analysis of major outcomes in the very elderly (age ≥85 years, n=99) showed no significant adverse effects of the intervention for all outcomes. Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages

  11. Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management

    PubMed Central

    Cheung, Ka-Shing; Leung, Wai K

    2017-01-01

    Novel oral anticoagulants (NOACs), which include direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding (GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran (150 mg b.i.d), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GIB compared with warfarin. Other risk factors of NOAC-related GIB include concomitant use of ulcerogenic agents, older age, renal impairment, Helicobacter pylori infection and a past history of GIB. Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs and in patients with renal impairment, correction of modifiable risk factors, and prescription of gastroprotective agents. Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment. In severe bleeding, additional measures include administration of activated charcoal, use of specific reversal agents such as idarucizumab for dabigatran and andexanent alfa for factor Xa inhibitors, and urgent endoscopic management. PMID:28373761

  12. Venous thromboembolism in the elderly: efficacy and safety of non-VKA oral anticoagulants

    PubMed Central

    2014-01-01

    Increasing age and renal impairment are risk factors for venous thrombosis but also for anticoagulant-induced bleeding. In large-scale phase III trials, non-VKA oral anticoagulants (NOACs) were at least as effective and safe for the treatment of acute venous thromboembolism as warfarin. Here, we review the efficacy and safety of dabigatran, rivaroxaban, apixaban and edoxaban in the subgroups of elderly patients (≥75 years) and patients with impaired renal function (creatinine clearance ≤50 ml/min). In all phase III trials, the efficacy of NOACs in the prevention of recurrent VTE was conserved both in the elderly subgroup and in the subgroup with impaired renal function. In a meta-analysis of the pooled results, NOACs reduced VTE recurrence compared with warfarin in elderly patients. In elderly patients and patients with impaired renal function, the safety of NOACs was in line with the results of the overall study. NOACs may offer an effective, safer and more convenient alternative for VKAs also in the elderly. However, the efficacy/safety profile of NOACs in the aged population needs to be confirmed in real-life. PMID:25650285

  13. Oral Anticoagulant Therapy in Patients Receiving Haemodialysis: Is It Time to Abandon It?

    PubMed Central

    Brodowska-Kania, Dorota; Niemczyk, Stanisław

    2013-01-01

    Oral anticoagulant (OAC) therapy in haemodialysis patients causes a great deal of controversy. This is because a number of pro- and anticoagulant factors play an important role in end-stage renal failure due to the nature of the disease itself. In these conditions, the pharmacokinetic and pharmacodynamic properties of the OACs used change as well. In the case of the treatment of venous thromboembolism, the only remaining option is OAC treatment according to regimens used for the general population. Prevention of HD vascular access thrombosis with the use of OACs is not very effective and can be dangerous. However, OAC treatment in patients with atrial fibrillation in dialysis population may be associated with an increase in the incidence of stroke and mortality. Doubts should be dispelled by prospective, randomised studies; at the moment, there is no justification for routine use of OACs in the above-mentioned indications. In selected cases of OAC therapy in this group of patients, it is absolutely necessary to control and monitor the applied treatment thoroughly. Indications for the use of OACs in patients with end-stage renal disease, including haemodialysis patients, should be currently limited. PMID:24379737

  14. Low-intensity international normalized ratio (INR) oral anticoagulant therapy in Chinese patients with mechanical heart valve prostheses.

    PubMed

    Haibo, Zhang; Jinzhong, Li; Yan, Liu; Xu, Meng

    2012-01-01

    The purpose of this study was to define the optimal international normalized ratio (INR) intensity of oral anticoagulant therapy in Chinese patients with valve replacement surgery. We studied 1,658 patients who underwent mechanical valve replacement in Beijing Anzhen Hospital; the focus of the study was on correlation between intensity of anticoagulant therapy and thromboembolism/hemorrhage complications. We further followed up 1,508 patients for 46 ± 16 months (range 1-61 months). Average INR was 2.13 ± 0.56, and warfarin dose was 3.09 ± 0.85 mg/day. The incidence rate of anticoagulation-related thromboembolism was 1.17 per 100 patient-years (%/pt-y), and the incidence rate of anticoagulation-related hemorrhage was 2.02%/pt-y. The incidence rate of total complications (i.e., combined thromboembolism and hemorrhages) was 3.24%/pt-y. The rate of total complications in group on INR 1.3-2.3 (aortic valve replacement: 1.3-1.8; mitral valve replacement and double valve replacement: 1.8-2.3) was the lowest among all anticoagulant therapy regimens followed. In conclusion, the relatively low anticoagulant strategy presented above efficiently prevents thrombosis and hemorrhage complications.

  15. Efficacy and safety of novel oral anticoagulants in patients with cervical artery dissections.

    PubMed

    Caprio, Fan Z; Bernstein, Richard A; Alberts, Mark J; Curran, Yvonne; Bergman, Deborah; Korutz, Alexander W; Syed, Faiz; Ansari, Sameer A; Prabhakaran, Shyam

    2014-01-01

    American and European guidelines support antiplatelet agents and anticoagulants as reasonable treatments of cervical artery dissection (CAD), though randomized clinical trials are lacking. The utility of novel oral anticoagulants (NOAC), effective in reducing embolic stroke risk in non-valvular atrial fibrillation (NVAF), has not been reported in patients with CAD. We report on the use, safety, and efficacy of NOACs in the treatment of CAD. We retrospectively identified patients diagnosed with CAD at a single academic center between January 2010 and August 2013. Patients were categorized by their antithrombotic treatment at hospital discharge with a NOAC (dabigatran, rivaroxaban, or apixaban), traditional anticoagulant (AC: warfarin or treatment dose low-molecular weight heparin), or antiplatelet agent (AP: aspirin, clopidogrel, or aspirin/extended-release dypyridamole). Using appropriate tests, we compared the baseline medical history, presenting clinical symptoms and initial radiographic characteristics among patients in the 3 treatment groups. We then evaluated for the following outcomes: recurrent stroke, vessel recanalization, and bleeding complications. p values <0.05 were considered significant. Of the 149 included patients (mean age 43.4 years; 63.1% female; 70.5% vertebral artery CAD), 39 (26.2%), 70 (47.0%), and 40 (26.8%) were treated with a NOAC, AC, and AP, respectively. More patients with severe stenosis or occlusion were treated with NOAC than with AC or AP (61.8 vs. 60.0 vs. 22.5%, p = 0.002). Other baseline clinical and radiographic findings, including the presence of acute infarction and hematoma, did not differ between the 3 treatment groups. One hundred and thirty-five (90.6%) patients had clinical follow-up (median time 7.5 months) and 125 (83.9%) had radiographic follow-up (median time 5 months) information. There were 2 recurrent strokes in the NOAC group and 1 in each of the AC and AP groups (p = 0.822). There were more major hemorrhagic

  16. Dabigatran: A new oral anticoagulant. Guidelines to follow in oral surgery procedures. A systematic review of the literature.

    PubMed

    Muñoz-Corcuera, M; Ramírez-Martínez-Acitores, L; López-Pintor, R-M; Casañas-Gil, E; Hernández-Vallejo, G

    2016-11-01

    Dabigatran is a newly commercialized drug that is replacing other anticoagulants in the prevention of venous thromboembolism, stroke and systemic arterial valve embolism. It acts directly on thrombin presenting in a dynamic and predictable way, which does not require monitoring these patients. Therefore, we consider the need to assess whether their use increases the risk of bleeding involved before any dental treatment. We performed a systematic review with a bibliographic search in PubMed/Medline along with the Cochrane Library. We excluded articles dealing with all anticoagulants other than dabigatran, and works about surgical treatments in anatomical locations other than the oral cavity. We included a total of 13 papers of which 1 was a randomized clinical trial, 9 narrative literature reviews, 1 case series, 2 clinical cases and 1 expert opinion. Because we did not obtain any properly designed clinical trials, we were unable to conduct a meta-analysis. Currently, there is no consensus on the procedure to be followed in patients taking dabigatran. However, all authors agree to treat each case individually in accordance to the risk of embolism, postoperative bleeding and renal function. Also, it is necessary to perform minimally invasive interventions, and take the appropriate local anti-hemolytic measures.

  17. New options for anticoagulation following total hip arthroplasty and total knee arthroplasty: new oral agents on the horizon.

    PubMed

    Amin, Alpesh

    2012-08-01

    Patients undergoing surgery for total hip arthroplasty (THA) or total knee arthroplasty (TKA) are at particularly high risk for developing venous thromboembolism (VTE). Despite the existence of effective therapies for VTE prevention, THA/TKA patients remain at risk for developing thrombi. Furthermore, the incidence of VTE is predicted to increase as an aging and increasingly obese population experiences joint damage necessitating THA and TKA. Current guidelines recommend the use of a wide range of antithrombotic agents in patients undergoing THA and TKA. These agents include vitamin K antagonists, low-molecular-weight heparins, fondaparinux, and the new oral anticoagulants. However, adherence to guidelines in clinical practice is disappointingly low. The limitations of traditional anticoagulants present management challenges following orthopedic surgery. Vitamin K antagonists present a number of drawbacks, including a narrow therapeutic window and unpredictable pharmacokinetics and pharmacodynamics. The subcutaneous route of administration of fondaparinux and low-molecular-weight heparins may make them unacceptable to patients in the outpatient setting. The introduction of a new generation of anticoagulants promises to address many of the drawbacks associated with the traditional agents. Clinical studies have shown the new oral anticoagulants to be as effective as traditional thromboprophylaxis, with good tolerability profiles. Clinical knowledge of these new agents will be essential to ensure that patients receive appropriate care following orthopedic surgery. This article will discuss the prevention of VTE after THA and TKA based on current evidence-based practice guidelines, the limitations of conventional anticoagulants, and the promise of new therapeutics.

  18. Unanswered questions and research priorities to optimise stroke prevention in atrial fibrillation with the new oral anticoagulants.

    PubMed

    Hankey, Graeme J

    2014-05-05

    This review article discusses the following, as yet unanswered, questions and research priorities to optimise patient management and stroke prevention in atrial fibrillation with the new direct oral anticoagulants (NOACs): 1. In patients prescribed a NOAC, can the anticoagulant effects or plasma concentrations of the NOACs be measured rapidly and reliably and, if so, can "cut-off points" between which anticoagulation is therapeutic (i.e. the "therapeutic range") be defined? 2. In patients who are taking a NOAC and bleeding (e.g. intracerebral haemorrhage), can the anticoagulant effects of the direct NOACs be reversed rapidly and, if so, can NOAC-associated bleeding and complications be minimised and patient outcome improved? 3. In patients taking a NOAC who experience an acute ischaemic stroke, to what degree of anticoagulation or plasma concentration of NOAC, if any, can thrombolysis be administered safely and effectively? 4. In patients with a recent cardioembolic ischaemic stroke, what is the optimal time to start (or re-start) anticoagulation with a NOAC (or warfarin)? 5. In anticoagulated patients who experience an intracranial haemorrhage, can anticoagulation with a NOAC be re-started safely and effectively, and if so when? 6. Are the NOACs effective and safe in multimorbid geriatric people (who commonly have atrial fibrillation and are at high risk of stroke but also bleeding)? 7. Can dose-adjusted NOAC therapy augment the established safety and efficacy of fixed-dose unmonitored NOAC therapy? 8. Is there a dose or dosing regimen for each NOAC that is as effective and safe as adjusted-dose warfarin for patients with atrial fibrillation who have mechanical prosthetic heart valves? 9. What is the long-term safety of the NOACs?

  19. Periprocedural management of anticoagulation in patients taking novel oral anticoagulants: Review of the literature and recommendations for specific populations and procedures.

    PubMed

    Mar, Philip L; Familtsev, Dmitry; Ezekowitz, Michael D; Lakkireddy, Dhanunjaya; Gopinathannair, Rakesh

    2016-01-01

    An increasing number of individuals are on novel oral anticoagulants (NOAC) for anticoagulation instead of vitamin K antagonists (VKA) and roughly 10% of these individuals will require interruption of these agents for procedures annually. Recent evidence surrounding bridging as well as the FDA approval of a new NOAC call for a comprehensive review and update regarding periprocedural NOAC management. The periprocedural management of NOACs involves striking a balance between the risks of bleeding and thromboembolism associated with interruption, bridging, and reinitiation of anticoagulation. NOACs have a distinct pharmacokinetic advantage in this setting with their quick onset and elimination from the body. Procedures at low risk for bleeding do not require interruption and can be scheduled at the start of the next dosing interval. Procedures at moderate-high risk of bleeding require interruption of NOAC for 5 half lives prior to the procedure to allow for adequate elimination of the drug. In light of new evidence highlighting the risks of bleeding, and given shorter "unprotected" times with NOAC interruption versus VKA, patients at low-moderate risk for thromboembolism should not be bridged when "unprotected" time is less than 96 h. For patients at high risk for thromboembolism, individual patient and surgical factors need to be considered before the decision to bridge is made. The benefit of bridging these patients who have a considerable risk of bleeding may not outweigh the benefits. Focused randomized studies on periprocedural management of NOACs are urgently needed.

  20. One-month versus six-month therapy with oral anticoagulants after symptomatic deep vein thrombosis.

    PubMed

    Holmgren, K; Andersson, G; Fagrell, B; Johnsson, H; Ljungberg, B; Nilsson, E; Wilhelmsson, S; Zetterquist, S

    1985-01-01

    The length of time for which deep vein thrombosis (DVT) should be treated with oral anticoagulants (OA) is controversial. In this study, 135 patients with symptomatic first period DVT (83% with proximal DVT) were randomly allocated to OA for one or six months. The diagnosis of initial and recurrent DVT was confirmed by phlebography or plethysmography and thermography, or by a combination of all these methods. Pulmonary emboli were confirmed by lung scans or at autopsy. The patients were followed for at least one year. One patient had to discontinue OA prematurely because of haemorrhage. Seventeen patients left the project for other reasons, ten during and seven after therapy; in one of these DVT recurred. The recurrence rate during the first year was high (17% symptomatic recurrences) irrespective of whether OA had been given for one or six months.

  1. [Treatment safety of non-vitamin K oral anticoagulants in patients with atrial fibrillation].

    PubMed

    Hohnloser, S H

    2016-02-01

    Non-vitamin K oral anticoagulants (NOAC) have now become established for stroke prevention in atrial fibrillation. The efficacy is at least as good if not better than that of vitamin K antagonists (VKA). The risk for major bleeding is less for NOAC than for VKA, with a particular superiority concerning the avoidance of intracerebral hemorrhage. The outcome after major bleeding is more favorable in patients receiving NOAC compared to those treated with VKA. Specific reversal agents for NOAC are currently being tested which neutralize the effects of NOAC within minutes and the clinical introduction of the first one for the thrombin inhibitor dabigatran is imminent. Such specific antidotes will further improve the safety profile of NAOC.

  2. Hypercoagulable states: an algorithmic approach to laboratory testing and update on monitoring of direct oral anticoagulants

    PubMed Central

    Nakashima, Megan O.

    2014-01-01

    Hypercoagulability can result from a variety of inherited and, more commonly, acquired conditions. Testing for the underlying cause of thrombosis in a patient is complicated both by the number and variety of clinical conditions that can cause hypercoagulability as well as the many potential assay interferences. Using an algorithmic approach to hypercoagulability testing provides the ability to tailor assay selection to the clinical scenario. It also reduces the number of unnecessary tests performed, saving cost and time, and preventing potential false results. New oral anticoagulants are powerful tools for managing hypercoagulable patients; however, their use introduces new challenges in terms of test interpretation and therapeutic monitoring. The coagulation laboratory plays an essential role in testing for and treating hypercoagulable states. The input of laboratory professionals is necessary to guide appropriate testing and synthesize interpretation of results. PMID:25025009

  3. Net Clinical Benefit of Oral Anticoagulants: A Multiple Criteria Decision Analysis

    PubMed Central

    Yang, Yea-Huei Kao; Lu, Christine Y.

    2015-01-01

    Background This study quantitatively evaluated the comparative efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, and apizaban) and warfarin for treatment of nonvalvular atrial fibrillation. We also compared these agents under different scenarios, including population with high risk of stroke and for primary vs. secondary stroke prevention. Methods We used multiple criteria decision analysis (MCDA) to assess the benefit-risk of these medications. Our MCDA models contained criteria for benefits (prevention of ischemic stroke and systemic embolism) and risks (intracranial and extracranial bleeding). We calculated a performance score for each drug accounting for benefits and risks in comparison to treatment alternatives. Results Overall, new agents had higher performance scores than warfarin; in order of performance scores: dabigatran 150 mg (0.529), rivaroxaban (0.462), apixaban (0.426), and warfarin (0.191). For patients at a higher risk of stroke (CHADS2 score≥3), apixaban had the highest performance score (0.686); performance scores for other drugs were 0.462 for dabigatran 150 mg, 0.392 for dabigatran 110 mg, 0.271 for rivaroxaban, and 0.116 for warfarin. Dabigatran 150 mg had the highest performance score for primary stroke prevention, while dabigatran 110 mg had the highest performance score for secondary prevention. Conclusions Our results suggest that new oral anticoagulants might be preferred over warfarin. Selecting appropriate medicines according to the patient’s condition based on information from an integrated benefit-risk assessment of treatment options is crucial to achieve optimal clinical outcomes. PMID:25897861

  4. How prepared are pharmacists to support atrial fibrillation patients in adhering to newly prescribed oral anticoagulants?

    PubMed

    Hamedi, Nadya; da Costa, Filipa Alves; Horne, Robert; Levitan, Michael; Begley, Amanda; Antoniou, Sotiris

    2017-09-05

    Background The New Medicines Service (NMS) was implemented in the United Kingdom in 2011 and first evaluated in 2014, showing 10% increase on adherence. Objective To assess community pharmacists' current practice, knowledge and confidence in supporting patients' adherence as part of the NMS for patients on Oral Anti-Coagulants (OACs) for stroke prevention in Atrial Fibrillation. Setting Community pharmacists in London. Method An online cross-sectional survey was sent to pharmacists from their Local Pharmaceutical Committees and advertised by the Royal Pharmaceutical Society. Analysis was undertaken in SPSs v23 considering a confidence level of 95%. Main outcome measures pharmacists reported confidence of providing the NMS on OACs; training needs and skills for supporting adherence. Results A total of 257 valid responses were analysed (6.8% response rate; {Cronbach's α = 0.676-0.892}). Data indicates that over a 2-month period, 25% of pharmacists had completed ≥6 NMS consultations for all OACs, of which 11% for new oral anticoagulants (NOACs). The key priorities in counselling items during the NMS consultation were to discuss actions to take when bleeding occurs, followed by supporting adherence. Pharmacists were more confident in their knowledge, skills and access to resources for Vitamin-K Antagonists (VKAs) than for NOACs (p < 0.005). Results also highlight pharmacists' unfamiliarity with alert cards, lower for NOACs than VKAs (p < 0.001), albeit perceived as critically important. Half the sample mentioned to use the British National Formulary as information resource. Conclusion Results suggest the provision of NMS for NOACs is low. Supporting pharmacists with tailored education and adherence support might foster dissemination.

  5. [Effectiveness of anticoagulant oral treatment in patients with thrombus in left ventricle after acute myocardial infarction].

    PubMed

    Carrillo, A M; Valdespino, A; Solorio, S; Badui, E; Enciso, R; Lepe, L; Lara, A; Ocampo, S; Alonso, R; Romero, M A

    1997-01-01

    Left ventricular mural thrombi (LVMT) is a complication of acute myocardial infarction (AMI), that may produce peripheral embolism which could be fatal. In order to establish an adequate time of oral anticoagulant (OA) therapy, we undertook a prospective study that included 45 patients with AMI and left ventricular thrombi detected by echocardiographic study, in the first 5 to 10 days postinfarction, the study was repeated, in 3 and 6 months. Treatment with oral anticoagulant was initiated at the point of the detection of thrombi maintaining an INR of 1.5 to 2. Thirty nine patients (79%) were males and 6 (11%) were females, with an age of 29 to 85 years and a range of 62 +/- 11 years. Forty four patients (98%) presented anterior wall infarction and 1 (2%) posteroinferior infarction. In patients with anterior infarction, in 38 (85%) the thrombi was located at the apical wall (p < 0.05), 5 (11%) in the septal wall and other (2%) in anterior and apical walls. The patient with the posteroinferior infarction presented extension to the right ventricle, where the thrombus was located (2%). The contractility alterations related with thrombi were diskinesia, followed by hipokinesia and finally akinesia. The ejection fraction had not relationship with thrombi formation. LVMT dissolved in 32 patients (71%) at 3 months (p < 0.05), in 8 (18%) in 6 months and in 5 (11%) it was maintained for more than 6 months. None of the patients presented complications of OA. We conclude that the LVMT are more frequent in anterior infarctions, essentially in those that present diskinesia. The majority of LVMT are resolved in 6 months with OA therapy.

  6. Decision making for oral anticoagulants in atrial fibrillation: the ATA-AF study.

    PubMed

    Gussoni, Gualberto; Di Pasquale, Giuseppe; Vescovo, Giorgio; Gulizia, Michele; Mathieu, Giovanni; Scherillo, Marino; Panuccio, Domenico; Lucci, Donata; Nozzoli, Carlo; Fabbri, Gianna; Colombo, Fabrizio; Riva, Letizia; Baldo, Concetta I; Maggioni, Aldo P; Mazzone, Antonino

    2013-06-01

    Oral anticoagulants offer the best long-term protection against ischemic stroke in patients with atrial fibrillation (AF). However, vitamin K antagonists (VKA) are cumbersome to use and their prescription is far from guidelines recommendations. We report the results of a large survey on the attitudes of prescription of VKA in patients with AF. 7148 patients were enrolled by 196 Internal Medicine (MED) and 164 Cardiology (CARD) centers, and VKA specifically analyzed. Thrombotic and hemorrhagic risks were evaluated by means of CHADS2 and CHA2DS2VASc scores, and a study-specific bleeding score (modified HAS-BLED). 63.9% of non-valvular patients had a CHADS2 score≥2 (MED: 75.3%-CARD: 53.1%), and 28.4% a bleeding score≥3 (41.9% MED-15.8% CARD). VKA were prescribed in 55.5% of non-valvular patients (46.3% MED and 64.2% CARD), in 81% of high-risk valvular patients and in 58.8% of the overall study population. Among patients at high risk of bleeding (score≥3), VKA were prescribed in 26.9% of subjects, while, in the subgroup at high risk of thrombosis (CHADS2 Score<2), these were prescribed in 54.4%. Age≥75, paroxysmal AF, cognitive impairment, need for assistance, CHADS2<2 and bleeding score≥3 were independent predictors of non-use of VKA. Oral anticoagulants are more frequently used in CARD than in MED, plausibly due to greater complexity of MED patients. Stratification of thrombotic and hemorrhagic risk significantly drives the choice for VKA. However the fraction of patients in whom prescription or non-prescription is based on other individual characteristics is not negligible. Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  7. Antiplatelet versus oral anticoagulant therapy as antithrombotic prophylaxis after mitral valve repair.

    PubMed

    Paparella, Domenico; Di Mauro, Michele; Bitton Worms, Keren; Bolotin, Gil; Russo, Claudio; Trunfio, Salvatore; Scrofani, Roberto; Antona, Carlo; Actis Dato, Guglielmo; Casabona, Riccardo; Colli, Andrea; Gerosa, Gino; Renzulli, Attilio; Serraino, Filiberto; Scrascia, Giuseppe; Zaccaria, Salvatore; De Bonis, Michele; Taramasso, Maurizio; Delgado, Luis; Tritto, Francesco; Marmo, Joseph; Parolari, Alessandro; Myaseodova, Veronika; Villa, Emmanuel; Troise, Giovanni; Nicolini, Francesco; Gherli, Tiziano; Whitlock, Richard; Conte, Manuela; Barili, Fabio; Gelsomino, Sandro; Lorusso, Roberto; Sciatti, Edoardo; Marinelli, Daniele; Di Giammarco, Gabriele; Calafiore, Antonio Maria; Sheikh, Azmat; Alfonso, Juan Jaime; Glauber, Mattia; Miceli, Antonio

    2016-05-01

    To verify the rate of thromboembolic and hemorrhagic complications during the first 6 months after mitral valve repair and to assess whether the type of antithrombotic therapy influenced clinical outcome. Retrospective data were retrieved from 19 centers. Inclusion criteria were isolated mitral valve repair with ring implantation. Exclusion criteria were ongoing or past atrial fibrillation and any combined intraoperative surgical procedures. The study cohort consisted of 1882 patients (aged 58 ± 15 years; 36% women), and included 1517 treated with an oral anticoagulant (VKA group) and 365 with antiplatelet drugs (APLT group). Primary efficacy outcome was the incidence of arterial thromboembolic events within 6 months and primary safety outcome was the incidence of major bleeding within 6 months. Propensity matching was performed to obtain 2 comparable cohorts (858 vs 286). No differences were detected for arterial embolic complications in matched cohort (1.6% VKA vs 2.1% APLT; P = .50). Conversely, patients in the APLT group showed lower incidence of major bleeding complications (3.9% vs 0.7%; P = .01). Six-month mortality rate was significantly higher in the VKA group (2.7% vs 0.3%; P = .02). Multivariable analysis in the matched cohort found VKA as independent predictor of major bleeding complications and mortality at 6 months. Vitamin K antagonist therapy was not superior to antiplatelet therapy to prevent thromboembolic complications after mitral valve repair. Our data suggest that oral anticoagulation may carry a higher bleeding risk compared with antiplatelet therapy, although these results should be confirmed in an adequately powered randomized controlled trial. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. Stroke prevention in atrial fibrillation: established oral anticoagulants versus novel anticoagulants-translating clinical trial data into practice.

    PubMed

    Ezekowitz, Michael D; Spahr, Judy; Ghosh, Pradeepto; Corelli, Kathryn

    2014-09-01

    Anticoagulation for stroke prevention in atrial fibrillation (AF) is effective. Pivotal trials RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE-AF TIMI 48 tested novel agents against warfarin (W). In RE-LY, an open-label trial, dabigatran 150 mg BID (D150) was superior (35%) and 110 mg BID (D110) was noninferior to W. D150 reduced ischemic strokes by 25% and intracerebral bleeds by 74%, but increased major GI bleeds by 0.5 % per year. In ROCKET AF, a double-blind study, rivaroxaban 20 mg daily, downtitrated to 15 mg daily (if CrCl was <49) was noninferior for efficacy and safety, with an increase in GI bleeds. In ARISTOTLE, a double-blind study, apixaban 5 mg BID (downtitrated to 2.5 mg BID if two of the following were present: age, >80; weight, <60 kg; or serum creatinine, >1.5 mg) was superior for safety (31%), efficacy (21%), and all-cause mortality (11%). In ENGAGE-AF TIMI 48, edoxaban 60 mg once daily (30 mg once daily if CrCl 30-50 ml/min, weight <60 kg, or concomitant verapamil or quinidine) was noninferior to W for efficacy, but reduced major bleeding (20%). To translate clinical trials to practice, understanding the disease and each anticoagulant is essential. For all novel agents, rapid anticoagulation, absence of monitoring, and a short half-life differentiate them from W. Bleed rates were either noninferior or lower than for W, without an antidote. Patient compliance is critical. Knowledge of renal function is essential and maintaining patients on therapy is key.

  10. Preclinical safety evaluation of low molecular weight heparin-deoxycholate conjugates as an oral anticoagulant.

    PubMed

    Kim, Ji-young; Jeon, Ok-Cheol; Moon, Hyun Tae; Hwang, Seung Rim; Byun, Youngro

    2016-01-01

    The preclinical safety of a newly developed oral anticoagulant, the low molecular weight heparin-deoxycholate conjugate (OH09208), was evaluated by a comprehensive evaluating program in compliance with standard guidelines. The single dose oral toxicity study in rats receiving 2000 and 5000 mg kg(-1) of OH09208 did not reveal any mortality, unusual body weight changes or necropsy findings. The results of the 4-week oral toxicity study with a 4-week recovery program in rats receiving OH09208 in doses of 100, 300 and 1000 mg kg(-1) day(-1) did not reveal any mortality, or indicate any unusual clinical signs, or show any toxicokinetic relationships to the administration of OH09208. Although the increase in liver enzymes in one male dog treated with 300 mg kg(-1) day(-1) and one female dog treated with 1000 mg kg(-1) day(-1) could not be excluded from the effect of the test substance, no other toxicologically significant changes were observed in the 4-week oral toxicity study with a 4-week recovery in beagle dogs. Thus, while the no-observed-adverse-effect level value from the 4-week study in both male and female rats was 1000 mg kg(-1) day(-1), those from the 4-week study in male and female beagle dogs were 300 and 1000 mg kg(-1) day(-1), respectively. Furthermore, OH09208 did not induce anaphylactic reactions in guinea pigs, micronucleated bone marrow cells in male ICR mice, chromosomal aberration in Chinese hamster lung cell lines, bacterial reverse mutation, and any abnormalities in hERG current assay, mouse central nervous system and dog cardiovascular studies. Overall, there were no unexpected toxicities in this preclinical study that might have precluded the safe administration of OH09208 to humans.

  11. 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

  12. 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.

  13. 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

  14. Oral anticoagulation with vitamin K inhibitors and determinants of successful self-management in primary care.

    PubMed

    Tamayo Aguirre, E; Galo-Anza, A; Dorronsoro-Barandiaran, O; Del Burgo, E Uranga-Saez; Ostiza Irigoyen, A; Garcia-Carro, A; Lopez-Fernandez, I; Colera, N; Saez-Garbayo, P; Tamayo-Uria, I

    2016-09-13

    Self-management may be an option to monitor oral anticoagulant therapy in health systems, but before recommending it, we need to assess patients' ability to take on this task. The purpose of the study was to describe patients' ability to self-manage and associated factors. This was a 3-year prospective quasi-experimental study with a control group. Overall, 333 patients on anticoagulant therapy from seven primary care health centres of the Basque Health Service were included in the intervention group and followed up for 6 months after the intervention, assessing their ability to self-test and self-manage. The intervention consisted of a patient training programme, providing detailed information on their condition and its treatment, and practical training in how to use a portable blood coagulation monitor and adjust their anticoagulant dose. Comparisons were made with a control group (333 patients receiving OAT under usual care from the same seven health centres). Outcome variables were ability to self-manage, quality of the outcome (in terms of time in therapeutic range), and quality of life in the intervention group, and general patient characteristics (age and sex), clinical variables (reason for OAT, INR range), and quality of the outcome (in terms of percentage of INR measurements in range and complications) in both groups. Overall, 26.13 % of patients invited to participate in the intervention agreed. Of these, 99 % successfully learned to self-manage their OAT. Just 4.2 % did not complete the follow-up, in all cases for reasons unrelated to self-management, and 4.5 % required additional learning support. Outcomes were better than under usual care in terms of percentage of INR measurements in range (12 %), rate of complications (4 %) and quality of life (9.2 %). Patients were only followed-up period for 6 months and the study was conducted in a single health organization. Though patients eligible to participate were selected randomly, they were not randomly

  15. 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

  16. Influence of decision aids on oral anticoagulant prescribing among physicians: a randomised trial.

    PubMed

    Baicus, Cristian; Delcea, Caterina; Dima, Alina; Oprisan, Emilia; Jurcut, Ciprian; Dan, Gheorghe Andrei

    2017-09-01

    Oral anticoagulants (OAC) are underused in treatment of atrial fibrillation (AF), with differences in patient and physician preferences. For risk communication, the graphic showing risks on treatment contains all the information, therefore, the graphic showing risks without treatment may not be necessary. Here, our objective was to assess whether decision aids require information of risks without treatment and specifically whether presentation of 5-year stroke risk in patients with AF increases use of OACs compared with presentation of 1-year risk and whether decisions on treatment are different when physicians decide their own treatment vs. that of the patient. Randomised controlled trial with 2(3) factorial design, performed at 12 university hospitals, one internal medicine course and one national medical conference. Of 968 physicians who participated, 83·3% prescribed anticoagulation therapy. Treatment decisions were not influenced by the number of graphics or by the time frame of risk estimation, with risk differences of 0·5% (95% confidence interval, -4·0% to 5·4%) and 3·4% (-1·3% to 8·1%). However, physician-to-patient prescription rates were 5·4% (0·2-10·6%) more frequent after seeing the 5-year risk graphic. Physician-to-self intentions to prescribe occurred less frequently, with risk difference of 15·4% (10·8-20%). Physicians considered the baseline risk and the absolute risk reduction only when prescribing to patients but not to themselves. Risks could be communicated using decision aids with only one graphic. Showing the risk of stroke at 5 years could increase the prescription of OACs to patients with AF. Faced with the same risk of stroke, physicians prescribed less to themselves than to patients. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  17. 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.

  18. Characteristics of Symptomatic Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulant Therapy

    PubMed Central

    2015-01-01

    Objectives The first non-vitamin K antagonist oral anticoagulant (NOAC) introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH) occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH. Methods We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014. Results ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years). Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset. Conclusion Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg) and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy. PMID:26171862

  19. "Zeus" a new oral anticoagulant therapy dosing algorithm: a cohort study.

    PubMed

    Cafolla, A; Melizzi, R; Baldacci, E; Pignoloni, P; Dragoni, F; Campanelli, M; Caraccini, R; Foà, R

    2011-10-01

    The demand for oral anticoagulant therapy (OAT) has constantly increased during the last ten years with an extended use of computer assistance. Many mathematical algorithms have been projected to suggest doses and time to next visit for patients on OAT. We designed a new algorithm: "Zeus". A "before-after" study was planned to compare the efficacy and safety of this algorithm dosing OAT with manual dosage decided by the same expert physicians according to the target of International Normalized Ratio (INR). The study analysed data of 1876 patients managed with each of the two modalities for eight months, with an interval of two years between them. The aim was to verify the increased quality of therapy by time spent in INR target and efficiency and safety of Zeus algorithm. Time in therapeutic range (TTR) was significantly (p < 0.0001) higher during the algorithm dosing period in comparison with the TTR during manual management period (62.3% vs 50.3%). The number of PT/INR tests above 5 was significantly (p < 0.001) reduced by algorithm suggested prescriptions in comparison with manual those (254 vs 537 times). The anticoagulant drug amount prescribed according to the algorithm suggestions was significantly (p < 0.0001) lower than that of the manual method. The number of clinical events observed in patients during the algorithm management time was significantly (p < 0.05) lower than that in those managed with the manual dosage. This study confirms the clinical utility of the computer-assisted OAT and shows the efficacy and safety of the Zeus algorithm.

  20. Reversal agents for oral antiplatelet and anticoagulant treatment during bleeding events: current strategies.

    PubMed

    Raimondi, Peter; Hylek, Elaine M; Aronis, Konstantinos N

    2016-12-05

    There is an increasing prevalence of cardiovascular diseases that warrant antithrombotic therapy. Antithrombotic therapy includes antiplatelet agents and anticoagulation therapy with vitamin K antagonists (VKAs) or non-Vitamin K oral anticoagulants (NOACs). Antithrombotic therapy is associated with increased rates of bleeding. In this review we summarize the evidence and provide strategies for the management of severe bleeding in the setting of antithrombotic therapy. There is limited data on the management of bleeding in the setting of antiplatelet therapy. We recommend discontinuation of the antiplatelet, as well as administration of platelet transfusions and desmopressin only in the setting of life-threatening bleeding. For patients presenting with severe bleeding in the setting of VKAs, we recommend discontinuation of VKA and prompt administration of 10 mg intravenous vitamin K plus 50 units/kg 4-factor prothrombin complex concentrate (PCC). If 4-factor PCC is not available 3-factor PCC or fresh frozen plasma (FFP) can be used, but these are inferior to 4-factor PCC. For patients presenting with severe bleeding while on dabigatran, we recommend discontinuation of dabigatran and intravenous administration of 5g idarucizumab. There is currently no available reversal agent for factor Xa inhibitors. Andexanet alpha is a factor Xa-specific inhibitor that is currently undergoing FDA review. Until andexanet alpha becomes available we recommend discontinuation of the factor Xa inhibitor and administration of 50 units/kg 4-factor PCC. The decision to discontinue and/or reverse antithrombotic therapy should be made on a case-by-case basis and the competing risk from discontinuation and/or reversal of antithrombotic therapy should be taken in consideration.

  1. Non-vitamin k antagonist oral anticoagulants do not increase cerebral microbleeds.

    PubMed

    Saito, Tsukasa; Kawamura, Yuichiro; Sato, Nobuyuki; Kano, Kohei; Takahashi, Kae; Asanome, Asuka; Sawada, Jun; Katayama, Takayuki; Hasebe, Naoyuki

    2015-06-01

    Atrial fibrillation (AF) is a cardiac arrhythmia that frequently induces ischemic strokes. Nowadays, non-vitamin K antagonist oral anticoagulants (NOACs) have come into widespread use for cardiogenic embolism prevention in place of warfarin. Recently, cerebral microbleeds (CMBs) have been noticed for their potential implication in cerebral small vessel disease. We hypothesized that NOACs do not have an unfavorable influence over cerebral small vessels and investigated whether NOACs increase CMBs in AF patients in a prospective manner. We performed baseline magnetic resonance imaging (MRI) examinations on the 69 enrolled AF patients and re-examined second round of MRI 1 year later. The enrolled patients continued the same anticoagulation therapy during the meantime. CMBs did not develop in the 23 patients with NOACs for 1 year. Nine patients with antiplatelets also did not develop CMBs. On the other hand, 3 of 21 patients continued on warfarin and 3 of 9 with warfarin and antiplatelets had CMBs. When divided into 2 groups according to whether the CMBs developed, significant differences in the incidence of using NOACs were observed between the 2 groups (P = .02). A multivariate regression analysis showed that warfarin was independently related to the new development of CMBs (hazard ratio, 10.75; 95% confidence interval, 1.22-94.99; P = .03). This is the first report to clarify that NOACs do not increase CMBs in AF patients longitudinally in 1 year. Further consideration will be continued with a much longer follow-up in large samples. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  2. Pregnancy outcome in patients exposed to direct oral anticoagulants - and the challenge of event reporting.

    PubMed

    Beyer-Westendorf, Jan; Michalski, Franziska; Tittl, Luise; Middeldorp, Saskia; Cohen, Hannah; Abdul Kadir, Rezan; Arachchillage, Deepa Jayakody; Arya, Roopen; Ay, Cihan; Marten, Sandra

    2016-09-27

    Today, direct oral anticoagulants (DOAC) are widely used alternatives to Vitamin-K antagonists (VKA). Women of reproductive age may become pregnant during anticoagulation and, while VKA carry an embryotoxic potential, the risk of DOAC embryopathy is unknown. As a result, some patients elect to terminate pregnancy for fear of DOAC embryotoxicity. To assess the risk of DOAC embryopathy, we reviewed cases of DOAC exposure in pregnancy collected from physicians, literature and pharmacovigilance systems of drug authorities and manufacturers. A total of 357 reports including duplicates were available from which 233 unique cases could be identified. Information on pregnancy outcome was available in only 137/233 cases (58.8 %): 67 live births (48.9 %); 31 miscarriages (22.6 %); 39 elective pregnancy terminations (28.5 %). In 93 cases (39.9 %) no outcome data were available (including 3 cases of ongoing pregnancy). Of the 137 pregnancies with reported outcomes, seven showed abnormalities (5.1 %) of which three (2.2 %) could potentially be interpreted as embryopathy: live birth with facial dysmorphism; miscarriage in week 10 with limb abnormality; elective pregnancy termination due to a foetal cardiac defect in a woman who had to terminate a previous pregnancy due to Fallot tetralogy. Within its limitations (small numbers, incomplete outcome data) our results do not indicate that DOAC exposure in pregnancy carries a high risk of embryopathy or that DOAC exposure per se should be used to direct patient counselling towards pregnancy termination. Pregnancy outcome data are inconsistently captured in pharmacovigilance databases indicating the strong need for a more robust system of reporting.

  3. Managing venous thromboembolism in Asia: winds of change in the era of new oral anticoagulants.

    PubMed

    Cohen, Alexander; Chiu, Kuan Ming; Park, Kihyuk; Jeyaindran, Sinnadurai; Tambunan, Karmel L; Ward, Christopher; Wong, Raymond; Yoon, Sung-Soo

    2012-09-01

    Despite advances in the management of venous thromboembolism (VTE), treatment of many patients worldwide, especially in Asia, remains inadequate and/or discordant with prevailing guidelines. Although epidemiological studies consistently report lower incidences of VTE in Asians than Caucasians, VTE rates in Asia have probably been gravely underestimated, partly due to comparatively lesser ascertainment. It is becoming evident that Asians are at much higher risk of VTE than was hitherto supposed. Nevertheless, VTE risk-assessment is not routine in Asia and thromboprophylaxis rates are much lower than in Western nations. It is important to base decisions about anticoagulation on individual circumstances and weigh the potential benefits and risks. The conventional VTE management paradigm is not ideal. New oral anticoagulants offer advantages over current modalities that may help to streamline patient care and reduce healthcare costs. Initially, they will be mainly used in uncomplicated cases and, in the absence of clear differences in efficacy or safety, convenience, tolerability/adherence and cost will determine treatment choice. There is clear scope to improve VTE prevention and treatment in Asia. Key priorities are raising awareness of best practice and properly implementing guidelines. Uncertainty about the burden of VTE and concern about bleeding are barriers. High-quality Asian epidemiological data are needed to guide healthcare policy and evidence-based practice. More data on the occurrence and management of bleeding complications in Asian patients are also required. Meanwhile, physicians should remain vigilant and strive to act early, decisively and appropriately to diagnose and treat VTE, particularly in patients at high risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Thulium laser vaporesection of the prostate: Can we operate without interrupting oral antiplatelet/anticoagulant therapy?

    PubMed Central

    Butticè, Salvatore; Macchione, Luciano; Netsch, Christopher; Tanidir, Yiloren; Dragos, Laurian; Pappalardo, Rosa; Magno, Carlo

    2017-01-01

    Purpose Thulium vaporesection of the prostate (ThuVARP) is a new and safe approach for patients receiving anticoagulant therapy in whom transurethral resection of the prostate (TURP) may possess a high bleeding risk. We aimed to demonstrate the efficacy and safety of ThuVARP in patients receiving oral antiplatelet/anticoagulant (OAP/OAC) therapy. Materials and Methods A total of 103 patients who underwent ThuVARP between 2011 and 2013 were enrolled in the study. Patients were divided into 2 groups. Group A consisted of 47 patients who underwent low molecular weight heparin (LMWH) bridging and group B consisted of 56 patients who were operated on while receiving OAP/OAC therapy. Results The drop in hemoglobin levels in the pre- and postoperative periods was significantly higher in group A than in group B. When subgroups were analyzed, the mean drop in hemoglobin was significantly lower in the warfarin and ticlopidine subgroups of group B than in group A. International Prostate Symptom Scores were significantly lower 3, 12, 18, and 24 months after surgery in group A than in group B. Quality of life scores, maximal flow rate values, and postmicturition residual urine volumes (mL) were similar between the 2 groups. A total of 38 and 41 patients in groups A and B, respectively, had no complications. Conclusions Our study showed the safety profile of continuing different OAP/OAC therapies in terms of bleeding problems in patients undergoing ThuVARP. We strongly recommend abandoning LMWH bridging and maintaining the OAP/OAC regimen patients are already receiving. PMID:28480345

  5. The need to clot: a review of current management strategies for adverse bleeding events with new oral anticoagulants.

    PubMed

    Whalley, D; Skappak, C; Lang, E S

    2014-07-01

    The new factor Xa inhibitors and direct thrombin inhibitors have offered alternatives to traditional anticoagulants, with benefits of no routine monitoring, less drug interactions, and oral administration. Current approved uses of these agents include prophylaxis of stroke in non-valvular atrial fibrillation and prevention of venous thromboembolism (VTE) following hip and knee arthroplasty. However, concern over bleeding risk in the context of having no specific antidotes available is a topic of focus for many physicians in an acute care setting. This manuscript examines the recent literature in the management of acute bleeding and the various methods of reversing anticoagulation in this setting. Literature published over the last 18 months (2011/07/01-present) was gathered from PubMed, Ovid, and Medline under a combined search strategy covering bleeding, reversal, and new oral anticoagulants, both factor Xa and direct thrombin inhibitors. The use of prothrombin complex concentrate, fresh frozen plasma, activated recombinant factor VII, activated prothrombin complex concentrate, as well as adjuncts of charcoal, hemodialysis, and antifibrinolytics are discussed. Recommendations are based on the determination of the severity of the bleed and physiological markers of anticoagulation, and involve the use of prothrombin complex concentrate, activated recombinant factor VII, and adjunctive therapy as appropriate.

  6. [Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex(TAT) and thrombophilia parameters in orally anticoagulated patients with inferior vena cava filters].

    PubMed

    Halbmayer, W M; Haushofer, A; Toth, E

    1993-01-01

    Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin-III-complex (TAT) levels were compared in 31 orally anticoagulated patients with inferior vena caval filters and a control group of 31 orally anticoagulated patients without caval filters and the incidence of markers of thrombophilia (deficiency of antithrombin-III, protein C, protein S and factor XII, presence of lupus anticoagulants) was determined. 8 of 31 patients (26%) from the group of caval filter carriers showed markers of thrombophilia (3 protein S deficiencies, 1 protein C deficiency, 2 factor XII deficiencies and 2 patients with lupus anticoagulants). In all orally anticoagulated patients a significant interdependence (p < 0.05) between F1 + 2- and TAT-levels and intensity (INR) of the oral anticoagulation could be observed. Comparison of F1 + 2- and TAT-levels of caval filter carriers and controls revealed no significant difference which leads to the conclusion that inferior vena caval filters do not induce detectable systemic activation of prothrombin under adequate oral anticoagulation therapy.

  7. The relationship between knowledge, health literacy, and adherence among patients taking oral anticoagulants for stroke thromboprophylaxis in atrial fibrillation.

    PubMed

    Rolls, Chanelle A; Obamiro, Kehinde O; Chalmers, Leanne; Bereznicki, Luke R E

    2017-09-04

    Patients' knowledge regarding their oral anticoagulant (OAC) treatment for stroke prevention in atrial fibrillation (AF), their level of medication adherence, and health literacy are known to affect treatment outcomes. However, contemporary data regarding the relationships between these variables are lacking. To investigate the relationships between anticoagulant knowledge, health literacy, and self-reported adherence in patients taking warfarin and the directly acting oral anticoagulants. A cross-sectional survey was conducted in 48 patients with AF identified from general practices. The Anticoagulation Knowledge Tool (AKT) was used to assess anticoagulation knowledge; the Short Test of Functional Health Literacy in Adults (s-TOFHLA) for health literacy; and the 8-item Morisky Medication Adherence Scale (MMAS) for medication adherence. Participants had mean scores of 61.6 ± 15.8, 7.2 ± 1.1, and 24.7 ± 9.5 for the AKT, MMAS-8 and s-TOFHLA, respectively. Significant correlations were observed between anticoagulation knowledge and health literacy with medication adherence (0.37, P < .01 and .30, P < .05, respectively). Participants with inadequate health literacy had a significantly lower mean knowledge score than those with adequate health literacy (55.8 ± 15.9 vs 66.1 ± 14.4, P < .05). Participants who self-reported adherence to their OAC had significantly higher knowledge scores than those who did not (67.5 ± 13.3 vs 56.1 ± 16.2, P < .05). Significant correlations between health literacy, OAC knowledge, and adherence were observed, and these relationships should to be considered by health professionals responsible for monitoring patients who are prescribed anticoagulants. We also observed serious gaps in OAC knowledge. Interventions designed to optimize the outcomes of anticoagulant treatment need to address these factors. © 2017 John Wiley & Sons Ltd.

  8. Novel oral anticoagulants versus warfarin therapy at various levels of anticoagulation control in atrial fibrillation--a cost-effectiveness analysis.

    PubMed

    You, Joyce H S

    2014-03-01

    The decision as to whether to use more expensive novel oral anticoagulants (NOACs) or invest resources for quality improvement of warfarin therapy requires input from both clinical and economic analyses. Cost-effectiveness of NOACs compared to warfarin therapy at various levels of patient-time in therapeutic range (TTR) in patients with atrial fibrillation was examined, from the healthcare provider's perspective. A Markov model was used to compare life-long economic and treatment outcomes of warfarin and NOACs in a hypothetical cohort of 65-year-old atrial fibrillation patients with CHADS2 scores of 2 or above. Model inputs were derived from clinical trials published in the literature. The outcome measure was incremental cost per quality-adjusted life-year (QALY) gained (ICER). Using United States Dollar (USD) 50,000 as the threshold of willingness-to-pay per QALY, NOACs therapy was cost-effective when TTR of warfarin therapy was 60 % or below, or monthly cost of warfarin management increased by two-fold or more to achieve 70 % TTR. Warfarin therapy was cost-effective when TTR of warfarin was 70 % with up to a 1.5-fold increment in monthly cost of care, or when TTR reached 75 % with monthly cost of warfarin care increased up to three-fold. At TTR 60 %, 70 % and 75 %, NOACs was cost-effective when monthly drug cost was < USD 200, < USD 122-185 and < USD 85-145, respectively. 10,000 Monte Carlo simulations showed NOACs to be cost-effective 83.6 %, 50.7 % and 32.7 % of the time at TTR of 60 %, 70 % and 75 %, respectively. The acceptance of NOACs as cost-effective was highly dependent upon drug cost, anticoagulation control for warfarin, and anticoagulation service cost.

  9. 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

  10. Cost-effectiveness of apixaban versus other new oral anticoagulants for stroke prevention in atrial fibrillation.

    PubMed

    Lip, Gregory Y H; Kongnakorn, Thitima; Phatak, Hemant; Kuznik, Andreas; Lanitis, Tereza; Liu, Larry Z; Iloeje, Uchenna; Hernandez, Luis; Dorian, Paul

    2014-02-01

    Apixaban (5 mg BID), dabigatran (available as 150 mg and 110 mg BID in Europe), and rivaroxaban (20 mg once daily) are 3 novel oral anticoagulants (NOACs) currently approved for stroke prevention in patients with atrial fibrillation (AF). The objective of this study was to evaluate the cost-effectiveness of apixaban against other NOACs from the perspective of the United Kingdom National Health Services. A Markov model was developed to evaluate the pharmacoeconomic impact of apixaban versus other NOACs over a lifetime. Pair-wise indirect treatment comparisons were conducted against other NOACs by using ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation), RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy), and ROCKET-AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial results for the following end points: ischemic stroke, hemorrhagic stroke, intracranial hemorrhage, other major bleeds, clinically relevant nonmajor bleeds, myocardial infarction, and treatment discontinuations. Outcomes were life-years, quality-adjusted life years gained, direct health care costs, and incremental cost-effectiveness ratios. Apixaban was projected to increase life expectancy versus other NOACs, including dabigatran (both doses) and rivaroxaban. A small increase in therapeutic management costs was observed with apixaban due to projected gains in life expectancy and lower discontinuation rates anticipated on apixaban versus other NOACs through lifetime. The estimated incremental cost-effectiveness ratio was £9611, £4497, and £5305 per quality-adjusted life-year gained with apixaban compared with dabigatran 150 mg BID, dabigatran 110 mg BID, and rivaroxaban 20 mg once daily, respectively. Sensitivity analyses indicated that results were robust over a wide range of inputs. Although our analysis was limited by

  11. Universal versus genotype-guided use of direct oral anticoagulants in atrial fibrillation patients: a decision analysis.

    PubMed

    You, Joyce H S

    2015-01-01

    This study aims to compare clinical and economic outcomes of CYP2C9 and VKORC1 genotype-guided (PG-DOAC) versus universal use of direct oral anticoagulant (DOAC) for stroke prevention in patients with atrial fibrillation (AF). Outcomes of oral anticoagulation therapy were simulated using life-long Markov modeling. In PG-DOAC, patients with genotype of high or low warfarin sensitivity were treated with DOAC, and patients with normal warfarin sensitivity genotype received warfarin. Expected quality-adjusted life-years (QALYs) and cost of DOAC were higher than PG-DOAC. Incremental cost per QALY (ICER) of DOAC versus PG-DOAC was 314,129 USD/QALY, exceeding willingness-to-pay threshold (50,000 USD/QALY). Using individual genotype to guide the use of DOAC versus warfarin appears to be the preferred strategy.

  12. [Validation of satisfaction questionnaire ACTS in outpatients with atrial fibrillation treated with oral anticoagulants in Spain. ALADIN Study].

    PubMed

    Suárez, Carmen; Pose, Antonio; Montero-Pérez-Barquero, Manuel; Roquer, Jaume; Gállego, Jaime; Ràfols, Carles; Cazorla, Daniel; Vivancos, José

    2016-09-02

    To validate the satisfaction questionnaire Anti-Clot-Treatment Scale (ACTS) in outpatients with nonvalvular atrial fibrillation (NVAF) treated with oral anticoagulants attended in Internal Medicine and Neurology departments in Spain. In this cross-sectional and multicentrer study, 1,337 outpatients aged≥18 years, with NVAF, treated with oral anticoagulants≥3 months, attended in Internal Medicine and Neurology departments in Spain were analyzed. The patients completed ACTS, Self-Assessment of Treatment Questionnaire (SAT-Q) and EuroQol-5 dimensions (EQ-5D) questionnaires. ACTS is a satisfaction tool that specifically analyzes burdens (higher score, lesser burden) and benefits (higher score, higher benefit) with anticoagulant treatment. The psychometric properties of the questionnaire were evaluated according to the classical test theory. The average time to complete the questionnaire was 8.99±6.06min and 63.70% of patients needed assistance to complete it. There was a high concordance between test and retest scores. Total reliability (Cronbach's alpha) was 0.95 in the ACTS Burdens scale and 0.82 in the ACTS Benefits scale. The factorial model was pertinent. All correlations with the SAT-Q questionnaire were positive, moderate and statistically significant. With regard to the EQ-5D-3L questionnaire, correlations were positive, low and statistically significant. Patient satisfaction was higher in the individuals being treated with new direct oral anticoagulants. In patients with NVAF treated with oral anticoagulants, the Spanish version of ACTS questionnaire was reliable, valid and feasible. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  13. Definition of indicators of the appropriateness of oral anticoagulant prescriptions in hospitalized adults: Literature review and consensus (PACHA study).

    PubMed

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

    2017-09-21

    Indicators of the appropriateness of oral anticoagulant prescriptions are lacking, despite the major contribution they could make to improve quality of care. To identify and select such indicators according to their utility and operational implementation. A literature review was conducted to identify indicators of the appropriateness of oral anticoagulant prescriptions according to the guidelines of health authorities and European learned societies. A first list of indicators was identified from guidelines related to general or targeted clinical situations. A two-round Delphi consensus process, completed by a synthesis meeting, was then set up to ask European experts to rate the utility and operational implementation of the indicators on a qualitative binary scale. An indicator was selected if ≥80% of the experts judged it both useful and implementable (strong consensus). We selected 32 references, from which 84 indicators were identified. Nineteen indicators were short-listed for submission to expert judgment. Twenty-two experts participated in the Delphi process. Sixteen indicators obtained strong consensus for selection; three indicators did not achieve consensus. Two-thirds of the selected indicators focused on the appropriateness of oral anticoagulant prescriptions in general or in patients with atrial fibrillation; the other third focused on the appropriateness of prescriptions in patients with a prosthetic heart valve, venous thromboembolism or trauma. This work addresses the current lack of indicators of the appropriateness of oral anticoagulant prescriptions. The selected indicators will be implemented from the hospital information system to assess their metrological properties to detect inappropriate prescriptions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Management of dental patients receiving antiplatelet therapy or chronic oral anticoagulation: A review of the latest evidence.

    PubMed

    Dézsi, Csaba András; Dézsi, Balázs Bence; Dézsi, András Döme

    2017-12-01

    The perioperative management of patients treated with antithrombotic medications who undergo surgical procedures represents a common clinical problem. Dental interventions are usually associated with a low risk of bleeding; however, the dental implications of new antithrombotic agents are not yet fully understood. The present review is based on the latest evidence and recommendations published on the periprocedural management of dental patients treated with single or dual antiplatelet therapy, vitamin K antagonists, or direct oral anticoagulants for a variety of indications.

  15. Treatment of menorrhagia associated with oral anticoagulation: efficacy and safety of the levonorgestrel releasing intrauterine device (Mirena coil).

    PubMed

    Pisoni, C N; Cuadrado, M J; Khamashta, M A; Hunt, B J

    2006-01-01

    Menorrhagia is common in women receiving oral anticoagulation. In healthy women, reductions of up to 90% of menstrual loss have been described with the levonorgestrel releasing intrauterine device (LNG-IUS). However there is no data about the use of LNG-IUS in women receiving oral anticoagulation and so we assessed the efficacy and safety of LNG-IUS in this setting. Patients with menorrhagia who used LNG-IUS and warfarin were contacted by post and asked to complete a questionnaire assessing the extent and duration of menstrual bleeding, quality of life and treatment satisfaction. The questionnaire was sent to 23 patients and returned by 17. The amount of bleeding was reduced with the LNG-IUS in 10 (58.8%) women; amenorrhea occurred in four (23.5%), no change in blood loss in one (5.9%) and greater blood loss in two (11.8%) patients. The number of sanitary pads used was less in 12 (70.6%) patients; same in one (5.9%) patient, more in two (11.8%) patients and two (11.8%) did not remember. Five patients (29.4%) had shorter duration of bleeding, four (23.5%) had amenorrhoea, four (23.5%) had longer periods and four (23.5%) had same duration by subjective assessment. Eight (47.1%) patients felt very satisfied, four (23.5%) felt satisfied, two (11.8%) felt dissatisfied with the treatment, one felt very dissatisfied (5.9%) and two (11.8%) did not respond to the question. This small study suggests LNG-IUS is effective in reducing the duration and amount of menstrual bleeding in women with menorrhagia associated with oral anticoagulation. We feel the use of LNG-IUS is a major advance in reducing menorrhagia in women on oral anticoagulation as the previous alternative--hysterectomy--is associated with an increased risk of thrombosis and bleeding.

  16. 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.

  17. close: Closure of patent foramen ovale, oral anticoagulants or antiplatelet therapy to prevent stroke recurrence: Study design.

    PubMed

    Mas, Jean-Louis; Derumeaux, Geneviève; Amarenco, Pierre; Arquizan, Caroline; Aubry, Pierre; Barthelet, Martine; Bertrand, Bernard; Brochet, Eric; Cabanes, Laure; Donal, Erwan; Dubois-Randé, Jean-Luc; Durand-Zaleski, Isabelle; Ernande, Laura; Finet, Gérard; Fraisse, Alain; Giroud, Maurice; Guérin, Patrice; Habib, Gilbert; Juliard, Jean-Michel; Leys, Didier; Lièvre, Michel; Lusson, Jean-René; Marcon, François; Michel, Patrick; Moulin, Thierry; Mounier-Vehier, François; Pierard, Luc; Piot, Christophe; Rey, Christian; Rodier, Gilles; Roudaut, Raymond; Schleich, Jean-Marc; Teiger, Emmanuel; Turc, Guillaume; Vuillier, Fabrice; Weimar, Christian; Woimant, France; Chatellier, Gilles

    2016-08-01

    Currently available data do not provide definitive evidence on the comparative benefits of closure of patent foramen ovale, oral anticoagulants and antiplatelet therapy in patients with patent foramen ovale-associated cryptogenic stroke To assess whether transcatheter patent foramen ovale closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy, for secondary stroke prevention in patients aged 16 to 60 years with a large patent foramen ovale or a patent foramen ovale associated with an atrial septal aneurysm, and an otherwise unexplained ischaemic stroke or retinal ischaemia. Six hundred and sixty-four patients were included in the study. CLOSE is an academic-driven, multicentre, randomized, open-label, three-group, superiority trial with blinded adjudication of outcome events. The trial has been registered with Clinical Trials Register (Clinicaltrials.gov, NCT00562289). Patient recruitment started in December 2007. Patient follow-up will continue until December 2016. Expected mean follow-up = 5.6 years. The primary efficacy outcome is the occurrence of fatal or nonfatal stroke. Safety outcomes include fatal, life-threatening or major procedure- or device-related complications and fatal, life-threatening or major haemorrhagic complications. CLOSE is the first specifically designed trial to assess the superiority of patent foramen ovale closure over antiplatelet therapy alone and the superiority of oral anticoagulants over antiplatelet therapy to prevent stroke recurrence in patients with patent foramen ovale-associated cryptogenic stroke. © 2016 World Stroke Organization.

  18. [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.

  19. New Insights into Nonvitamin K Antagonist Oral Anticoagulants' Reversal of Intracerebral Hemorrhage.

    PubMed

    Yasaka, Masahiro

    2015-01-01

    The nonvitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban are associated with an equal or lower incidence of stroke and systemic embolism and a much lower incidence of intracranial hemorrhage and hemorrhagic stroke than warfarin is, without the need for routine laboratory monitoring. However, reversal strategies are not currently established in the case of NOAC-related hemorrhagic stroke. In emergency situations, well-defined management for NOAC-related hemorrhagic stroke may improve clinical outcomes. Thus, in this chapter, general measures initially required to prevent the expansion of intracerebral hematomas, charcoal administration to reduce NOAC absorption from the gastrointestinal tract, application of hemodialysis to remove dabigatran, and coagulation factor therapy including 4-factor prothrombin complex concentrate and recombinant activated factor VII are reviewed. The specific reversal agents idarucizumab, which is a monoclonal antibody against dabigatran; andexanet alfa, a recombinant human factor Xa decoy for Xa inhibitors; and PER977, a small synthetic molecule for reversal of both Xa and thrombin inhibitors, are currently under development. These agents will facilitate the clinical management of NOAC-associated hemorrhagic stroke and other severe bleeding.

  20. An evidence summary of the management of patients taking direct oral anticoagulants (DOACs) undergoing dental surgery.

    PubMed

    Johnston, S

    2016-05-01

    Direct oral anticoagulant (DOAC) drugs (dabigatran, rivaroxaban, and apixaban) have emerged in the last decade to overcome some of the drawbacks of existing medications. To date, little is known about the dental management of patients taking these drugs. This study was undertaken to establish the evidence for the management of patients undergoing dental procedures while taking these medications. A rapid review approach was used to identify clinical and scientific research related to dental surgery performed in patients taking DOACs in order to produce an evidence summary. The rapid review did not identify any systematic reviews or original clinical trials and the overall quality of evidence found was poor. Most of the literature consisted of non-structured review articles and guidance documents based on assumptions from non-dental data and expert opinion, and recommendations on best practice varied throughout. The findings from the review of the literature varied considerably. Currently, recommendations are based on poor quality scientific data and clinical trials are required to establish best evidence-based practice guidance.

  1. 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.

  2. Randomized controlled trials of new oral anticoagulants for stroke prevention in atrial fibrillation.

    PubMed

    Liew, Aaron; Eikelboom, John W; O'Donnell, Martin

    2012-07-01

    The prevalence of atrial fibrillation is increasing because of an aging population. Vitamin K antagonists have been the standard therapy for stroke prevention in atrial fibrillation but are underutilized and often poorly managed because of their inherent limitations. This study critically reviews the recently completed phase 3 randomized controlled trials of new oral anticoagulants (OACs) for stroke prevention in patients with nonvalvular atrial fibrillation: RE-LY (dabigatran), AVERROES (apixaban), ARISTOTLE (apixaban) and ROCKET-AF (rivaroxaban). On the basis of their favorable pharmacological characteristics and excellent efficacy and safety profile as demonstrated by the results of the randomized controlled trials, the new OACs have the potential to replace vitamin K antagonists as the first-line treatment for stroke prevention in atrial fibrillation, with warfarin reserved for patients with contraindications to the new OACs and those unable to afford them. The new OACs represent a major advance for patients with atrial fibrillation with the potential to reduce morbidity and mortality due to cardioembolic stroke.

  3. Novel oral anticoagulants for stroke prevention in atrial fibrillation: a focus on the older patient

    PubMed Central

    Yates, Scott W

    2013-01-01

    Atrial fibrillation (AF) is a common arrhythmia that is associated with an increased risk of stroke, particularly in the elderly. Traditionally, a vitamin K antagonist such as warfarin is prescribed for stroke prevention. Warfarin is effective at lowering stroke risk but has several limitations due to food restrictions, drug interactions, and a narrow therapeutic window. Various novel oral anticoagulants (NOACs) are available or under development to provide alternative treatment options. This article reviews the efficacy and safety of three NOACs (dabigatran etexilate, rivaroxaban, and apixaban) in addition to warfarin and aspirin, for prevention of stroke in patients with AF, focusing on the elderly population. Results of clinical trials demonstrate that the efficacy of NOACs for stroke prevention in patients with AF is as good as or better than that of warfarin. The NOACs are also associated with an equivalent or lower risk of bleeding. Regardless of the medication chosen, older patients with AF must be treated cautiously due to an increased risk of stroke and bleeding, as well as potential challenges related to drug interactions and monitoring requirements. NOACs may be suitable alternatives to warfarin for stroke prevention in older patients due to several advantages, including a faster onset of action, few drug or food interactions, and no requirement for regular monitoring. However, dose adjustments may be required for certain patients, such as those with severe renal impairment or in the setting of drug interactions. PMID:23687449

  4. Direct oral anticoagulant use in nonvalvular atrial fibrillation with valvular heart disease: a systematic review.

    PubMed

    Owens, Ryan E; Kabra, Rajesh; Oliphant, Carrie S

    2016-12-22

    Direct oral anticoagulants (DOACs) are indicated for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), which, according to the American College of Cardiology/American Heart Association/Heart Rhythm Society atrial fibrillation (AF) guidelines, excludes patients with rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair. However, the data regarding use of DOACs in AF patients with other types of valvular heart disease (VHD) are unclear. We aimed to summarize and evaluate the literature regarding the safety and efficacy of DOAC use in NVAF patients with other types of VHD. After an extensive literature search, a total of 1 prospective controlled trial, 4 subanalyses, and 1 abstract were identified. Efficacy of the DOAC agents in NVAF patients with VHD mirrored the overall trial results. Bleeding risk was significantly increased in VHD patients treated with rivaroxaban, but not for dabigatran or apixaban. Of the bioprosthetic valve patients enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, no safety or efficacy concerns were identified. In conclusion, subanalyses of DOAC landmark AF trials revealed that dabigatran, rivaroxaban, and apixaban may be safely used in AF patients with certain types of VHD: aortic stenosis, aortic regurgitation, and mitral regurgitation. More evidence is needed before routinely recommending these agents for patients with bioprosthetic valves or mild mitral stenosis. Patients with moderate to severe mitral stenosis or mechanical valves should continue to receive warfarin, as these patients were excluded from all landmark AF trials.

  5. Socioeconomic Inequalities in the Prescription of Oral Anticoagulants in Stroke Patients With Atrial Fibrillation.

    PubMed

    Sjölander, Maria; Eriksson, Marie; Asplund, Kjell; Norrving, Bo; Glader, Eva-Lotta

    2015-08-01

    Oral anticoagulants (OACs) are effective against ischemic stroke in patients with atrial fibrillation. Our aim was to investigate differences in the prescribing of OACs after ischemic stroke in patients with atrial fibrillation based on age, sex, country of birth, and socioeconomic status. Patients with first-ever ischemic stroke and atrial fibrillation without OAC treatment were included from the Swedish stroke register from 2009 to 2012. The outcome was OAC prescribed at discharge. Income, education, country of birth, and risk factors were obtained from official registers. Risk factors and health status were controlled for in multivariable logistic regression. Of 12 088 stroke patients, 36.3% were prescribed an OAC. Prescribing was less common with older age and, in patients born in other Nordic countries (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.68-0.98) or countries outside of Europe (OR, 0.65; 95% CI, 0.42-0.99) compared with those born in Sweden. University education (OR, 1.20; 95% CI, 1.05-1.36) and highest income (OR, 1.19; 95% CI, 1.06-1.33) were associated with higher levels of OAC prescribing compared with those with primary school education or lowest income level. Differences by age, income, education, and country of birth were found in the prescribing of OACs after stroke. Differences were not explained by common risk factors. This indicates socioeconomic inequalities in the prescribing of preventive treatment after stroke. © 2015 American Heart Association, Inc.

  6. Discontinuation of oral anticoagulation preceding acute ischemic stroke--prevalence and outcomes: Comprehensive chart review.

    PubMed

    Vanga, Subba R; Satti, Sudhakar R; Williams, James; Weintraub, William; Doorey, Andrew

    2015-01-01

    Oral anticoagulants (OAC) are the therapy of choice to prevent thromboembolism in patients at risk. Discontinuation of OAC prior to elective medical and surgical procedures may reduce the risk of bleeding, but may expose patients to increased risk of thromboembolism and ischemic stroke. The current public health burden of ischemic strokes associated with OAC discontinuation is unknown. We aimed to study the prevalence OAC discontinuation in patients who presented with acute ischemic stroke as well as the outcomes of these strokes. Retrospective cross-sectional study by intensive chart review of all acute ischemic stroke patients over 6 months in a large tertiary care community hospital. A total of 431 patients with acute ischemic stroke were admitted during study period, of which 11 (2.6%) had OAC discontinuation within 120 days prior to the index admission. Several strokes occurred after relatively brief discontinuations. The patient group with discontinuation was older, had higher comorbidities and also had a clinically significant stroke and resulting higher mortality and morbidity. About 2.6% or 1 in every 38 of all ischemic stokes occurred after OAC discontinuation. Strokes occurring after OAC discontinuation also have higher mortality and morbidity. Our data suggest that any planned discontinuation of OAC, however brief, should be carefully considered.

  7. 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.

  8. Direct oral anticoagulants: Current indications and unmet needs in the treatment of venous thromboembolism.

    PubMed

    Bertoletti, Laurent; Ollier, Edouard; Duvillard, Cécile; Delavenne, Xavier; Beyens, Marie-Noëlle; De Magalhaes, Elodie; Bellet, Florelle; Basset, Thierry; Mismetti, Patrick; Laporte, Silvy

    2017-04-01

    The treatment of acute venous thromboembolism (VTE) is being completely modified with the development of direct oral anticoagulants (DOACs). Rivaroxaban, apixaban and edoxaban directly inhibit factor Xa, whereas dabigatran inhibits factor IIa. All these drugs are proposed orally, and share pharmacological similarities: fixed doses without any therapeutic drug monitoring, key role of the transporter proteins P-glycoprotein for all of them and metabolism mediated by CYP3A4 for the anti-Xa, short half-life with variable rate of renal elimination. More than 25 000 patients with acute VTE were included in phase-III studies. Rivaroxaban and apixaban challenged all the conventional therapy (parenteral heparins followed by anti-vitamin K antagonists) whereas edoxaban and dabigatran challenged only anti-vitamin K antagonists. All the DOACs met the non-inferiority efficacy endpoint (recurrent VTE during treatment), whereas the large non-inferiority margin was debated for dabigatran. However, they were associated with better safety and a decreased risk of major bleeding. According to indirect comparisons, there were no statistically significant differences between DOACs in terms of efficacy but some differences are not excluded in term of safety. Although DOACs allow for simplification of treatment in the majority of patients with acute VTE, their risk/benefit ratio is questioned in elderly patients, patients with mild-to-severe renal impairment, and in some clinical subgroups such as cancer or chronic thromboembolic pulmonary hypertension. Validated reversal strategies (potentially based on laboratory monitoring) are expected for patients with major bleeding, overdose or with a need for surgery.

  9. [Clinical perspectives on the management of bleeding in patients on oral anticoagulants: the DECOVER Study (DElphi Consensus on oral COagulation and therapy action reVERsal)].

    PubMed

    Vicente, Vicente; Martín, Alfonso; Lecumberri, Ramón; Coll-Vinent, Blanca; Suero, Coral; González-Porras, José Ramón; Marco, Pascual; Mateo, José; Roldán, Vanesa; Soulard, Stéphane; Crespo, Carlos; Camats, Míriam

    2017-02-01

    To evaluate the level of agreement between hematologists and emergency medicine physicians regarding the best clinical practices for managing bleeding and anticoagulant reversal. Nationwide Spanish multicenter Delphi method study with a panel of experts on anticoagulation and the management of bleeding. Two survey rounds were carried out between April and September 2015. Consensus was reached when more than 75% of the panelists scored items in the same tertile. Fifteen hematologists and 17 emergency medicine specialists from 14 Spanish autonomous communities participated. Consensus was reached on the use of both hemodialysis and an activated prothrombin complex concentrate (PCC) to antagonize significant/major bleeding in patients taking dabigatran. Use of an activated PCC was considered sufficient for patients on rivaroxaban or apixaban. The panel did not consider any PCC to be both effective and safe. Tests for activated partial thromboplastin, thrombin, diluted thrombin, and ecarin clotting times were considered useful in patients treated with dabigatran. A specific anti-Xa activity assay was suggested for patients who developed bleeds while treated with rivaroxaban or apixaban. Specific antidotes for direct-acting oral anticoagulants would be useful when severe bleeding occurs according to 97% of the panelists. Such antidotes would substantially change current treatment algorithms. The points of consensus were generally in line with clinical practice guidelines, but the Delphi process revealed that there are aspects of the clinical management of bleeding that require unified criteria. The need for specific antidotes for direct-acting oral anticoagulants was emphasized.

  10. 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.

  11. 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

  12. [Oral anticoagulation in atrial fibrillation: What is the guideline for using new drugs?

    PubMed

    Ibáñez Pérez de Viñaspre, J A; Gómez Bitrian, J; Royo Hernández, R; de Azúa Jiménez, M; Marco López, C; Urieta González, L

    2017-08-31

    To assess whether there are differences between atrial fibrillation (AF) patients initiating new direct-acting oral anticoagulants (DOAC) therapy and vitamin K antagonist (VKA) therapy in an emergency service. Descriptive, observational, prospective study. We enrolled patients with AF who were visited in a hospital emergency service over one year. This study included 492 patients with AF, and 189 subjects received anticoagulant therapy, 104 with VKA (55%), and 85 with DOAC (45%). The VKA group: mean age 76.1 years, male 50.9% and female 49.1%, CHA2DS2-VASc mean 3.2±1.3 points, and a HAS-BLED mean of 1.9±0.8 points. The DOAC group: mean age 73.4 years, male 37.6% and female 63.3%, CHA2DS2-VASc mean 3.1±1.6 points, and a HAS-BLED mean of 1.7±0.8 points. On analysing the medical history, 17.3% of patients in the VKA group had a previous stroke, and 13.5% significant valve disease, as well as 7.1 and 1.2% of patients, respectively, in the DOAC group. In the analysis of the DOAC types, 24.2% of patients in the dabigatran group had a previous stroke, 22.7% in the rivaroxaban group had ischaemic heart disease. Patients with AF who start on treatment in emergency services with VKA or with DOAC show a similar profile of age, gender, CHA2DS2-VASc score, and HAS-BLED score. The patients with a history of valvular or ischaemic heart disease received more VKA than DOAC. When the patient has a history of stroke, the DOAC more used is dabigatran, and in patients with ischaemic heart disease it is preferred to give rivaroxaban. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Sex-Specific Associations of Oral Anticoagulant Use and Cardiovascular Outcomes in Patients With Atrial Fibrillation.

    PubMed

    Palamaner Subash Shantha, Ghanshyam; Mentias, Amgad; Inampudi, Chakradhari; Kumar, Anita A; Chaikriangkrai, Kongkiat; Bhise, Viraj; Deshmukh, Abhishek; Patel, Nileshkumar; Pancholy, Samir; Horwitz, Phillip A; Mickelsen, Steven; Bhave, Prashant D; Giudici, Michael; Oral, Hakan; Vaughan Sarrazin, Mary S

    2017-08-18

    Sex-specific effectiveness of rivaroxaban (RIVA), dabigatran (DABI), and warfarin in reducing myocardial infarction (MI), heart failure (HF), and all-cause mortality among patients with atrial fibrillation are not known. We assessed sex-specific associations of RIVA, DABI, or warfarin use with the risk of MI, HF, and all-cause mortality among patients with atrial fibrillation. Medicare beneficiaries (men: 65 734 [44.8%], women: 81 135 [55.2%]) with atrial fibrillation who initiated oral anticoagulants formed the study cohort. Inpatient admissions for MI, HF, and all-cause mortality were compared between the 3 drugs separately for men and women using 3-way propensity-matched samples. In men, RIVA use was associated with a reduced risk of MI admissions compared with warfarin use (hazard ratio [95% confidence interval (CI): 0.59 [0.38-0.91]), with a trend towards reduced risk compared with DABI use (0.67 [0.44-1.01]). In women, there were no significant differences in the risk of MI admissions across all 3 anticoagulants. In both sexes, RIVA use and DABI use were associated with reduced risk of HF admissions (men: RIVA; 0.75 [0.63-0.89], DABI; 0.81 [0.69-0.96]) (women: RIVA; 0.64 [0.56-0.74], DABI; 0.73 [0.63-0.83]) and all-cause mortality (men: RIVA; 0.66 [0.53-0.81], DABI; 0.75 [0.61-0.93]) (women: RIVA; 0.76 [0.63-0.91], DABI; 0.77 [0.64-0.93]) compared with warfarin use. RIVA use and DABI use when compared with warfarin use was associated with a reduced risk of HF admissions and all-cause mortality in both sexes. However, reduced risk of MI admissions noted with RIVA use appears to be limited to men. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  14. Real-World Adherence and Persistence with Direct Oral Anticoagulants in Adults with Atrial Fibrillation.

    PubMed

    Manzoor, Beenish S; Lee, Todd A; Sharp, Lisa K; Walton, Surrey M; Galanter, William L; Nutescu, Edith A

    2017-07-21

    Evidence of adherence and persistence patterns in anticoagulation (AC) therapy comparing treatment-naïve and non-naïve patients is lacking. The objective of this study was to evaluate patterns of medication adherence and persistence in a real-world setting among AC-naïve and AC-experienced patients with atrial fibrillation (AF) who were treated with direct oral anticoagulants (DOACs). AF patients newly initiating a DOAC with a minimum of 6 months of continuous health plan enrollment pre and postindex date (first DOAC prescription) were identified from the Truven Health MarketScan Commercial and Medicare Supplemental databases (2009-2013). DOAC adherence (proportion of days covered [PDC]), persistence, and predictors of adherence were assessed at 6 and 12 months postindex. Of 66,090 AF patients included, 46.6% (n=30,826) were AC naïve and 53.4% (n=35,264) were AC experienced (age: 66.9 ± 12.7 vs 70.4 ± 11.4 yrs, p<0.001; male: n=19,132 [62.1%] vs n=21,691 [61.5%], p=0.14, respectively). A majority of patients received dabigatran as their index DOAC (n=49,210; 74.5%). The mean PDC in AC-naïve versus AC-experienced patients at 6 and 12 months of follow-up was 72.3% versus 83.3% (p<0.001) and 63.7% versus 79.9% (p<0.001), respectively. Persistence with DOAC therapy in AC-naïve and AC-experienced patients at 6 and 12 months ranged from 59.3% and 76.3% (p<0.0001) to 31.6% and 50.2% (p<0.0001), respectively. Predictors of higher DOAC adherence were older age and higher number of concomitant medications. Predictors of lower adherence were higher number of comorbidities and AC-naïve user status. Medication adherence and persistence with DOACs declined over time and both were suboptimal and lower (at 6 and 12 mo postindex) in AC-naïve compared to AC-experienced patients. These findings can help target future strategies or interventions for patient education and long-term AC management especially in those patients naïve to DOAC therapy. Future investigation should

  15. [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.

  16. 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

  17. 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

  18. 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.

  19. Novel Oral Anticoagulants for Venous Thromboembolism with Special Emphasis on Risk of Hemorrhagic Complications and Reversal Agents

    PubMed Central

    Ahmed, Zaheer; Hassan, Seemeen; Salzman, Gary A.

    2016-01-01

    Warfarin was the only oral anticoagulant available for the treatment of venous thromboembolism for about half a century until the recent approval of novel oral agents dabigatran, rivoraxaban and apixaban. This presents new classes of medications less cumbersome to use. They do not require frequent laboratory monitoring or have nurmerous drug interactions. On the other hand it also poses a challenge to the physicians deciding which agent to use in specific patient populations, how to predict the bleeding risk compared to warfarin and between the different novel agents and how to manage bleeding with relatively recent discovery of few potential antidotes. This review summarizes the major trials that led to the approval of these agents and their exclusion criteria helping physicians understand which patient types might not benefit from these agents. It provides clinical pearls invaluable in everyday practice such as transitioning between traditional and novel anticoagulants, dose adjustments for high risk populations, drug interactions and cost analysis. Futhermore, the review provides direct comparisons with warfarin and indirect comparisons among the novel agents in terms of efficacy and bleeding risk narrating the numbers of patients with intracranial, gastrointestinal and fatal hemorrhages in each of the major trials. We hope that this review will help the physicians inform their patients about the benefits and risks of these agents and enable them to make an informed selection of the most appropriate anticoagulant. PMID:27594818

  20. New orally active anticoagulant agents for the prevention and treatment of venous thromboembolism in cancer patients

    PubMed Central

    Gerotziafas, Grigoris T; Mahé, Isabelle; Elalamy, Ismail

    2014-01-01

    Patients with cancer have a 6–7-fold higher risk of venous thromboembolism (VTE) as compared with non-cancer patients. Effective and safe anticoagulation for the prevention and treatment of VTE is the cornerstone of the management of patients with cancer, aiming to decrease morbidity and mortality and to improve quality of life. Unfractionated heparin, low molecular weight heparins, fondaparinux and vitamin K antagonists (VKAs) are used in the prevention and treatment of VTE in cancer patients. Heparins and fondaparinux are administered subcutaneously. VKAs are orally active, but they have a narrow therapeutic window, numerous food and drug interactions, and treatment requires regular laboratory monitoring and dose adjustment. These limitations among others have important negative impact on the quality of life of patients and decrease adherence to the treatment. New orally active anticoagulant (NOAC) agents are specific inhibitors of activated factor Xa (FXa) (rivaroxaban and apixaban) or thrombin (dabigatran). It is expected that NOACs will improve antithrombotic treatment. Cancer patients are a particular group that could benefit from treatment with NOACs. However, NOACs present some significant interactions with drugs frequently used in cancer patients, which might influence their pharmacokinetics, compromising their efficacy and safety. In the present review, we analyzed the available data from the subgroups of patients with active cancer who were included in Phase III clinical trials that assessed the efficacy and safety of NOACs in the prevention and treatment of VTE. The data from the Phase III trials in prophylaxis of VTE by rivaroxaban or apixaban highlight that these two agents, although belonging to the same pharmacological group (direct inhibitors of factor Xa), have substantially different profiles of efficacy and safety, especially in hospitalized acutely ill medical patients with active cancer. A limited number of patients with VTE and active

  1. Efficacy and Safety of Direct-Acting Oral Anticoagulants Use in Acute Portal Vein Thrombosis Unrelated to Cirrhosis.

    PubMed

    Nery, Filipe; Valadares, Diana; Morais, Sara; Gomes, Manuel Teixeira; De Gottardi, Andrea

    2017-04-01

    In acute portal vein thrombosis (APVT) unrelated to cirrhosis, anticoagulant therapy is classically started with low molecular weight heparin or vitamin K antagonists. New direct-acting oral anticoagulants (DOACs) are used in the treatment of venous thrombosis outside the splanchnic vascular bed, but not in the latter. We report a young female with APVT occurring in a non-cirrhotic liver linked to heterozygosity of factor V-Leiden and prothrombin G20210A gene mutations. Rivaroxaban was started, with total recanalization of the left and partial recanalization of the right portal vein branches, without complications. New DOACs do not need daily subcutaneous injections nor routinely blood coagulation control tests, making its use attractive, eventually increasing patient's compliance. If proved to be safe and effective in the future studies, its use may be extended to PVT treatment. This case shows that rivaroxaban was safe, not only prevented the extension of thrombosis in the portal tract, but also resolved PVT, at least partially.

  2. A review of the fixed dose use of new oral anticoagulants in obese patients: Is it really enough?

    PubMed Central

    Güler, Ekrem; Güler, Gamze Babur; Demir, Gültekin Günhan; Hatipoğlu, Suzan

    2016-01-01

    Obesity is a significant cause of morbidity and mortality, and it is becoming increasingly prevalent worldwide. Altered pharmacodynamics and pharmacokinetics of drugs in obese patients require dose adjustment according to body weight. New oral anticoagulants (NOACs), which are more frequently used for anticoagulation, are recommended to be used at a fixed dose based on data derived from phase 2 and 3 studies. However, the representation of obese patients [>100 kg or a body mass index (BMI) of >30 kg/m2] in subgroups with a small sample size and reports of various emboli cases under drug treatment have raised suspicions about the adequacy of fixed dose use. To address this issue, we analyzed several patients with a body weight of >100 kg or BMI of >30 kg/m2 participating in NOAC studies and evaluated whether these numbers were sufficient to enable an accurate recommendation of fixed dose use in obese patients. PMID:26663225

  3. Novel oral anticoagulants for the secondary prevention of cerebral ischemia: a network meta-analysis

    PubMed Central

    Katsanos, Aristeidis H.; Mavridis, Dimitris; Parissis, John; Deftereos, Spyridon; Frogoudaki, Alexandra; Vrettou, Agathi-Rosa; Ikonomidis, Ignatios; Chondrogianni, Maria; Safouris, Apostolos; Filippatou, Angeliki; Voumvourakis, Konstantinos; Triantafyllou, Nikos; Ellul, John; Karapanayiotides, Theodore; Giannopoulos, Sotirios; Alexandrov, Anne W.; Alexandrov, Andrei V.; Tsivgoulis, Georgios

    2016-01-01

    Background: Novel oral anticoagulants (NOACs) have shown to be both safe and effective for ischemic stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We conducted a network meta-analysis (NMA) using published data from secondary prevention subgroups of different phase III randomized clinical trials (RCTs) comparing individual NOACs with warfarin. Methods: Eligible studies were identified by searching MEDLINE and SCOPUS and the Cochrane Central Register of Controlled Trials databases. First, we conducted a pairwise meta-analysis for each pairwise comparison, and then we performed NMA to combine direct and indirect evidence for any given pair of treatments. The comparative effects of all NOACs against warfarin were ranked with the surface under the cumulative ranking (SUCRA) curve for each outcome. Results: We identified four RCTs (including 15,240 patients) comparing individual NOACs (apixaban, dabigatran, rivaroxaban) with warfarin. Using indirect evidence, dabigatran was related to a significantly lower risk of hemorrhagic stroke compared with rivaroxaban [risk ratio (RR) 0.28; 95% confidence interval (CI) 0.11–0.75], while rivaroxaban was associated with a significantly lower risk of major gastrointestinal bleeding compared with dabigatran (RR 0.14; 95% CI 0.03–0.74). We also performed clustered ranking plot for the primary efficacy and safety endpoints to identify the treatment with the probably best benefit-to-risk ratio profile. Conclusions: The three NOACs showed differences in terms of safety and efficacy for secondary stroke prevention in NVAF. Our findings can serve only as hypothesis generation and require independent confirmation in head-to-head RCTs, owing to the sparse available evidence and increased uncertainty in both indirect effect estimates and ranking of treatments. PMID:27582891

  4. Patients' perspectives on self-testing of oral anticoagulation therapy: content analysis of patients' internet blogs.

    PubMed

    Shah, Syed Ghulam Sarwar; Robinson, Ian

    2011-02-03

    Patients on oral anticoagulant therapy (OAT) require regular testing of the prothrombin time (PT) and the international normalised ratio (INR) to monitor their blood coagulation level to avoid complications of either over or under coagulation. PT/INR can be tested by a healthcare professional or by the patient. The latter mode of the testing is known as patient self-testing or home testing. The objective of this study was to elicit patients' perspectives and experiences regarding PT/INR self-testing using portable coagulometer devices. Internet blog text mining was used to collect 246 blog postings by 108 patients, mainly from the USA and the UK. The content of these qualitative data were analysed using XSight and NVivo software packages. The key themes in relation to self-testing of OAT identified were as follows: Patient benefits reported were time saved, personal control, choice, travel reduction, cheaper testing, and peace of mind. Equipment issues included high costs, reliability, quality, and learning how to use the device. PT/INR issues focused on the frequency of testing, INR fluctuations and individual target (therapeutic) INR level. Other themes noted were INR testing at laboratories, the interactions with healthcare professionals in managing and testing OAT and insurance companies' involvement in acquiring the self-testing equipment. Social issues included the pain and stress of taking and testing for OAT. Patients' blogs on PT/INR testing provide insightful information that can help in understanding the nature of the experiences and perspectives of patients on self-testing of OAT. The themes identified in this paper highlight the substantial complexities involved in self-testing programmes in the healthcare system. Thus, the issues elicited in this study are very valuable for all stakeholders involved in developing effective self-testing strategies in healthcare that are gaining considerable current momentum particularly for patients with chronic

  5. Patients' perspectives on self-testing of oral anticoagulation therapy: Content analysis of patients' internet blogs

    PubMed Central

    2011-01-01

    Background Patients on oral anticoagulant therapy (OAT) require regular testing of the prothrombin time (PT) and the international normalised ratio (INR) to monitor their blood coagulation level to avoid complications of either over or under coagulation. PT/INR can be tested by a healthcare professional or by the patient. The latter mode of the testing is known as patient self-testing or home testing. The objective of this study was to elicit patients' perspectives and experiences regarding PT/INR self-testing using portable coagulometer devices. Methods Internet blog text mining was used to collect 246 blog postings by 108 patients, mainly from the USA and the UK. The content of these qualitative data were analysed using XSight and NVivo software packages. Results The key themes in relation to self-testing of OAT identified were as follows: Patient benefits reported were time saved, personal control, choice, travel reduction, cheaper testing, and peace of mind. Equipment issues included high costs, reliability, quality, and learning how to use the device. PT/INR issues focused on the frequency of testing, INR fluctuations and individual target (therapeutic) INR level. Other themes noted were INR testing at laboratories, the interactions with healthcare professionals in managing and testing OAT and insurance companies' involvement in acquiring the self-testing equipment. Social issues included the pain and stress of taking and testing for OAT. Conclusions Patients' blogs on PT/INR testing provide insightful information that can help in understanding the nature of the experiences and perspectives of patients on self-testing of OAT. The themes identified in this paper highlight the substantial complexities involved in self-testing programmes in the healthcare system. Thus, the issues elicited in this study are very valuable for all stakeholders involved in developing effective self-testing strategies in healthcare that are gaining considerable current momentum

  6. 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

  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. [Management of direct action oral anticoagulants in the peri-operative period and invasive techniques].

    PubMed

    Llau, J V; Ferrandis, R; Castillo, J; de Andrés, J; Gomar, C; Gómez-Luque, A; Hidalgo, F; Torres, L M

    2012-01-01

    The new direct-acting oral anticoagulants (ACOD) in patients on prolonged treatment require the need to balance the risk of haemorrhage by administering them against the risk of thrombosis on withdrawing them. Recommendations for their management are proposed in the present article: A) Thromboprophylaxis and general anaesthesia: the performing of regional anaesthesia if administered with an ACOD as thromboprophylaxis requires some safety intervals based on their pharmacokinetic parameters; B) Management of ACOD in elective surgery: in patients with normal renal function and a low haemorrhage/thrombosis risk, stop the ACOD two days before the surgery; it the haemorrhage/thrombosis risk is high and/or renal function is impaired, therapy with a low molecular weight heparin is proposed from 5 days prior to the surgery, and C) Management of ACOD in urgent surgery and associated haemorrhage: the systematic prophylactic administration of haemostatics is recommended. In the event of acute bleeding that may place the life of the patient at risk (due to volume or location), the administration of concentrated prothrombin complex, fresh plasma, or factor VIIa, must be assessed, together with general control measures of acute haemorrhage. These recommendations should be considered in the context of the use drugs that do have a specific antidote, where their monitoring by the usual coagulation tests is not routine, and with those in which there is limited experience. We believe they need to be reviewed in the future, depending on further studies and clinical experience obtained. Copyright © 2011 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  9. Comparison of treatment persistence with different oral anticoagulants in patients with atrial fibrillation.

    PubMed

    Forslund, Tomas; Wettermark, Björn; Hjemdahl, Paul

    2016-03-01

    Oral anticoagugulants (OACs) effectively reduce the risk for ischemic stroke in patients with atrial fibrillation (AF), but undertreatment and poor persistence with treatment are important problems. NOACs now provide alternatives to warfarin. This study compares the persistence with presently available antithrombotic treatments in AF patients with a CHA2DS2VASc score ≥2. All first claims of either warfarin (n = 9969), dabigatran (n = 2701), rivaroxaban (n = 2074), apixaban (n = 1352), or aspirin (n = 4540) from April 2011 until December 2014, in individuals with non-valvular AF and CHA2DS2VASc scores of 2-9, were identified in the administrative health data register (VAL) of the Stockholm region (2.1 million inhabitants). Prescription claims were analyzed with and without multivariate analysis in relation to age, sex, prescriber category, prior OAC treatment, number of drugs, and death. The overall persistence with any OAC was 88.2% (CI 87.5-88.9) at 1 year and 82.9% (CI 81.8-83.9) at 2 years. After 1 year, the crude persistence was 85.0% (CI 84.2-85.9) with warfarin, 85.9% (CI 81.8-90.1) with apixaban, 74.4% (CI 72.3-76.5) with dabigatran, and 77.4% (CI 74.6-80.2) with rivaroxaban. Multivariate analysis confirmed significantly higher persistence with warfarin and apixaban than with dabigatran or rivaroxaban. The adherence (proportion of days covered >80%) was above 90% for all NOACs; significantly higher with rivaroxaban compared to dabigatran (p < 0.001), but not compared to apixaban (p = 0.14). After 2 years, the persistence with any anticoagulant treatment was high in patients with non-valvular AF. Our results indicate better persistence with warfarin and apixaban than with dabigatran or rivaroxaban in regular care.

  10. 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.

  11. New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis.

    PubMed

    Oldgren, Jonas; Wallentin, Lars; Alexander, John H; James, Stefan; Jönelid, Birgitta; Steg, Gabriel; Sundström, Johan

    2013-06-01

    Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting. All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7-14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80-0.95), but more than doubled the bleeding (HR: 2.34; 2.06-2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies. In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.

  12. Safety and Efficacy of Underdosing Non-vitamin K Antagonist Oral Anticoagulants in Patients Undergoing Catheter Ablation for Atrial Fibrillation

    PubMed Central

    Murakami, Takashi; Hina, Kazuyoshi; Higashiya, Shunichi; Kawamura, Hiroshi; Murakami, Masaaki; Kamikawa, Shigeshi; Komatsubara, Issei; Kusachi, Shozo

    2017-01-01

    Background: Some patients with atrial fibrillation (AF) received underdoses of non-vitamin K antagonist oral anticoagulants (NOACs) in the real world. Underdosing is defined as administration of a dose lower than the manufacturer recommended dose. Objectives: To identify the efficacy and safety of underdosing NOACs as perioperative anticoagulation for atrial fibrillation ablation. Methods: We retrospectively analyzed patients who received rivaroxaban or dabigatran etexilate according to dosage: adjusted low dosage (reduced by disturbed renal function; n = 30), underdosage (n = 307), or standard dosage (n = 683). Non-vitamin K antagonist oral anticoagulants and dosing decisions were at the discretion of treating cardiologists. Results: Patients who received underdosed NOACs were older, more often female, and had lower body weight and lower renal function than those who received standard dosages. Activated clotting time at baseline in patients who received adjusted low dosage or underdosages was slightly longer than that in patients receiving standard dosages (156 ± 23, 151 ± 224, and 147 ± 24 seconds, respectively). Meaningful differences were not observed in other coagulation parameters. Adjusted low-, under-, and standard-dosing regimens did not differ in perioperative thromboembolic complications (0/30, 0.0%; 1/307, 0.3%; and 0/683, 0%, respectively) or major (0/30, 0.0%; 2/307, 0.6%; 3/683, 0.4%) and minor (1/30, 3.3%; 13/307, 4.2%; 25/683, 3.6%) bleeding episodes. When comparisons were performed for each NOAC, similar results were observed. Conclusions: With consideration of patient condition, age, sex, body weight, body mass index, and renal function, underdosing NOACs was effective and safe as a perioperative anticoagulation therapy for atrial fibrillation ablation. The therapeutic range of NOACs is potentially wider than manufacturer recommendations. PMID:28170360

  13. Effects of policy interventions on the introduction of novel oral anticoagulants in Stockholm: an interrupted time series analysis.

    PubMed

    Komen, Joris; Forslund, Tomas; Hjemdahl, Paul; Andersen, Morten; Wettermark, Björn

    2017-03-01

    The aim of the present study was to assess the effect of policy interventions - i.e. reimbursement decisions, guidelines and regional recommendations - on the prescribing of oral anticoagulant treatment in patients with atrial fibrillation (AF). Interrupted time series analyses were carried out using monthly data on all patients with a recorded diagnosis of AF newly initiated (switchers and anticoagulant-naïve patients alike) on warfarin, dabigatran, rivaroxaban or apixaban in the Stockholm region from April 2011 until February 2016. A total of 34 165 initiations in 27 942 patients were included. The publication of the European Guidelines was associated with an increase in novel oral anticoagulant (NOAC) initiations of 12.5% [95% confidence interval (CI) 7.3, 17.7] after 5 months. The choice between the different NOACs was mainly associated with changes in the regional recommendations, with apixaban initiations increasing by 19.5% (95% CI 16.3, 22.7) 5 months after the drug was recommended as a first-line alternative to warfarin. Dabigatran received a second-line recommendation but initiations decreased by -9.5% (95% CI -12.6, -6.4), and initiations of rivaroxaban, which had no specific recommendation, decreased by -9.2% (95% CI -12.7, -5.7). A steady decrease in warfarin and increase in NOAC initiations was seen throughout the study period and from November 2015, AF patients were more likely to receive apixaban than any other anticoagulant, while less than 20% of the initiations were with warfarin. After reimbursement and inclusion in the European guidelines, the NOACs started gaining in popularity, while changes in regional recommendations were associated with the biggest change in prescribers' choice between the different NOACs. © 2016 The British Pharmacological Society.

  14. The Prototype Compound for the Oral Anticoagulants: 3,3'-Methylene bis(4-hydroxycoumarin).

    ERIC Educational Resources Information Center

    Hayward, Rodney C.

    1984-01-01

    Provides background information on the development and action of the coumarin family of anticoagulants, focusing on an experimental procedure for the synthesis of dicumerol. Includes procedures used and safety considerations. (JM)

  15. Oral anticoagulation in patients with atrial fibrillation and medical non-neoplastic disease in a terminal stage.

    PubMed

    Díez-Manglano, Jesús; Bernabeu-Wittel, Máximo; Murcia-Zaragoza, José; Escolano-Fernández, Belén; Jarava-Rol, Guadalupe; Hernández-Quiles, Carlos; Oliver, Miguel; Sanz-Baena, Susana

    2017-02-01

    Many patients with non-neoplastic disease develop atrial fibrillation in advanced stages of their disease. The aim of this study is to determine the factors associated with the use of oral anticoagulants in patients with atrial fibrillation and non-neoplastic medical disease in a terminal stage, and whether their use is associated with a longer survival. Design is prospective, observational, multicentre study. Patients with atrial fibrillation and non-neoplastic disease (severe not reversible organ insufficiency) in a terminal stage were included between February 2009 and September 2010. A 6-month follow-up was carried out. We included 314 patients with a mean (SD) age of 82.6 (7.0) years. Their mean (SD) scores in CHADS2 and ATRIA scales were 3.4 (1.2) and 4.7 (2.0), respectively. Anticoagulants were prescribed to 112 (37.5 %) patients. The use of anticoagulants was associated with age (OR 0.96 95 % CI 0.93-0.99, p = 0.046) and to the Barthel index (OR 1.01 95 % CI 1.00-1.02; p = 0.034). After performing a propensity score matching analysis, 262 patients were included in the survival analysis. After 6 months, 133 (50.8 %) patients were dead. The mortality is higher among patients who are not treated with oral anticoagulants (57.1 vs. 39.4 %; p = 0.006), but it is independently associated only with the Barthel index score (HR 0.99 95 % CI 0.98-1.00; p = 0.039), delirium (HR 1.60, 95 % CI 1.08-2.36; p = 0.018), anorexia (HR 1.58 95 % CI 1.05-2.38; p = 0.027), and with the use of calcium channel blockers (HR 0.50 95 % CI 0.30-0.84; p = 0.009). In patients with atrial fibrillation and non-neoplastic disease in a terminal stage, the use of oral anticoagulants is not independently associated with a higher probability of survival.

  16. Age as a Risk Factor for Stroke in Atrial Fibrillation Patients: Implications in Thromboprophylaxis in the Era of Novel Oral Anticoagulants

    PubMed Central

    Mitrousi, Konstantina; Lip, Gregory Y H; Apostolakis, Stavros

    2013-01-01

    Atrial fibrillation is associated with significant morbidity and mortality. There is a strong relationship between atrial fibrillation and aging, thromboembolism, stroke, congestive heart failure and hypertension. In addition, advanced age is a powerful risk factor for stroke and thromboembolism in patients with atrial fibrillation. For many years, vitamin K antagonists were the only approved anticoagulants for the management of atrial fibrillation. Lately new anticoagulants made their appearance and large trials have already shown their superiority against vitamin K antagonists. Since the arrhythmia is encountered frequently in the elderly, it is crucial to identify the beneficial effects of the novel oral anticoagulants in this particular patient population. PMID:28496851

  17. Estimating the cost-effectiveness of quality-improving interventions in oral anticoagulation management within general practice.

    PubMed

    Claes, Neree; Moeremans, Karen; Frank, Buntinx; Jef, Arnout; Jos, Vermylen; Herman, Van Loon; Lieven, Annemans

    2006-01-01

    A clinical trial, "Belgian Improvement Study on Oral Anticoagulation Therapy (BISOAT)," significantly improved the quality after implementing four different quality-improving interventions in four randomly divided groups of general practitioners (GPs). The quality-improving interventions consisted of multifaceted education with or without feedback reports on their performance, international normalized ratio (INR) testing by the GP with a CoaguChek device or computer-assisted advice for adapting oral anticoagulation therapy. The quality improvement in INR control versus baseline was similar in the four groups. The aim of the current study was to calculate the cost-effectiveness and influencing factors of the four quality-improving interventions compared with usual care. Activity-based costing techniques with questionnaires were used to determine the global costs per patient per month in the different intervention groups. Effectiveness data were obtained from the BISOAT study. Cost-effectiveness was expressed as cost per additional day within a 0.5 range from INR target. The one-time cost of multifaceted education was 49,997 euro for the whole study. Monthly continuous costs per intervention ranged between 37 euro and 54 euro per patient. Using the CoaguChek in combination with the multifaceted education was associated with net savings and quality improvement, hence dominated usual care. Sensitivity analyses showed improved cost-effectiveness with extended duration and with increased program size. Implementation of the combination multifaceted education with the use of the CoaguChek is a cost-effective new organizational model of oral anticoagulation management in general practice.

  18. Prescription patterns of oral anticoagulants for patients with non-valvular atrial fibrillation: experience at a Japanese single institution.

    PubMed

    Tagaya, Manaka; Yoshikawa, Daiji; Sugishita, Yoshinori; Yamauchi, Fumi; Ito, Takehiro; Kamada, Tomohito; Yoshinaga, Masataka; Mukaide, Daisuke; Fujiwara, Wakaya; Yokoi, Hiroatsu; Hayashi, Mutsuharu; Watanabe, Eiichi; Ishii, Junichi; Ozaki, Yukio; Izawa, Hideo

    2016-06-01

    New oral anticoagulants (NOACs) are now clinically available. However, few studies have demonstrated which patients with non-valvular atrial fibrillation (NVAF) actually receive NOACs in a clinical setting. We analyzed 182 NVAF patients who received oral anticoagulants. Clinical backgrounds and the risk of stroke, systemic embolism, and bleeding associated with oral anticoagulants were investigated. Seventy-three (40 %) patients were treated with NOACs and 109 (60 %) patients were treated with warfarin. A significantly lower mean number of bleeding risk factors was observed among the patients treated with NOACs than among those treated with warfarin (P = 0.010). Of the bleeding risk factors, NOACs were significantly less frequently prescribed in patients with a bleeding history and elderly subjects (>65 years) than in those who received warfarin (P < 0.001 and P = 0.029). A multivariate logistic regression analysis revealed that CHF and bleeding history were independently and significantly associated with the administration of NOACs (P = 0.047 and P = 0.003). The rate of a history of intracranial hemorrhage was comparable between the patients treated with NOACs and those treated with warfarin (P = 1.000). Significantly lower rates of a history of gastrointestinal and other minor bleeding were observed in the patients who received NOACs versus those who received warfarin (P = 0.001 and P = 0.026). NOACs were less frequently prescribed in patients with a history of bleeding, especially those with a history of gastrointestinal bleeding in a clinical setting.

  19. 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.

  20. [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.

  1. Novel oral anticoagulants for stroke prevention in atrial fibrillation: results of the European Heart Rhythm Association survey.

    PubMed

    Lip, Gregory Y H; Bongiorni, Maria Grazia; Dobreanu, Dan; Lewalter, Thorsten; Hastrup Svendsen, Jesper; Blomström-Lundqvist, Carina

    2013-10-01

    The purpose of this European Heart Rhythm Association (EHRA) survey was to assess clinical practice in relation to stroke prevention in atrial fibrillation (AF), particularly into the use of novel oral anticoagulants (NOACs) for stroke prevention, among members of the EHRA electrophysiology (EP) research network. In this EP Wire survey, we have provided some insights into current practice in Europe for the use of NOACs for stroke prevention in AF. There were clear practice differences evident, and also the need for greater adherence to the guidelines, especially since guideline adherent management results in better outcomes in AF.

  2. [Direct oral anticoagulants: what is the exact assessment of coagulation tests and plasma levels by laboratory tests in clinical practice?].

    PubMed

    Gendron, Nicolas; Smadja, David M

    2016-01-01

    Direct oral anticoagulants (DAO), anti-IIa or anti-Xa, are intended to be widely used for the treatment and prevention of thrombotic disorders in venous thromboembolic disease and atrial fibrillation as an alternative of vitamin K antagonists (VKA). Despite predictable pharmacological properties, spontaneous or provoked hemorrhagic risks by DAO are major limitations. Thus, after few years of inconsistence concerning biological implication and in particular coagulation tests, it is now established that we need biology to evaluate hemorrhagic risk before surgery or in hemorrhagic cases.

  3. Predictors of common femoral artery access site complications in patients on oral anticoagulants and undergoing a coronary procedure

    PubMed Central

    Shammas, Nicolas W; Shammas, Gail A; Jones-Miller, Susan; Gumpert, Mileah Rose; Gumpert, Miranda Jade; Harb, Christine; Chammas, Majid Z; Shammas, W John; Khalafallah, Rommy A; Barzgari, Amy; Bou Dargham, Bassel; Daher, Ghassan E; Rachwan, Rayan Jo; Shammas, Andrew N

    2017-01-01

    Background It is unclear whether patients on oral anticoagulants (OAC) undergoing a procedure using common femoral artery access have higher adverse events when compared to patients who are not anticoagulated at the time of the procedure. Methods We retrospectively reviewed data from consecutive patients who underwent a cardiac procedure at a tertiary medical center. Patients were considered (group A) fully or partially anticoagulated if they had an international normalized ratio (INR) ≥1.6 on the day of the procedure or were on warfarin or new OAC within 48 h and 24 h of the procedure, respectively. The nonanticoagulated group (group B) had an INR <1.6 or had stopped their warfarin and new OAC >48 h and >24 h preprocedure, respectively. The index primary end point of the study was defined as the composite end point of major bleeding, vascular complications, or cardiovascular-related death during index hospitalization. The 30-day primary end point was defined as the occurrence of the index primary end point and up to 30 days postprocedure. Results A total of 779 patients were included in this study. Of these patients, 27 (3.5%) patients were in group A. The index primary end point was met in 11/779 (1.4%) patients. The 30-day primary composite end point was met in 18/779 (2.3%) patients. There was no difference in the primary end point at index between group A (1/27 [3.7%]) and group B (10/752 [1.3%]; P=0.3155) and no difference in the 30-day primary composite end point between group A (2/27 [7.4%]) and group B (16/752 [2.1%]; P=0.1313). Multivariable analysis showed that a low creatinine clearance (odds ratio [OR] =0.56; P=0.0200) and underweight patients (<60 kg; OR =3.94; P=0.0300) were independent predictors of the 30-day primary composite end point but not oral anticoagulation (P=0.1500). Conclusion Patients on OAC did not have higher 30-day major adverse events than those who were not anticoagulated at index procedure. PMID:28408835

  4. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary.

    PubMed

    Heidbuchel, Hein; Verhamme, Peter; Alings, Marco; Antz, Matthias; Hacke, Werner; Oldgren, Jonas; Sinnaeve, Peter; Camm, A John; Kirchhof, Paulus

    2013-07-01

    New oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients will have to learn how to use these drugs effectively and safely in specific clinical situations. This text is an executive summary of a practical guide that the European Heart Rhythm Association (EHRA) has assembled to help physicians in the use of the different NOACs. The full text is being published in EP Europace. Practical answers have been formulated for 15 concrete clinical scenarios: (i) practical start-up and follow-up scheme for patients on NOACs; (ii) how to measure the anticoagulant effect of NOACs; (iii) drug-drug interactions and pharmacokinetics of NOACs; (iv) switching between anticoagulant regimens; (v) ensuring compliance of NOAC intake; (vi) how to deal with dosing errors; (vii) patients with chronic kidney disease; (viii) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding?; (ix) management of bleeding complications; (x) patients undergoing a planned surgical intervention or ablation; (xi) patients undergoing an urgent surgical intervention; (xii) patients with AF and coronary artery disease; (xiii) cardioversion in a NOAC-treated patient; (xiv) patients presenting with acute stroke while on NOACs; (xv) NOACs vs. VKAs in AF patients with a malignancy. Since new information is becoming available at a rapid pace, an EHRA web site with the latest updated information accompanies the guide (www.NOACforAF.eu). It also contains links to the ESC AF Guidelines, a key message pocket booklet, print-ready files for a proposed universal NOAC anticoagulation card, and feedback possibilities.

  5. Real-world persistence and adherence to oral anticoagulation for stroke risk reduction in patients with atrial fibrillation.

    PubMed

    Beyer-Westendorf, Jan; Ehlken, Birgit; Evers, Thomas

    2016-08-01

    To assess persistence and adherence to rivaroxaban, dabigatran, and vitamin K antagonist (VKA) treatment in primary care patients with non-valvular atrial fibrillation (AF) newly starting anticoagulant therapy. Prescription data for oral anticoagulants were obtained from 7265 eligible patients from primary care practices across Germany. Persistence with and adherence to anticoagulation were assessed in anticoagulant-naïve patients with AF newly treated with dabigatran, rivaroxaban, or VKA during follow-up periods of at least 180 days, respectively 360 days after the prescription date. Persistence probabilities after 180 days were 66.0% for rivaroxaban, 60.3% for dabigatran, and 58.1% for VKA (P < 0.001 for rivaroxaban vs. VKA and P = 0.008 for rivaroxaban vs. dabigatran). After 360 days, persistence probabilities were 53.1, 47.3, and 25.5%, respectively (P < 0.001 for rivaroxaban and dabigatran vs. VKA). Considering the development over 360 days rivaroxaban demonstrated a better persistence compared with dabigatran (P = 0.026). Male gender and the presence of diabetes mellitus were associated with increased persistence, while renal impairment and antiplatelet drug use decreased persistence. High adherence (MPR ≥0.80) was observed in 61.4% of rivaroxaban users and in 49.5% of dabigatran users, with means of 0.76 [95% confidence interval (CI) 0.74-0.78] for rivaroxaban and 0.67 (95% CI 0.65-0.69) for dabigatran (P < 0.001). Rivaroxaban and dabigatran demonstrated better persistence than VKA at Day 360. Furthermore, rivaroxaban was associated with better persistence and adherence than dabigatran. Further studies are needed to identify factors responsible for this difference and evaluate the impact on outcomes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  6. 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

  7. 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.

  8. Epidemiology of Intracranial Haemorrhages Associated with Vitamin K Antagonist Oral Anticoagulants in Spain: TAC Registry

    PubMed Central

    Zapata-Wainberg, Gustavo; Ximénez-Carrillo Rico, Álvaro; Benavente Fernández, Lorena; Masjuan Vallejo, Jaime; Gállego Culleré, Jaime; Freijó Guerrero, María del Mar; Egido, José; Gómez Sánchez, José Carlos; Martínez Domeño, Alejandro; Purroy García, Francisco; Vives Pastor, Bárbara; Blanco González, Miguel; Vivancos, José

    2015-01-01

    Background Vitamin K antagonist oral anticoagulants (VKA-OACs) are effective for primary and secondary prevention of embolic events. The rate of haemorrhagic neurological complications in patients admitted to neurology departments in Spain is not yet known. Aims We aimed to determine the clinical and epidemiological characteristics of patients with intracranial haemorrhage secondary to VKA-OACs as well as the incidence of this severe complication. Methods We conducted a retrospective, descriptive, multi-centre study using information from the medical records of all patients admitted to neurology departments, diagnosed with spontaneous intracranial haemorrhage, and treated with VKA-OACs within a 1-year period. We collected demographic and care data from centres, patients' medical records [demographic data, medical history, haemorrhage origin, vascular risk factors, concomitant treatment, and National Institutes of Health Stroke Scale (NIHSS) scores], and patients' outcome at 3 months [independence (modified Rankin Scale score <3) and mortality rate]. Results Twenty-one hospitals serving a population of 8,155,628 inhabitants participated in the study. The total number of cases was 235, the mean age was 78.2 (SD 9.4) years, and the baseline NIHSS score was 11.6 (SD 9.5; median 9; interquartile range 14). The VKA-OACs used were acenocoumarol in 95.3% (224 patients) and warfarin in 4.7% (11 patients). The haemorrhage origin was deep in 29.8%, lobar in 25.5%, intraventricular in 11.5%, extensive in 17.4% (>100 ml), cerebellar in 12.3%, and in the brainstem in 3.4%. The international normalised ratio was within therapeutic ranges at admission (according to indication) in 29.4% (69 patients). The global incidence (cases per 100,000 inhabitants per year) is 2.88. The in-hospital mortality rate was 40%, and 24.3% of the patients were independent at 3 months, while the mortality at 3 months was 42.6%. Conclusion VKA-OAC treatment is associated with a large percentage of all

  9. 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

  10. 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.

  11. 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

  12. Identifying potential predictors of high-quality oral anticoagulation assessed by time in therapeutic international normalized ratio range: a prospective, long-term, single-center, observational study.

    PubMed

    Costa, Gustavo Lamego de Barros; Lamego, Rosana Morais; Colosimo, Enrico A; Valacio, Reginaldo Aparecido; Moreira, Maria da Consolação Vieira

    2012-07-01

    The efficacy and risks of oral anticoagulation are largely associated with maintaining the quality of anticoagulation control. Nevertheless, few studies have addressed which factors, if any, are associated with this control. This study aimed to identify predictors of high-quality oral anticoagulation. A prospective observational study enrolled all adult patients on intended long-term oral anticoagulation attending a public anticoagulation clinic. Patients with high-quality anticoagulation, defined as percentage of time in therapeutic international normalized ratio (INR) range (TTR) ≥66%, were compared with those with poor anticoagulation control (TTR <66%). Measures included cognitive, psychological, and relevant behavioral factors, in addition to traditionally implicated ones, such as age, comorbidity, and concurrent medications. Participation was requested from all 233 patients followed up at the anticoagulation clinic. Eighty-six did not meet the inclusion criteria (49 due to intended anticoagulation duration <90 days, 37 due to the need for a caregiver responsible for medications). A total of 147 patients were enrolled, of whom 13 (8.8%) were lost to follow-up. Therefore, data were analyzed from 134 patients (mean [SD] age, 55 [14.2] years [range, 19-87 years]), who were followed up for a mean (SD) duration of 272 (87) days. The total mean TTR was 64.7%, which is comparable to values achieved in clinical trials. The good-control group had 61 patients (45.5%) (mean TTR, 77.7% [8.5%]) and the poor-control group had 73 patients (54.5%) (mean TTR, 50.4 [11.7%]). On multivariate logistic regression analysis, high-quality anticoagulation was independently associated with regular vitamin K intake, expressed by its variability in daily dosage (odds ratio [OR] = 0.79; 95% CI, 0.64-0.98); male sex (OR = 2.41; 95% CI, 1.06-5.49); duration of anticoagulation treatment >2 months (OR = 3.23; 95% CI, 1.25-8.36); presence of family support (OR = 3.32; 95% CI, 1

  13. [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.

  14. 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.

  15. [New oral anticoagulants for prophylaxis of stroke. Results of an expert conference on practical use in geriatric patients].

    PubMed

    Bahrmann, Philipp; Harms, Fred; Schambeck, Christian Martin; Wehling, Martin; Flohr, Jürgen

    2016-04-01

    Geriatric patients with non-valvular atrial fibrillation (AF) are increasingly being treated with novel oral anticoagulants (NOAC) to prevent ischemic stroke. This article highlights the outcome of an expert meeting on the practical use of NOAC in elderly patients. An interdisciplinary group of experts discussed the current situation of stroke prevention in geriatric patients and its practical management in daily clinical practice. The topic was examined through focused impulse presentations and critical analyses as the basis for the expert consensus. The key issues are summarized in this paper. The European Society of Cardiology (ESC) guidelines from 2012 for the management of patients with non-valvular AF recommend NOAC as the preferred treatment and vitamin K antagonists (VKA) only as an alternative option. Currently, the NOAC factor Xa inhibitors apixaban and rivaroxaban and the thrombin inhibitor dabigatran are more commonly used in clinical practice for patients with AF. Although these drugs have many similarities and are often grouped together it is important to recognize that the pharmacology and dose regimes differ between compounds. Especially n elderly patients NOAC drugs have some advantages compared to VKA, e.g. less drug-drug interactions with concomitant medication and a more favorable risk-benefit ratio mostly driven by the reduction of bleeding. Treatment of anticoagulation in geriatric patients requires weighing the serious risk of stroke against an equally high risk of major bleeding and pharmacoeconomic considerations. Geriatric patients in particular have the greatest benefit from NOAC, which can also be administered in cases of reduced renal function. Regular control of the indications is indispensable, as also for all other medications of the patient. The use of NOAC should certainly not be withheld from geriatric patients who have a clear need for oral anticoagulation.

  16. Comparison of laboratory and immediate diagnosis of coagulation for patients under oral anticoagulation therapy before dental surgery

    PubMed Central

    Kruse-Loesler, Birgit; Kelker, Matthias; Kleinheinz, Johannes

    2005-01-01

    Background Dental surgery can be carried out on patients under oral anticoagulation therapy by using haemostyptic measures. The aim of the study was a comparative analysis of coagulation by laboratory methods and immediate patient diagnosis on the day of the planned procedure. Methods On the planned day of treatment, diagnoses were carried out on 298 patients for Prothrombin Time (PT), the International Normalised Ratio (INR), and Partial Thromboplastin Time (PTT). The decision to proceed with treatment was made with an INR < 4.0 according to laboratory results. Results Planned treatment did not go ahead in 2.7% of cases. Postoperatively, 14.8% resulted in secondary bleeding, but were able to be treated as out-patients. 1.7% had to be treated as in-patients. The average error between the immediate diagnosis and the laboratory method: 95% confidence interval was -5.8 ± 15.2% for PT, -2.7 ± 17.9 s for PTT and 0.23 ± 0.80 for INR. The limits for concordance were 9.4 and -21.1% for PT, 15.2 and -20.5 s for PTT, and 1.03 and -0.57 for INR. Conclusion This study showed a clinically acceptable concordance between laboratory and immediate diagnosis for INR. Concordance for PT and PTT did not meet clinical requirements. For patients under oral anticoagulation therapy, patient INR diagnosis enabled optimisation of the treatment procedure when planning dental surgery. PMID:16316464

  17. A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient.

    PubMed

    Chang, Jeremy B; Quinnies, Kayla M; Realubit, Ronald; Karan, Charles; Rand, Jacob H; Tatonetti, Nicholas P

    2016-07-21

    A central challenge in designing and administering effective anticoagulants is achieving the proper therapeutic window and dosage for each patient. The Hill coefficient, nH, which measures the steepness of a dose-response relationship, may be a useful gauge of this therapeutic window. We sought to measure the Hill coefficient of available anticoagulants to gain insight into their therapeutic windows. We used a simple fluorometric in vitro assay to determine clotting activity in platelet poor plasma after exposure to various concentrations of anticoagulants. The Hill coefficient for argatroban was the lowest, at 1.7 ± 0.2 (95% confidence interval, CI), and the Hill coefficient for fondaparinux was the highest, at 4.5 ± 1.3 (95% CI). Thus, doubling the dose of fondaparinux from its IC50 would decrease coagulation activity by nearly a half, whereas doubling the dose of argatroban from its IC50 would decrease coagulation activity by merely one quarter. These results show a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay.

  18. [Direct oral anticoagulants in atrial fibrillation patients aged 75 years or older: Efficacy and safety balance].

    PubMed

    Fomin, V V; Svistunov, A A; Napalkov, D A; Sokolova, A A; Gabitova, M A

    2017-01-01

    Atrial fibrillation (AF) is one of the most common heart rhythm disorders in the population. Researchers revealed a direct relationship between their incidence and a patient's age long ago. One of the most challenging issues of clinical practice in patients with AF is anticoagulant therapy used in the so-called very elderly patients aged 75 years and older when age itself is a risk factor for developing both thromboembolic and hemorrhagic events due to anticoagulants, regardless of the mechanism of action of the latter. However, scientific data regarding the treatment and prevention of thromboembolic events in elderly and senile patients with AF are very scarce and often uninformative. The data from the EURObservational Research Programme-Atrial Fibrillation Registry Pilot Phase (EORP-AF Pilot) and the randomized clinical studies RELY, ROCKET AF, ARISTOTLE, and AVERROES were analyzed to identify the most safe and most effective anticoagulant for elderly patients (over 75 years). Relying on the analyses of literature data, the authors propose an algorithm based on clinical characteristics for choosing the anticoagulant for patients older than 75 years.

  19. Use of Non-Vitamin K Antagonist Oral Anticoagulants in Special Patient Populations with Nonvalvular Atrial Fibrillation: A Review of the Literature and Application to Clinical Practice.

    PubMed

    Kalabalik, Julie; Rattinger, Gail B; Sullivan, Jesse; Slugocki, Malgorzata; Carbone, Antonia; Rivkin, Anastasia

    2015-06-01

    Atrial fibrillation is a commonly encountered arrhythmia associated with increased risk for thromboembolic events. Anticoagulation is necessary to decrease the risk of ischemic stroke. Traditionally, warfarin has been the only oral pharmacotherapeutic option for long-term anticoagulation in patients with nonvalvular atrial fibrillation (NVAF). Recently, non-vitamin K antagonist oral anticoagulants (NOAC), including dabigatran, rivaroxaban, apixaban, and edoxaban, have become available as alternatives for warfarin in the prevention of stroke in patients with NVAF. Recently published atrial fibrillation guidelines contain new recommendations for risk stratification tools in determining the need for anticoagulant therapy and incorporate NOAC pharmacotherapy options for stroke prevention in patients with NVAF. NOACs offer several advantages over warfarin, including the elimination of routine laboratory monitoring, fewer drug and food interactions, and rapid therapeutic onset and offset. However, the lack of antidote in the case of serious bleeding and lack of data for long-term use in patient populations at risk for bleeding is problematic. Older adults are at high risk for thromboembolic and bleeding events as a result of anticoagulation and require special consideration when selecting anticoagulant therapy. The risk of drug accumulation and bleeding is concerning in the presence of renal impairment. The objective of this review is to provide the clinician with an update on the use of NOACs for NVAF, focusing on older adults and patients with renal impairment in light of recently published atrial fibrillation guidelines. Available data on using NOACs in coronary artery stenting, cardioversion, and ablation are also reviewed.

  20. 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 Central

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

    2016-01-01

    Introduction 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. Aim 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. Materials and Methods 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. Results 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 1st and 3rd day respectively) was significantly lower than the control sites (4.0,1.87 on 1st and 3rd day respectively) p-value (0.001, 0.001 respectively). HDD treated oral surgery wounds achieved statistically significant improved healing both at 1st and 3rd post-operative days (p <0.0001). Conclusion 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. PMID:27790577

  1. 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.

  2. A randomized trial of patient self-managed versus physician-managed oral anticoagulation.

    PubMed

    Sunderji, Rubina; Gin, Kenneth; Shalansky, Karen; Carter, Cedric; Chambers, Keith; Davies, Cheryl; Schwartz, Linda; Fung, Anthony

    2004-09-01

    Self-management (SM) of warfarin by patients is an attractive strategy, particularly if it improves anticoagulation control and can be done safely under minimal physician supervision. To compare the effect of SM with physician-management (PM) on the maintenance of therapeutic anticoagulation. A randomized, open-label eight-month trial was performed. Patients 18 years of age and older were eligible if they were receiving warfarin for at least one month before enrolment and required anticoagulation for at least one year to a target international normalized ratio (INR) of 2.0 to 3.0 or 2.5 to 3.5. Exclusion criteria were a known hypercoaguable disorder, mental incompetence, a language barrier or an inability to attend training sessions. Patients randomly assigned to SM tested their INR using a point-of-care device (Pro Time Microcogulation System, International Technidyne Corporation, USA) and adjusted their warfarin doses using a nomogram. Patients randomly assigned to PM received usual care from their general practitioner. The primary outcome was to demonstrate 20% improvement in anticoagulation control by SM. One hundred forty patients were randomly assigned (70 per group). Thirteen patients dropped out of SM early due to an inability to self-manage. Based on intention-to-treat analysis, there was no difference in the proportion of INR in range (SM 64.8% versus PM 58.7%, P=0.23) or time in target range (SM 71.8% versus PM 63.2%, P=0.14). Patients managing their own therapy spent less time below the therapeutic range (15.0% versus 27.3%, P=0.04). There were three major complications of thrombosis or bleeding, all occurring in the PM arm. All patients who completed SM preferred to continue with that strategy. SM was not significantly better than PM in maintaining therapeutic anticoagulation. SM was feasible and appeared safe in the present study population.

  3. A multifaceted intervention to improve treatment with oral anticoagulants in atrial fibrillation (IMPACT-AF): an international, cluster-randomised trial.

    PubMed

    Vinereanu, Dragos; Lopes, Renato D; Bahit, M Cecilia; Xavier, Denis; Jiang, Jie; Al-Khalidi, Hussein R; He, Wensheng; Xian, Ying; Ciobanu, Andrea O; Kamath, Deepak Y; Fox, Kathleen A; Rao, Meena P; Pokorney, Sean D; Berwanger, Otavio; Tajer, Carlos; de Barros E Silva, Pedro G M; Roettig, Mayme L; Huo, Yong; Granger, Christopher B

    2017-08-25

    Oral anticoagulation is underused in patients with atrial fibrillation. We assessed the impact of a multifaceted educational intervention, versus usual care, on oral anticoagulant use in patients with atrial fibrillation. This study was a two-arm, prospective, international, cluster-randomised, controlled trial. Patients were included who had atrial fibrillation and an indication for oral anticoagulation. Clusters were randomised (1:1) to receive a quality improvement educational intervention (intervention group) or usual care (control group). Randomisation was carried out centrally, using the eClinicalOS electronic data capture system. The intervention involved education of providers and patients, with regular monitoring and feedback. The primary outcome was the change in the proportion of patients treated with oral anticoagulants from baseline assessment to evaluation at 1 year. The trial is registered at ClinicalTrials.gov, number NCT02082548. 2281 patients from five countries (Argentina, n=343; Brazil, n=360; China, n=586; India, n=493; and Romania, n=499) were enrolled from 48 clusters between June 11, 2014, and Nov 13, 2016. Follow-up was at a median of 12·0 months (IQR 11·8-12·2). Oral anticoagulant use increased in the intervention group from 68% (804 of 1184 patients) at baseline to 80% (943 of 1184 patients) at 1 year (difference 12%), whereas in the control group it increased from 64% (703 of 1092 patients) at baseline to 67% (732 of 1092 patients) at 1 year (difference 3%). Absolute difference in the change between groups was 9·1% (95% CI 3·8-14·4); odds ratio of change in the use of oral anticoagulation between groups was 3·28 (95% CI 1·67-6·44; adjusted p value=0·0002). Kaplan-Meier estimates showed a reduction in the secondary outcome of stroke in the intervention versus control groups (HR 0·48, 95% CI 0·23-0·99; log-rank p value=0·0434). A multifaceted and multilevel educational intervention, aimed to improve use of oral

  4. 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.

  5. Adherence to Rivaroxaban Compared with Other Oral Anticoagulant Agents Among Patients with Nonvalvular Atrial Fibrillation.

    PubMed

    McHorney, Colleen A; Ashton, Veronica; Laliberté, François; Germain, Guillaume; Wynant, Willy; Crivera, Concetta; Schein, Jeffrey R; Lefebvre, Patrick; Peterson, Eric D

    2017-09-01

    Adherence to oral anticoagulant (OAC) agents is important for patients with nonvalvular atrial fibrillation (NVAF) to prevent potentially severe adverse events. To compare real-world adherence rates and time to discontinuation for rivaroxaban versus other OACs (apixaban, dabigatran, and warfarin) among patients with NVAF using claims-based data. Health care claims from the IMS Health Real-World Data Adjudicated Claims database (July 2012-June 2015) were analyzed. Adherence rate was defined as the percentage of patients with proportion of days covered (PDC) ≥ 0.80 and ≥ 0.90. Discontinuation was defined as a gap of more than 30 days between the end of a dispensing days of supply and the start date of the next fill, if any. Patients were included if they had ≥ 2 dispensings of rivaroxaban, apixaban, dabigatran, or warfarin at least 180 days apart (the first was considered the index date), had > 60 days of supply, had ≥ 6 months of pre-index eligibility, had ≥ 1 atrial fibrillation (AF) diagnosis pre-index or at index date, and had no valvular involvement. A logistic regression model was used to evaluate adherence to OAC therapy, while a Cox model was used to compare time to discontinuation; both models adjusted for baseline confounders. A total of 13,645 rivaroxaban, 6,304 apixaban, 3,360 dabigatran, and 13,366 warfarin patients were identified. A significantly higher proportion of rivaroxaban users (80.1%) was adherent to therapy (PDC ≥ 0.80 at 6 months) versus apixaban (75.8%), dabigatran (69.2%), and warfarin users (64.5%). After adjustment, the proportion of patients adherent to therapy remained significantly higher for rivaroxaban users versus apixaban (absolute difference [AD] = 5.8%), dabigatran (AD = 9.5%), and warfarin users (AD = 13.6%; all P < 0.001). More pronounced differences were found with a PDC ≥0.90. In addition, rivaroxaban users were significantly less likely to discontinue therapy compared with other OACs after adjustments (all P

  6. 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).

  7. 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 Central

    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

    2016-01-01

    The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage versus 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 British Society of Gastroenterology (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 h 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 h 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). PMID:26873868

  8. Rationale and design of the ODIn-AF Trial: randomized evaluation of the prevention of silent cerebral thromboembolism by oral anticoagulation with dabigatran after pulmonary vein isolation for atrial fibrillation.

    PubMed

    Schrickel, Jan W; Linhart, Markus; Bänsch, Dietmar; Thomas, Daniel; Nickenig, Georg

    2016-02-01

    Oral anticoagulation treatment following clinically successful catheter ablation of atrial fibrillation is controversial. Recent guidelines recommend continuation of oral anticoagulation in all patients with CHA2DS2VASc score ≥ 2 even if there is no evidence of recurrent atrial fibrillation. Due to lack of prospective data, the net clinical benefit of oral anticoagulation after successful ablation in these patients is unclear. As oral anticoagulation bears the risk of severe bleeding events, the ODIn-AF study aims to evaluate the effect of oral anticoagulation on the incidence of silent cerebral embolic events in patients with a high risk for embolic events, but free from symptomatic atrial fibrillation after successful pulmonary vein ablation.

  9. Outpatient treatment of low-risk venous thromboembolism with monotherapy oral anticoagulation: patient quality of life outcomes and clinician acceptance

    PubMed Central

    Kline, Jeffrey A; Kahler, Zachary P; Beam, Daren M

    2016-01-01

    Background Oral monotherapy anticoagulation has facilitated home treatment of venous thromboembolism (VTE) in outpatients. Objectives The aim of this study was to measure efficacy, safety, as well as patient and physician perceptions produced by a protocol that selected VTE patients as low-risk patients by the Hestia criteria, and initiated home anticoagulation with an oral factor Xa antagonist. Methods Patients were administered the Venous Insufficiency Epidemiological and Economic Study Quality of life/Symptoms questionnaire [VEINEs QoL/Sym] and the physical component summary [PCS] from the Rand 36-Item Short Form Health Survey [SF36]). The primary outcomes were VTE recurrence and hemorrhage at 30 days. Secondary outcomes compared psychometric test scores between patients with deep vein thrombosis (DVT) to those with pulmonary embolism (PE). Patient perceptions were abstracted from written comments and physician perceptions specific to PE outpatient treatment obtained from structured survey. Results From April 2013 to September 2015, 253 patients were treated, including 67 with PE. Within 30 days, 2/253 patients had recurrent DVT and 2/253 had major hemorrhage; all four had DVT at enrollment. The initial PCS scores did not differ between DVT and PE patients (37.2±13.9 and 38.0±12.1, respectively) and both DVT and PE patients had similar improvement over the treatment period (42.2±12.9 and 43.4±12.7, respectively), consistent with prior literature. The most common adverse event was menorrhagia, present in 15% of women. Themes from patient-written responses reflected satisfaction with increased autonomy. Physicians’ (N=116) before-to-after protocol comfort level with home treatment of PE increased 48% on visual analog scale. Conclusion Hestia-negative VTE patients treated with oral monotherapy at home had low rates of VTE recurrence and bleeding, as well as quality of life measurements similar to prior reports. PMID:27143861

  10. Patient compliance with new oral anticoagulants after major orthopaedic surgery: rivaroxaban and dabigatran compared with subcutaneous injection of fondaparinux

    PubMed Central

    DI BENEDETTO, PAOLO; VETRUGNO, LUIGI; DE FRANCESCHI, DANIA; GISONNI, RENATO; CAUSERO, ARALDO; ROCCA, GIORGIO DELLA

    2016-01-01

    Purpose the main purpose of our study was to compare patient compliance with the orally administered new oral anticoagulants (NOCs) dabigatran and rivaroxaban compared with subcutaneously injected fondaparinux after major orthopaedic surgery, and to assess patient preference for the oral vs subcutaneous administration route. Methods prophylactic antithrombotic drug therapy with dabigatran (group D; GD, n=32 patients), rivaroxaban (group R; GR, n=38 patients) or fondaparinux (group F; GF, n=30 patients), to prevent deep vein thrombosis, was started immediately after surgery in 100 patients submitted to total hip arthroplasty. Results the patients had a mean age of 68.7±11 years and 62% were female. In GD, 87.5% of patients indicated that they preferred oral intake of medications to subcutaneous injection (12.5%). In GR, 84.2% declared a preference for oral administration over subcutaneous injection (15.8%). In GF, a surprisingly high proportion of patients (73.3%; p < 0.001) declared that they preferred subcutaneous administration of medications over the oral route (26.7%). Overall, the rate of compliance with antithrombotic drug therapy was very high, at 99%. Conclusions intake of the NOAs dabigatran and rivaroxaban following hospital discharge is entirely the responsibility of the patient; a high level of patient compliance with these drugs must therefore be demonstrated in order for them to become well accepted within the medical community. The results of this study showed a very high level of compliance both with orally and subcutaneously administered drugs. Level of evidence Level I, randomized clinical study. PMID:28217657

  11. Safety and efficacy of oral anticoagulation therapy in Chinese patients with concomitant atrial fibrillation and hypertension.

    PubMed

    Ho, L Y; Siu, C W; Yue, W S; Lau, C P; Lip, G Y; Tse, H F

    2011-05-01

    Limited evidence is available on the safety and efficacy of anticoagulants in non-valvular atrial fibrillation (AF) patients with concomitant hypertension. We investigated the safety and efficacy of 476 consecutive anticoagulated Chinese outpatients with non-valvular AF and hypertension. Occurrence of ischaemic stroke and major bleeding, and international normalized ratio (INR) values during these events were recorded. There was no significant difference in anticoagulation control between patients with or without hypertension. INR-specific incidence rates of the events were calculated, which showed no excessive risk for ischaemic stroke (2.5 vs 1.6% per year, P=0.22) or major bleeding (3.9 vs 3.2% per year, P=0.29) in non-valvular AF patients with or without hypertension. In multivariate analysis, congestive heart failure, smoking and high CHADS2 score were independent predictors for ischaemic stroke, whereas use of antiplatelet agents was an independent predictor for bleeding. It can be noted that hypertension was not associated with ischaemic stroke or major bleeding. Hypertensive patients who achieved target blood pressure control (<130/80 mm Hg) had a lower ischaemic stroke (0.9 vs 3.1% per year, P=0.01), but similar bleeding risk compared with those not achieving target blood pressure. Our findings demonstrate the effects of hypertension on the outcomes of warfarin therapy; further investigation is needed to clarify whether more aggressive antihypertensive therapy could result in better outcomes in hypertensive patients with non-valvular AF.

  12. Balancing efficacy and bleeding risk in the prevention of stroke due to atrial fibrillation with newer oral anticoagulants.

    PubMed

    Agarwal, M B; Verma, Subhash; Mahapatra, Manoranjan; Tripathi, A K; Bhave, Abhay; Deshpande, Anand; Vora, Amit; Dalal, Jamshed J; Shah, A B; Bichu, S

    2012-09-01

    With the evaluation and approval of newer oral anticoagulants such as the factor IIa inhibitor, dabigatran etexilate and the factor Xa inhibitors, rivaroxaban and apixaban, strategies for stroke prevention in atrial fibrillation need a thorough re-evaluation of current options. Clinicians are naturally excited about the imminent introduction of these newer drugs that do not need international normalized ratio (INR) monitoring, besides having no drug-food and minimal drug-drug interactions. However, as with all new drugs, it is always prudent to use these judiciously so that they stay in our therapeutic armamentarium for a long time. More than 56 years after the introduction of warfarin we now have three drugs, viz., dabigatran 150 mg bid, rivaroxaban 20 mg od, and apixaban 5 mg bid which were effective in comparison with warfarin in reducing the risk of stroke and bleeding in the landmark trials, RE-LY, ROCKET-AF, and ARISTOTLE respectively. There is a thin dividing line between physiological hemostasis and pathological thrombosis. Routine INR monitoring may not be required but in special situations, such as prior to major surgery, overdose, non-compliance or stroke while on the anticoagulant, one may wish to know whether there are any laboratory measures of efficacy or means of reversal of over anticoagulation. Similar questions may be raised about other situations such as renal dysfunction, cardioversion, ablation procedures, post-stenting, or switch to and from warfarin, heparin or LMWH? This document is an attempt to address these concerns based on available evidence and give physicians a perspective and practice guidelines on how best to use these agents, both old and new, for optimal patient outcomes, maximizing efficacy and minimizing risk.

  13. Effectiveness of self-managed oral anticoagulant therapy in patients with recurrent venous thromboembolism. A propensity-matched cohort study.

    PubMed

    Larsen, Torben Bjerregaard; Skjøth, Flemming; Grove, Erik Lerkevang; Nielsen, Peter Brønnum; Christensen, Thomas Decker

    2016-08-30

    Patient-self-management (PSM) of oral anticoagulant therapy (OAT) with vitamin K antagonists for venous thromboembolism (VTE) has demonstrated efficacy in randomised, controlled trials. The aim of this study was to evaluate the effectiveness of PSM of OAT in everyday clinical practice. Prospectively registered patient data were obtained from databases at two hospitals, and cross-linkage with national patient registries provided detailed information on comorbidities and events. Patients with VTE performing PSM affiliated to major PSM centres were included as cases (N=444). A control group of patients on conventional treatment was propensity score selected in a ratio of 1:5 (N=2220) within matched groups. The effectiveness and safety was estimated using recurrent VTE, major bleeding events and all-cause death as outcomes. We found a lower rate of recurrent VTE among PSM patients compared to the control group with a hazard ratio (HR) of 0.63; 95 % confidence interval (CI) 0.42-0.95, whereas no difference was seen with bleeding (HR: 0.95; 95 % CI 0.44-2.02). The risk of all-cause death was lower for PSM patients (HR: 0.41; 95 % CI 0.21-0.81). A net clinical benefit analysis sums the effect on recurrent VTE and bleeding up to a weighted rate difference of 0.86 (95 % CI 0.00-1.72) in favour of PSM. In conclusion, PSM of anticoagulant treatment was associated with a statistically significant lower rate of recurrent VTE and all-cause death compared to patients on conventionally managed anticoagulant treatment. All major thromboembolic outcomes were less frequent among self-managed patients, whereas bleedings were observed with similar frequency.

  14. Prevention of venous thromboembolism in acutely ill medical patients after the results of recent trials with the new oral anticoagulants.

    PubMed

    Imberti, Davide; Benedetti, Raffaella; Ageno, Walter

    2013-12-01

    Venous thromboembolism (VTE) is a common potentially life-threatening complication in acutely ill medical patients; over 70 % of the fatal episodes of pulmonary embolism during hospitalization occur in non-surgical patients. In the absence of thromboprophylaxis, the incidence of venographically detected deep vein thrombosis is about 15 % in medical patients. Several trials and meta-analyses have clearly demonstrated the prophylactic role of unfractionated heparin, low molecular weight heparin and fondaparinux. Although over the past few years the knowledge of epidemiology, clinical features and prophylaxis in medical patients has significantly improved, there remain a number of controversial areas that require further investigation. Newer VTE risk assessment models have been proposed to select high risk hospitalized medical patients, but they still require external validation; scarce data are available to stratify patients to identify their individual bleeding risk. The optimal duration of thromboprophylaxis in medical patients is still a matter of debate; currently, extended prophylaxis after discharge is not recommended, but it may be required for subgroup of patients with persistently high VTE risk and a negligible risk of bleeding. Based on the results of recent studies, the new oral anticoagulants appear to have a very limited role, if any. However, a better risk stratification of patients who have a persistently increased risk of VTE is warranted to improve the risk to benefit profile of any anticoagulant drug to be used in this setting.

  15. Rivaroxaban and dabigatran etexilate: two new oral anticoagulants for extended postoperative prevention of venous thromboembolism after elective total hip arthroplasty.

    PubMed

    Borris, Lars C

    2010-05-01

    Extended thromboprophylaxis is vital in patients undergoing total hip arthroplasty (THA) because of the prolonged risk of venous thromboembolism (VTE). Despite evidence that extended prophylaxis can reduce the incidence of symptomatic VTE in this high-risk patient population and the evidence-based guideline recommendations, a large proportion of patients still do not receive an adequate duration of thromboprophylaxis. This is partly due to the limitations of conventional anticoagulants, such as the subcutaneous route of administration or the requirement for routine coagulation monitoring and dose adjustment. New oral anticoagulants (such as the direct thrombin inhibitor dabigatran etexilate and the Factor Xa inhibitor rivaroxaban) could address the current unmet need. Phase III clinical studies in VTE prevention in patients undergoing THA and total knee arthroplasty (TKA) showed that dabigatran etexilate was non-inferior to the EU regimen of enoxaparin, but did not achieve non-inferiority to the US regimen of enoxaparin. In contrast, rivaroxaban demonstrated superiority to both enoxaparin regimens for the prevention of VTE after THA and TKA, without a significant increase in major bleeding rates. Their convenient, once-daily, fixed dosing, with no need for routine coagulation monitoring, could facilitate adherence to evidence-based guideline recommendations of extended thromboprophylaxis after THA.

  16. Efficacy and Safety of Direct-Acting Oral Anticoagulants Use in Acute Portal Vein Thrombosis Unrelated to Cirrhosis

    PubMed Central

    Nery, Filipe; Valadares, Diana; Morais, Sara; Gomes, Manuel Teixeira; De Gottardi, Andrea

    2017-01-01

    In acute portal vein thrombosis (APVT) unrelated to cirrhosis, anticoagulant therapy is classically started with low molecular weight heparin or vitamin K antagonists. New direct-acting oral anticoagulants (DOACs) are used in the treatment of venous thrombosis outside the splanchnic vascular bed, but not in the latter. We report a young female with APVT occurring in a non-cirrhotic liver linked to heterozygosity of factor V-Leiden and prothrombin G20210A gene mutations. Rivaroxaban was started, with total recanalization of the left and partial recanalization of the right portal vein branches, without complications. New DOACs do not need daily subcutaneous injections nor routinely blood coagulation control tests, making its use attractive, eventually increasing patient’s compliance. If proved to be safe and effective in the future studies, its use may be extended to PVT treatment. This case shows that rivaroxaban was safe, not only prevented the extension of thrombosis in the portal tract, but also resolved PVT, at least partially. PMID:28496539

  17. 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

  18. Anticoagulation Drug Therapy: A Review

    PubMed Central

    Harter, Katherine; Levine, Michael; Henderson, Sean O.

    2015-01-01

    Historically, most patients who required parenteral anticoagulation received heparin, whereas those patients requiring oral anticoagulation received warfarin. Due to the narrow therapeutic index and need for frequent laboratory monitoring associated with warfarin, there has been a desire to develop newer, more effective anticoagulants. Consequently, in recent years many novel anticoagulants have been developed. The emergency physician may institute anticoagulation therapy in the short term (e.g. heparin) for a patient being admitted, or may start a novel anticoagulation for a patient being discharged. Similarly, a patient on a novel anticoagulant may present to the emergency department due to a hemorrhagic complication. Consequently, the emergency physician should be familiar with the newer and older anticoagulants. This review emphasizes the indication, mechanism of action, adverse effects, and potential reversal strategies for various anticoagulants that the emergency physician will likely encounter. PMID:25671002

  19. New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis

    PubMed Central

    Oldgren, Jonas; Wallentin, Lars; Alexander, John H.; James, Stefan; Jönelid, Birgitta; Steg, Gabriel; Sundström, Johan

    2013-01-01

    Background Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting. Methods and results All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7–14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59–0.84], but increased clinically significant bleeding (HR: 1.79; 1.54–2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80–0.95), but more than doubled the bleeding (HR: 2.34; 2.06–2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies. Conclusion In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with

  20. New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs) Versus Direct Oral Anticoagulants (DOACs)

    PubMed Central

    van Gorp, Rick H.; Schurgers, Leon J.

    2015-01-01

    Vitamin K-antagonists (VKA) are the most widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis for the past 50 years. Due to unfavorable pharmacokinetics VKA have a small therapeutic window, require frequent monitoring, and are susceptible to drug and nutritional interactions. Additionally, the effect of VKA is not limited to coagulation, but affects all vitamin K-dependent proteins. As a consequence, VKA have detrimental side effects by enhancing medial and intimal calcification. These limitations stimulated the development of alternative anticoagulant drugs, resulting in direct oral anticoagulant (DOAC) drugs, which specifically target coagulation factor Xa and thrombin. DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs). As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis. Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake. This review gives an update on oral anticoagulant treatment on the vasculature with a special focus on calcification and vitamin K interaction. PMID:26593943

  1. 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.

  2. Oral Anticoagulants Initiation in Patients with Atrial Fibrillation: Real-World Data from a Population-Based Cohort

    PubMed Central

    Rodríguez-Bernal, Clara L.; Hurtado, Isabel; García-Sempere, Aníbal; Peiró, Salvador; Sanfélix-Gimeno, Gabriel

    2017-01-01

    Objective: Little is known about initial prescription of currently used oral anticoagulants (OAC), and correlated characteristics in real-world practice. We aimed to assess patterns of initiation of Vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOAC) in naive patients with non-valvular atrial fibrillation and the factors associated with starting treatment with NOAC. Methods: Population-based retrospective cohort study of all patients with NVAF who had a first prescription of OAC from November 2011 to February 2014 in the Valencia region, Spain (n = 21,881). Temporal trends of OAC initiation are described for the whole population and by type of OAC and therapeutic agent. Factors associated with starting treatment with NOAC (vs. VKA) were identified using logistic multivariate regression models. Results: Among the patients initiating OAC, 25% started with NOAC 2 years after market release. Regarding temporal trends, prescription of NOAC doubled during the study period. VKA prescription also increased (by around 13%), resulting in a 30% rise in total treatment initiation with OAC during 2011–2014. NOAC initiation (vs. VKA) was associated with a lower baseline risk of thromboembolism and higher income. Conclusions: In this Spanish population-based cohort, initiation of OAC therapy saw a rapid increase, mainly but not exclusively, due to a two-fold rise in the use of NOAC. Initiation with NOAC was associated with a lower baseline risk of thromboembolism and higher income, which opposes the indications of NOAC use and reflects disparities in care. Inadequate prescription patterns might threaten the effectiveness and safety of these therapies, thus monitoring OAC prescription is necessary and should be setting-specific. PMID:28261098

  3. The optimal management of patients on oral anticoagulation undergoing coronary artery stenting. The 10th Anniversary Overview.

    PubMed

    Rubboli, A; Faxon, D P; Juhani Airaksinen, K E; Schlitt, A; Marín, F; Bhatt, D L; Lip, G Y H

    2014-12-01

    Even 10 years after the first appearance in the literature of articles reporting on the management of patients on oral anticoagulation (OAC) undergoing percutaneous coronary intervention with stent (PCI-S), this issue is still controversial. Nonetheless, some guidance for the everyday management of this patient subset, accounting for about 5-8 % of all patients referred for PCI-S, has been developed. In general, a period of triple therapy (TT) of OAC, with either vitamin K-antagonists (VKA) or non-vitamin K-antagonist oral anticoagulants (NOAC), aspirin, and clopidogrel is warranted, followed by the combination of OAC, and a single antiplatelet agent for up to 12 months, and then OAC alone. The duration of the initial period of TT is dependent on the individual risk of thromboembolism, and bleeding, as well as the clinical context in which PCI-S is performed (elective vs acute coronary syndrome), and the type of stent implanted (bare-metal vs drug-eluting). In this article, we aim to provide a comprehensive, at-a-glance, overview of the management strategies, which are currently suggested for the peri-procedural, medium-term, and long-term periods following PCI-S in OAC patients. While acknowledging that most of the evidence has been obtained from patients on OAC because of atrial fibrillation, and with warfarin being the most frequently used VKA, we refer in this overview to the whole population of OAC patients undergoing PCI-S. We refer to the whole population of patients on OAC undergoing PCI-S also when OAC is carried out with NOAC rather than VKA, pointing out, when appropriate, the particular management issues.

  4. A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants

    PubMed Central

    Halvorsen, Sigrun; Ghanima, Waleed; Fride Tvete, Ingunn; Hoxmark, Cecilie; Falck, Pål; Solli, Oddvar; Jonasson, Christian

    2017-01-01

    Aims We aimed to evaluate bleeding risk in clinical practice in patients with atrial fibrillation (AF) being prescribed dabigatran, rivaroxaban, or apixaban compared with warfarin. Methods Using nationwide registries (Norwegian Patient Registry and Norwegian Prescription Database), we identified AF patients with a first prescription of oral anticoagulants between January 2013 and June 2015. Patients were followed until discontinuation or switching of oral anticoagulants, death, or end of follow-up. The primary endpoint was major or clinically relevant non-major (CRNM) bleeding. Results In total 32 675 AF patients were identified (58% men, median age 74 years): 11 427 patients used warfarin, 7925 dabigatran, 6817 rivaroxaban, and 6506 apixaban. After a median follow-up of 173 days (25th, 75th percentile 84, 340), 2081 (6.37%) patients experienced a first major or CRNM bleeding. Using a Cox proportional hazard model adjusting for baseline characteristics, use of apixaban [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.61–0.80, P < 0.001] and dabigatran (HR 0.74, 95% CI 0.66–0.84, P < 0.001) were associated with a lower risk of major or CRNM bleeding compared with warfarin whereas use of rivaroxaban was not (HR: 1.05, 95% CI 0.94–1.17, P = 0.400). Use of dabigatran and rivaroxaban were associated with higher risk of gastrointestinal bleeding, whereas use of apixaban and dabigatran were associated with lower risk of intracranial bleeding, compared with warfarin. Conclusion In this nationwide cohort study in AF patients, apixaban and dabigatran were associated with a lower risk of major or CRNM bleeding compared with warfarin. The risk of gastrointestinal bleeding was higher with rivaroxaban and dabigatran compared with warfarin. PMID:27680880

  5. Oral Anticoagulants Initiation in Patients with Atrial Fibrillation: Real-World Data from a Population-Based Cohort.

    PubMed

    Rodríguez-Bernal, Clara L; Hurtado, Isabel; García-Sempere, Aníbal; Peiró, Salvador; Sanfélix-Gimeno, Gabriel

    2017-01-01

    Objective: Little is known about initial prescription of currently used oral anticoagulants (OAC), and correlated characteristics in real-world practice. We aimed to assess patterns of initiation of Vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOAC) in naive patients with non-valvular atrial fibrillation and the factors associated with starting treatment with NOAC. Methods: Population-based retrospective cohort study of all patients with NVAF who had a first prescription of OAC from November 2011 to February 2014 in the Valencia region, Spain (n = 21,881). Temporal trends of OAC initiation are described for the whole population and by type of OAC and therapeutic agent. Factors associated with starting treatment with NOAC (vs. VKA) were identified using logistic multivariate regression models. Results: Among the patients initiating OAC, 25% started with NOAC 2 years after market release. Regarding temporal trends, prescription of NOAC doubled during the study period. VKA prescription also increased (by around 13%), resulting in a 30% rise in total treatment initiation with OAC during 2011-2014. NOAC initiation (vs. VKA) was associated with a lower baseline risk of thromboembolism and higher income. Conclusions: In this Spanish population-based cohort, initiation of OAC therapy saw a rapid increase, mainly but not exclusively, due to a two-fold rise in the use of NOAC. Initiation with NOAC was associated with a lower baseline risk of thromboembolism and higher income, which opposes the indications of NOAC use and reflects disparities in care. Inadequate prescription patterns might threaten the effectiveness and safety of these therapies, thus monitoring OAC prescription is necessary and should be setting-specific.

  6. Current Status and Outcomes of Direct Oral Anticoagulant Use in Real-World Atrial Fibrillation Patients - Fushimi AF Registry.

    PubMed

    Yamashita, Yugo; Uozumi, Ryuji; Hamatani, Yasuhiro; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Ogawa, Hisashi; Abe, Mitsuru; Morita, Satoshi; Akao, Masaharu

    2017-08-25

    The current status and outcomes of direct oral anticoagulant (DOAC) use have not been widely evaluated in unselected patients with atrial fibrillation (AF) in the real world.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of AF patients who visited the participating medical institutions (n=80) in Fushimi, Kyoto, Japan. Follow-up data with oral anticoagulant (OAC) status were available for 3,731 patients by the end of November 2015. We evaluated OAC status and clinical outcomes according to OAC status. The number (incidence rate) of stroke/systemic embolism (SE) and major bleeding events during the median follow-up of 3.0 years was 224 (2.3%/year) and 177 (1.8%/year), respectively. After the release of DOAC, the prevalence of DOAC use increased gradually and steadily, and that of warfarin, DOAC and no OAC was 37%, 26% and 36%, respectively in 2015. On Cox proportional hazards modeling incorporating change in OAC status as a time-dependent covariate for stroke/SE and major bleeding events, use of DOAC compared with warfarin was not associated with stroke/SE events (HR, 0.95; 95% CI: 0.59-1.51, P=0.82) or major bleeding events (HR, 0.82; 95% CI: 0.50-1.36, P=0.45). In real-world clinical practice, there were no significant differences in stroke/SE events or major bleeding events for DOAC compared with warfarin in patients with AF.

  7. [Cost-effectiveness of apixaban compared to other new oral anticoagulants in patients with non-valvular atrial fibrillation].

    PubMed

    Rudakova, A V; Tatarskiĭ, B A

    2014-01-01

    Atrial fibrillation is associated with development of thromboembolic events. New oral anticoagulants (apixaban, rivaroxaban and dabigatran) are recommended for antithrombotic therapy in patients with non-valvular atrial fibrillation (NVAF) with moderate and high risk of stroke. The objective of this study was to evaluate the cost-effectiveness ratio of apixaban compared to dabigatran and rivaroxaban in patients with NVAF from the Russian Federation national health care system perspective. This analysis used a Markov model that allowed estimation of the incremental cost-effectiveness ratio (ICER) for apixaban compared to rivaroxaban and dabigatran 110 mg and 150 mg over lifetime horizon for patients with NVAF. The model enclosed cardiovascular event rates based on the results of the indirect treatment comparison that combined data from the randomized clinical trials comparing clinical effectiveness and safety of apixaban, rivaroxaban and dabigatran with warfarin (ARISTOTLE, ROCKET-AF, RE-LY). The following cardiovascular events were considered: ischemic and hemorrhagic stroke, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds and myocardial infarction. Direct medical costs were determined based on the rates of the compulsory national medical insurance system. The price of the new oral anticoagulants was taken as a weighted average tender price for the year 2013. In the model both costs and benefits (quality-adjusted life years and life-years) were discounted at 3.5%. Cost-effectiveness threshold was set at 1.4 million rubles per quality-adjusted life year (QALY) gained and corresponded to the three times GDP per capita in 2013 in the Russian Federation. In the base case analysis it was demonstrated that apixaban compared to dabigatran 110 mg and 150 mg and rivaroxaban provided additional 0.101, 0.060 and 0.072 life years as well as additional 0.063; 0.038 and 0.041 QALYs respectively. Over lifetime horizon apixaban

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

    PubMed Central

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

    2016-01-01

    Background 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. Objective To investigate patients’ viewpoints on educational needs and preferred modalities of information delivery. Methods 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. Results 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. Conclusion 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

  9. 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

  10. Oral anticoagulation to prevent thrombosis recurrence in polycythemia vera and essential thrombocythemia.

    PubMed

    Hernández-Boluda, Juan-Carlos; Arellano-Rodrigo, Eduardo; Cervantes, Francisco; Alvarez-Larrán, Alberto; Gómez, Montse; Barba, Pere; Mata, María-Isabel; González-Porras, José-Ramón; Ferrer-Marín, Francisca; García-Gutiérrez, Valentín; Magro, Elena; Moreno, Melania; Kerguelen, Ana; Pérez-Encinas, Manuel; Estrada, Natàlia; Ayala, Rosa; Besses, Carles; Pereira, Arturo

    2015-06-01

    It is unclear whether anticoagulation guidelines intended for the general population are applicable to patients with polycythemia vera (PV) and essential thrombocythemia (ET). In the present study, the risk of thrombotic recurrence was analyzed in 150 patients with PV and ET treated with vitamin K antagonists (VKA) because of an arterial or venous thrombosis. After an observation period of 963 patient-years, the incidence of re-thrombosis was 4.5 and 12 per 100 patient-years under VKA therapy and after stopping it, respectively (P < 0.0005). After a multivariate adjustment for other prognostic factors, VKA treatment was associated with a 2.8-fold reduction in the risk of thrombotic recurrence. Notably, VKA therapy offset the increased risk of re-thrombosis associated with a prior history of remote thrombosis. Both the protective effect of VKA therapy and the predisposing factors for recurrence were independent of the anatomical site involved in the index thrombosis. Treatment periods with VKA did not result in a higher incidence of major bleeding as compared with those without VKA. These findings support the use of long-term anticoagulation for the secondary prevention of thrombosis in patients with PV and ET, particularly in those with history of remote thrombosis.

  11. Reversal of direct oral anticoagulants in hemophilia treatment: ASH meeting 2015.

    PubMed

    Feistritzer, Clemens; Schmidt, Stefan

    2016-01-01

    During the 57(th) annual meeting of the American Society of Hematology 2015 in Orlando, Florida, various aspects in the field of hemostaseology were presented. The Choosing Wisely® campaign pointed out the importance of the critical use of diagnostic tools to rule out pulmonary embolism and questioned the relevance of thrombophilia testing in women undergoing routine infertility evaluation. Furthermore, the approval of idarucizumab, a specific antidote for the reversal of the anticoagulant effects of the direct thrombin inhibitor dabigatran, was highlighted. Finally, hemophilia specialists awaited the results of the SIPPET Trial, which were presented for the first time during the plenary session. Replacement therapy of previously untreated hemophilia A patients with plasma-derived factor VIII containing von Willebrand factor resulted in a lower incidence of inhibitors compared with patients treated with recombinant factor VIII.

  12. 10 years of oral anticoagulant pharmacogenomics: what difference will it make? A critical appraisal.

    PubMed

    Kurnik, Daniel; Loebstein, Ronen; Halkin, Hillel; Gak, Eva; Almog, Shlomo

    2009-12-01

    Since the first report on warfarin pharmacogenetics in 1999, genetic variants have emerged as an important predictor of warfarin maintenance doses before therapy is initiated, raising expectations of greatly improved clinical outcomes. However, much of the information on warfarin sensitivity conveyed by genetic variants is captured by early international normalized ratio values traditionally used to guide dose titration. Thus, inclusion of early international normalized ratios in prediction models reduces the contribution of genetics. Moreover, in large population cohorts, genetics explained only 20-30% of variance in warfarin doses. Finally, even pharmacogenetic prediction models did not predict doses reliably in the majority of at-risk patients with warfarin requirements at the low or high end of the dose range. Currently, the clinical utility and cost-effectiveness of pharmacogenetic-based dosing are being assessed in large prospective trials in various settings. In the interim, enthusiasm for warfarin pharmacogenetics should not supersede strict adherence to traditional measures used to optimize coumarin anticoagulation.

  13. Addressing barriers to optimal oral anticoagulation use and persistence among patients with atrial fibrillation: Proceedings, Washington, DC, December 3-4, 2012.

    PubMed

    Hess, Paul L; Mirro, Michael J; Diener, Hans-Christoph; Eikelboom, John W; Al-Khatib, Sana M; Hylek, Elaine M; Bosworth, Hayden B; Gersh, Bernard J; Singer, Daniel E; Flaker, Greg; Mega, Jessica L; Peterson, Eric D; Rumsfeld, John S; Steinberg, Benjamin A; Kakkar, Ajay K; Califf, Robert M; Granger, Christopher B

    2014-09-01

    Approximately half of patients with atrial fibrillation and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3-4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to define reasons for oral anticoagulant underuse classified in ways that can guide intervention and improve use, to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational data sets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives.

  14. Self-management of oral anticoagulants with a whole blood prothrombin-time monitor in elderly patients with atrial fibrillation.

    PubMed

    Eldor, Amiram; Schwartz, Joseph

    2002-01-01

    The efficacy of oral anticoagulants (OAC) in reducing the incidence of stroke in elderly patients with atrial fibrillation (AF) has been well documented. The intensity of OAC therapy and deviations in the prothrombin time (PT) are the strongest risk factor for bleeding complications in elderly patients. The aim of this study was to evaluate a more rigorous regulation of OAC by the use of a portable whole blood PT-monitor (CoaguChek) in elderly patients with AF (age 65-80 years). The study group consisted of 20 patients, of whom 17 were evaluable, which were trained to use to CoaguChek monitor and adjust their anticoagulant dose for 12 months. The control group, 20 patients matched for age, gender and the duration of OAC treatment, were tested in an anticoagulant clinic and their OAC dose was adjusted by a physician. To validate the PT-monitor results, the patients performed a total of 129 simultaneous venous blood PT tests at various time points. The correlation coefficient R(2) was 0.707 indicating the accuracy of the CoaguChek results. The self-managed patients perform more frequent measurements 46 +/- 8.9 vs. 15.7 +/- 3.1 PT tests per patient. They demonstrated a within the therapeutic range INR in 80.5% of the tests (95% confidence interval, 76.5-84.1%) as compared to 72.4% (95% confidence interval, 68.5-76.5%) in the control group (p = 0.057). The median value for all CoaguChek International Normalized Ratio (INR) recordings was within therapeutic range in the self-management group as well as in the control group. There were fewer INR results below or above the therapeutic range in the study group. None of the patients had hemorrhagic or thrombotic events during the study. Overall, the study group expressed high satisfaction from using the home monitor. We conclude that home PT monitoring and self-management of OAC are feasible in a motivated population of elderly patients with atrial fibrillation and are probably cost effective.

  15. Supporting patients to self-monitor their oral anticoagulation therapy: recommendations based on a qualitative study of patients’ experiences

    PubMed Central

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

    2015-01-01

    Background Clinical trials suggest that oral anticoagulation therapy (OAT) self-monitoring is safe and effective, however little is known about the patient experience of this process. There is a lack of understanding about how best to train and support patients embarking on OAT self-monitoring. Aim To collect in-depth information about patients’ experiences of OAT self-monitoring outside of clinical trial conditions and to produce a set of recommendations on how best to support such patients. Design and setting Semi-structured qualitative interviews with patients who self-monitor and live in England. Method In total, 26 of the 267 (9.7%) who participated in the Cohort study of Anticoagulation Self-Monitoring (CASM) and were still self-monitoring after 12 months’ follow-up were interviewed. Topics discussed included experiences of OAT self-monitoring, healthcare support, training, and decision making. Framework analysis was used. Results Following initial problems using the monitoring device, interviewees described a mostly positive experience. Although less effort was expended attending monitoring appointments with health professionals, effort was required to conduct self-monitoring tests and to interpret and act on the results. Desire to self-manage was variable, especially when dosing advice systems worked promptly and reliably. Interviewees overcame patchy healthcare system knowledge and support of self-monitoring by educating themselves. Family and friends provided support with learning to use the monitor and managing OAT dosage adjustments. Conclusion Better, more-consistent training and health-service support would have alleviated a number of problems encountered by these patients who were self-monitoring. This training and support will become even more important if self-monitoring becomes more accessible to the general population of people on OAT. PMID:26077266

  16. Direct oral anticoagulants in the treatment of acute venous thromboembolism: a systematic review and meta-analysis.

    PubMed

    Gómez-Outes, Antonio; Terleira-Fernández, Ana Isabel; Lecumberri, Ramón; Suárez-Gea, M Luisa; Vargas-Castrillón, Emilio

    2014-10-01

    Acute venous thromboembolism (VTE) is a common disease associated to significant morbidity and mortality. We systematically reviewed and meta-analysed clinical outcomes with direct oral anticoagulants (DOAC: dabigatran, rivaroxaban, apixaban or edoxaban) for treatment of acute VTE. We used MEDLINE and CENTRAL, clinical trials registers, conference proceedings, and websites of regulatory agencies to identify randomised clinical trials of DOAC compared with conventional treatment [parenteral anticoagulant followed by a vitamin K antagonist (VKA)] for acute VTE. Two investigators independently extracted data. Relative risk of recurrent VTE, bleeding events, deaths and a net clinical endpoint (composite of recurrent VTE, major bleeding, and death) were estimated using a random effect meta-analysis (RevMan software). Six trials including 27,127 patients were selected. The risk of recurrent VTE was similar with the DOAC and standard treatment (relative risk 0.91, 95% confidence interval 0.79 to 1.06). The DOAC reduced the risk of major bleeding in comparison with standard treatment (0.62, 0.45 to 0.85) (absolute risk difference, -0.6%; 95% confidence interval -1.0% to -0.3%), but there was heterogeneity across trials in the relative risk of bleeding. No between treatment differences were found in the relative risk of all-cause mortality (0.98, 0.84 to 1.14). The DOAC and conventional treatment differed on the net clinical endpoint (0.85, 0.75 to 0.97). Subgroup analyses in relevant subgroups (index pulmonary embolism, heparin lead-in, age, gender, renal function, presence of cancer), as well as sensitivity analyses, were consistent with the main analysis. The DOAC seem as effective as, and probably safer than standard treatment of acute VTE. The relative efficacy and safety of the DOAC was consistent across a wide range of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Von Willebrand Factor: Multimeric Structure and Functional Activity in Patients With Atrial Fibrillation With and Without Oral Anticoagulation.

    PubMed

    Lopez-Castaneda, Sandra; Valencia-Hernández, Ignacio; Arean, Carlos; Godínez-Hernández, Daniel; Viveros-Sandoval, Martha Eva

    2017-01-01

    von Willebrand factor (vWF) is a multimeric glycoprotein present in blood plasma. It is synthesized in megakaryocytes and endothelial cells, secreted into circulation in the form of high-molecular-weight multimers (HMWMs), and cleaved into shorter, less active multimers by ADAMTS13. It is essential for platelet adhesion and aggregation. Previous studies have investigated the relationship between vWF levels and thromboembolic events with little regard to vWF multimeric structure. Patients with atrial fibrillation (AF) exhibit higher plasma vWF and lower ADAMTS13 levels. One hundred seven patients with AF, 51 anticoagulated and 56 nonanticoagulated, were eligible for the study. Plasma samples were analyzed for vWF antigen, vWF activity, and ADAMTS13; vWF multimers were analyzed by Western blot in 1% to 1.3% sodium dodecyl sulfate agarose gel electrophoresis. Patients with AF without oral anticoagulation (OAC) had significantly higher vWF plasma levels (154.00 [75-201] UI/dL) and vWF activity (60.00% [20%-210%]) compared to patients with OAC (133.50 [90-192] UI/dL, P = <.001; 50.00% [20%-160%], P = .02). Both were specially decreased in patients treated with acenocumarin. Patients without OAC also showed lower ADAMTS13 levels and presence of vWF HMWMs. Patients with AF show higher plasma levels and vWF activity. Moreover, treatment with traditional OAC (acenocumarin) significantly reduced vWF levels. Patients without OAC might have an increased risk of thrombotic events showing lower ADAMTS13 and higher vWF levels. Patients with stroke had higher plasma levels, vWF activity, and HMWMs. Our study suggests that increased vWF levels and presence of HMWMs could be related to cerebrovascular disease and may represent useful biomarkers for stroke in AF.

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

    PubMed

    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

    2016-02-04

    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.

  19. Non-vitamin K antagonist oral anticoagulants versus warfarin for cardioversion of atrial fibrillation in clinical practice: A single-center experience.

    PubMed

    Shibata, Naoki; Morishima, Itsuro; Okumura, Kenji; Morita, Yasuhiro; Takagi, Kensuke; Yoshida, Ruka; Nagai, Hiroaki; Tomomatsu, Toshiro; Ikai, Yoshihiro; Terada, Kazushi; Tsuzuki, Kazuhito; Tsuboi, Hideyuki; Sone, Takahito; Murohara, Toyoaki

    2017-02-01

    Anticoagulation therapy with the vitamin K antagonist (VKA) warfarin has been demonstrated to reduce thromboembolic risk after electrical cardioversion (ECV). However, data concerning ECV with non-VKA oral anticoagulants (NOACs) is limited. The objective of this study was to determine the efficacy and safety of NOACs in patients undergoing ECV in a real-world clinical practice at a single center in Japan. We retrospectively analyzed the data of 406 consecutive patients who underwent ECV for atrial fibrillation (AF) or flutter under anticoagulation with one of the three NOACs (n=149) or with a VKA (n=257). The CHADS2 and HAS-BLED scores were significantly higher in the VKA group, whereas the NOACs group had a tendency toward greater spontaneous echo contrast grades. After ECV, ischemic stroke occurred in three patients of the VKA group and one patient in the NOAC group, all of whom had persistent AF, indicating no significant difference in the thromboembolic event rate within 30 days following ECV. No other thromboembolic events, major bleeding, or death occurred in either group. Among the NOAC and VKA patients in whom we newly introduced an oral anticoagulant to perform ECV, the number of days leading to ECV was significantly lesser for the NOAC patients. NOACs may be used as an alternative to VKAs for ECV and may allow prompt ECV in clinical practices.

  20. Minor oral surgery and interference with anticoagulation in patients taking warfarin: a retrospective study.

    PubMed

    Malden, Nicholas J; Santini, Ario; Mather, Craig I; Gardner, Andrew

    2007-12-01

    Fundamental to the surgical treatment of patients taking warfarin is the monitoring of the international normalised ratio (INR) before and after operation. A postoperative rise in INR was observed to be more common than a postoperative fall, so we decided to test the null hypothesis that there is no difference in the INR before and after minor dentoalveolar surgery. Data from the dental records of 71 patients treated consecutively over an 18-month period were examined, and INR before and after operation tested by a Friedman non-parametric test (ANOVA). Six cases were removed from the study because they required perioperative adjustment of their warfarin. There was a significant increase in the postoperative INR for the whole group. Further analysis showed that a significant increase in the postoperative INR for the multiple extraction and surgical removal group was the most likely cause for the rise in the whole group. There was no significant increase between men and women, those taking antibiotics preoperatively, and those not doing so, or in those having a single tooth extracted. We found an association between the degree of surgical intervention and the likelihood of anticoagulation being affected. Postoperative INR in this group should be monitored carefully.

  1. The new oral anticoagulants and the future of haemostasis laboratory testing

    PubMed Central

    Favaloro, Emmanuel J; Lippi, Giuseppe

    2012-01-01

    The tests currently employed within most haemostasis laboratories to monitor anticoagulant therapy largely comprise the prothrombin time (PT)/ International Normalised Ratio (INR) and the activated partial thromboplastin time (APTT). These are respectively used to monitor Vitamin K antagonists (VKAs) such as warfarin, and unfractionated heparin. Additional tests that laboratories may also employ for assessing or monitoring unfractionated heparin include thrombin time (TT) and the anti-Xa assay, which can also be used to monitor low molecular weight heparin. Several new anti-thrombotic agents have recently emerged, or are in the final process of clinical evaluation. These novel drugs that include Dabigatran etexilate and Rivaroxaban would not theoretically require monitoring; however, testing is useful in specific situations. The tests currently used to monitor VKAs and heparin are typically either too sensitive or too insensitive to the new drugs to be used as ‘typically performed in laboratories’, and may thus require some methodological adjustments to increase or decrease their sensitivity. Alternately, different tests may be better employed in these assessments. Whatever the case, laboratories may soon be performing a reduced or possibly increased number of tests, the same kind of tests but perhaps differently, or conceivably different assay panels. Specific laboratory guidance on the choice of the appropriate test to be ordered according to the drug being administered, as well as on appropriate interpretation of test results, will also be necessary. The current report reviews the current state of play and provides a glimpse to the possible future of the coagulation laboratory. PMID:23092064

  2. 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.

  3. 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

  4. Monitoring oral anticoagulant treatment with the TAS near-patient test system: comparison with conventional thromboplastins.

    PubMed Central

    Kitchen, S; Preston, F E

    1997-01-01

    BACKGROUND: A number of instruments have been developed for determination of prothrombin time (PT) and International Normalised Ratio (INR) at locations not limited to central laboratories. AIM: To evaluate one such portable instrument, the Thrombolytic Assessment System (TAS), which can be used in a near-patient setting. METHODS: Samples from 20 normal subjects and 48 patients treated with warfarin for venous thromboembolic disease were studied. The warfarin group was divided into: initiation phase (n = 10), combined warfarin and heparin (n = 10), stabilised therapy (n = 20), and over anticoagulated patients (n = 8). PTs and INRs were determined in each group using three conventional thromboplastins (Diagen Activated, Manchester Reagent, and Instrumentation Laboratory) and two TAS techniques (whole blood or plasma). An independent International Sensitivity Index (ISI) calibration of the TAS system was performed. RESULTS: Calculated ISIs for the TAS were 1.028 and 0.984 for plasma and whole blood analysis, respectively, compared with manufacturer's values of 0.98 and 0.97. INR results with TAS (whole blood) were 11% less than those obtained with Diagen Activated (p < 0.01) and 16% less than those obtained with Instrumentation Laboratory (p < 0.001) when manufacturers' mean normal PT and ISI were used for TAS INRs. TAS (whole blood) results were similar to TAS plasma or Manchester Reagent results. The use of a locally determined mean normal prothrombin time (MNPT) improved agreement between TAS and the other reagents, abolishing the significant difference between INRs determined with TAS (whole blood) and Diagen Activated techniques. CONCLUSION: The TAS system can be used with whole blood or plasma and produces similar INRs to those obtained with Diagen Activated or Manchester Reagent using manufacturer's ISI and a locally determined MNPT. Results were lower with TAS or Manchester Reagent compared with those obtained with Instrumentation Laboratory thromboplastin

  5. Monitoring oral anticoagulant treatment with the TAS near-patient test system: comparison with conventional thromboplastins.

    PubMed

    Kitchen, S; Preston, F E

    1997-11-01

    A number of instruments have been developed for determination of prothrombin time (PT) and International Normalised Ratio (INR) at locations not limited to central laboratories. To evaluate one such portable instrument, the Thrombolytic Assessment System (TAS), which can be used in a near-patient setting. Samples from 20 normal subjects and 48 patients treated with warfarin for venous thromboembolic disease were studied. The warfarin group was divided into: initiation phase (n = 10), combined warfarin and heparin (n = 10), stabilised therapy (n = 20), and over anticoagulated patients (n = 8). PTs and INRs were determined in each group using three conventional thromboplastins (Diagen Activated, Manchester Reagent, and Instrumentation Laboratory) and two TAS techniques (whole blood or plasma). An independent International Sensitivity Index (ISI) calibration of the TAS system was performed. Calculated ISIs for the TAS were 1.028 and 0.984 for plasma and whole blood analysis, respectively, compared with manufacturer's values of 0.98 and 0.97. INR results with TAS (whole blood) were 11% less than those obtained with Diagen Activated (p < 0.01) and 16% less than those obtained with Instrumentation Laboratory (p < 0.001) when manufacturers' mean normal PT and ISI were used for TAS INRs. TAS (whole blood) results were similar to TAS plasma or Manchester Reagent results. The use of a locally determined mean normal prothrombin time (MNPT) improved agreement between TAS and the other reagents, abolishing the significant difference between INRs determined with TAS (whole blood) and Diagen Activated techniques. The TAS system can be used with whole blood or plasma and produces similar INRs to those obtained with Diagen Activated or Manchester Reagent using manufacturer's ISI and a locally determined MNPT. Results were lower with TAS or Manchester Reagent compared with those obtained with Instrumentation Laboratory thromboplastin.

  6. The evolution of anticoagulant therapy

    PubMed Central

    Franchini, Massimo; Liumbruno, Giancarlo M.; Bonfanti, Carlo; Lippi, Giuseppe

    2016-01-01

    Arterial and venous thromboembolism are leading causes of morbidity and mortality around the world. For almost 70 years, heparins (unfractionated heparin and low molecular weight heparins) and vitamin K antagonists have been the leading therapeutic medical options for the treatment and prevention of thromboembolic disorders. Nevertheless, the many limitations of these traditional anticoagulants have fuelled the search for novel agents over the past 15 years, and a new class of oral anticoagulants that specifically target activated factor X and thrombin has been developed and is now commercially available. In this narrative review, the evolution of anticoagulant therapy is summarised, with a focus on newer oral anticoagulants. PMID:26710352

  7. Comparative effectiveness and safety of oral anticoagulants for atrial fibrillation in real-world practice: a population-based cohort study protocol

    PubMed Central

    Holbrook, Anne; Dormuth, Colin; Morrow, Richard; Lee, Agnes; Troyan, Sue; Li, Guowei; Pullenyegum, Eleanor

    2016-01-01

    Introduction Anticoagulants are arguably the most important drug family of all, based on the frequency and duration of their use, and the clinical importance and frequency of benefits and harms. Several direct acting oral anticoagulants (DOACs) have recently joined warfarin for the treatment of atrial fibrillation, with a resultant significant expansion in use of oral anticoagulants (OACs). Our objectives are to compare safety and effectiveness of DOACs versus warfarin in a full population where anticoagulation management is good and to identify which types of patients do better with DOACs versus warfarin and vice versa. Methods and analysis This is a retrospective cohort study of all adults living in British Columbia who have a diagnosis of atrial fibrillation in hospital or medical service data, and a first prescription for an OAC. Coprimary outcomes are ischaemic stroke and systemic embolism (benefit) and major bleeding (harm). Secondary outcomes include net clinical benefit (composite of stroke, systemic embolism, major bleeds, myocardial infarction, pulmonary embolism and death), drug discontinuation and individual composite item occurrence. We will estimate the effects of treatment in a 2-year follow-up period, using time-to-event models with propensity score adjustment to control confounding. Secondary analyses will examine ‘as treated’ outcomes. Ethics and dissemination The protocol, data creation plan, privacy impact statement and data sharing agreements have been approved. Dissemination is planned via conferences and publications as well as directly to drug policy leaders. Information on the overall comparative effectiveness and safety of DOACs versus warfarin in a country with high quality anticoagulation management, as well as for vulnerable subgroups, will be an important addition to the literature. PMID:27884850

  8. Upper Digestive Bleeding in Atrial Fibrillation: Evaluation of Gastroscopy Prior to Oral Anticoagulant Therapy (GOAT), Prospective, Randomized, Double Blind Study on a Community Population

    PubMed Central

    Lagi, Alfonso; Spini, Simona; Meucci, Elisa; Cartei, Alessandro; Cencetti, Simone

    2011-01-01

    Background The aim of this study was to investigate the incidence of digestive hemorrhages in patients with non-valvular atrial fibrillation (NVAF), scheduled for oral anticoagulant therapy. Methods We conducted, over 24 months, a prospective, randomized, population-based observational study on consecutive patients with recurrent paroxysmal, persistent, or permanent NVAF, scheduled for oral anticoagulant therapy. The study initially included 268 patients with NVAF (162 males and 106 females) with a mean age of 74 years (range 42-86 years). Patients were split into two groups: those undergoing preventive Esophago-Gastro-Duodenoscopy (EGD) (Group A) and those who did not (Group B). All patients positive by EGD underwent medical treatment and subsequent 30-day endoscopic controls showed complete healing. The primary outcome of the study was to determine if previous EGD in patients with NVAF resulted in a low risk of bleeding during oral anticoagulant therapy. The two groups were comparable for most variables. Results Significant differences were found between groups for the incidence of antiarrhythmic drugs and for early hemorrhage (P <0.001). The incidences of early hemorrhages were significantly different between the two groups with 12 in group B (12%) and 2 in group A (1.7%). Conclusions Preventive EGD can identify hidden digestive diseases, which may increase the incidence of early hemorrhages.

  9. Risks and benefits of low molecular-weight heparin and target-specific oral anticoagulant use for thromboprophylaxis in medically ill patients.

    PubMed

    Hale, Genevieve; Brenner, Michael

    2015-10-01

    Venous thromboembolism is the third most common cardiovascular disease and a major cause of inpatient mortality as over 50 % of deep vein thrombosis and pulmonary embolism are undetected in medically treated patients. Several agents are approved for thromboprophylaxis, including warfarin, unfractionated heparin, low molecular-weight heparins, fondaparinux, and target-specific oral anticoagulants. The purpose of this literature review is to discuss the increased risk of venous thromboembolism in medically ill patients and the literature surrounding the efficacy and tolerability of low molecular-weight heparins and target-specific oral anticoagulants for this indication. PubMed, MEDLINE, EBSCOhost, and clinicaltrials.gov were used as search engines in the literature review. Search limits included articles containing human subjects, scholarly (peer-reviewed) journals written in English, and publication dates from 2004 to 2014. Animal studies, non-English articles, and publications dated prior to 2004 were excluded. Recurrent venous thromboembolism remains an ongoing problem affecting thousands of people in the non-surgical population annually. With limited data, it is not likely that target-specific oral anticoagulants will soon replace low molecular-weight heparins or even be considered an alternative until efficacy and tolerability have been established. Until further evidence is disclosed, low molecular-weight heparins and fondaparinux (in the absence of renal dysfunction and low body weight) should continue to be utilized as first-line agents for thromboprophylaxis in medically ill patients. The use of apixaban and rivaroxaban is discouraged for thromboprophylaxis in medically ill patients.

  10. 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.

  11. Rivaroxaban and other novel oral anticoagulants: pharmacokinetics in healthy subjects, specific patient populations and relevance of coagulation monitoring

    PubMed Central

    2013-01-01

    Unlike traditional anticoagulants, the more recently developed agents rivaroxaban, dabigatran and apixaban target specific factors in the coagulation cascade to attenuate thrombosis. Rivaroxaban and apixaban directly inhibit Factor Xa, whereas dabigatran directly inhibits thrombin. All three drugs exhibit predictable pharmacokinetic and pharmacodynamic characteristics that allow for fixed oral doses in a variety of settings. The population pharmacokinetics of rivaroxaban, and also dabigatran, have been evaluated in a series of models using patient data from phase II and III clinical studies. These models point towards a consistent pharmacokinetic and pharmacodynamic profile, even when extreme demographic factors are taken into account, meaning that doses rarely need to be adjusted. The exception is in certain patients with renal impairment, for whom pharmacokinetic modelling provided the rationale for reduced doses as part of some regimens. Although not routinely required, the ability to measure plasma concentrations of these agents could be advantageous in emergency situations, such as overdose. Specific pharmacokinetic and pharmacodynamic characteristics must be taken into account when selecting an appropriate assay for monitoring. The anti-Factor Xa chromogenic assays now available are likely to provide the most appropriate means of determining plasma concentrations of rivaroxaban and apixaban, and specific assays for dabigatran are in development. PMID:23809871

  12. [The use of the new direct oral anticoagulants among older subjects: The limits of the evidence-based medicine?].

    PubMed

    Vogel, T; Lang, P-O; Kaltenbach, G; Karcher, P

    2015-12-01

    The growing use of direct oral anticoagulants, in particular among older subjects, raises questions about the limits of the evidence-based medicine. The phase III studies that have validated the efficacy and the safety profile of these molecules (dabigatran, rivaroxaban, apixaban, edoxaban) in their both indications, the venous thromboembolic disease and the non-valvular atrial fibrillation raise concerns in four major fields: the financial support of pharmaceutical companies, the links of interest for many authors with the industry, the study design (exclusively non-inferiority studies), and the poor representativeness of the older subjects included. All these points are discussed, using data of sub-groups studies, post-marketing studies and recent meta-analysis. The lack of data for the very old subjects, with frailty or comorbidities, remains the main concern from these phase III studies. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  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. Impact of valvular heart disease on oral anticoagulant therapy in non-valvular atrial fibrillation: results from the RAMSES study.

    PubMed

    Başaran, Özcan; Dogan, Volkan; Beton, Osman; Tekinalp, Mehmet; Aykan, Ahmet Çağrı; Kalaycıoğlu, Ezgi; Bolat, Ismail; Taşar, Onur; Şafak, Özgen; Kalçık, Macit; Yaman, Mehmet; İnci, Sinan; Altıntaş, Bernas; Kalkan, Sedat; Kırma, Cevat; Biteker, Murat

    2017-02-01

    The definition of non-valvular atrial fibrillation (NVAF) is controversial. We aimed to assess the impact of valvular heart disease on stroke prevention strategies in NVAF patients. The RAMSES study was a multicenter and cross-sectional study conducted on NVAF patients (ClinicalTrials.gov identifier NCT02344901). The study population was divided into patients with significant valvular disease (SVD) and non-significant valvular disease (NSVD), whether they had at least one moderate valvular disease or not. Patients with a mechanical prosthetic valve and mitral stenosis were excluded. Baseline characteristics and oral anticoagulant (OAC) therapies were compared. In 5987 patients with NVAF, there were 3929 (66%) NSVD and 2058 (34%) SVD patients. The predominant valvular disease was mitral regurgitation (58.1%), followed by aortic regurgitation (24.1%) and aortic stenosis (17.8%). Patients with SVD had higher CHA2DS2VASc [3.0 (2.0; 4.0) vs. 4.0 (2.0; 5.0), p < 0.001] and HAS-BLED [2.0 (1.0; 2.0) vs. 2.0 (1.0; 2.0), p = 0.004] scores compared to patients with NSVD. Overall, 2763 (71.2%) of NSVD and 1515 (73.8%) of SVD patients were on OAC therapy (p = 0.035). When the patients with SVD were analyzed separately, the mean CHA2DS2VASc and HAS-BLED scores were higher in patients with mitral regurgitation compared to patients with aortic regurgitation and aortic stenosis [4.0 (3.0; 5.0), 3.0 (2.0; 4.0), 3.0 (2.0; 4.0) p < 0.001 and 2.0 (1.0; 3.0), 1.0 (1.0; 2.0), 1.0 (0.0; 2.0) p < 0.001, respectively]. In patients with SVD, 65.7% of mitral regurgitation, 82.6% of aortic regurgitation and 88.0% of aortic stenosis patients were on OAC therapy. One out of three NVAF patients had at least one moderate valvular heart disease with the predominance of mitral regurgitation. Patients with SVD were at greater risk of stroke and bleeding compared to patients with NSVD. Although patients with mitral regurgitation should be given more aggressive anticoagulant therapy

  15. Safety of intramuscular influenza vaccine in patients receiving oral anticoagulation therapy: a single blinded multi-centre randomized controlled clinical trial

    PubMed Central

    Casajuana, Josep; Iglesias, Begoña; Fàbregas, Mireia; Fina, Francesc; Vallès, Joan-Antoni; Aragonès, Rosa; Benítez, Mència; Zabaleta, Edurne

    2008-01-01

    Background Influenza vaccines are recommended for administration by the intramuscular route. However, many physicians use the subcutaneous route for patients receiving an oral anticoagulant because this route is thought to induce fewer hemorrhagic side effects. Our aim is to assess the safety of intramuscular administration of influenza vaccine in patients on oral anticoagulation therapy. Methods Design: Randomised, controlled, single blinded, multi-centre clinical trial. Setting: 4 primary care practices in Barcelona, Spain. Participants: 229 patients on oral anticoagulation therapy eligible for influenza vaccine during the 2003–2004 season. Interventions: intramuscular administration of influenza vaccine in the experimental group (129 patients) compared to subcutaneous administration in the control group (100 patients). Primary outcome: change in the circumference of the arm at the site of injection at 24 hours. Secondary outcomes: appearance of local reactions and pain at 24 hours and at 10 days; change in INR (International Normalized Ratio) at 24 hours and at 10 days. Analysis was by intention to treat using the 95% confidence intervals of the proportions or mean differences. Results Baseline variables in the two groups were similar. No major side effects or major haemorrhage during the follow-up period were reported. No significant differences were observed in the primary outcome between the two groups. The appearance of local adverse reactions was more frequent in the subcutaneous administration group (37,4% vs. 17,4%, 95% confidence interval of the difference 8,2% to 31,8%). Conclusion This study shows that the intramuscular administration route of influenza vaccine in patients on anticoagulant therapy does not have more side effects than the subcutaneous administration route. Registration number NCT00137579 at clinicaltrials.gov PMID:18507871

  16. Post-operative Bleeding Risk in Dental Surgery for Patients on Oral Anticoagulant Therapy: A Meta-analysis of Observational Studies

    PubMed Central

    Shi, Quan; Xu, Juan; Zhang, Tong; Zhang, Bin; Liu, Hongchen

    2017-01-01

    Background and Objective: Minor dental surgery is invasive and hemorrhagic. Thus, in patients treated with anticoagulants, the bleeding risk related to these invasive procedures is concerning. The aim of this meta-analysis is to evaluate this risk by comparing the post-operative bleeding rates of oral anticoagulation treatment (OAT) patients (without interrupted or altered anticoagulant intake) with non-OAT patients. Methods: PubMed, Embase and the Cochrane Library were searched for eligible studies that compared the post-operative (following minor dental surgery) bleeding rates of OAT patients without interrupted or altered therapy with those of non-OAT patients. Relative risk (RR) and 95% confidence interval (CI) were calculated. Subgroup analyses were used to identify the association between the bleeding rate and different dental surgeries or anticoagulants. Results: Thirty two full text articles were assessed for eligibility and 20 studies were excluded according to the selection criteria. Finally, 12 studies and a total of 2102 OAT patients and 2271 non-OAT patients were included. A pooled analysis indicated that the post-operative bleeding risk in OAT patients is higher than that of non-OAT patients (RR: 2.794, 95% CI: 1.722–4.532, P = 0.000). The pooled RRs in the dental implant surgery and dental extraction subgroups were 2.136 (95% CI: 0.825–5.531, P = 0.118) and 2.003 (95% CI: 0.987–4.063, P = 0.054), respectively. As for the different oral anticoagulants, the pooled RR in the subgroup of new oral anticoagulants (NOACs) was 1.603 (95% CI: 0.430–5.980, P = 0.482), while the pooled RR in the vitamin K antagonists subgroup was 3.067 (95% CI: 1.838–5.118, P = 0.000). Conclusion: Under current evidence, OAT patients were under a higher post-operative bleeding risk than the non-OAT patients following minor dental surgery. For the dental implant surgeries and dental extractions, our study failed to demonstrate a higher risk of bleeding in the OAT

  17. Post-operative Bleeding Risk in Dental Surgery for Patients on Oral Anticoagulant Therapy: A Meta-analysis of Observational Studies.

    PubMed

    Shi, Quan; Xu, Juan; Zhang, Tong; Zhang, Bin; Liu, Hongchen

    2017-01-01

    Background and Objective: Minor dental surgery is invasive and hemorrhagic. Thus, in patients treated with anticoagulants, the bleeding risk related to these invasive procedures is concerning. The aim of this meta-analysis is to evaluate this risk by comparing the post-operative bleeding rates of oral anticoagulation treatment (OAT) patients (without interrupted or altered anticoagulant intake) with non-OAT patients. Methods: PubMed, Embase and the Cochrane Library were searched for eligible studies that compared the post-operative (following minor dental surgery) bleeding rates of OAT patients without interrupted or altered therapy with those of non-OAT patients. Relative risk (RR) and 95% confidence interval (CI) were calculated. Subgroup analyses were used to identify the association between the bleeding rate and different dental surgeries or anticoagulants. Results: Thirty two full text articles were assessed for eligibility and 20 studies were excluded according to the selection criteria. Finally, 12 studies and a total of 2102 OAT patients and 2271 non-OAT patients were included. A pooled analysis indicated that the post-operative bleeding risk in OAT patients is higher than that of non-OAT patients (RR: 2.794, 95% CI: 1.722-4.532, P = 0.000). The pooled RRs in the dental implant surgery and dental extraction subgroups were 2.136 (95% CI: 0.825-5.531, P = 0.118) and 2.003 (95% CI: 0.987-4.063, P = 0.054), respectively. As for the different oral anticoagulants, the pooled RR in the subgroup of new oral anticoagulants (NOACs) was 1.603 (95% CI: 0.430-5.980, P = 0.482), while the pooled RR in the vitamin K antagonists subgroup was 3.067 (95% CI: 1.838-5.118, P = 0.000). Conclusion: Under current evidence, OAT patients were under a higher post-operative bleeding risk than the non-OAT patients following minor dental surgery. For the dental implant surgeries and dental extractions, our study failed to demonstrate a higher risk of bleeding in the OAT patients

  18. [Giant thrombus in the left atrium after mitral bioprosthesis implantation: is standard oral anticoagulation always sufficient?].

    PubMed

    Tomaszuk-Kazberuk, Anna; Lisowska, Anna; Sobkowicz, Bożena; Młodawska, Elżbieta; Łopatowska, Paulina; Kosacka, Urszula; Krajewska, Agnieszka; Musiał, Włodzimierz J

    2013-01-01

    We present a case of 70-year old male after coronary by-pass surgery and mitral bioprosthesis implantation due to infective endocarditis, with continuous atrial fibrillation, who was admitted to the hospital due to the worsening of the heart failure. He was on oral antivitamine K agents with therapeutic value of INR. On echocardiography we found enlargement of all cavities with extremely big left atrium (9.5 cm) and poor contractile left ventricular function (EF 25%). An enormously big old thrombus was found in the left atrium. The patient was disqualified from surgical treatment. Treatment with unfractionated heparin was unsuccessful. We discuss if standard antithrombotic treatment is always sufficient in such unusual cases.

  19. Hospital-based clinical implications of the novel oral anticoagulant, dabigatran etexilate, in daily practice.

    PubMed

    Wilcox, Ryan; Pendleton, Robert C; Smock, Kristi J; Rodgers, George M

    2011-08-01

    Dabigatran etexilate is an oral direct thrombin inhibitor that has been approved by the US Food and Drug Administration for the prevention of stroke and systemic embolization in patients with nonvalvular atrial fibrillation. It has also been studied for the prevention of venous thromboembolism in patients after hip and knee arthroplasty and for treatment of venous thromboembolism. Although routine laboratory monitoring is not needed, there are clinical scenarios in which physicians will need to have a clear understanding of drug pharmacology, laboratory assessment, and reversibility of this drug to make appropriate clinical decisions. We review the pharmacology of dabigatran etexilate, pertinent clinical trials, and the effects of dabigatran etexilate on prothrombin time, activated partial thromboplastin time, thrombin time, and ecarin clotting time. We also provide an approach to patients on dabigatran etexilate who are bleeding, have a suspected therapeutic failure, or require periprocedural management.

  20. Safety of dental extraction among consecutive patients on oral anticoagulant treatment managed using a specific dental management protocol.

    PubMed

    Zanon, Ezio; Martinelli, Franco; Bacci, Christian; Cordioli, GianPiero; Girolami, Antonio

    2003-01-01

    We found no prospective studies on dental extraction in anticoagulated patients in the literature, even though most authors suggest that there is no need to change anticoagulant treatment and to utilize a local haemostatic measure after extraction. In the present study, we have verified the incidence of bleeding complications after dental extraction in a group of 250 consecutive anticoagulated patients. Two hundred and fifty non-anticoagulated subjects requiring dental extraction represented the control group. In all patients, anticoagulant treatment was not changed (International Normalized Ratio, 1.8-4) and local haemostatic measures (fibrin sponge, silk suture and a gauze saturated with tranexamic acid) were used. All procedures were performed in an outpatient clinic setting. We registered four bleeding complications in the group of anticoagulated patients and three in the control group. The difference of bleeding complications in the two groups was not statistically different (relative risk, 1.14; 95% confidence interval, 0.29-6.04; P = 0.7). None of the post-operative late bleeding required hospitalization and/or blood transfusions, and further local measures were sufficient to stop the bleeding. The protocol proposed in the present study makes dental extractions in anticoagulated patients possible on an outpatient basis with a cost reduction for the community and minor discomfort for the patients.

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

    PubMed

    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

    2016-02-04

    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.

  2. A disease management protocol for outpatient perioperative bridge therapy with enoxaparin in patients requiring temporary interruption of long-term oral anticoagulation.

    PubMed

    Spyropoulos, Alex C; Jenkins, Patti; Bornikova, Larissa

    2004-05-01

    Traditional perioperative bridge therapy for patients receiving long-term oral anticoagulation involves weight-adjusted intravenous unfractionated heparin (UFH) in the perioperative period during temporary discontinuation of the oral anticoagulant. We sought to determine whether an alternate strategy of outpatient-based perioperative disease management with low-molecular-weight heparin (LMWH) as bridge therapy provides the potential for cost savings. Retrospective review of all clinic notes from an anticoagulation clinic. An integrated, staff-model health maintenance organization. Patients receiving long-term warfarin therapy from January 1998-March 2002 who received perioperative bridge therapy with the LMWH enoxaparin 1 mg/kg twice/day subcutaneously A total of 126 bridge therapy encounters in 84 patients receiving LMWH as perioperative bridge therapy were identified, with 48 of those encounters involving patients with at least one mechanical heart valve. A total of 1108 hospital bed days were saved. Based on 1996 cost estimates, the total approximate cost savings for the 4.25 years of the outpatient bridge therapy program was dollars 903,020. No thrombotic events were reported. Three major hemorrhagic events that required discontinuation of LMWH were reported. Outpatient-based disease management protocols and the LMWH enoxaparin as bridge therapy during temporary discontinuation of warfarin for an elective surgical procedure resulted in cost savings of approximately dollars 212,475/year in an integrated health maintenance organization. In addition, this strategy appears both safe and effective.

  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. Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study.

    PubMed

    Nielsen, Peter Brønnum; Skjøth, Flemming; Søgaard, Mette; Kjældgaard, Jette Nordstrøm; Lip, Gregory Y H; Larsen, Torben Bjerregaard

    2017-02-10

    Objective To examine clinical effectiveness and safety of apixaban 2.5 mg, dabigatran 110 mg, and rivaroxaban 15 mg compared with warfarin among patients with atrial fibrillation who had not previously taken an oral anticoagulant.Design Propensity weighted (inverse probability of treatment weighted) nationwide cohort study.Setting Individual linked data from three nationwide registries in Denmark.Participants Patients with non-valvular atrial fibrillation filling a first prescription for an oral anticoagulant from August 2011 to February 2016. Patients who filled a prescription for a standard dose non-vitamin K antagonist oral anticoagulant (novel oral anticoagulants, NOACs) were excluded. To control for baseline differences in the population, a propensity score for receipt of either of the four treatment alternatives was calculated to apply an inverse probability treatment weight.Intervention Initiated anticoagulant treatment (dabigatran 110 mg, rivaroxaban 15 mg, apixaban 2.5 mg, and warfarin).Main outcome measures Patients were followed in the registries from onset of treatment for the primary effectiveness outcome of ischaemic stroke/systemic embolism and for the principal safety outcome of any bleeding events.Results Among 55 644 patients with atrial fibrillation who met inclusion criteria, the cohort was distributed according to treatment: apixaban n=4400; dabigatran n=8875; rivaroxaban n=3476; warfarin n=38 893. The overall mean age was 73.9 (SD 12.7), ranging from a mean of 71.0 (warfarin) to 83.9 (apixaban). During one year of follow-up, apixaban was associated with higher (weighted) event rate of ischaemic stroke/systemic embolism (4.8%), while dabigatran, rivaroxaban, and warfarin had event rates of 3.3%, 3.5%, and 3.7%, respectively. In the comparison between a non-vitamin K antagonist oral anticoagulant and warfarin in the inverse probability of treatment weighted analyses and investigation of the effectiveness outcome, the hazard ratios

  5. Practical and clinical considerations in assessing patients with atrial fibrillation for switching to non-vitamin K antagonist oral anticoagulants in primary care

    PubMed Central

    Guimarães, Patrícia O; Kaatz, Scott; Lopes, Renato D

    2015-01-01

    Atrial fibrillation (AF) is an important risk factor for thromboembolic events, and anticoagulation therapy can reduce this risk. Vitamin K antagonists (VKAs), such as warfarin, have been used for decades in patients with AF for stroke prevention. Currently, non-VKA oral anticoagulants (NOACs) are approved and available for non-valvular AF patients who are at increased risk of stroke. These agents are safe and effective and have important advantages over VKAs, such as significant reduction in intracranial hemorrhage and no need for routine laboratory monitoring. Thus, should all VKA-treated patients be switched to a NOAC? The aims of this article are: 1) to review the advantages of NOACs over VKAs; 2) to identify the group of patients who most benefit from receiving a NOAC and, therefore, are higher priority to be switched from VKAs; and 3) to provide clinical and practical guidance on how to switch patients safely from VKAs to NOACs. PMID:26379443

  6. Direct oral anticoagulants in the secondary prevention of stroke and transient ischemic attack in patients with atrial fibrillation.

    PubMed

    Arnao, Valentina; Agnelli, Giancarlo; Paciaroni, Maurizio

    2015-08-01

    In patients with non-valvular atrial fibrillation (NVAF) and history of transient ischemic attack (TIA) or stroke, the rate of vascular events is higher in comparison to patients without history of stroke or TIA. A meta-analysis of direct oral anticoagulants (DOACs) studies, including only patients with history of stroke or TIA, report a significant reduction of 15 % in the rates of composite of stroke and systemic embolism in patients treated with DOACs, compared to those treated with warfarin. Furthermore, a reduction of 14 % for major bleeding, as well as a 56 % reduction for hemorrhagic stroke over a median follow-up of 1.8-2.0 years is reported. The combination of DOACs and antiplatelet agents carries the potential of additive benefits in patients with NVAF and other vascular diseases. However, the rate of major bleeding is higher among patients who receive concomitantly antiplatelet agents, compared to those taking only a single drug category. The risk of major bleeding seems to be higher among patients receiving dual antiplatelet agents, compared to those receiving a single antiplatelet drug. When NVAF is associated with an acute coronary syndrome requiring dual antiplatelet therapy (e.g. coronary angioplasty and stenting), DOACs plus this therapy should be considered. However, this therapy has to be administered for the shortest possible time, according to the patient's haemorrhagic and thrombotic risks, and stent type. When NVAF is associated with carotid stenosis, a single antiplatelet therapy should be considered. Regarding carotid revascularization, it seems preferable to treat these patients with endarterectomy, so to avoid dual antiplatelet therapy, which is generally administered after stenting.

  7. 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.

  8. Asian Patients with Stroke plus Atrial Fibrillation and the Dose of Non-Vitamin K Oral Anticoagulants

    PubMed Central

    Bang, Oh Young; Hong, Keun-Sik; Heo, Ji Hoe

    2016-01-01

    After recent randomized control trials (RCTs), non-vitamin K oral anticoagulants (NAOAs) are now widely being used in patients with atrial fibrillation (AF) worldwide. However, current guidelines for the use of NOACs in patients with AF are derived mostly using a Caucasian population and non-stroke patients. Relatively few Asian patients with AF and stroke are included in the recent RCTs. As a result, the optimal use of NOACs in this particular group of patients is remains to be settled. The optimal dose of NOACs and response to current dose of NOACs of Asian patients with AF and stroke may differ from those of westerners and patients without stroke. We reviewed available research on NOACs by searching PubMed and ClinicalTrials.gov published in English up to December 2015. In this review, the characteristics of Asian AF patients with prior stroke/transient ischemic attack, which might influence the efficacy and safety profiles of NOACs, are discussed. In addition, we summarize the risk factors for bleeding complications on NOACs, which are related or unrelated with the blood level of NOACs. Lastly, we provide recent data of reduced dose of NOACs from RCTs or large cohorts. The results reviewed herein call for clinical trials to test whether a reduced dose of NOACs is beneficial in Asian patients with AF and stroke. In the meantime, further researches are needed to establish the safety and efficacy of dose-adjusted NOACs considering both blood levels of NOACs and fragility of patients in Asian patients with AF and stroke. PMID:27170995

  9. A novel prothrombin time method to measure all non-vitamin K-dependent oral anticoagulants (NOACs).

    PubMed

    Lindahl, Tomas L; Arbring, Kerstin; Wallstedt, Maria; Rånby, Mats

    2017-09-11

    There is a clinical need for point-of-care (POC) methods for non-vitamin K-dependent oral anticoagulants (NOACs). We modified a routine POC procedure: Zafena's Simple Simon™ PT-INR, a room-temperature, wet-chemistry prothrombin time method of the Owren-type. To either increase or decrease NOAC interference, two assay variants were devised by replacing the standard 10 µL end-to-end capillary used to add the citrated plasma sample to 200 µL of prothrombin time (PT) reagent by either a 20 µL or a 5 µL capillary. All assay variants were calibrated to show correct PT results in plasma samples from healthy and warfarin-treated persons. For plasmas spiked with dabigatran, apixaban, or rivaroxaban, the 20 µL variant showed markedly higher PT results than the 5 µL. The effects were even more pronounced at room temperature than at +37 °C. In plasmas from patients treated with NOACs (n = 30 for each) there was a strong correlation between the PT results and the concentration of NOACs as determined by the central hospital laboratory. For the 20 µL variant the PT response of linear correlation coefficient averaged 0.90. The PT range was INR 1.1-2.1 for dabigatran and apixaban, and INR 1.1-5.0 for rivaroxaban. Using an INR ratio between the 20 µL and 5 µL variants (PTr20/5) made the NOAC assay more robust and independent of the patient sample INR value in the absence of NOAC. Detection limits were 80 µg/L for apixaban, 60 µg/L for dabigatran, and 20 µg/L for rivaroxaban. A wet-chemistry POC PT procedure was modified to measure the concentrations of three NOACs using a single reagent.

  10. 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.

  11. Drug persistence with rivaroxaban therapy in atrial fibrillation patients—results from the Dresden non-interventional oral anticoagulation registry

    PubMed Central

    Beyer-Westendorf, Jan; Förster, Kati; Ebertz, Franziska; Gelbricht, Vera; Schreier, Thomas; Göbelt, Maria; Michalski, Franziska; Endig, Heike; Sahin, Kurtulus; Tittl, Luise; Weiss, Norbert

    2015-01-01

    Aims Worldwide, rivaroxaban is increasingly used for stroke prevention in atrial fibrillation (SPAF) but little is known about the rates of or reasons for rivaroxaban discontinuations in daily care. Using data from a prospective, non-interventional oral anticoagulation (NOAC) registry, we analysed rivaroxaban treatment persistence. Methods and results Persistence with rivaroxaban in SPAF was assessed in an ongoing, prospective, non-interventional registry of >2600 NOAC patients from daily care using the Kaplan–Meier time-to-first-event analysis. Reasons for and management of rivaroxaban discontinuation were assessed. Potential baseline risk factors for treatment discontinuation were evaluated using Cox regression analysis. Between October 2011 and April 2014, 1204 rivaroxaban SPAF patients were enrolled [39.3% switched from vitamin K antagonists (VKAs) and 60.7% newly treated patients]. Of these, 223 patients (18.5%) stopped rivaroxaban during follow-up (median 544 days), which translates into a discontinuation rate of 13.6 (95% CI 11.8–15.4) per 100 patient-years. Most common reasons for treatment discontinuations were bleeding complications (30% of all discontinuations), followed by other side-effects (24.2%) and diagnosis of stable sinus rhythm (9.9%). A history of chronic heart failure (HR 1.43; 95% CI 1.09–1.87; P = 0.009) or diabetes (HR 1.39; 95% CI 1.06–1.82; P = 0.018) were the only statistically significant baseline risk factors for rivaroxaban discontinuation. After discontinuation of rivaroxaban, patients received antiplatelet therapy (31.8%), VKA (24.2%), another NOAC (18.4%), heparin (9.9%), or nothing (15.7%). Conclusion Our data indicate that overall persistence with rivaroxaban therapy is high, with a discontinuation rate of ∼15% in the first year of treatment and few additional discontinuations thereafter. PMID:25694537

  12. Thromboprophylaxis with enoxaparin and direct oral anticoagulants in major orthopedic surgery and acutely ill medical patients: a meta-analysis.

    PubMed

    Cimminiello, Claudio; Prandoni, Paolo; Agnelli, Giancarlo; Di Minno, Giovanni; Polo Friz, Hernan; Scaglione, Francesco; Boracchi, Patrizia; Marano, Giuseppe; Harenberg, Job

    2017-07-29

    Subjects undergoing major orthopedic surgery and acutely ill hospitalized medical patients represent a population at medium-high risk for venous thromboembolism (VTE). They are treated with low molecular weight heparin (LMWH) and direct oral anticoagulants [DOACs] for VTE prevention. We conducted a meta-analysis of phase III randomized clinical trials evaluating LMWH enoxaparin versus DOACs for prophylaxis of VTE by combining studies including patients undergoing elective total hip and knee replacement surgery, and acutely ill hospitalized medical subjects. Studies were searched using PubMed, MEDLINE, and EMBASE databases until December 2016. Differences in clinical outcomes for efficacy and safety endpoints between treatment groups were expressed as risk differences with 95% confidence intervals (95% CI), using random effects regression models. Fourteen RCTs were considered (60,467 subjects). Overall mortality, symptomatic deep venous thrombosis, non-fatal pulmonary embolism (PE) major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) are not different between treatment regimens. Treatment with LMWH enoxaparin is associated with a lower risk of fatal PE plus VTE-related death compared therapy with DOACs (RD = 0.040%, 95% CI 0.001-0.080%, p = 0.0434). Subgroup analysis shows an incidence of MB (RD = 0.181%, 95% CI 0.029-0.332%, p = 0.0033) and CRNMB (RD = 0.546%, 95% CI 0.009-1.082%, p = 0.0462) in patients treated with 40 mg OD enoxaparin compared to DOACs. In major orthopedic surgery and acutely ill hospitalized medical patients, DOACs do not offer clear advantages in terms of clinical efficacy compared to enoxaparin. The advantage of the latter in terms of major and CRNMB, when used at a dose of 40 mg, is statistically significant, but small in terms of clinical relevance.

  13. Effects of oral anticoagulant therapy in older medical in-patients with atrial fibrillation: a prospective cohort observational study.

    PubMed

    Bo, Mario; Li Puma, Federica; Badinella Martini, Marco; Falcone, Yolanda; Iacovino, Marina; Grisoglio, Enrica; Menditto, Elena; Fonte, Gianfranco; Brunetti, Enrico; Isaia, Giovanni Carlo; D'Ascenzo, Fabrizio; Gaita, Fiorenzo

    2017-06-01

    Uncertainties about efficacy and safety of oral anticoagulant therapy (OAT) among older and frail medical patients with atrial fibrillation (AF) largely contribute to under-prescription of these drugs. In this prospective observational cohort study, we investigated mortality, and ischemic and hemorrhagic events, in hospital-discharged older patients with AF. Stroke and bleeding risk were evaluated using CHA2DS2-VASC and HAS-BLED scores. Comorbidity, frailty, cognitive and nutritional status and functional autonomy were evaluated using standardized scales. Independent associations between clinical variables, including OAT use, and all-cause mortality, fatal and non-fatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. Of 452 patients included (mean age 81.6 years, 54.9 % women, roughly 30 % cognitively impaired and/or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.6 and 2.8, respectively), 151 (33.4 %) died during a mean follow-up period of 300.5 days; ischemic and hemorrhagic stroke occurred in 4.0 and 0.4 % of patients, respectively, and major bleedings in 6.2 %. After multivariate analysis, OAT at discharge was associated with lower overall mortality and reduced occurrence of ischemic stroke, the first finding being confirmed in propensity score matched analysis. Among older vulnerable AF patients with high post discharge death rate, OAT was associated, among other multiple factors, with reduced mortality and lower occurrence of ischemic stroke.

  14. Efficacy and safety of the drugs used to reverse direct oral anticoagulants: a systematic review and meta-analysis.

    PubMed

    da Luz, Luis Teodoro; Marchand, Mylene; Nascimento, Bartolomeu; Tien, Homer; Nathens, Avery; Shah, Prakesh

    2017-07-01

    Direct oral anticoagulants (DOACs) are effective and safe for prophylaxis and treatment of thromboembolic phenomena. However, managing DOACs during bleeding emergencies is challenging. A systematic review and meta-analysis was conducted on studies addressing efficacy and safety of the drugs used for reversal of DOACs. Medline, Embase, Cochrane Library, and ClinicalTrials.gov were searched up to September 2016. Studies that examined clinical and laboratory effects of drugs used to reverse DOACs were included. Risk of bias was assessed using Newcastle-Ottawa scale and Cochrane Collaboration tool. Primary and secondary outcomes assessed were reversal of clinical bleeding, clotting assays, and safety, respectively. Overall effect estimates were pooled, and clinical and statistical heterogeneity were assessed. Meta-analysis was conducted using random-effects model. Four cohort studies in bleeding patients (n = 230) and eight randomized controlled trials in healthy volunteers (n = 381) were included, both with moderate risk of bias. Reversal of clotting assays in healthy volunteers was frequently reported, demonstrating that prothrombin complex concentrate (PCC) reversed prothrombin time (PT) and endogenous thrombin potential (ETP) substantially. For PT, pooled mean difference was 1.68 seconds (95% confidence interval [CI], -0.33 to 3.70 sec; p < 0.01; I(2)  = 97%). For ETP, pooled mean difference was 2.16 seconds (95% CI, 0.57 to 3.75 sec; p < 0.01; I(2)  =( ) 98%). Andexanet alfa and idarucizumab both reverse clotting assays. No important safety concerns were identified. Clotting assays are partially reversed by PCC in healthy volunteers. Idarucizumab and andexanet alfa have solid laboratory reversal effect and potential to be clinically efficacious and safe. However, clinical evidence is still lacking for all agents. © 2017 AABB.

  15. 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

  16. Potential Effect of Substituting Estimated Glomerular Filtration Rate for Estimated Creatinine Clearance for Dosing of Direct Oral Anticoagulants.

    PubMed

    Schwartz, Janice B

    2016-10-01

    To determine the potential effect of substituting glomerular filtration rate (GFR) estimates for renal clearance estimated using the Cockcroft-Gault method (CrCL-CG) to calculate direct oral anticoagulant (DOAC) dosing. Simulation and retrospective data analysis. Community, academic institution, nursing home. Noninstitutionalized individuals aged 19 to 80 from the National Health and Nutrition Examination Survey (NHANES) (2011/12) (n = 4,687) and medically stable research participants aged 25 to 105 (n = 208). Age, height, weight, sex, race, serum creatinine, CrCL-CG, and GFR (according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations). Outcome measures were dosing errors if GFR were to be substituted for CrCL-CG. Renal clearance estimates according to all methods were highly correlated (P < .001), although at lower clearances, substitution of GFR estimates for CrCL-CG resulted in failure to recognize needs for dose reductions of rivaroxaban or edoxaban in 28% of NHANES subjects and 47% to 56% of research subjects. At a CrCL-CG of less than 30 mL/min, GFR estimates missed indicated dosage reductions for dabigatran in 18% to 21% of NHANES subjects and 57% to 86% of research subjects. Age and weight contributed to differences between renal clearance estimates (P < .001), but correction of GFR for body surface area (BSA) did not reduce dosing errors. At a CrCL-CG greater than 95 mL/min, edoxaban is not recommended, and GFR esimates misclassified 24% of NHANES and 39% of research subjects. Correction for BSA reduced misclassification to 7% for NHANES and 14% in research subjects. Substitution of GFR estimates for estimated CrCl can lead to failure to recognize indications for reducing DOAC dose and potentially higher bleeding rates than in randomized trials. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  17. Evaluation of the main coagulation tests in the presence of hemolysis in healthy subjects and patients on oral anticoagulant therapy.

    PubMed

    D'Angelo, G; Villa, C; Tamborini, A; Villa, S

    2015-12-01

    Our study was designed to evaluate, on healthy subjects and patients on oral anticoagulant therapy vitamin K antagonist (OAT-vka), the possible interference caused by hemolysis on the main coagulation tests. To obtain hemolyzed samples, two methods were used: heat shock and mechanical system. The coagulation tests on hemolyzed samples were performed employing optical automated analyser BCSxp (Siemens Healthcare(®)). Moreover, the prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests were also carried out manually using an electromechanical device (KC4 - Amelung). The PT test, on healthy subjects, in case of moderate hemolysis can be performed without significant interference on automatic instrument. On manual instrument, the PT test can be performed even in case of marked hemolysis. For patients on OAT-vka, the PT test in case of marked hemolysis can be performed both on automatic and manual instrument. For the aPTT test, it can be carried out manually, because also in case of marked hemolysis a statistically significant difference was not observed. For the fibrinogen test, a dramatic concentration decrease was already clear for weak hemolysis. A decreased function on antithrombin test was statistically significant for mild-moderate hemolysis. The D-dimer test showed increased values for mild hemolysis. The rejection of hemolyzed sample and/or the request of a second sample are not always the proper attitudes to take for performing clotting tests. The rational management of the hemolyzed samples decreases the employment of both nursing and technical staff significantly, the turnaround time and, consequently, does not lead to additional costs for each patient involved. © 2015 John Wiley & Sons Ltd.

  18. 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.

  19. Anticoagulation-related nephropathy.

    PubMed

    Wheeler, D S; Giugliano, R P; Rangaswami, J

    2016-03-01

    Anticoagulation-related nephropathy (ARN) is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. Originally described in patients receiving supratherapeutic doses of warfarin who had a distinct pattern of glomerular hemorrhage on kidney biopsy, ARN is currently defined as acute kidney injury (AKI) without obvious etiology in the setting of an International Normalized Ratio (INR) of > 3.0. The underlying molecular mechanism is thought to be warfarin-induced thrombin depletion; however, newer studies have hinted at an alternative mechanism involving reductions in activated protein C and endothelial protein C receptor signaling. Prompt recognition of ARN is critical, as it is associated with accelerated progression of chronic kidney disease, and significant increases in short-term and long-term all-cause mortality. Prior investigations into ARN have almost universally focused on anticoagulation with warfarin; however, recent case reports and animal studies suggest that it can also occur in patients taking novel oral anticoagulants. Differences in the incidence and severity of ARN between patients taking warfarin and those taking novel oral anticoagulants are unknown; a post hoc analysis of routinely reported adverse renal outcomes in clinical trials comparing warfarin and novel oral anticoagulants found no significant difference in the rates of AKI, a prerequisite for ARN. Given the significant impact of ARN on renal function and all-cause mortality, a thorough understanding of the pathophysiology, molecular mechanisms, clinical spectrum and therapeutic interventions for ARN is crucial to balance the risks and benefits of anticoagulation and optimize treatment.

  20. Point-of-Care International Normalized Ratio (INR) Monitoring Devices for Patients on Long-term Oral Anticoagulation Therapy

    PubMed Central

    2009-01-01

    Executive Summary Subject of the Evidence-Based Analysis The purpose of this evidence based analysis report is to examine the safety and effectiveness of point-of-care (POC) international normalized ratio (INR) monitoring devices for patients on long-term oral anticoagulation therapy (OAT). Clinical Need: Target Population and Condition Long-term OAT is typically required by patients with mechanical heart valves, chronic atrial fibrillation, venous thromboembolism, myocardial infarction, stroke, and/or peripheral arterial occlusion. It is estimated that approximately 1% of the population receives anticoagulation treatment and, by applying this value to Ontario, there are an estimated 132,000 patients on OAT in the province, a figure that is expected to increase with the aging population. Patients on OAT are regularly monitored and their medications adjusted to ensure that their INR scores remain in the therapeutic range. This can be challenging due to the narrow therapeutic window of warfarin and variation in individual responses. Optimal INR scores depend on the underlying indication for treatment and patient level characteristics, but for most patients the therapeutic range is an INR score of between 2.0 and 3.0. The current standard of care in Ontario for patients on long-term OAT is laboratory-based INR determination with management carried out by primary care physicians or anticoagulation clinics (ACCs). Patients also regularly visit a hospital or community-based facility to provide a venous blood samples (venipuncture) that are then sent to a laboratory for INR analysis. Experts, however, have commented that there may be under-utilization of OAT due to patient factors, physician factors, or regional practice variations and that sub-optimal patient management may also occur. There is currently no population-based Ontario data to permit the assessment of patient care, but recent systematic reviews have estimated that less that 50% of patients receive OAT on a

  1. Prestroke Antiplatelet Effect on Symptomatic Intracranial Hemorrhage and Functional Outcome in Intravenous Thrombolysis

    PubMed Central

    Choi, Jay Chol; Lee, Ji Sung; Park, Tai Hwan; Cho, Yong-Jin; Park, Jong-Moo; Kang, Kyusik; Lee, Kyung Bok; Lee, Soo Joo; Kim, Jae Guk; Lee, Jun; Park, Man-Seok; Choi, Kang-Ho; Kim, Joon-Tae; Yu, Kyung-Ho; Lee, Byung-Chul; Oh, Mi-Sun; Cha, Jae-Kwan; Kim, Dae-Hyun; Nah, Hyun-Wook; Kim, Dong-Eog; Ryu, Wi-Sun; Kim, Beom Joon; Bae, Hee-Joon; Kim, Wook-Joo; Shin, Dong-Ick; Yeo, Min-Ju; Sohn, Sung Il; Hong, Jeong-Ho; Lee, Juneyoung; Hong, Keun-Sik

    2016-01-01

    Background and Purpose About 30%-40% of stroke patients are taking antiplatelet at the time of their strokes, which might increase the risk of symptomatic intracranial hemorrhage (SICH) with intravenous tissue plasminogen activator (IV-TPA) therapy. We aimed to assess the effect of prestroke antiplatelet on the SICH risk and functional outcome in Koreans treated with IV-TPA. Methods From a prospective stroke registry, we identified patients treated with IV-TPA between October 2009 and November 2014. Prestroke antiplatelet use was defined as taking antiplatelet within 7 days before the stroke onset. The primary outcome was SICH. Secondary outcomes were discharge modified Rankin Scale (mRS) score and in-hospital mortality. Results Of 1,715 patients treated with IV-TPA, 441 (25.7%) were on prestroke antiplatelet. Prestroke antiplatelet users versus non-users were more likely to be older, to have multiple vascular risk factors. Prestroke antiplatelet use was associated with an increased risk of SICH (5.9% vs. 3.0%; adjusted odds ratio [OR] 1.79 [1.05-3.04]). However, at discharge, the two groups did not differ in mRS distribution (adjusted OR 0.90 [0.72-1.14]), mRS 0-1 outcome (34.2% vs. 33.7%; adjusted OR 1.27 [0.94-1.72), mRS 0-2 outcome (52.4% vs. 52.9%; adjusted OR 1.21 [0.90-1.63]), and in-hospital mortality (6.1% vs. 4.2%; adjusted OR 1.19 [0.71-2.01]). Conclusions Despite an increased risk of SICH, prestroke antiplatelet users compared to non-users had comparable functional outcomes and in-hospital mortality with IV-TPA therapy. Our results support the use of IV-TPA in eligible patients taking antiplatelet therapy before their stroke onset. PMID:27733024

  2. 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 VO2) 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 VO2 in individuals with acute stroke. We hypothesized that (1) estimated prestroke peak VO2 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 VO2 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 VO2 was estimated using a nonexercise prediction equation. IGF-1 and IGFBP-3 levels were quantified using enzyme-linked immunoassay. Results Estimated prestroke peak VO2 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.

  3. Use of a Nonexercise Estimate for Prestroke Peak Vo2 During the Acute Stroke Hospital Stay

    PubMed Central

    Mattlage, Anna E.; Redlin, Sara A.; Rosterman, Lee R.; Harn, Nick; Sisante, Jason-Flor V.; Abraham, Michael G.; Billinger, Sandra A.

    2016-01-01

    Purpose For individuals with acute stroke, it is difficult to conduct an exercise test to assess peak oxygen consumption (peak Vo2). Therefore, the purpose of this study was to use a clinically feasible tool for assessing prestroke peak Vo2 using a nonexercise estimation equation to test whether estimated prestroke peak Vo2 was related to the functional outcome measures at discharge from the hospital in individuals after an acute stroke. We hypothesized that the estimated prestroke peak Vo2 would be significantly related to discharge Physical Performance Test (PPT), 6-minute walk test (6MWT), and lower extremity Fugl-Meyer (LEFM) assessment. Methods Estimated prestroke peak Vo2 was calculated using a previously validated prediction equation using the following variables: body mass index, age, sex, resting heart rate, and a self-reported measure of physical activity. Outcome measures were assessed 4 days after enrollment or immediately before discharge (whichever occurred first). Results Thirty-four participants (mean age = 56.0, SD = 12.6 years; 20 men) with acute stroke were enrolled within 48 hours of admission. For all individuals, mean estimated prestroke peak Vo2 was 27.3 (SD = 7.4) mL·kg−1·min−1 and had a weak, nonsignificant relationship with the PPT (r = 0.19; P = .28), 6MWT (r = 0.10; P = .56), and LEFM (r = 0.32; P = .06). However, when considering sex, women, but not men, had a significant relationship with LEFM (r = 0.73; P = .005) and moderate but nonsignificant relationship with PPT (r = 0.53; P = .06) and 6MWT (r = 0.47; P = .10). Conclusions Within 48 hours of stroke admission, we were able to administer a nonexercise equation to estimate prestroke peak Vo2. For the entire sample, functional measures conducted at discharge were not related to estimated prestroke peak Vo2. However, when considering sex, the relationship between prestroke Vo2 and the functional measures was strengthened. PMID:27478424

  4. Immediate post-procedure bridging with unfractioned heparin versus low molecular weight heparin in patients undergoing radiofrequency ablation for atrial fibrillation with an interrupted oral anticoagulation strategy.

    PubMed

    Loughlin, Gerard; Romaniega, Tomás Datino; Garcia-Fernandez, Javier; Calvo, David; Salgado, Ricardo; Alonso, Andres; Li, Xin; Arenal, Angel; González-Torrecilla, Esteban; Atienza, Felipe; Fernández-Avilés, Francisco

    2016-03-01

    Many centers perform catheter ablation for atrial fibrillation (AF) with periprocedural interruption of oral vitamin K antagonists. In this scenario, the optimal post-procedural anticoagulation strategy is still under debate. We sought to compare the incidence of major complications associated with post-procedural use of low molecular weight heparin (LMWH) versus unfractioned heparin (UFH) as a bridge to reinitiation of oral anticoagulation after an AF ablation procedure. We retrospectively reviewed medical history data of all patients undergoing catheter ablation for AF at three Spanish referral centers between January 2009 and January 2014. A total of 702 patients were included in the analysis. We compared the incidence of major complications (a combination of major bleeding and thromboembolic events) between patients receiving UFH (291) and those receiving LMWH (411) after the procedure. The overall incidence of major complications was 4.1%, including five thromboembolic events (0.7%) and 24 major bleeding events (3.4%), with no significant differences in patients treated with LMWH vs. UFH (2.9 vs. 4.1%; P = NS). The presence of peripheral vascular disease emerged as the only independent predictor of major complications (adjusted odds ratio (OR) 9.1; confidence interval (CI) 95% 1.7-49.3; P < 0.01). Immediate post-procedural bridging with UFH or with LMWH are equally safe strategies in patients undergoing catheter ablation for AF in whom oral anticoagulation is interrupted for the procedure. Due to its greater simplicity of use, LMWH may be the preferred option. The presence of peripheral vascular disease is a potent predictor of major post-procedural complications.

  5. Comparison of non-vitamin K antagonist oral anticoagulants and warfarin on clinical outcomes in atrial fibrillation patients with renal dysfunction.

    PubMed

    Lee, Ki Hong; Park, Hyung Wook; Cho, Jeong Gwan; Yoon, Nam Sik; Kim, Sung Soo; Kim, Mi Ran; Kim, Min Chul; Cho, Kyung Hoon; Kim, Hyun Kuk; Kim, Cheol Hwan; Kim, Kyung Hwan; Jun, Seung Jin; Kim, Woo Jin; Lee, Kyoung Jin; Jeong, Hae Chang; Cho, Jae Yeong; Park, Keun-Ho; Sim, Doo sun; Yoon, Hyun Ju; Kim, Kye Hun; Hong, Young Joon; Kim, Ju Han; Ahn, Youngkeun; Jeong, Myung Ho; Park, Jong Chun

    2015-10-01

    We aimed to compare the efficacy and safety between non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in atrial fibrillation (AF) patients according to renal dysfunction. We analysed 1319 patients who had been taken oral anticoagulants. They were classified into patients taking NOACs (n = 326) and warfarin (n = 993). Renal dysfunction was defined as the estimated glomerular filtration rate <60 mL/min by using the Chronic Kidney Disease Epidemiology Collaboration equation. The composite clinical outcomes were defined as the composite of death, hospitalization, and new-onset strokes. Safety outcomes were composed of major and minor bleeding. Subgroup analyses for clinical and safety outcomes were performed according to renal dysfunction during median 596 (506-612) follow-up days. The prevalence of renal dysfunction was similar between the two groups. The incidences of death, hospitalization, and strokes were not different between the two groups. However, the incidences of major bleeding was significantly higher in patients taking warfarin. In the subgroup analysis with renal dysfunction, the use of NOACs significantly improved the composite clinical outcomes (adjusted hazard ratio, HR, 0.30, 95% confidence interval, CI, 0.11-0.77, interaction P = 0.018) and major bleeding (adjusted HR 0.18, 95% CI 0.07-0.45, interaction P = 0.199) even after the covariate adjustment. However, in patients without renal dysfunction, there were no differences in the incidences of the composite clinical outcomes between the two groups. The benefit of NOACs was more prominent in AF patients with renal dysfunction than without renal dysfunction. These results suggest that NOACs as the first choice oral anticoagulant in AF patients with renal dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  6. [Treatment of very old patients with non valvular atrial fibrillation. The valuable opportunity offered by new oral anticoagulants, to be cautiously used].

    PubMed

    Orso, Francesco; Barucci, Riccardo; Fracchia, Stefania; Mannarino, Giulio; Pratesi, Alessandra; Fattirolli, Francesco

    2013-12-01

    Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia and its incidence increases with age reaching a 10% prevalence in the oldest old. Patients with AF have a five-fold increase in the risk of stroke. Current guidelines on AF management recommend the prescription of oral anticoagulant therapy in patients at medium and high risk of thromboembolic events. Advanced age is a risk factor for stroke in AF, but despite clear evidences a high rate of OAT under prescription is reported and particularly in the oldest old. Among the main causes of this phenomenon an enhanced risk of bleeding is often reported: this due to several factors: risk of falls, the presence of comorbidity and polifarmacy and a reduction in compliance and adherence that are common in the elderly. In recent years the international scenario in the management of OAT has significantly changed since the introduction of the new oral anticoagulants (NOA): Dabigatran, a direct thrombin inhibitor, and two oral factor Xa inhibitors Rivaroxaban and Apixaban, which have all been tested in randomized clinical trial (RELY, ROCKET-AF e ARISTOTLE) which have demonstrated non inferiority compared to warfarin in the prevention of thromboembolic events with an optimal safety profile. NOA could be an important therapeutic opportunity for stroke prevention in elderly patients with AF even if the substantial differences in mean age, anthropometric measures and comorbidity of the patients enrolled in these trials compared with those of the real world setting, oblige some caution and discussion.

  7. Efficacy and safety of the target-specific oral anticoagulants for stroke prevention in atrial fibrillation: the real-life evidence

    PubMed Central

    Russo, Vincenzo; Rago, Anna; Proietti, Riccardo; Di Meo, Federica; Antonio Papa, Andrea; Calabrò, Paolo; D’Onofrio, Antonio; Nigro, Gerardo; AlTurki, Ahmed

    2016-01-01

    The aim of our article is to provide a concise review for clinicians entailing the main studies that evaluated the efficacy and safety of target-specific oral anticoagulants (TSOAs) for thromboembolic stroke prevention in the real-world setting. Atrial fibrillation (AF) is one of the most common supraventricular arrhythmias that requires anticoagulation therapy to prevent stroke and systemic embolism. TSOAs, dabigatran, apixaban and rivaroxaban have become available as an alternative to warfarin anticoagulation in nonvalvular atrial fibrillation (NVAF). Randomized clinical trials showed non-inferior or superior results in efficacy and safety of the TSOAs compared with warfarin for stroke prevention in NVAF patients. For this reason, the 2012 update to the European Society of Cardiology guidelines for the management of AF recommends TSOAs as broadly preferable to vitamin K antagonists (VKAs) in the vast majority of patients with NVAF [Camm et al. 2012]. Although the clinical trial results and the guideline’s indications, there is a need for safety and efficacy data from unselected patients in everyday clinical practice. Recently, a large number of studies testing the efficacy and the safety of TSOAs in clinical practice have been published. The aim of our article is to provide a concise review for clinicians, outlining the main studies that evaluated the efficacy and safety of TSOAs for thromboembolic stroke prevention in the real-world setting. PMID:28255434

  8. Non-Vitamin K Antagonist Oral Anticoagulants and Antiplatelet Therapy for Stroke Prevention in Patients With Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Kumar, Shashi; Danik, Stephan B; Altman, Robert K; Barrett, Conor D; Lip, Gregory Y H; Chatterjee, Saurav; Roubin, Gary S; Natale, Andrea; Danik, Jacqueline S

    2016-01-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) are frequently used to prevent stroke in patients with atrial fibrillation. These patients are often also on aspirin or other antiplatelet agents. It is possible that treatment with both NOACs and aspirin or other antiplatelet drug may be effective in decreasing stroke, but data are sparse regarding the efficacy and safety of using both agents for stroke prevention. To address these issues, data were pooled from the 4 recent randomized, controlled trials of NOACs: apixaban, rivaroxaban, dabigatran, and edoxaban, which included 42,411 patients; 14,148 (33.4%) were also on aspirin or other antiplatelet drug. The number of thromboembolic events among participants on NOAC and aspirin/antiplatelet was compared with the number of events in patients on NOAC alone. Bleeding rates were also compared between those on NOAC + aspirin/antiplatelet and on NOAC alone. These results were compared with thromboembolic and bleeding events in the warfarin + aspirin/antiplatelet versus warfarin alone. No greater risk for thromboembolism was seen in patients on NOACs compared with patients on both NOACs and aspirin/antiplatelet drug. In this nonrandomized comparison, there was initially a signal toward higher thromboembolic rates among NOAC users also on aspirin/antiplatelet drugs (relative risk, 1.16; 95% confidence intervals, 1.05, 1.29) when compared with NOAC alone. This likely reflected the higher CHADS2 scores of those on aspirin/antiplatelet drugs. When the analysis was limited to studies that included aspirin rather than other antiplatelet drugs, no difference was seen for thromboembolic rates comparing dual therapy to NOAC alone (relative risk, 1.02; 95% confidence intervals, 0.90, 1.15). Higher rates of bleeding were seen with aspirin/antiplatelet drug in conjunction with NOAC. In this meta-analysis and nonrandomized comparison of aspirin/antiplatelet users and nonusers also on anticoagulation, there was no additional

  9. Real-world comparison of non-vitamin K antagonist oral anticoagulants and warfarin in Asian octogenarian patients with atrial fibrillation

    PubMed Central

    Kwon, Chang Hee; Kim, Minsu; Kim, Jun; Nam, Gi-Byoung; Choi, Kee-Joon; Kim, You-Ho

    2016-01-01

    Background The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asian octogenarian atrial fibrillation (AF) patients have not been established in a real-world setting. We aimed to evaluate the efficacy and safety of NOACs and warfarin in Korean octogenarian patients. Methods A total of 293 consecutive patients aged ≥ 80 years with non-valvular AF who had taken either NOACs (148 cases, 50.5%) or warfarin (145 cases, 49.5%) were retrospectively reviewed. The efficacy outcome was the composite of stroke or systemic embolism. The safety outcome was major bleeding. Results The follow-up duration was 375 patient-years (172 patient-years with NOACs and 203 patient-years with warfarin). Patients on NOACs were slightly older (P = 0.006) and had slightly higher HAS-BLED scores (P = 0.034). The efficacy of both anticoagulants was high (1.16% for NOACs vs. 2.98% for warfarin per 100 patient-years, P = 0.46). The safety outcome was relatively high in both NOACs and warfarin groups (8.96% vs. 12.46%, P = 0.29). The efficacy and safety outcomes tended to decrease non-significantly in low dose NOACs than in common dose NOACs or warfarin (0.85% vs. 1.84% vs. 2.98% in efficacy outcome, P = 0.69; and 6.97% vs. 13.29% vs. 12.46% in safety outcome, P = 0.34). Conclusions NOACs were highly effective for prevention of stroke or systemic embolism in Asian octogenarian AF patients. However, major bleeding occurred excessively high in both anticoagulant groups. Further study is required on the optimal anticoagulant regimen in octogenarian population. PMID:27605936

  10. Canalization effect in the coagulation cascade and the interindividual variability of oral anticoagulant response. a simulation Study

    PubMed Central

    2011-01-01

    Background Increasing the predictability and reducing the rate of side effects of oral anticoagulant treatment (OAT) requires further clarification of the cause of about 50% of the interindividual variability of OAT response that is currently unaccounted for. We explore numerically the hypothesis that the effect of the interindividual expression variability of coagulation proteins, which does not usually result in a variability of the coagulation times in untreated subjects, is unmasked by OAT. Results We developed a stochastic variant of the Hockin-Mann model of the tissue factor coagulation pathway, using literature data for the variability of coagulation protein levels in the blood of normal subjects. We simulated in vitro coagulation and estimated the Prothrombin Time and the INR across a model population. In a model of untreated subjects a "canalization effect" can be observed in that a coefficient of variation of up to 33% of each protein level results in a simulated INR of 1 with a clinically irrelevant dispersion of 0.12. When the mean and the standard deviation of vitamin-K dependent protein levels were reduced by 80%, corresponding to the usual Warfarin treatment intensity, the simulated INR was 2.98 ± 0.48, a clinically relevant dispersion, corresponding to a reduction of the canalization effect. Then we combined the Hockin-Mann stochastic model with our previously published model of population response to Warfarin, that takes into account the genetical and the phenotypical variability of Warfarin pharmacokinetics and pharmacodynamics. We used the combined model to evaluate the coagulation protein variability effect on the variability of the Warfarin dose required to reach an INR target of 2.5. The dose variance when removing the coagulation protein variability was 30% lower. The dose was mostly related to the pretreatment levels of factors VII, X, and the tissue factor pathway inhibitor (TFPI). Conclusions It may be worth exploring in experimental

  11. Racial Disparities in Poststroke Activity Limitations Are Not due to Differences in Prestroke Activity Limitation.

    PubMed

    Burke, James F; Skolarus, Lesli E; Freedman, Vicki A

    2015-07-01

    African Americans experience greater poststroke disability than whites. We explored whether these differences are because of differences in prestroke function. The Panel Study of Income Dynamics (PSID) is a nationally representative US panel survey of families and their descendants. We included all PSID respondents who reported an incident stroke between 2001 and 2011. Our primary outcome was an index representing the sum of total activities of daily living (ADL) limitations (0-7), and the secondary outcome was an index of instrumental activities of daily living (IADL) limitations (0-6). Survey-weighted descriptive statistics and Poisson regression were used to estimate racial differences in ADL and IADL before, with, and after the wave when incident stroke was reported. A total of 534 incident strokes were identified, 198 (37%) in African Americans. There were no prestroke racial differences in activity limitations (.7 versus .7, P = .99). In the wave of the incident stroke (between 0 and 2 years from incident stroke), African Americans had considerably more ADL limitations than whites (2.2 versus 1.5, P = .048). These racial differences persisted after adjusting for age, sex, and comorbidities. For IADLs, adjusted models suggested small prestroke racial differences and larger poststroke differences. Racial disparities in poststroke ADL limitations are not due to prestroke activity limitations. Instead, differences appear largest in the first 2 years after stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  12. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study

    PubMed Central

    Skjøth, Flemming; Nielsen, Peter Brønnum; Kjældgaard, Jette Nordstrøm; Lip, Gregory Y H

    2016-01-01

    Objective To study the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulant naïve patients with atrial fibrillation. Design Observational nationwide cohort study. Setting Three Danish nationwide databases, August 2011 to October 2015. Participants 61 678 patients with non-valvular atrial fibrillation who were naïve to oral anticoagulants and had no previous indication for valvular atrial fibrillation or venous thromboembolism. The study population was distributed according to treatment type: warfarin (n=35 436, 57%), dabigatran 150 mg (n=12 701, 21%), rivaroxaban 20 mg (n=7192, 12%), and apixaban 5 mg (n=6349, 10%). Main outcome measures Effectiveness outcomes defined a priori were ischaemic stroke; a composite of ischaemic stroke or systemic embolism; death; and a composite of ischaemic stroke, systemic embolism, or death. Safety outcomes were any bleeding, intracranial bleeding, and major bleeding. Results When the analysis was restricted to ischaemic stroke, NOACs were not significantly different from warfarin. During one year follow-up, rivaroxaban was associated with lower annual rates of ischaemic stroke or systemic embolism (3.0% v 3.3%, respectively) compared with warfarin: hazard ratio 0.83 (95% confidence interval 0.69 to 0.99). The hazard ratios for dabigatran and apixaban (2.8% and 4.9% annually, respectively) were non-significant compared with warfarin. The annual risk of death was significantly lower with apixaban (5.2%) and dabigatran (2.7%) (0.65, 0.56 to 0.75 and 0.63, 0.48 to 0.82, respectively) compared with warfarin (8.5%), but not with rivaroxaban (7.7%). For the combined endpoint of any bleeding, annual rates for apixaban (3.3%) and dabigatran (2.4%) were significantly lower than for warfarin (5.0%) (0.62, 0.51 to 0.74). Warfarin and rivaroxaban had comparable annual bleeding rates (5

  13. [Impact of an education program on patient behaviour favoring prevention of drug-related adverse events: a pilot study in patients receiving oral anticoagulants for thromboembolic venous disease].

    PubMed

    Léger, S; Allenet, B; Pichot, O; Figari, G; Calop, J; Carpentier, P; Bosson, J L

    2004-07-01

    Adverse events related to oral anticoagulants represent a major public health problem. Including patient education as part of the prevention strategy could contribute to improved effectiveness and safer use of drugs. The present study aimed at evaluating the outcomes of a patient education program inspired by recommendations from French Health Authorities (AFSSAPS) and based on an "individual guidance" approach. The study was conducted in two groups of hospitalized patients treated with oral anticoagulants for thromboembolic disease. Each patient in the first (intervention) group attended an individual teaching session conducted at discharge by a trained pharmacist. Patients in the second (control) group were given usual care. These two groups were compared at inclusion (before intervention) and three months later. The outcomes considered were the acquisition of: 1) knowledge, 2) risk anticipation and compliance behaviours characterized by the stability of INR and the incidence of hemorrhagic episodes during the period of observation. Fifty-nine patients (average age 65 years) were included (29 in the intervention group and 30 in the control group). Three months after the intervention, the intervention group exhibited 1) better knowledge (higher rate of restitution of treatment-related information--name of the drug, administration plan, targeted range for INR (...), interpretation of INR results (p<0.05), management of a specific scenario where INR declines concomitant to elevation of anticoagulant dose (p<0.05)); 2) higher rates of relevant behaviours (p<0.05)--in the event of a missed dose, anticipating an event with a high risk of bleeding, dealing with signs of overdose--and higher compliance profile (ns) (stability of INR, and number of hemorragic episodes). A multivariate model integrating the potential explanatory variables for frequency of hemorrhagic episodes at 3 months (demographic data, history of thrombotic disease, INR stability, reference group

  14. Quality assurance for point-of-care testing of oral anticoagulation: a large-scale evaluation of the Hemochron Junior Signature Microcoagulation System.

    PubMed

    Maddox, J M; Bogo, P H; McGregor, E; Pippard, M J; Kerr, R

    2009-04-01

    We report the first large-scale evaluation of the Hemochron Junior Signature (HJS) Microcoagulation System for community monitoring of oral anticoagulation and establishment of a programme of internal and external quality assurance. Over 1600 HJS results, with a simultaneous venous sample for central analysis, were obtained over a 19 month period. Monitoring of an initial period of HJS results (n = 135) revealed an International Normalized Ratio (INR) over estimation (mean +1.05), with only 27% of results within 0.5 of the central laboratory INR. A correction factor was introduced which reduced the INR bias to +0.07 and improved the percentage of results within 0.5 of the central laboratory INR to 76% (n = 353). A revised correction factor was later introduced to adjust for an under estimation at higher INR values. This changed the INR bias to -0.05, with 76% of results within 0.5 of the central laboratory INR (n = 1174). Local external quality assurance samples were distributed monthly with a total of 791 samples during the study period. 84% of test results were within 15% of the median value (range 73-97% per month). These results emphasize the value of a robust quality assurance programme when using point-of-care devices for community monitoring of oral anticoagulation.

  15. [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.

  16. Treatment discontinuations with new oral agents for long-term anticoagulation: insights from a meta-analysis of 18 randomized trials including 101,801 patients.

    PubMed

    Chatterjee, Saurav; Sardar, Partha; Giri, Jay S; Ghosh, Joydeep; Mukherjee, Debabrata

    2014-07-01

    To systematically examine discontinuation rates with new US Food and Drug Administration-approved oral anticoagulants (NOACs) in patients with various indications for long-term anticoagulation. Poor adherence to medications is considered a potential and frequent cause of treatment failure. We searched the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, EBSCO, Web of Science, and CINAHL databases for articles published from January 1, 2001, through September 15, 2013. The following Medical Subject Heading terms and/or keywords were used for our database searches: rivaroxaban, dabigatran, apixaban, new oral anticoagulants, oral thrombin inhibitors, and oral factor Xa inhibitors. Articles in English that focused on randomized controlled trials (RCTs) comparing NOACs (apixaban, dabigatran, and rivaroxaban) with conventional therapy or placebo were abstracted. Independent extraction of relevant data was performed by 2 authors. The primary end point of interest was discontinuation due to all causes. Other end points of interest were discontinuation due to adverse events, consent withdrawal, and nonadherence. Eighteen RCTs including a total of 101,801 patients were included for analysis. Total study drug discontinuation rates were not statistically different with NOACs in comparison to pharmacologically active comparators for treatment of venous thromboembolism/pulmonary embolism (risk ratio [RR], 0.91; 95% CI, 0.74-1.13; P=.40) and for NOACs in comparison to warfarin and aspirin for prevention of stroke in patients with atrial fibrillation (RR, 1.01; 95% CI, 0.87-1.17; P=.92). In contrast, in acute coronary syndromes, total study drug discontinuation with NOACs was significantly higher than with placebo (RR, 1.40; 95% CI, 1.07-1.83; P=.01). Overall discontinuations were comparable to those with active comparators. Study drug discontinuations with NOACs were not significantly different from those with conventional drugs in treatment of venous

  17. Oral anticoagulant therapy for stroke prevention in patients with atrial fibrillation undergoing ablation: results from the First European Snapshot Survey on Procedural Routines for Atrial Fibrillation Ablation (ESS-PRAFA).

    PubMed

    Potpara, Tatjana S; Larsen, Torben B; Deharo, Jean Claude; Rossvoll, Ole; Dagres, Nikolaos; Todd, Derick; Pison, Laurent; Proclemer, Alessandro; Purefellner, Helmut; Blomström-Lundqvist, Carina

    2015-06-01

    The European Snapshot Survey on Procedural Routines in Atrial Fibrillation Ablation (ESS-PRAFA) is a prospective, multicentre snapshot survey of patients undergoing atrial fibrillation (AF) ablation, conducted to collect patient-based data on current clinical practices in AF ablation in context of the latest AF Guidelines and contemporary oral anticoagulant therapies. The EP Research Network Centres were asked to prospectively enrol consecutive patients during a 6-week period (September/October 2014). Data were collected via the web-based case report form. We present the results pertinent to the use of antithrombotic therapies. Thirteen countries prospectively enrolled 455 eligible consecutive patients [mean age 59 ± 10.8 years, 131 (28.8%) females]. The mean CHA2DS2-VASc score was 1.12 ± 1.06 [137 patients (30.1%) had a score of ≥2]. Before ablation, 443 patients (97.4%) were on anticoagulant therapy [143 (31.4%) on non-vitamin K antagonist oral anticoagulants (NOACs) and 264 (58.0%) on vitamin K antagonists (VKAs)]. Of the latter, 79.7% underwent ablation without VKA interruption, whilst a variety of strategies were used in patients taking NOAC. After ablation, most patients (89.3%) continued the same anticoagulant as before, and 2 (0.4%) were not prescribed any anticoagulation. At discharge, 280 patients (62.2%) were advised oral anticoagulation for a limited period of mean 3.8 ± 2.2 months. On multivariate analysis, CHA2DS2-VASc, AF duration, prior VKA use, and estimated AF ablation success were significantly associated with the decision on short-term anticoagulation. Our results show the increasing use of NOAC in patients undergoing AF ablation and emphasize the need for more information to guide the periprocedural use of both NOACs and VKAs in real-world setting.

  18. Coagulation assays and anticoagulant monitoring.

    PubMed

    Funk, Dorothy M Adcock

    2012-01-01

    Anticoagulant therapy, including conventional agents and a variety of new oral, fast-acting drugs, is prescribed for millions of patients annually. Each anticoagulant varies in its effect on routine and specialty coagulation assays and each drug may require distinct laboratory assay(s) to measure drug concentration or activity. This review provides an overview of the assorted assays that can measure anticoagulant drug concentration or activity and includes key assay interferences. The effect of these conventional and new anticoagulant agents on specialty coagulation assays used to evaluate for bleeding or clotting disorders, and whether this impact is physiological or factitious, is included. Also provided is a short review of superwarfarin poisoning and features distinguishing this from warfarin overdose. Knowledge of clinically significant pearls and pitfalls pertinent to coagulation assays in relation to anticoagulant therapy are important to optimize patient care.

  19. [Dental extractions in patients taking anticoagulants: is alteration of the anticoagulant regime necessary?].

    PubMed

    Madrid, Carlos

    2005-05-25

    A major concern in the management of patients under anticoagulants is the potential for excessive bleeding after dental procedures. Recommendations for the administration of oral anticoagulants in conjunction with oral surgery range from complete withdrawal of anticoagulants to the maintenance of an unchanged therapy. Rising evidences show that the alteration of anticoagulation is not necessary for patients with INR of 4 or less previous to tooth extractions. Topical antifibrinolytics as tranexamic acid control successfully alveolar bleeding. It is time to stop interrupting anticoagulant therapy for oral surgery. A theoretical risk of hemorrhage after dental surgery in patients at therapeutic levels of anticoagulation exists but it is minimal and is greatly overweighed by the risk of thromboembolism after alteration of the anticoagulant therapy.

  20. Case Fatality Rates of Recurrent Thromboembolism and Bleeding in Patients Receiving Direct Oral Anticoagulants for the Initial and Extended Treatment of Venous Thromboembolism: A Systematic Review.

    PubMed

    Gómez-Outes, Antonio; Lecumberri, Ramón; Suárez-Gea, M Luisa; Terleira-Fernández, Ana-Isabel; Monreal, Manuel; Vargas-Castrillón, Emilio

    2015-09-01

    In patients with venous thromboembolism (VTE), the study of the case fatality rate (CFR) of VTE recurrences and bleeding complications may be of help to balance the risks and benefits of anticoagulant therapy. To investigate the CFR with the direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, and edoxaban) in patients with VTE. We conducted a systematic review and meta-analysis of randomized clinical trials testing the DOACs versus standard initial treatment of VTE (parenteral anticoagulant for ≥5 days plus vitamin K antagonists [VKAs] for ≥3 months) and DOACs versus placebo or VKA for extended treatment. Two investigators independently extracted the data. A random effects meta-analysis was conducted using StatsDirect software. Overall, 10 trials in 35 029 patients were included. During initial treatment, the rate of recurrent VTE per 100 patient-years (%/yr) and CFR (%) was similar in patients receiving DOACs or standard therapy (4.1%/yr vs 4.4%/yr; P = .21 and 16% vs 13%; P = .61, respectively). However, major bleeding (1.8%/yr vs 3.1%/yr; P = .003), fatal bleeding (0.1%/yr vs 0.3%/yr; P = .02), and CFR (6% vs 10%; P = .18) were lower with DOACs than with standard therapy. During extended treatment, both all-cause mortality and recurrent VTE per 100 patient-years were lower with DOACs than with placebo (0.6%/yr vs 1.1%/yr; P = .01 and 1.9%/yr vs 10.9%/yr; P < .0001, respectively), but there were no statistical differences between treatments on CFR of VTE recurrences (P = .17). No fatal bleeding events were reported during extended treatment. The use of DOACs was associated with fewer major and fatal bleedings and corresponding CFR than standard initial treatment of VTE, and fewer recurrent VTEs and mortality than placebo during extended therapy, although the CFR of recurrent VTE was not reduced. © The Author(s) 2015.

  1. Pharmacogenetic-guided selection of warfarin versus novel oral anticoagulants for stroke prevention in patients with atrial fibrillation: a cost-effectiveness analysis.

    PubMed

    You, Joyce H S

    2014-01-01

    To compare clinical and economic outcomes of two anticoagulation therapy strategies, (i) pharmacogenetic-guided selection (PG-AC) of warfarin versus novel oral anticoagulants (NOACs), and (ii) usual anticoagulation care (usual AC) in patients with atrial fibrillation (AF), from the perspective of US healthcare payers. A Markov model was used to simulate long-term outcomes in a hypothetical cohort of 65-year-old patients with newly diagnosed AF: (i) all usual AC patients received warfarin therapy, and (ii) all PG-AC patients were genotyped. Patients with normal warfarin sensitivity genotypes would receive warfarin. Patients with high or low warfarin sensitivity genotypes would receive NOAC. Model inputs were derived from clinical trials published in the literature. The outcome measure was incremental cost per quality-adjusted life-year (QALY) gained (ICER). PG-AC gained higher QALYs with higher cost (9.912 QALYs and USD94 396) when compared with usual AC (9.721 QALYs and USD93 853) in base-case analysis. The ICER of PG-AC was 2843 USD/QALY. The ICER of PG-AC would exceed 50 000 USD/QALY if the monthly cost of NOAC was more than USD285 or the risk of stroke with NOAC versus warfarin was more than 0.93. In 10 000 Monte Carlo simulations, PG-AC was cost-effective 96.4% of the time and usual AC was cost-effective 3.6% of the time. PG-AC was more costly than usual AC with a mean cost difference of USD1927 (95% confidence interval 1.877-1.977, P<0.001), and gained higher QALYs by 0.209 (95% confidence interval 0.208-0.210, P<0.001). Compared with warfarin therapy with time in therapeutic range of 60%, using genotype to triage AF patients to warfarin or NOAC appears to be highly cost-effective.

  2. Novel oral anticoagulants and trauma: The results of a prospective American Association for the Surgery of Trauma Multi-Institutional Trial.

    PubMed

    Kobayashi, Leslie; Barmparas, Galinos; Bosarge, Patrick; Brown, Carlos V; Bukur, Marko; Carrick, Matthew M; Catalano, Richard D; Holly-Nicolas, Jan; Inaba, Kenji; Kaminski, Stephen; Klein, Amanda L; Kopelman, Tammy; Ley, Eric J; Martinez, Ericca M; Moore, Forrest O; Murry, Jason; Nirula, Raminder; Paul, Douglas; Quick, Jacob; Rivera, Omar; Schreiber, Martin; Coimbra, Raul

    2017-05-01

    The number of anticoagulated trauma patients is increasing. Trauma patients on warfarin have been found to have poor outcomes, particularly after intracranial hemorrhage (ICH). However, the effect of novel oral anticoagulants (NOAs) on trauma outcomes is unknown. We hypothesized that patients on NOAs would have higher rates of ICH, ICH progression, and death compared with patients on traditional anticoagulant and antiplatelet agents. This was a prospective observational trial across 16 trauma centers. Inclusion criteria was any trauma patient admitted on aspirin, clopidogrel, warfarin, dabigatran, rivaroxaban, or apixaban. Demographic data, admission vital signs, mechanism of injury, injury severity scores, laboratory values, and interventions were collected. Outcomes included ICH, progression of ICH, and death. A total of 1,847 patients were enrolled between July 2013 and June 2015. Mean age was 74.9 years (SD ± 13.8), 46% were female, 77% were non-Hispanic white. At least one comorbidity was reported in 94% of patients. Blunt trauma accounted for 99% of patients, and the median Injury Severity Score was 9 (interquartile range, 4-14). 50% of patients were on antiplatelet agents, 33% on warfarin, 10% on NOAs, and 7% on combination therapy or subcutaneous agents.Patients taking NOAs were not at higher risk for ICH on univariate (24% vs. 31%) or multivariate analysis (incidence rate ratio, 0.78; confidence interval 0.61-1.01, p = 0.05). Compared with all other agents, patients on aspirin (90%, 81 mg; 10%, 325 mg) had the highest rate (35%) and ris