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Sample records for aggressive statin therapy

  1. Combination therapy with statins.

    PubMed

    Gylling, Helena; Miettinen, Tatu A

    2002-09-01

    Statins effectively inhibit cholesterol synthesis and are currently the most commonly used drugs for the treatment of hypercholesterolemia. However, patients with familial hypercholesterolemia and those unwilling to take, or who cannot tolerate statins, and patients with combined hyperlipidemia require a combination treatment. Statins combined with cholesterol malabsorption, caused, e.g., by plant stanol esters or ezetimibe (Schering-Plough Corp/Merck & Co Inc), or with bile acid malabsorption, caused by bile acid binding resins or guar gum, inhibit compensatory increases in cholesterol synthesis and effectively lower LDL cholesterol levels. Combination therapy of statins with fibrates should be controlled by lipidology experts. Recent information on indications and advantages of combining statins with n-3 fatty acids, hormone replacement therapy, or niacin, will also be discussed. PMID:12498007

  2. Viewpoint: personalizing statin therapy.

    PubMed

    Keidar, Shlomo; Gamliel-Lazarovich, Aviva

    2013-04-01

    Cardiovascular disease (CVD), associated with vascular atherosclerosis, is the major cause of death in Western societies. Current risk estimation tools, such as Framingham Risk Score (FRS), based on evaluation of multiple standard risk factors, are limited in assessment of individual risk. The majority (about 70%) of the general population is classified as low FRS where the individual risk for CVD is often underestimated but, on the other hand, cholesterol lowering with statin is often excessively administered. Adverse effects of statin therapy, such as muscle pain, affect a large proportion of the treated patients and have a significant influence on their quality of life. Coronary artery calcification (CAC), as assessed by computed tomography, carotid artery intima-media thickness (CIMT), and especially presence of plaques as assessed by B-mode ultrasound are directly correlated with increased risk for cardiovascular events and provide accurate and relevant information for individual risk assessment. Absence of vascular pathology as assessed by these imaging methods has a very high negative predictive value and therefore could be used as a method to reduce significantly the number of subjects who, in our opinion, would not benefit from statins and only suffer from their side-effects. In summary, we suggest that in very-low-risk subjects, with the exception of subjects with low FRS with a family history of coronary artery disease (CAD) at young age, if vascular imaging shows no CAC or normal CIMT without plaques, statin treatment need not be administered. PMID:23908858

  3. An echo-guided case report of rapid regression of unstable mobile thrombus aortic atheroma after aggressive statin and antiplatelet combination therapy.

    PubMed

    Dʼaloia, Antonio; Vizzardi, Enrico; Caretta, Giorgio; Zanini, Gregoriana; Bugatti, Silvia; Curnis, Antonio; Dei Cas, Livio

    2014-01-01

    We describe a case report that documented the efficacy and safety of medical therapy in stabilizing and resolving a complex and unstable aortic atheroma after a relatively short period. The patient had a large protruding, mobile, calcified nonulcerated atheroma involving the descending aorta and was therefore treated with aggressive combination therapy with high statin dosages (atorvastatin = 80 mg) and dual antiplatelet treatment (clopidogrel = 75 mg and aspirin = 100 mg). At follow-up, the echocardiogram showed a significant regression in the atheroma volume, with no signs suggestive of ulceration on its surface with the complete mobile component resolution. PMID:23817345

  4. Successful reintroduction of statin therapy after statin-associated rhabdomyolysis.

    PubMed

    Simons, Janet E; Holbrook, Anne M; Don-Wauchope, Andrew C

    2015-01-01

    The case report demonstrates the successful use of an alternative statin after a statin-related episode of rhabdomyolysis. Statin-associated rhabdomyolysis is a serious adverse event with a very low incidence and is considered the most severe of the muscle-related side effects of the statins. Rechallenge with statins is not a recommended practice after rhabdomyolysis. The patient experienced a myocardial infarct 1 y after the episode of rhabdomyolysis. He used alternative lipid-lowering therapy for 2 y. His low-density lipoprotein cholesterol was not meeting typical secondary prevention targets. An alternative statin was introduced and the patient has been followed for 4 years without recurrence of the rhabdomyolysis. This case suggests it may be time to reconsider the accepted practice of permanently avoiding statin therapy after rhabdomyolysis. PMID:26228678

  5. Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial

    PubMed Central

    Golomb, Beatrice A.; Dimsdale, Joel E.; Koslik, Hayley J.; Evans, Marcella A.; Lu, Xun; Rossi, Steven; Mills, Paul J.; Criqui, Michael H.

    2015-01-01

    Background Low/ered cholesterol is linked to aggression in some study designs. Cases/series have reported reproducible aggression increases on statins, but statins also bear mechanisms that could reduce aggression. Usual statin effects on aggression have not been characterized. Methods 1016 adults (692 men, 324 postmenopausal women) underwent double-blind sex-stratified randomization to placebo, simvastatin 20mg, or pravastatin 40mg (6 months). The Overt-Aggression-Scale-Modified–Aggression-Subscale (OASMa) assessed behavioral aggression. A significant sex-statin interaction was deemed to dictate sex-stratified analysis. Exploratory analyses assessed the influence of baseline-aggression, testosterone-change (men), sleep and age. Results The sex-statin interaction was significant (P=0.008). In men, statins tended to decrease aggression, significantly so on pravastatin: difference=-1.0(SE=0.49)P=0.038. Three marked outliers (OASMa-change ≥40 points) offset otherwise strong significance-vs-placebo: statins:-1.3(SE=0.38)P=0.0007; simvastatin:-1.4(SE=0.43)P=0.0011; pravastatin:-1.2(SE=0.45)P=0.0083. Age≤40 predicted greater aggression-decline on statins: difference=-1.4(SE=0.64)P=0.026. Aggression-protection was emphasized in those with low baseline aggression: age<40-and-low-baseline-aggression (N=40) statin-difference-vs-placebo=-2.4(SE=0.71)P=0.0016. Statins (especially simvastatin) lowered testosterone, and increased sleep problems. Testosterone-drop on statins predicted aggression-decline: β=0.64(SE=0.30)P=0.034, particularly on simvastatin: β=1.29(SE=0.49)P=0.009. Sleep-worsening on statins significantly predicted aggression-increase: β=2.2(SE=0.55)P<0.001, particularly on simvastatin (potentially explaining two of the outliers): β=3.3(SE=0.83)P<0.001. Among (postmenopausal) women, a borderline aggression-increase on statins became significant with exclusion of one younger, surgically-menopausal woman (N=310) β=0.70(SE=0.34)P=0.039. The increase was

  6. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    SciTech Connect

    Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul; Taussky, Daniel

    2012-07-15

    Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

  7. Statin combination therapy and cardiovascular risk reduction.

    PubMed

    Toth, Peter P; Farnier, Michel; Tomassini, Joanne E; Foody, JoAnne M; Tershakovec, Andrew M

    2016-05-01

    In numerous clinical trials, lowering LDL-C with statin therapy has been demonstrated to reduce the risk of cardiovascular disease (CVD) in primary and secondary prevention settings. Guidelines recommend statins for first-line therapy in cholesterol-lowering management of patients with CVD risk. Despite increased statin monotherapy use over the last decade, a number of patients with high CVD risk do not achieve optimal LDL-C lowering. Guidelines recommend consideration of statin combination therapy with nonstatin agents for these patients. However, combination therapy approaches have been hampered by neutral findings. Recently, ezetimibe added to simvastatin therapy reduced cardiovascular events in acute coronary syndrome patients, more than simvastatin alone. This article provides an overview of various agents in combination with statin therapy on cardiovascular outcomes. Other lipid-lowering agents in development, including PCSK9 and CETP inhibitors in development, are also described. PMID:27079178

  8. [Metabolic rhabdomyolysis during statin therapy].

    PubMed

    Vergely, N; Leca, V; Antoine, J-C; Germain, N; Khalfallah, Y; Estour, B

    2009-08-01

    The occurrence of rhabdomyolysis during statin treatment for dyslipidemia is a well-known side effect. However, the differential diagnosis of rhabdomyolysis is large. We report on a patient treated with statin who presented a rhabdomyolysis. The persistence of laboratory abnormalities allowed to discover a metabolic rhabdomyolysis, namely a carnitine palmitoyltransférase II deficiency. The diagnosis of the genetic abnormality allows to modify the therapeutic care. PMID:19419805

  9. Statins

    MedlinePlus

    Statins are drugs used to lower cholesterol. Your body needs some cholesterol to work properly. But if ... to take medicine. Often, this medicine is a statin. Statins interfere with the production of cholesterol in ...

  10. Statins Decrease Oxidative Stress and ICD Therapies

    PubMed Central

    Bloom, Heather L.; Shukrullah, Irfan; Veledar, Emir; Gutmann, Rebecca; London, Barry; Dudley, Samuel C.

    2010-01-01

    Recent studies demonstrate that statins decrease ventricular arrhythmias in internal cardioverter defibrillator (ICD) patients. The mechanism is unknown, but evidence links increased inflammatory and oxidative states with increased arrhythmias. We hypothesized that statin use decreases oxidation. Methods. 304 subjects with ICDs were surveyed for ventricular arrhythmia. Blood was analyzed for derivatives of reactive oxygen species (DROMs) and interleukin-6 (IL-6). Results. Subjects included 252 (83%) men, 58% on statins, 20% had ventricular arrhythmias. Average age was 63 years and ejection fraction (EF) 20%. ICD implant duration was 29 ± 27 months. Use of statins correlated with lower ICD events (r = 0.12, P = .02). Subjects on statins had lower hsCRP (5.2 versus 6.3; P = .05) and DROM levels (373 versus 397; P = .03). Other factors, including IL-6 and EF did not differ between statin and nonstatin use, nor did beta-blocker or antiarrhythmic use. Multivariate cross-correlation analysis demonstrated that DROMs, statins, IL-6 and EF were strongly associated with ICD events. Multivariate regression shows DROMs to be the dominant predictor. Conclusion. ICD event rate correlates with DROMs, a measure of lipid peroxides. Use of statins is associated with reduced DROMs and fewer ICD events, suggesting that statins exert their effect through reducing oxidation. PMID:20369058

  11. Statin therapy, myopathy and exercise--a case report.

    PubMed

    Semple, Stuart J

    2012-01-01

    In a bid to reduce the morbidity and mortality associated with coronary artery disease, statin therapy has become a cornerstone treatment for patients with dyslipideamia. Statins, or HMG-CoA reductase inhibitors, are effective in blocking hepatic synthesis of cholesterol and are generally regarded as safe. Although rare, severe adverse side effects such as rhabdomyolysis have been reported, however, the more common complaint from patients is that related to myopathy. There is also mounting evidence that exercise may exacerbate these side effects, however the mechanisms are yet to be fully defined and there is controversy regarding the role that inflammation may play in the myopathy. This paper reports a patients experience during 6 months of simvastatin therapy and provides some insight into the white cell count (inflammation) following two bouts of moderate intensity exercise before and during statin therapy. It also highlights the need for rehabilitation practitioners to be aware of the adverse effects of statins in exercising patients. PMID:22420409

  12. A Comparison of Statin Therapies in Hypercholesterolemia in Women: A Subgroup Analysis of the STELLAR Study

    PubMed Central

    Lewis, Sandra J.; Friday, Karen E.; Cain, Valerie A.; Anzalone, Deborah A.

    2016-01-01

    Abstract Objective: Cardiovascular disease is the leading cause of mortality in women in the United States. Aggressive treatment of modifiable risk factors (e.g., hypercholesterolemia) is essential in reducing disease burden. Despite guidelines recommending the use of statin treatment in hypercholesterolemic women, this patient group is often undertreated. This subgroup analysis of the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial examines the effects of statin therapy in hypercholesterolemic women. Methods: As part of the STELLAR trial, 1,146 women with elevated low-density lipoprotein cholesterol (LDL-C ≥160 and <250 mg/dL) and triglycerides <400 mg/dL were randomized to rosuvastatin 10–40 mg, atorvastatin 10–80 mg, simvastatin 10–80 mg, or pravastatin 10–40 mg for 6 weeks. Results: LDL-C reduction with rosuvastatin 10 mg, atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg was 49%, 39%, 37%, and 30%, respectively, after 6 weeks. High-intensity statins (rosuvastatin 20–40 mg and atorvastatin 40–80 mg) reduced LDL-C to the greatest extent: 53% with rosuvastatin 20 mg, 57% with rosuvastatin 40 mg, 47% with atorvastatin 40 mg, and 51% with atorvastatin 80 mg. Similar results were observed for non-high-density lipoprotein cholesterol (non-HDL-C). Increases in HDL-C were greater with rosuvastatin across doses than with other statins. All treatments were well tolerated, with similar safety profiles across dose ranges. Conclusions: Statin therapies in the STELLAR trial led to reductions in LDL-C, non-HDL-C, and triglycerides and increases in HDL-C among hypercholesterolemic women, with rosuvastatin providing the greatest reductions in LDL-C and non-HDL-C. PMID:26539650

  13. Outcome of rheumatoid arthritis following adjunct statin therapy

    PubMed Central

    Das, Subham; Mohanty, Manjushree; Padhan, Prasanta

    2015-01-01

    Objective: Rheumatoid arthritis (RA) is characterized by symmetric peripheral polyarthritis, inflammatory synovitis, and articular destruction. Statins, 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors, mediate significant vascular risk reduction in patients with coronary artery disease by promoting reduction in plasma levels of low-density-lipoprotein cholesterol. Extensive in vitro data, experimental studies and more recently few clinical trials have strongly suggested statins to possess an important role in RA mainly mediated by their anti-inflammatory and immunomodulatory properties. The objective of this study was to evaluate the effect of adjunct statin therapy in comparison to standard disease modifying antirheumatic drugs (DMARD) therapy in patients with RA. Materials and Methods: In this observational study, diagnosed RA patients of age group between 40 and 60 years were selected as per the inclusion criteria from the rheumatology outdoor. From the selected patients, we identified two separate groups of patients. Group 1 included 30 patients of RA currently under DMARD therapy with adjunct statin medication. Group 2 included 30 patients of RA currently under DMARD therapy. Patients were followed up over 6 months. Standard parameters such as disease activity score (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were recorded for comparing the outcome of RA in both groups. Results: Out of a total of 60 patients who took part in the study, significant beneficial role of adjunct statin medication was found in this study when prescribed along with conventional DMARDs in active RA patients. The mean DAS28, considered by far as the most important index of clinical disease activity in RA, was found to be significantly lower (P < 0.05) in the adjunct statin-treated group (group 1) than that of the conventional DMARD treated group (group 2) after 6 months of continuous therapy. Other two important biochemical markers of RA

  14. Combination therapy in cholesterol reduction: focus on ezetimibe and statins

    PubMed Central

    Grigore, Liliana; Norata, Giuseppe Danilo; Catapano, Alberico L

    2008-01-01

    Although widely used in lipid lowering therapy, HMG CoA reductase inhibitors (even when administered at high doses) are frequently insufficient to achieve guideline-recommended LDL-C goals for many patients with hypercholesterolemia in everyday clinical practice. Many patients do not achieve LDL-C goal on the initial dose of statin and the majority of these patients does not reach their goal after 6 months. As a consequence, a wide therapeutic gap exists between target LDL-C levels and those typically achieved in clinical practice. A recent and more effective therapeutic hypocholesterolemic strategy is to treat the two main sources of cholesterol simultaneously (production of cholesterol, mainly in the liver, and absorption of cholesterol in the intestine) with a complementary mechanism of action, by co-administering ezetimibe, a novel agent inhibiting cholesterol absorption, with a statin, which inhibits cholesterol production in the liver. Ezetimibe can be effectively and safely co-administered with any dose of any statin and, compared with the single inhibition of cholesterol production, afforded by statins alone, provides consistently greater reductions in LDL-C through dual inhibition of both cholesterol production and absorption. We summarize the pivotal role of both the liver and intestine in the overall balance of cholesterol in the body and describe the clinical impact and relevance of using ezetimibe either alone or co-administered with statins in controlling elevated levels of plasma LDL cholesterol. PMID:18561502

  15. Role of Serum Cholesterol and Statin Use in the Risk of Prostate Cancer Detection and Tumor Aggressiveness

    PubMed Central

    Morote, Juan; Celma, Anna; Planas, Jacques; Placer, José; de Torres, Inés; Olivan, Mireia; Carles, Juan; Reventós, Jaume; Doll, Andreas

    2014-01-01

    The aim of this study was to analyze the relationship between statin use along with serum cholesterol levels and prostate cancer (PCa) detection and aggressiveness. Statin users of three years or more and serum cholesterol levels (SC) were assessed in 2408 men scheduled for prostate biopsy. SC was classified as normal (NSC: <200 mg/dL) or high (HSC: >200 mg/dL). High-grade PCa (HGPCa) was considered if the Gleason score was greater than 7. Statin users comprised 30.9% of those studied. The PCa detection rate was 31.2% of men on statins and 37% of non-statin users (p < 0.006). The PCa detection rate was 26.3% in men with NSC and 40.6% in those with HSC (p < 0.001). In the subset of NSC men, the PCa rate was 26.5% for statin users and 26.2% for non-users (p = 0.939), while in men with HSC, the PCa rate was 36.4% for statin users and 42.0% for non-statin users (p = 0.063). The HGPCa rate was 41.8% for statin users and 32.5% for non-users (p = 0.012). NSC men had a 53.8% rate of HGPCa, while the rate was only 27.6% in HSC men (p < 0.001). NSC men on statins had an HGPCa rate of 70.2%, while non-statin users had a rate of 41.2% (p < 0.001). The HGPCa rate for HSC men on statins was 18.8%, while the rate was 30.0% (p = 0.011) for non-users. Logistic regression analysis suggested that serum cholesterol levels could serve as an independent predictor of PCa risk, OR 1.87 (95% CI 1.56–2.24) and HGPCa risk, OR 0.31 (95% CI 0.23–0.44), while statin usage could not. Statin treatment may prevent PCa detection through serum cholesterol-mediated mechanisms. A disturbing increase in the HGPCa rate was observed in statin users who normalized their serum cholesterol. PMID:25101846

  16. Rhabdomyolysis in the Setting of Induced Hypothyroidism and Statin Therapy: A Case Report

    PubMed Central

    Jbara, Yaser; Bricker, Dean

    2015-01-01

    Mild elevation of creatine kinase (CK) is common in untreated hypothyroidism, but severe myositis and overt rhabdomyolysis are rare. Similarly, muscle pain and CK elevation are potential side effects of statin therapy, yet rhabdomyolysis is likewise rare in the absence of medication interactions adversely affecting statin metabolism. The coexistence of statin therapy and hypothyroid states may synergistically increase the risk of myopathy. We describe a case of rhabdomyolysis attributable to induced hypothyroidism in a patient on chronic statin medication who was anticipating adjuvant radioiodine (131I) therapy for a thyroid carcinoma PMID:25960964

  17. Can adherence to antihypertensive therapy be used to promote adherence to statin therapy?

    PubMed Central

    Chapman, Richard H; Pelletier, Elise M; Smith, Paula J; Roberts, Craig S

    2009-01-01

    Objective: To compare adherence with statin therapy in patients switching to single-pill amlodipine besylate/atorvastatin calcium with patients adding a separate statin to their amlodipine regimen. Methods: We identified hypertensive patients prescribed amlodipine who switched to amlodipine/atorvastatin (switch) or added a statin to their amlodipine regimen (add-on) from July 2004 to June 2007. Propensity score matching (1 switch:3 add-on) was applied based on ‘nearest neighbor’ approach. The primary adherence measure was patients with proportion of days covered (PDC) ≥0.80 at 180 days; secondary measures included mean PDC and persistence. A sensitivity analysis was performed, accounting for total statin/amlodipine exposure. Results: Among 4556 matched patients (n = 1139 switch; n = 3417 add-on), mean age was 53.9 years and 52.1% were male. After 180 days, adherence with statin therapy was higher for the switch vs add-on cohort (50.8% vs 44.3%; P < 0.001). After adjusting for pre-index amlodipine adherence, the switch cohort was more likely to be adherent than the add-on cohort (odds ratio: 1.64 [95% confidence interval: 1.42 to 1.89]). Persistence was higher in the switch than the add-on cohort (127.6 vs 117 days; P < 0.001). Conclusion: Hypertensive patients taking amlodipine who initiated statin therapy via single-pill amlodipine/atorvastatin were more likely to remain adherent to their statin than patients adding a separate statin to their antihypertensive regimen. PMID:19936170

  18. Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study).

    PubMed

    McKenney, James M; Jones, Peter H; Bays, Harold E; Knopp, Robert H; Kashyap, Moti L; Ruoff, Gary E; McGovern, Mark E

    2007-06-01

    International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides for patients at moderately high to high coronary heart disease (CHD) risk. Combination therapy is often required to achieve multiple lipid treatment goals, and > or =50% reduction in low-density lipoprotein cholesterol (LDL-C) is needed in some patients to achieve aggressive LDL-C targets. In this context, we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin (niacin ER), a statin plus ezetimibe, and a highly potent statin alone. This was an open-label, multicenter, 12-week study in 292 patients (50% women) who qualified for drug therapy based on number of CHD risk factors. Patients were randomized to four parallel arms, titrated from low to moderate or high doses: atorvastatin/niacin ER, rosuvastatin/niacin ER, simvastatin/ezetimibe, or rosuvastatin alone. Baseline mean values were, for LDL-C 197 mg/dL (5.1 mmol/L), HDL-C 49 mg/dL (1.3 mmol/L), triglycerides 168 mg/dL (1.9 mmol/L). There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment. All groups lowered LDL-C by approximately 50% or more (range -49 to -57%), achieving mean levels of 82-98 mg/dL (2.1-2.5 mmol/L). Changes in non-HDL-C (range -46 to -55%) mirrored those for LDL-C and did not differ among treatment groups. Statin/niacin ER combination regimens also increased HDL-C and large HDL (HDL2) and lowered triglycerides and lipoprotein (a) significantly more than other regimens. No drug-related myopathy or hepatotoxicity was observed. In this study, low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD. PMID:17239888

  19. Benefits & risks of statin therapy for primary prevention of cardiovascular disease in Asian Indians – A population with the highest risk of premature coronary artery disease & diabetes

    PubMed Central

    Enas, Enas A.; Kuruvila, Arun; Khanna, Pravien; Pitchumoni, C.S.; Mohan, Viswanathan

    2013-01-01

    Several reviews and meta-analyses have demonstrated the incontrovertible benefits of statin therapy in patients with cardiovascular disease (CVD). But the role for statins in primary prevention remained unclear. The updated 2013 Cochrane review has put to rest all lingering doubts about the overwhelming benefits of long-term statin therapy in primary prevention by conclusively demonstrating highly significant reductions in all-cause mortality, major adverse cardiovascular events (MACE) and the need for coronary artery revascularization procedures (CARPs). More importantly, these benefits of statin therapy are similar at all levels of CVD risk, including subjects at low (<1% per year) risk of a MACE. In addition to preventing myocardial infarction (MI), stroke, and death, primary prevention with statins is also highly effective in delaying and avoiding expensive CARPs such as angioplasties, stents, and bypass surgeries. There is no evidence of any serious harm or threat to life caused by statin therapy, though several adverse effects that affect the quality of life, especially diabetes mellitus (DM) have been reported. Asian Indians have the highest risk of premature coronary artery disease (CAD) and diabetes. When compared with Whites, Asian Indians have double the risk of CAD and triple the risk of DM, when adjusted for traditional risk factors for these diseases. Available evidence supports the use of statin therapy for primary prevention in Asian Indians at a younger age and with lower targets for low-density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein (non-HDL-C), than those currently recommended for Americans and Europeans. Early and aggressive statin therapy offers the greatest potential for reducing the continuing epidemic of CAD among Indians. PMID:24434254

  20. Statin myopathy.

    PubMed

    Radcliffe, Kristofer A; Campbell, William W

    2008-01-01

    Many different classes of medications can cause toxic myopathy. One of the most frequently implicated classes is the statins. Statin myotoxicity ranges from asymptomatic creatine kinase elevations or myalgias to muscle necrosis and fatal rhabdomyolysis. Statins may also cause an autoimmune myopathy requiring immunosuppressive treatment. The mechanisms of statin myotoxicity are unclear. If unrecognized in its early manifestations, complications from continued statin therapy may lead to rhabdomyolysis and death. Risk factors for myotoxicity include concomitant medication use and medical conditions, and the patient's underlying genetic constitution. We review these considerations along with the recommended evaluation and treatment for patients presenting with statin myotoxicity. PMID:18367041

  1. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management.

    PubMed

    Stroes, Erik S; Thompson, Paul D; Corsini, Alberto; Vladutiu, Georgirene D; Raal, Frederick J; Ray, Kausik K; Roden, Michael; Stein, Evan; Tokgözoğlu, Lale; Nordestgaard, Børge G; Bruckert, Eric; De Backer, Guy; Krauss, Ronald M; Laufs, Ulrich; Santos, Raul D; Hegele, Robert A; Hovingh, G Kees; Leiter, Lawrence A; Mach, Francois; März, Winfried; Newman, Connie B; Wiklund, Olov; Jacobson, Terry A; Catapano, Alberico L; Chapman, M John; Ginsberg, Henry N

    2015-05-01

    Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7-29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential. PMID:25694464

  2. Regarding long-term statin therapy: are we trading stronger hearts for weaker brains?

    PubMed

    Goldstein, Mark R; Mascitelli, Luca

    2014-09-01

    Ideally, the benefits of long-term statin therapy should outweigh the risks in all populations. However, some data suggest that long-term statin therapy might promote cerebral small vessel disease and impair myelination, perhaps resulting from cholesterol depletion and pleiotropic effects on amyloid-β metabolism and oligodendrocyte function. The clinical ramifications can be problematic and have a negative impact on the quality of life. Questions are proposed and the answers should be found by analysis of randomized prospective trials specifically investigating the effects of statin therapy on brain structure and function. Those trials should not be funded by drug companies and the investigators should not have financial ties to the pharmaceutical industry. The relevance of the aforementioned is amplified in light of the new cardiovascular guidelines that might culminate in more than a billion people receiving statin therapy worldwide. PMID:24986644

  3. Aggressive Adolescents Benefit from Massage Therapy.

    ERIC Educational Resources Information Center

    Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Shaw, Jon A.; Rothe, Eugenio M.; Castellanos, Daniel; Mesner, Linda

    2002-01-01

    Seventeen aggressive adolescents were assigned to a massage therapy group or a relaxation therapy group to receive 20-minute therapy sessions, twice a week for five weeks. The massaged adolescents had lower anxiety after the first and last sessions. By the end of the study, they also reported feeling less hostile and they were perceived by their…

  4. Statin therapy in cardiac allograft vasculopathy progression in heart transplant patients: Does potency matter?

    PubMed

    Sieg, Adam; Weeks, Phillip; Krustchinsky, Lori; Rajapreyar, Indranee

    2016-07-01

    Cardiac allograft vasculopathy (CAV) is a unique multi-factorial pathologic process encountered following heart transplantation. Several risk factors have been identified including a combination of immunologic and non-immunologic processes. Significant research has been conducted to elucidate the driving forces of CAV as well as improved identification, prevention and treatment strategies. Statin therapy following transplant remains the standard of care to help prevent the progression of CAV. The benefits of statin therapy following transplantation correspond to cholesterol control, anti-inflammatory and immunomodulatory mechanisms as well as potentially unknown mechanisms. Despite known drug interactions with calcineurin inhibitors, the use of statins is highly recommended in the current International Society for Heart and Lung Transplantation guidelines. Limited research has been conducted on the impact of higher intensity statin therapy following heart transplant and the relative risks and benefits are unknown. This review focuses on risk factors and pathophysiology of CAV, the role of statin therapy in heart transplantation, and the potential added benefit of more intense statin therapy to limit the progression of this graft-limiting complication. PMID:27079752

  5. Adherence to statin therapy in patients with type 2 diabetes: An important dilemma

    PubMed Central

    Farsaei, Shadi; Sabzghabaee, Ali Mohammad; Amini, Masoud; Zargarzadeh, Amir Hooshang

    2015-01-01

    Background: Despite the importance of patients’ adherence to their drug treatments for achieving desired therapeutic goals and the proven role 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) for the health status of patients with cardiovascular diseases, there is not enough information regarding diabetic patients’ adherence to statin therapy in developing countries. In this clinical study we aimed to assess the adherence of diabetes type 2 patients to statin therapy in a research based community clinic in Iran. Materials and Methods: In this prospective clinical study which was done at Isfahan Endocrinology and Metabolism Research Center, 204 diabetic type 2 patients under treatment with statin were interviewed twice and their demographic data (age, gender, body mass index, education), statin information (type, dose) and their serum lipid profile were recorded. Three months after the initial visits, patients were assessed using pill counting method and according to patients’ self-reporting and also assessed low-density lipoprotein (LDL) cholesterol goal attainment <100 mg/dl. Results: Adherence rate was 79.7% and 69% according to pill counting and self-reporting among study population. Moreover, 68.4% of patients achieved their LDL cholesterol goal of <100 mg/dl and adherent patients reached therapeutic goal significantly more than those who were considered non-adherence to statin therapy (P < 0.01). Conclusion: Adherence to statin therapy, as reflected by pill count method, is significantly related to LDL cholesterol goal achievement in patients with diabetes and dyslipidemia. Pill count method can be used to identify patients who are nonadherent to statin therapy and at high risk for failure to attain LDL cholesterol goals. PMID:25983760

  6. Statin-Based Palliative Therapy for Hepatocellular Carcinoma

    PubMed Central

    Shao, Joni Yu-Hsuan; Lee, Fei-Peng; Chang, Chia-Lun; Wu, Szu-Yuan

    2015-01-01

    Abstract Most hepatocellular carcinoma (HCC) patients worldwide do not receive curative treatments. Alternative treatments for most HCC patients include palliative treatments, such as transarterial chemoembolization (TACE), chemotherapy, and radiotherapy. Although statins may be a chemopreventive treatment option for reducing hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related HCC risks, their therapeutic effects are unknown. This study evaluated the effects of statin on HCC patients receiving palliative treatment. Data from the National Health Insurance claims database and cancer registry databases of The Collaboration Center of Health Information Application, Taiwan, were analyzed. We included HCC patients who were treated between January 1, 2001, and December 31, 2010, and followed them from the index date to December 31, 2012. The inclusion criteria were presence of HBV carrier-related HCC, age >20 years, and having received TACE, radiotherapy, or chemotherapy as palliative treatment. The exclusion criteria were cancer diagnosis before HCC was confirmed, surgery, liver transplantation, radiofrequency ablation, or percutaneous ethanol injection as curative treatment, missing sex-related information, HCC diagnosis before HBV, and age <20 years. We enrolled 20,200 HCC patients. The median follow-up duration was 1.66 years (interquartile range, 0.81). In total, 1988 and 18,212 patients received palliative treatment with and without statin use, respectively. HCC patients who received palliative treatment with statin use had lower HCC-specific deaths in all stages than those who received palliative treatment without statin use (P = 0.0001, 0.0002, 0.0012, and 0.0002, and relative risk (RR) = 0.763, 0.775, 0.839, and 0.718, for stages I–IV, respectively). In all-cause and HCC-specific deaths, decreasing trends (P for trend <0.0001) of adjusted hazard ratios (aHRs) were observed in all stages with no treatment, statin use only, palliative treatment

  7. Association between statin therapy and tendon rupture: a case-control study.

    PubMed

    Beri, Abhimanyu; Dwamena, Francesca C; Dwamena, Ben A

    2009-05-01

    Although case reports of a possible association between statin therapy and tendon rupture have been published, no analytical studies exploring this relationship have been reported. We conducted a case-control study using the electronic medical records at Michigan State University from 2002 to 2007 to assess whether statin use is a risk factor for tendon rupture. We compared exposure to statins in 93 cases of tendon rupture with similar exposure in 279 sex- and age-matched controls. Exposure to statins was defined as documentation in the electronic medical record of statin use in the 12 months preceding tendon rupture. For controls, the exposure period was defined as 1 year preceding the last office visit. We used a multivariate logistic regression model, controlling for diabetes, renal disease, rheumatologic disease, and steroid use, to calculate the adjusted odds ratios (ORs). There was no significant difference between cases and controls in the rates of statin use, with either univariate [OR = 1.0, 95% confidence interval (CI) 0.54-1.84] or multivariate analyses (OR = 1.10, 95% CI 0.57-2.13). Based on predetermined subgroup analyses, statin exposure was found to be a significant risk factor for tendon rupture in women (adjusted OR = 3.76, 95% CI 1.11-12.75) but not in men (adjusted OR = 0.66, 95% CI 0.29-1.51). In conclusion, we found no overall association between statin use and tendon rupture, but subgroup analysis suggested that women with tendon rupture were more likely to be on statins. PMID:19454900

  8. High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis.

    PubMed

    Pandit, A K; Kumar, P; Kumar, A; Chakravarty, K; Misra, S; Prasad, K

    2016-07-01

    Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database 'PubMed', 'EMBASE', and 'Google Scholar' as well as from many trial databases. The following search terms were used: 'Statin therapy' AND 'Cardiovascular Disease', AND 'Dose' AND 'Intracerebral hemorrhage', AND 'Randomized Controlled Trials' AND 'High Dose Statin'. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed-effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random-effect model was used. Begg's funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high-dose statin and 31,105 subjects receiving placebo were analyzed in our meta-analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16-2.01; P = 0.002). There was no difference in all-cause mortality between the two groups (RR = 0.95; 95% CI: 0.86-1.06; P = 0.36). No publication bias was observed through Begg's funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings. PMID:26647879

  9. Statin Therapy Alters Lipid Storage in Diabetic Skeletal Muscle

    PubMed Central

    Rebalka, Irena A.; Raleigh, Matthew J.; Snook, Laelie A.; Rebalka, Alexandra N.; MacPherson, Rebecca E. K.; Wright, David C.; Schertzer, Jonathan D.; Hawke, Thomas J.

    2016-01-01

    While statins significantly reduce cholesterol levels and thereby reduce the risk of cardiovascular disease, the development of myopathy with statin use is a significant clinical side effect. Recent guidelines recommend increasing inclusion criteria for statin treatment in diabetic individuals; however, the impact of statins on skeletal muscle health in those with diabetes (who already suffer from impairments in muscle health) is ill defined. Here, we investigate the effects of fluvastatin treatment on muscle health in wild type (WT) and streptozotocin (STZ)-induced diabetic mice. WT and STZ-diabetic mice received diet enriched with 600 mg/kg fluvastatin or control chow for 24 days. Muscle morphology, intra and extracellular lipid levels, and lipid transporter content were investigated. Our findings indicate that short-term fluvastatin administration induced a myopathy that was not exacerbated by the presence of STZ-induced diabetes. Fluvastatin significantly increased ectopic lipid deposition within the muscle of STZ-diabetic animals, findings that were not seen with diabetes or statin treatment alone. Consistent with this observation, only fluvastatin-treated diabetic mice downregulated protein expression of lipid transporters FAT/CD36 and FABPpm in their skeletal muscle. No differences in FAT/CD36 or FABPpm mRNA content were observed. Altered lipid compartmentalization resultant of a downregulation in lipid transporter content in STZ-induced diabetic skeletal muscle was apparent in the current investigation. Given the association between ectopic lipid deposition in skeletal muscle and the development of insulin-resistance, our findings highlight the necessity for more thorough investigations into the impact of statins in humans with diabetes. PMID:27486434

  10. Statin Therapy Alters Lipid Storage in Diabetic Skeletal Muscle.

    PubMed

    Rebalka, Irena A; Raleigh, Matthew J; Snook, Laelie A; Rebalka, Alexandra N; MacPherson, Rebecca E K; Wright, David C; Schertzer, Jonathan D; Hawke, Thomas J

    2016-01-01

    While statins significantly reduce cholesterol levels and thereby reduce the risk of cardiovascular disease, the development of myopathy with statin use is a significant clinical side effect. Recent guidelines recommend increasing inclusion criteria for statin treatment in diabetic individuals; however, the impact of statins on skeletal muscle health in those with diabetes (who already suffer from impairments in muscle health) is ill defined. Here, we investigate the effects of fluvastatin treatment on muscle health in wild type (WT) and streptozotocin (STZ)-induced diabetic mice. WT and STZ-diabetic mice received diet enriched with 600 mg/kg fluvastatin or control chow for 24 days. Muscle morphology, intra and extracellular lipid levels, and lipid transporter content were investigated. Our findings indicate that short-term fluvastatin administration induced a myopathy that was not exacerbated by the presence of STZ-induced diabetes. Fluvastatin significantly increased ectopic lipid deposition within the muscle of STZ-diabetic animals, findings that were not seen with diabetes or statin treatment alone. Consistent with this observation, only fluvastatin-treated diabetic mice downregulated protein expression of lipid transporters FAT/CD36 and FABPpm in their skeletal muscle. No differences in FAT/CD36 or FABPpm mRNA content were observed. Altered lipid compartmentalization resultant of a downregulation in lipid transporter content in STZ-induced diabetic skeletal muscle was apparent in the current investigation. Given the association between ectopic lipid deposition in skeletal muscle and the development of insulin-resistance, our findings highlight the necessity for more thorough investigations into the impact of statins in humans with diabetes. PMID:27486434

  11. Statin Therapy May not Effect NLR and MPV Levels in Patients With Hypercholesterolemia: A Retrospective Study.

    PubMed

    Gungoren, Fatih; Besli, Feyzullah; Caliskan, Serhat; Polat, Ufuk; Basar, Cengiz; Serdar, Osman Akin

    2016-07-01

    Statins may exert pleiotropic effects in coronary artery disease (CAD), diabetes mellitus, and familial hypercholesterolemia. We evaluated the effects of statins on the neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV) in 261 consecutive patients with hypercholesterolemia having CAD or at high cardiovascular (CV) risk and 50 healthy participants who were retrospectively included in this study. Patients were treated with 10 to 80 mg atorvastatin or 10 to 40 mg rosuvastatin for 24 weeks according to baseline levels of cholesterol, triglycerides, and CV risk. Baseline NLR and MPV were significantly higher in patients with CAD or at high risk compared to the control group (1.89 [0.37-6.78]) vs 1.44 [0.75-2.41], P < .001 and 8.8 [6.27-18.6] vs 8.45 [6-11] fL, P = .038, respectively). The NLR, MPV, and lipid parameters were also compared in the patient group after statin treatment for 24 weeks. Lipid levels decreased but the NLR and MPV did not change significantly after the statin therapy. Further studies are needed to clarify the effect of statin therapy on NLR and MPV in patients with CAD or at high CV risk. PMID:26341259

  12. Lipids and cardiovascular disease: where does dietary intervention sit alongside statin therapy?

    PubMed

    Megson, Ian L; Whitfield, Phillip D; Zabetakis, Ioannis

    2016-06-15

    The Seven Countries Study suggested an association between serum cholesterol and cardiovascular disease (CVD). However, the association was not consistent across the various cohorts of participants in different countries; while it was very clear in US and Northern European cohorts, it was weak in Southern European and Japanese cohorts. Nevertheless, the study triggered research into cholesterol-lowering drug strategies, ultimately leading to the development of statins amongst others. Clinical evidence in support of statins is strong and the vast majority of the medical community advocate these drugs as highly effective first-line therapeutics in primary and secondary prevention of CVD. However, growing evidence of side-effects associated with statins in a significant proportion of patients suggests that these drugs are not a universal solution to CVD. There is a need, therefore, to revisit the evidence and to re-appraise the relative importance of cholesterol amongst many other lipids as potential modulators of atherogenesis. In this review, we assess the relative merits of statin therapy in CVD versus dietary interventions that impact on lipids other than cholesterol, including omega-3 fatty acids and polar lipid fractions of various foods (e.g. fish and olive oil). We conclude that careful design around the lipid components of dietary interventions presents a credible alternative in patients who are intolerant to statins or averse to taking such drugs. PMID:27109548

  13. Protocol for analyses of adverse event data from randomized controlled trials of statin therapy.

    PubMed

    2016-06-01

    The Cholesterol Treatment Trialists' (CTT) Collaboration was originally established to conduct individual participant data meta-analyses of major vascular events, cause-specific mortality, and site-specific cancers in large, long-term, randomized trials of statin therapy (and other cholesterol-modifying treatments). The results of the trials of statin therapy and their associated meta-analyses have shown that statins significantly reduce the risk of major vascular events without any increase in the risk of nonvascular causes of death or of site-specific cancer, but do produce small increases in the incidence of myopathy, diabetes, and, probably, hemorrhagic stroke. The CTT Collaboration has not previously sought data on other outcomes, and so a comprehensive meta-analysis of all adverse events recorded in each of the eligible trials has not been conducted. This protocol prospectively describes plans to extend the CTT meta-analysis data set so as to provide a more complete understanding of the nature and magnitude of any other effects of statin therapy. PMID:27264221

  14. Statin Therapy and the Expression of Genes that Regulate Calcium Homeostasis and Membrane Repair in Skeletal Muscle

    PubMed Central

    Draeger, Annette; Sanchez-Freire, Verónica; Monastyrskaya, Katia; Hoppeler, Hans; Mueller, Matthias; Breil, Fabio; Mohaupt, Markus G.; Babiychuk, Eduard B.

    2010-01-01

    In skeletal muscle of patients with clinically diagnosed statin-associated myopathy, discrete signs of structural damage predominantly localize to the T-tubular region and are suggestive of a calcium leak. The impact of statins on skeletal muscle of non-myopathic patients is not known. We analyzed the expression of selected genes implicated in the molecular regulation of calcium and membrane repair, in lipid homeostasis, myocyte remodeling and mitochondrial function. Microscopic and gene expression analyses were performed using validated TaqMan custom arrays on skeletal muscle biopsies of 72 age-matched subjects who were receiving statin therapy (n = 38), who had discontinued therapy due to statin-associated myopathy (n = 14), and who had never undergone statin treatment (n = 20). In skeletal muscle, obtained from statin-treated, non-myopathic patients, statins caused extensive changes in the expression of genes of the calcium regulatory and the membrane repair machinery, whereas the expression of genes responsible for mitochondrial function or myocyte remodeling was unaffected. Discontinuation of treatment due to myopathic symptoms led to a normalization of gene expression levels, the genes encoding the ryanodine receptor 3, calpain 3, and dystrophin being the most notable exceptions. Hence, even in clinically asymptomatic (non-myopathic) patients, statin therapy leads to an upregulation in the expression of genes that are concerned with skeletal muscle regulation and membrane repair. PMID:20489141

  15. Effect of hyperlipidemia on response to nonsurgical periodontal therapy: Statin users versus nonusers

    PubMed Central

    Sangwan, Aditi; Tewari, Shikha; Singh, Harpreet; Sharma, Rajinder Kumar; Narula, Satish Chander

    2016-01-01

    Objective: To evaluate the response to nonsurgical periodontal therapy among hyperlipidemic subjects and whether statin use by hyperlipidemic subjects influences the response. Materials and Methods: This study was conducted on 107 chronic periodontitis subjects (35 normolipidemic [NL] controls, 36 hyperlipidemics on nonpharmacological therapy and 36 hyperlipidemics on statins). Periodontal (plaque index, gingival index [GI], probing depth [PD], and clinical attachment level [CAL]) and biochemical (plasma triglyceride [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-DL-C [HDL-C] levels) examination was done at baseline and 3 months after nonsurgical periodontal treatment. Results: Both the NL and statin groups exhibited significantly greater improvement in GI as compared to the hyperlipidemic group on nonpharmacological therapy (P = 0.004 and 0.006, respectively). Mean change in PD correlated negatively with baseline TC (r = −0.306) and LDL-C (r = −0.360) while mean change in GI positively correlated with baseline HDL-C (r = 0.219). Regression analyses revealed that mean change in PD was negatively associated with LDL-C (β = −0.358, P < 0.001) while mean change in GI was positively associated with HDL-C (β = 0.219, P = 0.023). Conclusions: While higher baseline lipid levels were somewhat detrimental to the resolution of inflammation postperiodontal treatment, the inclusion of statin therapy among hyperlipidemic subjects seemed to improve clinical response as compared to those devoid of the drug. The findings of the study are suggestive of a possible adjunctive role of statins in periodontal treatment that warrants future studies. PMID:27011743

  16. National Assessment of Statin Therapy in Patients Hospitalized with Acute Myocardial Infarction: Insight from China PEACE-Retrospective AMI Study, 2001, 2006, 2011

    PubMed Central

    Zhang, Lihua; Li, Jing; Li, Xi; Nasir, Khurram; Zhang, Haibo; Wu, Yongjian; Hu, Shuang; Wang, Qing; Downing, Nicholas S.; Desai, Nihar R.; Masoudi, Frederick A.; Spertus, John A.; Krumholz, Harlan M.; Jiang, Lixin

    2016-01-01

    Background Statin therapy is among the most effective treatments to improve short- and long-term mortality after acute myocardial infarction. The use of statin, and the intensity of their use, has not been described in acute myocardial infarction patients in China, a country with a rapidly growing burden of cardiovascular disease. Methods and Results Using a nationally representative sample of patients with acute myocardial infarction admitted to 162 Chinese hospitals in 2001, 2006 and 2011, we identified 14,958 patients eligible for statin therapy to determine rates of statin use and the intensity of statin therapy, defined as those statin regimens with expected low-density lipoprotein cholesterol lowering of at least 40%, to identify factors associated with the use of statin therapy. Statin use among hospitalized patients with acute myocardial infarction increased from 27.9% in 2001 to 72.5% in 2006, and 88.8% in 2011 (P<0.001 for trend). Regional variation in statin use correspondingly decreased over time. Among treated patients, those receiving intensive statin therapy increased from 1.0% in 2001 to 24.2% in 2006 to 57.2% in 2011(P<0.001 for trend). Patients without low-density lipoprotein cholesterol measured were less likely to be treated with statin or to receive intensive therapy. Conclusions The use of statin therapy has dramatically increased over the past decade in Chinese patients with acute myocardial infarction. However, half of patients still did not receive intensive statin therapy in 2011.Given that guidelines strongly endorse intensive statin therapy for acute myocardial infarction patients, initiatives promoting the use of statin therapy, with attention to treatment intensity, would support further improvements in practice. PMID:27058862

  17. The Interaction Between Statins and Exercise: Mechanisms and Strategies to Counter the Musculoskeletal Side Effects of This Combination Therapy

    PubMed Central

    Deichmann, Richard E.; Lavie, Carl J.; Asher, Timothy; DiNicolantonio, James J.; O'Keefe, James H.; Thompson, Paul D.

    2015-01-01

    Background Broad indications for the use of statin medications are resulting in more patients using these therapies. Simultaneously, healthcare professionals are strongly advocating recommendations to increase exercise training (ET) as a means of decreasing cardiovascular disease (CVD) risk and improving other parameters of fitness. Methods We review the literature to explore mechanisms that may increase the risk of statin/ET interactions, examine the benefits and risks of combining ET and statin use, and offer strategies to minimize the hazards of this combination therapy. Results The combined use of statins and ET can result in health gains and decreased CVD risk; however, multiple factors may increase the risk of adverse events. Some of the events that have been reported with the combination of statins and ET include decreased athletic performance, muscle injury, myalgia, joint problems, decreased muscle strength, and fatigue. The type of statin, the dose, drug interactions, genetic variants, coenzyme Q10 deficiency, vitamin D deficiency, and underlying muscle diseases are among the factors that may predispose patients to intolerance of this combined therapy. Conclusion Effective strategies exist to help patients who may be intolerant of combined statin therapy and ET so they may benefit from this proven therapy. Careful attention to identifying high-risk groups and strategies to prevent or treat side effects that may occur should be employed. PMID:26730228

  18. The role of statin therapy in the prevention of atrial fibrillation: a meta-analysis of randomized controlled trials

    PubMed Central

    Fang, Wen-tong; Li, Hong-jian; Zhang, Haibo; Jiang, Su

    2012-01-01

    AIMS The use of statins has been suggested to protect against atrial fibrillation (AF) in some clinical observational and experimental studies but has remained inadequately explored. This study was designed to examine whether statins can reduce the risk of AF. METHODS Meta-analysis of randomized, controlled trials with use of statins on incidence or recurrence of AF was performed. RESULTS Twenty studies with 23 577 patients were included in the analysis. Seven studies investigated the use of statins in patients with AF, 11 studies investigated the primary prevention of statins in patients without AF, and two studies investigated mixed populations of patients. The incidence or recurrence of AF occurred in 1543 patients. Overall, statin therapy was significantly associated with a decreased risk of AF compared with control (odds ratio 0.49, 95% confidence interval 0.37–0.65; P < 0.00001). A beneficial effect was found in the atorvastatin subgroup and the simvastatin subgroup, but not in the pravastatin subgroup or the rosuvastatin subgroup. The benefit of statin therapy appeared to be more pronounced in secondary prevention (odds ratio 0.34, 95% confidence interval 0.18–0.64; P < 0.0008) than in primary prevention (odds ratio 0.54, 95% confidence interval 0.40–0.74; P < 0.0001). CONCLUSIONS Statin therapy was significantly associated with a decreased risk of incidence or recurrence of AF. Heterogeneity was explained by differences in statin types, patient populations and surgery types. The benefit of statin therapy seemed more pronounced in secondary than in primary prevention. PMID:22376147

  19. Long-Term Safety and Efficacy of Lowering Low-Density Lipoprotein Cholesterol With Statin Therapy

    PubMed Central

    Ford, Ian; Murray, Heather; Packard, Chris J.

    2016-01-01

    Background— Extended follow-up of statin-based low-density lipoprotein cholesterol lowering trials improves the understanding of statin safety and efficacy. Examining cumulative cardiovascular events (total burden of disease) gives a better appreciation of the clinical value of statins. This article evaluates the long-term impact of therapy on mortality and cumulative morbidity in a high-risk cohort of men. Methods and Results— The West of Scotland Coronary Prevention Study was a primary prevention trial in 45- to 64-year-old men with high low-density lipoprotein cholesterol. A total of 6595 men were randomized to receive pravastatin 40 mg once daily or placebo for an average of 4.9 years. Subsequent linkage to electronic health records permitted analysis of major incident events over 20 years. Post trial statin use was recorded for 5 years after the trial but not for the last 10 years. Men allocated to pravastatin had reduced all-cause mortality (hazard ratio, 0.87; 95% confidence interval, 0.80–0.94; P=0.0007), attributable mainly to a 21% decrease in cardiovascular death (hazard ratio, 0.79; 95% confidence interval, 0.69–0.90; P=0.0004). There was no difference in noncardiovascular or cancer death rates between groups. Cumulative hospitalization event rates were lower in the statin-treated arm: by 18% for any coronary event (P=0.002), by 24% for myocardial infarction (P=0.01), and by 35% for heart failure (P=0.002). There were no significant differences between groups in hospitalization for noncardiovascular causes. Conclusion— Statin treatment for 5 years was associated with a legacy benefit, with improved survival and a substantial reduction in cardiovascular disease outcomes over a 20-year period, supporting the wider adoption of primary prevention strategies. PMID:26864092

  20. Drivers of the Sex Disparity in Statin Therapy in Patients with Coronary Artery Disease: A Cohort Study

    PubMed Central

    Zhang, Huabing; Plutzky, Jorge; Shubina, Maria; Turchin, Alexander

    2016-01-01

    Background Women are less likely to be prescribed statins than men. Existing reports explain only a fraction of this difference. We conducted a study to identify factors that account for sex differences in statin therapy among patients with coronary artery disease (CAD). Methods and Results We retrospectively studied 24,338 patients with CAD who were followed for at least a year between 2000 and 2011 at two academic medical centers. Women (9,006 / 37% of study patients) were less likely to either have initiated statin therapy (81.9% women vs. 87.7% men) or to have persistent statin therapy at the end of follow-up (67.0% women vs. 71.4% men). Women were older (72.9 vs. 68.4 years), less likely to have ever smoked (49.8% vs. 65.6%), less likely to have been evaluated by a cardiologist (57.5% vs. 64.5%) and more likely to have reported an adverse reaction to a statin (27.1% vs. 21.7%) (p < 0.0001 for all). In multivariable analysis, patients with history of smoking (OR 1.094; p 0.017), younger age (OR 1.013 / year), cardiologist evaluation (OR 1.337) and no reported adverse reactions to statins (OR 1.410) were more likely (p < 0.0001 for all) to have persistent statin therapy. Together, these four factors accounted for 90.4% of the sex disparity in persistent statin therapy. Conclusions Several specific factors appear to underlie divergent statin therapy in women vs. men. Identifying such drivers may facilitate programmatic interventions and stimulate further research to overcome sex differences in applying proven interventions for cardiovascular risk reduction. PMID:27148965

  1. Personalized Prediction of Lifetime Benefits with Statin Therapy for Asymptomatic Individuals: A Modeling Study

    PubMed Central

    Ferket, Bart S.; van Kempen, Bob J. H.; Heeringa, Jan; Spronk, Sandra; Fleischmann, Kirsten E.; Nijhuis, Rogier L. G.; Hofman, Albert; Steyerberg, Ewout W.; Hunink, M. G. Myriam

    2012-01-01

    Background Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. Methods and Findings A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk. Conclusions We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be

  2. Statin therapy: rationale for a new agent, rosuvastatin.

    PubMed

    Korlipara, K

    2002-06-01

    Cardiovascular disease (CVD) remains a major cause of death in industrialised societies, and elevated serum lipids are a significant, highly prevalent and undertreated risk factor for this condition. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have revolutionised the treatment of hyperlipidaemia, and results from large-scale, long-term clinical trials have shown that the substantial reductions in low-density lipoprotein cholesterol (LDL-C) achieved with these drugs are associated with dramatic decreases in cardiovascular risk. Results from recent comparative clinical trials that have included a new drug in this class, rosuvastatin (Crestor), have demonstrated that it is significantly superior to atorvastatin, pravastatin and simvastatin in reducing total cholesterol, LDL-C and apolipoprotein B (Apo B). It is also significantly more effective than atorvastatin in increasing high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (Apo A-I). Rosuvastatin was also superior to all these agents in helping patients meet European Atherosclerosis Society (EAS) and National Cholesterol Education Programme (NCEP) goals for LDL-C. The results of an increasing number of studies indicate that statins have a wide range of pleiotropic properties that almost certainly contribute to their ability to decrease cardiovascular risk and may also make them valuable for treatment of other diseases. These actions include plaque stabilisation, improvement of endothelial function, inhibition of smooth muscle cell proliferation and migration, reduction of expression of adhesion molecules, prevention of cholesterol esterification and accumulation, reduction of secretion of matrix metalloproteinases by macrophages, reduction of platelet activity, reduction of formation of thrombogenic factors, chemoprotection and induction of bone morphogenic protein-2 (BMP-2). Further exploration of these actions will provide key information about class effects

  3. Efficacy of Statin Therapy in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis

    PubMed Central

    Rysz-Górzynska, Magdalena; Gluba-Brzózka, Anna; Sahebkar, Amirhossein; Serban, Maria-Corina; Mikhailidis, Dimitri P.; Ursoniu, Sorin; Toth, Peter P.; Bittner, Vera; Watts, Gerald F.; Lip, Gregory Y. H.; Rysz, Jacek; Catapano, Alberico L.; Banach, Maciej

    2016-01-01

    Since the evidence regarding statin therapy in PAH has not been conclusive, we assessed the impact of statin therapy in PAH through a systematic review and meta-analysis of available studies. We searched selected databases up to August 1, 2015 to identify the studies investigating the effect of statin administration on PAH. Meta-analysis was performed using either a fixed-effects or random-effect model according to I2 statistic. Meta-analysis of 8 studies with 665 patients did not suggest any significant improvement in 6-min walking distance (6MWD) by statin therapy (weighed mean difference [WMD]: −6.08 m, 95% confidence interval [CI]: −25.66, 13.50, p = 0.543; Q = 8.41, I2 = 28.64%). Likewise, none of the other indices including pulmonary arterial pressure (WMD: −0.97 mmHg, 95%CI: −4.39, 2.44, p = 0.577; Q = 14.64, I2 = 79.51%), right atrial pressure (WMD: 1.01 mmHg, 95%CI: −0.93, 2.96, p = 0.307; Q = 44.88, I2 = 95.54%), cardiac index (WMD: 0.05 L/min/m2, 95%CI: −0.05, 0.15, p = 0.323; Q = 3.82, I2 = 21.42%), and pulmonary vascular resistance (WMD: −1.42 dyn*s/cm5, 95%CI: −72.11, 69.27, p = 0.969; Q = 0.69, I2 = 0%) was significantly altered by statin therapy. In conclusion, the results of the meta-analysis did not show a statistically significant effect of statin therapy in the improvement of 6MWD, pulmonary arterial pressure, right atrial pressure, cardiac index and pulmonary vascular resistance. PMID:27444125

  4. Efficacy of Statin Therapy in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis.

    PubMed

    Rysz-Górzynska, Magdalena; Gluba-Brzózka, Anna; Sahebkar, Amirhossein; Serban, Maria-Corina; Mikhailidis, Dimitri P; Ursoniu, Sorin; Toth, Peter P; Bittner, Vera; Watts, Gerald F; Lip, Gregory Y H; Rysz, Jacek; Catapano, Alberico L; Banach, Maciej

    2016-01-01

    Since the evidence regarding statin therapy in PAH has not been conclusive, we assessed the impact of statin therapy in PAH through a systematic review and meta-analysis of available studies. We searched selected databases up to August 1, 2015 to identify the studies investigating the effect of statin administration on PAH. Meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Meta-analysis of 8 studies with 665 patients did not suggest any significant improvement in 6-min walking distance (6MWD) by statin therapy (weighed mean difference [WMD]: -6.08 m, 95% confidence interval [CI]: -25.66, 13.50, p = 0.543; Q = 8.41, I(2) = 28.64%). Likewise, none of the other indices including pulmonary arterial pressure (WMD: -0.97 mmHg, 95%CI: -4.39, 2.44, p = 0.577; Q = 14.64, I(2) = 79.51%), right atrial pressure (WMD: 1.01 mmHg, 95%CI: -0.93, 2.96, p = 0.307; Q = 44.88, I(2) = 95.54%), cardiac index (WMD: 0.05 L/min/m(2), 95%CI: -0.05, 0.15, p = 0.323; Q = 3.82, I(2) = 21.42%), and pulmonary vascular resistance (WMD: -1.42 dyn*s/cm(5), 95%CI: -72.11, 69.27, p = 0.969; Q = 0.69, I(2) = 0%) was significantly altered by statin therapy. In conclusion, the results of the meta-analysis did not show a statistically significant effect of statin therapy in the improvement of 6MWD, pulmonary arterial pressure, right atrial pressure, cardiac index and pulmonary vascular resistance. PMID:27444125

  5. Aspirin and Statin Nonuse Associated With Early Biochemical Failure After Prostate Radiation Therapy

    SciTech Connect

    Zaorsky, Nicholas G.; Buyyounouski, Mark K.; Li, Tianyu; Horwitz, Eric M.

    2012-09-01

    Purpose: To present the largest retrospective series investigating the effect of aspirin and statins, which are hypothesized to have antineoplastic properties, on biochemical failure (nadir plus 2 ng/mL) after prostate radiation therapy (RT). Methods and Materials: Between 1989 and 2006, 2051 men with clinically localized prostate cancer received definitive RT alone (median dose, 76 Gy). The rates of aspirin use and statin use (defined as any use at the time of RT or during follow-up) were 36% and 34%, respectively. The primary endpoint of the study was an interval to biochemical failure (IBF) of less than 18 months, which has been shown to be the single strongest predictor of distant metastasis, prostate cancer survival, and overall survival after RT. Patient demographic characteristics and tumor staging factors were assessed with regard to associations with the endpoint. Univariate analysis was performed with the {chi}{sup 2} test for categorical variables and the Wilcoxon test for continuous variables. Multivariable analysis was performed with a multiple logistic regression. Results: The median follow-up was 75 months. Univariate analysis showed that an IBF of less than 18 months was associated with aspirin nonuse (P<.0001), statin nonuse (P<.0001), anticoagulant nonuse (P=.0006), cardiovascular disease (P=.0008), and prostate-specific antigen (continuous) (P=.008) but not with Gleason score, age, RT dose, or T stage. On multivariate analysis, only aspirin nonuse (P=.0012; odds ratio, 2.052 [95% confidence interval, 1.328-3.172]) and statin nonuse (P=.0002; odds ratio, 2.465 [95% confidence interval, 1.529-3.974]) were associated with an IBF of less than 18 months. Conclusions: In patients who received RT for prostate cancer, aspirin or statin nonuse was associated with early biochemical failure, a harbinger of distant metastasis and death. Further study is needed to confirm these findings and to determine the optimal dosing and schedule, as well as the relative

  6. The effect of statins therapy in aortic stenosis: Meta-analysis comparison data of RCTs and observationals

    PubMed Central

    Zhao, Ying; Nicoll, Rachel; He, Yi hua; Henein, Michael Y.

    2016-01-01

    Aortic stenosis has been shown to share the same risk factors as atherosclerosis which suggested a potential benefit from statins therapy. Fourteen studies which provided the effect of statins treatment on aortic stenosis (AS) were meta-analyzed, including 5 randomized controlled trials (RCTs) and 9 observational studies. In the RCTs, statins did not have any influence on peak aortic valve velocity, peak valve gradient, mean valve gradient, aortic valve area and aortic calcification compared to controls. In the observational studies, the peak valve velocity, peak gradient and aortic valve area showed less progression in the statins group compared to controls. This article describes data related article title “The effect of statins on valve function and calcification in aortic stenosis: a meta-analysis” (Zhao et al., 2016) [1]. PMID:26977437

  7. The effect of statins therapy in aortic stenosis: Meta-analysis comparison data of RCTs and observationals.

    PubMed

    Zhao, Ying; Nicoll, Rachel; He, Yi Hua; Henein, Michael Y

    2016-06-01

    Aortic stenosis has been shown to share the same risk factors as atherosclerosis which suggested a potential benefit from statins therapy. Fourteen studies which provided the effect of statins treatment on aortic stenosis (AS) were meta-analyzed, including 5 randomized controlled trials (RCTs) and 9 observational studies. In the RCTs, statins did not have any influence on peak aortic valve velocity, peak valve gradient, mean valve gradient, aortic valve area and aortic calcification compared to controls. In the observational studies, the peak valve velocity, peak gradient and aortic valve area showed less progression in the statins group compared to controls. This article describes data related article title "The effect of statins on valve function and calcification in aortic stenosis: a meta-analysis" (Zhao et al., 2016) [1]. PMID:26977437

  8. Ultrasound Assessment of Carotid Plaque Echogenicity Response to Statin Therapy: A Systematic Review and Meta-Analysis

    PubMed Central

    Ibrahimi, Pranvera; Jashari, Fisnik; Bajraktari, Gani; Wester, Per; Henein, Michael Y.

    2015-01-01

    Objective: To evaluate in a systematic review and meta-analysis model the effect of statin therapy on carotid plaque echogenicity assessed by ultrasound. Methods: We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to April, 2015, for studies evaluating the effect of statins on plaque echogenicity. Two researchers independently determined the eligibility of studies evaluating the effect of statin therapy on carotid plaque echogenicity that used ultrasound and grey scale median (GSM) or integrated back scatter (IBS). Results: Nine out of 580 identified studies including 566 patients’ carotid artery data were meta-analyzed for a mean follow up of 7.2 months. A consistent increase in the echogenicity of carotid artery plaques, after statin therapy, was reported. Pooled weighted mean difference % (WMD) on plaque echogenicity after statin therapy was 29% (95% CI 22%–36%), p < 0.001, I2 = 92.1%. In a meta-regression analysis using % mean changes of LDL, HDL and hsCRP as moderators, it was shown that the effects of statins on plaque echogenicity were related to changes in hsCRP, but not to LDL and HDL changes from the baseline. The effect of statins on the plaque was progressive; it showed significance after the first month of treatment, and the echogenicity continued to increase in the following six and 12 months. Conclusions: Statin therapy is associated with a favorable increase of carotid plaque echogenicity. This effect seems to be dependent on the period of treatment and hsCRP change from the baseline, independent of changes in LDL and HDL. PMID:25984600

  9. Understanding patients’ perspective of statin therapy: can we design a better approach to the management of dyslipidaemia? A literature review

    PubMed Central

    Chee, Ying Jie; Chan, Hian Hui Vincent; Tan, Ngiap Chuan

    2014-01-01

    INTRODUCTION Dyslipidaemia leads to atherosclerosis and is a major risk factor for cardiovascular diseases. In clinical trials, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been shown to effectively reduce dyslipidaemia. Despite the availability and accessibility of statins, myocardial infarctions and cerebrovascular accidents remain among the top causes of mortality in developed countries, including Singapore. This enigma could be attributed to suboptimal adherence to statin therapy. The present literature review aimed to evaluate patients’ perceptions of statin therapy. METHODS We searched PubMed and other databases for articles published in English from October 1991 to May 2012 containing keywords such as ‘patient’, ‘views’, ‘perceptions’, ‘adherence’, ‘statin’ and ‘dyslipidaemia’. Of the 122 eligible studies retrieved, 58 were reviewed. The findings were categorised and framed in accordance with the Health Belief Model. RESULTS Patients with dyslipidaemia appeared to underestimate their susceptibility to dyslipidaemia-related complications, partly due to their demographic profiles. Failure to appreciate the severity of potential complications was a major hindrance toward adherence to statin therapy. Other factors that affected a patient’s adherence included lack of perceived benefits, perceived side effects, the cost of statins, poor physician-patient relationship, and overestimation of the effectiveness of diet control as a treatment modality. CONCLUSION Existing evidence suggests that the cause of poor adherence to statin therapy is multifactorial. The use of the Health Belief Model to present the results of our literature review provides a systematic framework that could be used to design a patient-centric approach for enhancing adherence to statin therapy. PMID:25189302

  10. Statin therapy and plasma cortisol concentrations: A systematic review and meta-analysis of randomized placebo-controlled trials.

    PubMed

    Sahebkar, Amirhossein; Rathouska, Jana; Simental-Mendía, Luis E; Nachtigal, Petr

    2016-01-01

    This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) in order to calculate the effect size of statin therapy in changing plasma cortisol concentrations. Following a systematic search in Medline, SCOPUS, Web of Science and Google Scholar databases (by up to March 01, 2015), 7 eligible RCTs were selected. Random-effects meta-analysis suggested a significant increase in plasma cortisol concentrations following statin therapy (WMD: 6.34%, 95% CI: 1.80, 10.87, p=0.006). Subgroup analysis confirmed the significance of the effect with lipophilic statins comprising atorvastatin, simvastatin, and lovastatin (WMD: 7.00%, 95% CI: 2.21, 11.79, p=0.004) but not with hydrophilic statins (rosuvastatin and pravastatin) (WMD: 0.60%, 95% CI: -13.46, 14.66, p=0.933). In the meta-regression analysis, changes in plasma cortisol concentrations following statin therapy were found to be independent of treatment duration. Results of this meta-analysis of RCTs suggest a significant elevation in plasma cortisol levels following statin therapy. PMID:26546969

  11. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry

    PubMed Central

    Kumbhani, Dharam J.; Steg, Ph. Gabriel; Cannon, Christopher P.; Eagle, Kim A.; Smith, Sidney C.; Goto, Shinya; Ohman, E. Magnus; Elbez, Yedid; Sritara, Piyamitr; Baumgartner, Iris; Banerjee, Subhash; Creager, Mark A.; Bhatt, Deepak L.

    2014-01-01

    Aims Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. Methods Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. Results A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72–0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73–0.96; P = 0.01). Conclusion Among patients with PAD in the REACH registry, statin use was associated with an ∼18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD. PMID:24585266

  12. Statin Therapy for Primary Prevention of Atrial Fibrillation: Guided by CHADS2/CHA2DS2VASc Score

    PubMed Central

    Hung, Chen-Ying; Hsieh, Yu-Cheng; Huang, Jin-Long; Lin, Ching-Heng

    2014-01-01

    Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased cardiovascular morbidity and mortality. The anti-arrhythmic effect of statins on AF prevention appears to be highly significant in most clinical studies. However, some discrepancies do exist among different clinical studies. Different clinical settings and types of stains used may explain these differences between trials. The CHADS2 and CHA2DS2VASc scoring systems have been used for stroke risk stratification in AF patients. The recent study suggested that these scores can also be used to guide statin therapy for AF prevention. Patients with higher scores had a higher risk of developing AF and gained more benefits from statins therapy than those with lower scores. This review article focused on the ability of these scores to predict AF prevention by statins. PMID:25089130

  13. Secondary prevention after PCI: the cost-effectiveness of statin therapy in the Netherlands

    PubMed Central

    Chaplin, S.; Scuffham, P.A.; Alon, M.; van den Boom, G.

    2004-01-01

    Background Little is known about the cost-effectiveness of secondary prevention after percutaneous coronary intervention (PCI). The aim of this study was to estimate the cost-effectiveness of statin therapy. Methods A cost-effectiveness analysis was performed using data from the Lescol Intervention Prevention Study (LIPS). In the LIPS trial, patients with normal-to-moderate hypercholesterolaemia who had undergone a first PCI were randomised to receive either fluvastatin 40 mg twice-daily plus dietary counselling or dietary counselling alone. A Markov model was used to estimate the incremental costs per quality-adjusted life year (QALY) and life year gained (LYG). Costs were based on prices and reimbursed charges, utility data were drawn from literature. Monte Carlo simulations and multivariate analysis were used to assess uncertainty. Results Routine statin treatment costs an additional €734 (SD €686) per patient over ten years compared with controls. It resulted in an additional 0.078 (0.047) QALYs or 0.082 (0.041) LYG. The incremental costs per QALY and LYG were €9312 (€14,648) and €8954 (€16,617) respectively. Anticipating a willingness to pay of €20,000 per QALY, there is a 75.1% chance that fluvastatin treatment is cost-effective. Conclusion Statin therapy with fluvastatin is economically efficient with regard to reducing heart disease in the Netherlands when given routinely to all patients following PCI. PMID:25696357

  14. [Consensus for pharmacologic treatment of atherogenic dyslipidemia with statin-fenofibrate combined therapy].

    PubMed

    2016-01-01

    LDLc levels are associated with increase of cardiovascular risk, and statins are currently used for their control. Nevertheless, a despite of LDLc levels at goal, a residual risk is persistent, commonly associated with persistent lipids modifications (high triglycerides and low HDLc). So, it is necessary to evaluate triglycerides and HDL to assessment cardiovascular risk. Clinical data are consistent with efficacy and safety of combination therapy with statin and other lipid lowering drugs, for instance fenofibrate. Patients with hipertriglyceridemia and low HDLc are the group with most potential improve. In that patients with atherogenic dyslipidemia, the target for therapeutic objectives related with non-HDL-cholesterol is a priority, because non-HDL-cholesterol is considered as a more accuracy measure to assessment cardiovascular risk. PMID:26811267

  15. Molecular Targeted Therapies of Aggressive Thyroid Cancer

    PubMed Central

    Ferrari, Silvia Martina; Fallahi, Poupak; Politti, Ugo; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro

    2015-01-01

    Differentiated thyroid carcinomas (DTCs) that arise from follicular cells account >90% of thyroid cancer (TC) [papillary thyroid cancer (PTC) 90%, follicular thyroid cancer (FTC) 10%], while medullary thyroid cancer (MTC) accounts <5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC, and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts toward the development of new drugs. Several genetic alterations in different molecular pathways in TC have been shown in the past few decades, associated with TC development and progression. Rearranged during transfection (RET)/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs) are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the aforementioned molecular pathways involved in growth, angiogenesis, local, and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC, and anaplastic thyroid cancer, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds and to personalize the therapy in

  16. Statin therapy and thromboxane generation in patients with coronary artery disease treated with high-dose aspirin.

    PubMed

    Bliden, K P; Singla, A; Gesheff, M G; Toth, P P; Tabrizchi, A; Ens, G; Guyer, K; Singh, M; Franzese, C J; Stapleton, D; Tantry, U S; Gurbel, P A

    2014-08-01

    Aspirin and statin therapy are mainstay treatments in patients with coronary artery disease (CAD). The relation between statin therapy, in vivo thromboxane (Tx) generation; a marker of inflammation, and blood thrombogenicity has never been explored. Urinary 11-dehydro (dh) TxB2 was determined in patients with suspected CAD on 325 mg daily aspirin therapy prior to undergoing cardiac catheterisation (n=281). Thrombogenicity was estimated by thrombelastographic measurement of thrombin-induced platelet-fibrin clot strength (TIP-FCS) and lipids/lipoproteins were determined by vertical density gradient ultracentrifugation/ELISA. The influence of statin therapy and dose was analysed by the atorvastatin equivalent dose (5-10 mg, 20-40 mg, or 80 mg daily). Statin therapy (n=186) was associated with a dose-dependent reduction in urinary 11-dh TxB2 (p=0.046) that was independent of LDL and apo B100 levels but was strongly related to TIP-FCS (p=0.006). By multivariate analysis, no statin therapy (n=95) and female gender were independently associated with high urinary 11-dh TxB2 [OR=2.95 (0.1.57-5.50, p=0.0007); OR=2.25 (1.24-4.05, p=0.007)], respectively. In aspirin-treated patients, statin therapy was independently and inversely associated with inflammation in a dose-dependent manner. Elevated 11-dh TxB2 was associated with a prothrombotic state indicated by high TIP-FCS. Our data suggest that measurement of urinary 11-dTxB2 may be a useful method to optimise statin dosing in order to reduce thrombotic risk. PMID:24763965

  17. Effects of Statin Therapy on Clinical Outcomes of Survivors of Acute Myocardial Infarction with Severe Systolic Heart Failure

    PubMed Central

    Kim, Hyun Soo; Kim, Jin Bae; Kim, Woo-Shik; Kim, Kwon Sam; Jeong, Myung Ho; Kim, Weon

    2015-01-01

    Objective Large randomized trials have failed to show a beneficial effect of statin treatment in chronic HF. The investigators tried to evaluate the long-term effects of statin therapy in patients with new onset heart failure (HF) following acute myocardial infarction (AMI). Methods Between January 2008 and December 2011, a total of 13,616 AMI patients were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) which was a prospective, multi-center, nationwide, web-based database of AMI in Korea. From this database, we studied 1,055 patients with AMI who had newly developed severe acute HF [left ventricular ejection fraction ≤ 40%] and were discharged alive. The patients were divided into two groups, a statin group (n = 756) and a no-statin group (n = 299). We investigated the one-year major adverse cardiovascular events (MACEs), including all-cause mortality, MI, and any revascularization of each group. We then performed a propensity-score matched analysis. Results In the original cohort, one-year MACEs were similar between the two groups (16.5% vs. 14.7% in the statin or no-statin groups; p = 0.47). Propensity-score matching yielded 256 pairs, and in that population we observed comparable results in terms of MACEs (18.0% vs. 12.5% in the statin or no-statin groups, p = 0.11) and mortality (5.1% vs. 3.5% in the statin or no-statin groups, p = 0.51). Cox-regression analysis revealed that statin therapy was not an independent predictor for occurrence of a MACE [Hazard ratio (HR) 1.11, 95% CI 0.79–1.57, p = 0.54] or all-cause mortality (HR 1.42, 95% CI 0.75–2.70, p = 0.28). Conclusion Statin therapy was not associated with a reduction in the long-term occurrence of MACEs or mortality in survivors of AMI with severe acute HF in this retrospective cohort study. PMID:26658751

  18. Lack of Effect of Lowering LDL Cholesterol on Cancer: Meta-Analysis of Individual Data from 175,000 People in 27 Randomised Trials of Statin Therapy

    PubMed Central

    2012-01-01

    Background Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials. Methods and Findings Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py

  19. Influence of Peripheral Artery Disease and Statin Therapy on Apolipoprotein Profiles

    PubMed Central

    Gardner, Andrew W.; Parker, Donald E.; Montgomery, Polly S.; Esponda, Omar L.; Casanegra, Ana I.

    2013-01-01

    Apolipoprotein B is a stronger predictor of myocardial infarction than LDL cholesterol, and it is inversely related to physical activity and modifiable with exercise training. As such, apolipoprotein measures may be of particular relevance for subjects with PAD and claudication. We compared plasma apolipoprotein profiles in 29 subjects with peripheral artery disease (PAD) and intermittent claudication and in 39 control subjects. Furthermore, we compared the plasma apolipoprotein profiles of subjects with PAD either treated (n = 17) or untreated (n = 12) with statin medications. For the apolipoprotein subparticle analyses, subjects with PAD had higher age-adjusted Lp-B:C (P < 0.05) and lower values of Lp-A-I:A-II (P < 0.05) than controls. The PAD group taking statins had lower age-adjusted values for apoB (P < 0.05), Lp-A-II:B:C:D:E (P < 0.05), Lp-B:E + Lp-B:C:E (P < 0.05), Lp-B:C (P < 0.05), and Lp-A-I (P < 0.05) than the untreated PAD group. Subjects with PAD have impaired apolipoprotein profiles than controls, characterized by Lp-B:C and Lp-A-I:A-II. Furthermore, subjects with PAD on statin medications have a more favorable risk profile, particularly noted in multiple apolipoprotein subparticles. The efficacy of statin therapy to improve cardiovascular risk appears more evident in the apolipoprotein sub-particle profile than in the more traditional lipid profile of subjects with PAD and claudication. This trial is registered with ClinicalTrials.gov NCT00618670. PMID:24102029

  20. Influence of peripheral artery disease and statin therapy on apolipoprotein profiles.

    PubMed

    Gardner, Andrew W; Alaupovic, Petar; Parker, Donald E; Montgomery, Polly S; Esponda, Omar L; Casanegra, Ana I

    2013-01-01

    Apolipoprotein B is a stronger predictor of myocardial infarction than LDL cholesterol, and it is inversely related to physical activity and modifiable with exercise training. As such, apolipoprotein measures may be of particular relevance for subjects with PAD and claudication. We compared plasma apolipoprotein profiles in 29 subjects with peripheral artery disease (PAD) and intermittent claudication and in 39 control subjects. Furthermore, we compared the plasma apolipoprotein profiles of subjects with PAD either treated (n = 17) or untreated (n = 12) with statin medications. For the apolipoprotein subparticle analyses, subjects with PAD had higher age-adjusted Lp-B:C (P < 0.05) and lower values of Lp-A-I:A-II (P < 0.05) than controls. The PAD group taking statins had lower age-adjusted values for apoB (P < 0.05), Lp-A-II:B:C:D:E (P < 0.05), Lp-B:E + Lp-B:C:E (P < 0.05), Lp-B:C (P < 0.05), and Lp-A-I (P < 0.05) than the untreated PAD group. Subjects with PAD have impaired apolipoprotein profiles than controls, characterized by Lp-B:C and Lp-A-I:A-II. Furthermore, subjects with PAD on statin medications have a more favorable risk profile, particularly noted in multiple apolipoprotein subparticles. The efficacy of statin therapy to improve cardiovascular risk appears more evident in the apolipoprotein sub-particle profile than in the more traditional lipid profile of subjects with PAD and claudication. This trial is registered with ClinicalTrials.gov NCT00618670. PMID:24102029

  1. Effect of preoperative statin therapy on early postoperative memory impairment after off-pump coronary artery bypass surgery

    PubMed Central

    Das, Sambhunath; Nanda, Sunil K.; Bisoi, Akshya K.; Wadhawan, Ashima N.

    2016-01-01

    Context: Frequent incidence of early postoperative memory impairment (POMI) after cardiac surgery remains a concern because of associated morbidity, impaired quality of life, and increased health care cost. Aim: To assess the effect of preoperative statin therapy on POMI in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. Setting and Design: Prospective observational study in a tertiary level hospital. Methods: Sixty patients aged 45–65 years undergoing OPCAB surgery were allocated into two groups of 30 each. Group A patients were receiving statin and Group B patients were not receiving statins. All patients underwent memory function assessment preoperatively after admission to hospital and on the 6th postoperative day using postgraduate institute memory scale. Statistical Analysis: Appropriate tests were applied with SPSS 20 to compare both groups. The value P < 0.05 was considered statistically significant. Multiple regression analysis was performed with confounding factors to determine the effect on memory impairment. Results: Patients in Group A showed significant postoperative deterioration in 6 of the 10 functions and in Group B showed deterioration in 9 of 10 functions tested compared to preoperative scores. Intergroup comparison detected less POMI in Group A compared to Group B and was statistically significant in 8 memory functions. Multiple regression analysis detected statin as an independent factor in preventing memory impairment. Conclusions: Preoperative statin therapy attenuates the early POMI in patients undergoing OPCAB. Future long-term studies will define the efficacy of statin on POMI. PMID:26750672

  2. High-intensity statin therapy in patients with chronic kidney disease: a systematic review and meta-analysis

    PubMed Central

    Yan, Yu-Ling; Qiu, Bo; Wang, Jing; Deng, Song-Bai; Wu, Ling; Jing, Xiao-Dong; Du, Jian-Lin; Liu, Ya-Jie; She, Qiang

    2015-01-01

    Objective To evaluate the efficacy and safety of high-intensity statin therapy in patients with chronic kidney disease (CKD). Design A systematic review and meta-analysis. Data sources Randomised controlled trials (RCTs) comparing high-intensity statin therapy (atorvastatin 80 mg or rosuvastatin 20/40 mg) with moderate/mild statin treatment or placebo were derived from the databases (PubMed, Embase, Ovid, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, and ISI Web of Knowledge). Outcome measure Primary end points: clinical events (all-cause mortality, stroke, myocardial infarction and heart failure); secondary end points: serum lipid, renal function changes and adverse events. Results A total of six RCTs with 10 993 adult patients with CKD were included. A significant decrease in stroke was observed in the high-intensity statin therapy group (RR 0.69, 95% CI 0.56 to 0.85). However, the roles of high-intensity statin in decreasing all-cause mortality (RR 0.85, 95% CI 0.67 to 1.09), myocardial infarction (RR 0.69, 95% CI 0.40 to 1.18) and heart failure (RR 0.73, 95% CI 0.48 to 1.13) remain unclear with low evidence. High-intensity statin also had obvious effects on lowering the LDL-C level but no clear effects on renal protection. Although pooled results showed no significant difference between the intervention and control groups in adverse event occurrences, it was still insufficient to put off the doubts that high-intensity statin might increase adverse events because of limited data sources and low quality evidences. Conclusions High-intensity statin therapy could effectively reduce the risk of stroke in patients with CKD. However, its effects on all-cause mortality, myocardial infarction, heart failure and renal protection remain unclear. Moreover, it is hard to draw conclusions on the safety assessment of intensive statin treatment in this particular population. More studies are needed to credibly evaluate the effects

  3. Statin-related myotoxicity.

    PubMed

    Fernandes, Vera; Santos, Maria Joana; Pérez, Antonio

    2016-05-01

    Statin therapy has a very important role in decreasing cardiovascular risk, and treatment non-compliance may therefore be a concern in high cardiovascular risk patients. Myotoxicity is a frequent side effect of statin therapy and one of the main causes of statin discontinuation, which limits effective treatment of patients at risk of or with cardiovascular disease. Because of the high proportion of patients on statin treatment and the frequency of statin-related myotoxicity, this is a subject of concern in clinical practice. However, statin-related myotoxicity is probably underestimated because there is not a gold standard definition, and its diagnosis is challenging. Moreover, information about pathophysiology and optimal therapeutic options is scarce. Therefore, this paper reviews the knowledge about the definition, pathophysiology and predisposing conditions, diagnosis and management of statin-related myotoxicity, and provides a practical scheme for its management in clinical practice. PMID:27005745

  4. Impact of baseline lipoprotein and C-reactive protein levels on coronary atheroma regression following high-intensity statin therapy.

    PubMed

    Puri, Rishi; Nissen, Steven E; Shao, Mingyuan; Uno, Kiyoko; Kataoka, Yu; Kapadia, Samir R; Tuzcu, E Murat; Nicholls, Stephen J

    2014-11-15

    Guidelines now recommend high-intensity statin therapy in all patients with proven atherosclerotic disease. Yet the impact of baseline lipoprotein and C-reactive protein (CRP) levels on measures of disease regression to this therapy are unknown. The aim of this study was to test the hypothesis that high-intensity statin therapy causes equivalent degrees of coronary atheroma regression irrespective of baseline lipoprotein and CRP levels. In 8 prospective randomized trials using serial coronary intravascular ultrasound, 1,881 patients who maintained or switched to 18- to 24 months of high-intensity statin therapy (rosuvastatin 40 mg or atorvastatin 80 mg) were stratified according to baseline lipoprotein and CRP levels. Changes in coronary percentage atheroma volume (PAV) and total atheroma volume (TAV) were evaluated. High-intensity statin therapy produced significant reductions from baseline in low-density lipoprotein cholesterol by 38.4%, non-high-density lipoprotein (HDL) cholesterol by 33.6%, triglycerides by 13.1%, and CRP by 33.3%, while increasing HDL cholesterol by 11.7% (p <0.001 for all). This was associated with regression of PAV by 0.7% and of TAV by 8.2 mm(3) (p <0.001 for both). No significant differences of changes in PAV and TAV were observed across baseline quintiles of low-density lipoprotein cholesterol, HDL cholesterol, non-HDL cholesterol, triglycerides, or CRP. Moreover, across all measured lipoproteins and CRP, most patients demonstrated plaque regression (defined as any change from baseline in PAV or TAV <0). In conclusion, high-intensity statin therapy attenuated the natural progression of coronary atherosclerosis in all strata of patients with coronary artery disease irrespective of baseline lipoprotein or CRP levels. These findings provide support for the latest United States guideline recommendations for the broad use of high-intensity statin therapy in all patients with atherosclerosis, regardless of baseline lipid status. PMID:25282317

  5. Sleep changes following statin therapy: a systematic review and meta-analysis of randomized placebo-controlled polysomnographic trials

    PubMed Central

    Broncel, Marlena; Gorzelak-Pabiś, Paulina; Sahebkar, Amirhossein; Serejko, Katarzyna; Ursoniu, Sorin; Rysz, Jacek; Corina Serban, Maria; Możdżan, Monika

    2015-01-01

    Introduction Statin use might be associated with an increased risk of sleep disturbances including insomnia, but the evidence regarding sleep changes following statin therapy has not been conclusive. Therefore we assessed the impact of statin therapy on sleep changes through a systematic review and meta-analysis of available randomized controlled trials (RCTs). Material and methods We searched MEDLINE and SCOPUS up to October 1, 2014 to identify placebo-controlled RCTs investigating the effect of statin therapy on sleep changes. A meta-analysis was performed using either a fixed-effects or a random-effect model according to the I2 statistic. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Results Overall, the impact of statin therapy on polysomnography (PSG) indices of sleep was reported in 5 trials comprising 9 treatment arms. Overall, statin therapy had no significant effect on total sleep duration (WMD: –7.75 min, 95% CI: –18.98, 3.48, p = 0.176), sleep efficiency (WMD: 0.09%, 95% CI: –2.27, 2.46, p = 0.940), entries to stage I (WMD: 0.36, 95% CI: –0.91, 1.63, p = 0.580), or latency to stage I (WMD: –1.92 min, 95% CI: –4.74, 0.89, p = 0.181). In contrast, statin therapy significantly reduced wake time (WMD: –4.43 min, 95% CI: –7.77, –0.88, p = 0.014) and number of awakenings (WMD: –0.40, 95% CI: –0.46, –0.33, p < 0.001). Meta-regression did not suggest any correlation between changes in wake time and awakening episodes with duration of treatment and LDL-lowering effect of statins. Conclusions The results indicated that statins have no significant adverse effect on sleep duration and efficiency, entry to stage I, or latency to stage I sleep, but significantly reduce wake time and number of awakenings. PMID:26528331

  6. Does Combination Therapy with Statins and Fibrates Prevent Cardiovascular Disease in Diabetic Patients with Atherogenic Mixed Dyslipidemia?

    PubMed Central

    Agouridis, Aris P.; Rizos, Christos V.; Elisaf, Moses S.; Filippatos, Theodosios D.

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is associated with the development and progression of cardiovascular disease (CVD). Statins have an established efficacy in the management of dyslipidemia primarily by decreasing the levels of low-density lipoprotein cholesterol and thus decreasing CVD risk. They also have a favorable safety profile. Despite the statin-mediated benefit of CVD risk reduction a residual CVD risk remains, especially in T2DM patients with high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) values. Fibrates decrease TG levels, increase HDL-C concentrations, and improve many other atherosclerosis-related variables. Fibrate/statin co-administration improves the overall lipoprotein profile in patients with mixed dyslipidemia and may reduce the residual CVD risk during statin therapy. However, limited data exists regarding the effects of statin/fibrate combination on CVD outcomes in patients with T2DM. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study the statin/fibrate combination did not significantly reduce the rate of CVD events compared with simvastatin/placebo in patients with T2DM. However, it did show a possible benefit in a pre-specified analysis in the subgroup of patients with high TG and low HDL-C levels. Furthermore, in the ACCORD study the simvastatin/fenofibrate combination significantly reduced the rate of progression of retinopathy compared with statin/placebo administration in patients with T2DM. The present review presents the available data regarding the effects of statin/fibrate combination in patients with T2DM and atherogenic mixed dyslipidemia. PMID:24380091

  7. Pleiotropic effects of statins.

    PubMed

    Farmer, J A

    2000-05-01

    The advent of statin therapy has revolutionized the ability of the clinician to manage patients at risk for the development of an ischemic event due to dyslipidemia. Large-scale clinical trials involving thousands of patients in both primary and secondary prevention have clearly demonstrated that statin therapy will reduce cardiovascular mortality across a broad spectrum of patient subgroups. Additionally, in adequately powered trials, total mortality has been successfully decreased by the use of statin therapy. However, the precise mechanism underlying the benefit of statin therapy has been controversial due to the multiplicity of potential benefits that statins have demonstrated in addition to pure lipid lowering. The causal theory of pharmacologic benefit reiterates the lipid hypothesis, which states that dyslipidemia is central to the process of atherosclerosis and the clinical benefit which accrues from statin therapy is a function of the degree of lipid lowering. The noncausal theory supports the premise that clinical benefits are related primarily to pleiotropic effects of statins (endothelial function, inflammation, coagulation and plaque vulnerability) as being the major modulators of clinical benefit. This review will focus on the potential beneficial effects of statin therapy on a number of the pleiotropic effects of statins and the potential role that these activities play in the reduction of risk for ischemic events. PMID:11122746

  8. Statin-Associated Side Effects.

    PubMed

    Thompson, Paul D; Panza, Gregory; Zaleski, Amanda; Taylor, Beth

    2016-05-24

    Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated, but associated with various statin-associated symptoms (SAS), including statin-associated muscle symptoms (SAMS), diabetes mellitus (DM), and central nervous system complaints. These are "statin-associated symptoms" because they are rare in clinical trials, making their causative relationship to statins unclear. SAS are, nevertheless, important because they prompt dose reduction or discontinuation of these life-saving mediations. SAMS is the most frequent SAS, and mild myalgia may affect 5% to 10% of statin users. Clinically important muscle symptoms, including rhabdomyolysis and statin-induced necrotizing autoimmune myopathy (SINAM), are rare. Antibodies against HMG-CoA reductase apparently provoke SINAM. Good evidence links statins to DM, but evidence linking statins to other SAS is largely anecdotal. Management of SAS requires making the possible diagnosis, altering or discontinuing the statin treatment, and using alternative lipid-lowering therapy. PMID:27199064

  9. Elevated oxidative stress among coronary artery disease patients on statin therapy: A cross sectional study

    PubMed Central

    Palazhy, Sabitha; Kamath, Prakash; Vasudevan, Damodaran M.

    2015-01-01

    Background Statins are a major group of drugs that reduces LDL-C levels, which are proven to have other beneficial effects such as preventing coronary events. The objective of this study was to evaluate oxidative stress and select novel coronary artery disease risk factors among coronary artery disease patients on statins. Methods In this observational, cross-sectional study, we compared total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apolipoprotein B, lipoprotein (a), homocysteine, reduced glutathione, glutathione peroxidase, superoxide dismutase, ascorbic acid, malondialdehyde and oxidized LDL among male coronary artery disease patients on statin therapy (group 2, n = 151) with sex-matched, diabetic patients (group 3, n = 80) as well as healthy controls (group 1, n = 84). Results Total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol were significantly lower among subjects of group 2 compared to other two groups. The novel risk factors studied did not differ significantly between groups, except for a higher homocysteine level among group 2 subjects compared to the other two groups. Elevated oxidative stress, indicated by lower reduced glutathione, glutathione peroxidase, and ascorbic acid as well as higher malondialdehyde and oxidized LDL was observed among group 2 subjects. Triglycerides, HDL-cholesterol, ascorbic acid and malondialdehyde were found to be independent predictors for coronary artery disease among this study population. Conclusions Though coronary artery disease subjects had healthy lipid profile, oxidative stress, a recognized risk factor for coronary events, was still elevated among this patient group. Novel risk factors were not found to be major predictors for coronary artery disease among the study subjects. PMID:26138179

  10. The influence of statin therapy on platelet activity markers in hyperlipidemic patients after ischemic stroke

    PubMed Central

    Chmielewski, Henryk; Kaczorowska, Beata; Przybyła, Monika; Baj, Zbigniew

    2015-01-01

    Introduction Low-density lipoprotein cholesterol (LDL-C) has been reported to increase platelet activation. Reducing the level of LDL-C with statins induces important pleiotropic effects such as platelet inhibition. This association between platelet activity and statin therapy may be clinically important in reducing the risk of ischemic stroke. We investigated the effect of simvastatin therapy on platelet activation markers (platelet CD62P, sP-selectin, and platelet-derived microparticles (PDMPs)) in hyperlipidemic patients after ischemic stroke. Material and methods The study group consisted of 21 hyperlipidemic patients after ischemic stroke confirmed by CT, and 20 healthy subjects served as controls. We assessed the CD62P expression on resting and thrombin-activated blood platelets. CD62P and PDMPs were analyzed by the use of monoclonal antibodies anti-CD61 and anti-CD62 on a flow cytometer. The level of sP-selectin in serum was measured by the ELISA (enzyme-linked immunosorbent assay) method. All markers were re-analyzed after 6 months of treatment with simvastatin (20 mg/day). Results Hyperlipidemic patients presented a significantly higher percentage of CD62+ platelets and higher reactivity to thrombin compared to control subjects. After simvastatin therapy hyperlipidemic patients showed a reduction of the percentage of resting CD62P(+) platelets (p = 0.005) and a reduction of expression and percentage of CD62P(+) platelets after activation by thrombin (median p < 0.05; percentage: p = 0.001). A decrease of sP-selectin levels (p = 0.001) and percentage of PDMPs (p < 0.05) in this group was also observed. Conclusions HMG-CoA reductase inhibitor therapy in stroke patients with hyperlipidemia may be useful not only due to the lipid-lowering effect but also because of a significant role in reduction of platelet activation and reactivity. PMID:25861297

  11. Individual with Subclinical Atherosclerosis Have Impaired Proliferation of Blood Outgrowth Endothelial Cells, Which Can Be Restored by Statin Therapy

    PubMed Central

    Hofman, Menno; Bierings, Ruben; Creemers, Esther E.; Meijers, Joost C. M.; Voorberg, Jan; Pinto-Sietsma, Sara-Joan

    2014-01-01

    Background To study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis. Methods and Results Patients with premature CAD (men <51 yr, women <56 yr) and their FDRs were included. Based on coronary calcification (CAC) scores FDRs were divided in a group of healthy subjects (CAC = 0) and subjects with subclinical atherosclerosis (CAC>0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21–0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy. Conclusion BOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration. PMID:24955753

  12. The effect of statins on prostate cancer recurrence and mortality after definitive therapy: a systematic review and meta-analysis

    PubMed Central

    Tan, Ping; Wei, Shiyou; Yang, Lu; Tang, Zhuang; Cao, Dehong; Liu, Liangren; Lei, Junhao; Fan, Yu; Gao, Liang; Wei, Qiang

    2016-01-01

    In this work, we aim to further analyze the association of statins use with biochemical recurrence (BCR) of prostate cancer (PCa) and PCa-specific mortality after definitive therapy. A systematic literature search of PubMed, MEDLINE, and EMBASE through Jul 2015 was conducted. Pooled Hazard ratio (HR) estimates with corresponding 95% confidence intervals (CIs) were calculated using random-effects model. STATA version 10 (Stata corporation, college station, TX) was employed to conduct all statistical analyses. A total of 22 and 8 studies contributed to the biochemical recurrence analysis and PCa-specific mortality, respectively. 13 trials were included for BCR-free survival analysis. The combined result showed statins users had lowered 12% BCR risk of PCa compared with non-users (HR = 0.88, 95%CI: 0.765–0.998) (p < 0.05). The association was null among the men who underwent radical prostatectomy as primary therapy (HR = 0.96, 95%CI: 0.83–1.09), while the improved outcomes had be seen among patients who received radiation therapy (HR = 0.67, 95%CI: 0.48–0.86). After excluding the patients undergoing ADT, participants did not benefit from statins use (HR = 0.94, 95%CI: 0.77–1.11). Meanwhile, long-term statins using did not alter recurrence risk. A lower risk of prostate cancer-specific mortality was observed among statins users (HR = 0.68, 95%CI: 0.56–0.80). There was a plausible trend towards increasing the BCR-free survival rate among statins users. PMID:27384548

  13. Combination Therapy of Metformin and Statin May Decrease Hepatocellular Carcinoma Among Diabetic Patients in Asia

    PubMed Central

    Chen, Hsin-Hung; Lin, Ming-Chia; Muo, Chih-Hsin; Yeh, Su-Yin; Sung, Fung-Chang; Kao, Chia-Hung

    2015-01-01

    Abstract Previous studies have shown that metformin or statins may decrease hepatocellular carcinoma (HCC) in diabetic patients. Accordingly, this article evaluates whether combination therapy may further reduce HCC. Newly diagnosed type 2 diabetes mellitus (DM) patients, excluding those with history of malignancy prior to the date of DM diagnosis, were recruited to a DM cohort. DM patients developed HCC as the cancer cohort and the date for HCC diagnosis as index date. Non-cancer cohort was frequency matched with 4:1 according to age, sex, DM-year, and index date as case group from DM cohort. Patients who were treated with statins showed a 63% decreased risk of HCC (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.27–0.49). Patients who consumed simvastatin, atorvastatin, or rosuvastatin significantly decreased risk for HCC (OR = 0.32, 0.31, and 0.22; 95% CI = 0.18–0.58, 0.19–0.52, and 0.08–0.61, respectively). Metformin combinations with simvastatin, atorvastatin, or rosuvastatin may decrease HCC (OR = 0.30, 0.30, and 0.24; 95% CI = 0.15–0.59, 0.16–0.54, and 0.08–0.70, respectively). The comorbidities for HCC were decreased by consuming simvastatin and atorvastatin (OR = 0.31 and 0.29; 95% CI = 0.14–0.67 and 0.15–0.57, respectively). Only combination therapy of metformin and simvastatin may significantly decreased HCC comorbidities (OR = 0.26; 95% CI = 0.11–0.60) in our study. In Asia, not all metformin combinations with statins may reduce the incidence of HCC and not all of this kind of combination therapy may decrease the HCC comorbidities. PMID:26091447

  14. The Effect of Statin Therapy on Coronary Plaque Composition Using Virtual Histology Intravascular Ultrasound: A Meta-Analysis

    PubMed Central

    Zheng, Guian; Li, Yuxin; Huang, Huishan; Wang, Jinghan; Hirayama, Atsushi; Lin, Jinxiu

    2015-01-01

    Objective Previous studies have indicated that statin therapy may promote plaque regression. However, the impact of statin therapy on plaque composition has not been clearly elucidated. We performed a meta-analysis to investigate the effect of statin therapy on coronary plaque composition as assessed by virtual histology intravascular ultrasound (VH-IVUS). Methods Online databases were searched from inception to March 1, 2015. Studies providing VH-IVUS volumetric analyses of coronary plaque composition at baseline and follow-up in patients receiving statin therapy were included. Weighted mean difference (WMD) using a random-effects model was used. Results Ten studies involving 682 patients were included. There was a substantial reduction in fibrous volume between baseline and follow-up (WMD: -2.37 mm3, 95% confidence interval (CI) -4.01 to -0.74 mm3, P=0.004), and a significant increase in dense calcium (DC) volume (WMD: 0.89 mm3, 95% CI 0.70 to 1.08 mm3, P<0.00001). No significant change was seen in fibro-fatty and necrotic core (NC) volumes. In stratified analyses, the fibrous volume was decreased significantly (WMD: -3.39 mm3, 95% CI -6.56 to -0.21 mm3, P=0.04) and the absolute DC volume (WMD: 0.99 mm3, 95% CI 0.23 to 1.76 mm3, P=0.01) was increased in the subgroup with ≥12 months follow-up, whereas no significant change was observed in the subgroup with < 12 months follow-up. Similarly, a substantial decrease in fibrous volume (WMD: -2.01 mm3, 95% CI -3.05 to -0.96 mm3, P< 0.0002) and an increase in DC volume (WMD: 0.90 mm3, 95% CI 0.70 to 1.10 mm3, P< 0.00001) were observed in the subgroup with high-intensive statin therapy, while the change in fibrous and DC volumes approached statistical significance (P=0.05 and P=0.05, respectively) in the subgroup with low-intensive statin therapy. Conclusions Statin treatment, particularly of high-intensity and long-term duration, induced a marked modification in coronary plaque composition including a decrease in

  15. Clinical- and cost-effectiveness of LDL particle-guided statin therapy: a simulation study.

    PubMed

    Folse, Henry J; Goswami, Devesh; Rengarajan, Badri; Budoff, Matthew; Kahn, Richard

    2014-09-01

    We used the Archimedes Model, a mathematical simulation model (Model) to estimate the clinical- and cost-effectiveness of using LDL particle concentration (LDL-P) as an adjunct or alternative to LDL cholesterol (LDL-C) to guide statin therapy. LDL-P by NMR has been shown to be a better measure of cardiovascular disease (CVD) risk than LDL-C, and may therefore be a better gauge of the need for and response to statin treatment. Using the Model, we conducted a virtual clinical trial comparing the use of LDL-C alone, LDL-P alone, and LDL-C and LDL-P together to guide treatment in the general adult population, and in high-risk, dyslipidemic subpopulations. In the general population, the 5-year major adverse cardiovascular event (MACE) relative risk reduction (RRR) of LDL-P alone compared to the control arm (LDL-C alone) was 5.0% (95% CI, 4.7-5.3; p < .0001); using both LDL-C and LDL-P (dual markers) led to 3.0% RRR compared to the control arm (95% CI, 2.8-3.3; p < .0001). For individuals with diabetes, the RRR was 7.3% (95% CI, 6.4-8.2; p < .0001) for LDL-P alone and 6.9% for dual markers (95% CI, 6.1-7.8; both, p < .0001). In the general population, the costs per quality-adjusted life year (QALY) associated with the use of LDL-P alone were $76,052 at 5 years and $8913 at 20 years and $142,825 at 5 years and $25,505 at 20 years with the use of both markers. In high-risk subpopulations, the use of LDL-P alone was cost-saving at 5 years; whereas the cost per QALY for the use of both markers was $14,250 at 5 years and $859 at 20 years for high-risk dyslipidemics, $19,192 at 5 years and $649 at 20 years for diabetics, and $9030 at 5 years and $7268 at 20 years for patients with prior CHD. In conclusion, the model estimates that using LDL-P to guide statin therapy may reduce the risk of CVD events to a greater extent than does the use of LDL-C alone and maybe cost-effective or cost-saving for high-risk patients. PMID:25050538

  16. Childhood Adversity as a Predictor of Non-Adherence to Statin Therapy in Adulthood

    PubMed Central

    Korhonen, Maarit Jaana; Halonen, Jaana I.; Brookhart, M. Alan; Kawachi, Ichiro; Pentti, Jaana; Karlsson, Hasse; Kivimäki, Mika; Vahtera, Jussi

    2015-01-01

    Purpose To investigate whether adverse experiences in childhood predict non-adherence to statin therapy in adulthood. Methods A cohort of 1378 women and 538 men who initiated statin therapy during 2008–2010 after responding to a survey on childhood adversities, was followed for non-adherence during the first treatment year. Log-binomial regression was used to estimate predictors of non-adherence, defined as the proportion of days covered by dispensed statin tablets <80%. In fully adjusted models including age, education, marital status, current smoking, heavy alcohol use, physical inactivity, obesity, presence of depression and cardiovascular comorbidity, the number of women ranged from 1172 to 1299 and that of men from 473 to 516, because of missing data on specific adversities and covariates. Results Two in three respondents reported at least one of the following six adversities in the family: divorce/separation of the parents, long-term financial difficulties, severe conflicts, frequent fear, severe illness, or alcohol problem of a family member. 51% of women and 44% of men were non-adherent. In men, the number of childhood adversities predicted an increased risk of non-adherence (risk ratio [RR] per adversity 1.11, 95% confidence interval [CI] 1.01–1.21], P for linear trend 0.013). Compared with those reporting no adversities, men reporting 3–6 adversities had a 1.44-fold risk of non-adherence (95% CI 1.12–1.85). Experiencing severe conflicts in the family (RR 1.27, 95% CI 1.03–1.57]) and frequent fear of a family member (RR 1.27, 95% CI 1.00–1.62]) in particular, predicted an increased risk of non-adherence. In women, neither the number of adversities nor any specific type of adversity predicted non-adherence. Conclusions Exposure to childhood adversity may predict non-adherence to preventive cardiovascular medication in men. Usefulness of information on childhood adversities in identification of adults at high risk of non-adherence deserves

  17. [Statins and the risk of diabetes].

    PubMed

    Simonyi, Gábor

    2013-10-27

    Statins have a relevant role in decreasing cardiovascular mortality. Statins are effective in primary and secondary prevention. Recently, it has been suggested that statins may have a diabetogenic effect, because a moderate increase in the risk of newly developed diabetes mellitus was observed. The diabetogenic effect of statins is a group effect and it is dose-dependent, too. The effect of statins which lower the cardiovascular risk attenuates the risk of developing diabetes during statin therapy, too. Hence, statins remain the first line therapy of reaching LDL-cholesterol targets. PMID:24140507

  18. Statins and myotoxicity.

    PubMed

    Farmer, John A

    2003-03-01

    The significant age-adjusted decline in cardiovascular mortality that has occurred over the past three decades is multifactorial. However, the advent of statin therapy has markedly facilitated the optimization of dyslipidemia in patients at risk for coronary events. Statin therapy has proven to be effective in reducing morbidity and mortality in large-scale primary and secondary prevention trials. As with all therapies, the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co A) reductase inhibitors is not without clinical risks. Myopathy, albeit uncommon, was one of the earliest clinical problems associated with statin therapy. Recent data from the large-scale statin mega-trials have clarified the quantitative clinical risk-benefit relationship of reductase inhibitors relative to the induction of muscle toxicity. Histopathologic studies have clarified the potential role of statins in the syndrome of myalgias and normal creatine kinase levels. However, the precise mechanism of statin-associated muscle toxicity remains unclear and is potentially related to genetically mediated muscle enzyme defects, drug interactions, intracellular depletion of metabolic intermediates, and intrinsic properties of the statins per se. PMID:12573193

  19. Comparative Effects of Statin Therapy versus Renin-Angiotensin System Blocking Therapy in Patients with Ischemic Heart Failure Who Underwent Percutaneous Coronary Intervention

    PubMed Central

    Won, Jumin; Jeong, Myung Ho; Park, Hyuk Jin; Kim, Min Chul; Kim, Woo Jin; Kim, Hyun Kuk; Sim, Doo Sun; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun

    2016-01-01

    Statins and renin-angiotensin system (RAS) blockers are key drugs for treating patients with an acute myocardial infarction (AMI). This study was designed to show the association between treatment with statins or RAS blockers and clinical outcomes and the efficacy of two drug combination therapies in patients with ischemic heart failure (IHF) who underwent revascularization for an AMI. A total of 804 AMI patients with a left ventricular ejection fraction <40% who undertook percutaneous coronary interventions (PCI) were analyzed using the Korea Acute Myocardial Infarction Registry (KAMIR). They were divided into four groups according to the use of medications [Group I: combination of statin and RAS blocker (n=611), Group II: statin alone (n=112), Group III: RAS blocker alone (n=53), Group IV: neither treatment (n=28)]. The cumulative incidence of major adverse cardiac and cerebrovascular events (MACCEs) and independent predictors of MACCEs were investigated. Over a median follow-up study of nearly 1 year, MACCEs had occurred in 48 patients (7.9%) in Group I, 16 patients (14.3%) in Group II, 3 patients (5.7%) in Group III, 7 patients (21.4%) in Group IV (p=0.013). Groups using RAS blocker (Group I and III) showed better clinical outcomes compared with the other groups. By multivariate analysis, use of RAS blockers was the most powerful independent predictor of MACCEs in patients with IHF who underwent PCI (odds ratio 0.469, 95% confidence interval 0.285-0.772; p=0.003), but statin therapy was not found to be an independent predictor. The use of RAS blockers, but not statins, was associated with better clinical outcomes in patients with IHF who underwent PCI. PMID:27231678

  20. Intensive Statin Therapy in NSTE-ACS Patients Undergoing PCI: Clinical and Biochemical Effects

    PubMed Central

    Fayez, George; Nassar, Ahmed

    2015-01-01

    Early initiation of statin therapy in acute coronary syndrome patients has a favorable prognostic impact because of its anti-inflammatory and antithrombotic properties. In this study, we explored the effect of atorvastatin-loading, followed by intensive atorvastatin therapy, on clinical and biochemical outcomes in non-ST-segment-elevation acute coronary syndrome patients who were scheduled for percutaneous coronary intervention. We prospectively enrolled 140 patients (mean age, 56 ± 9 years, 68% men). Once eligible, patients were randomly assigned to receive either a moderate 20-mg daily dose of atorvastatin (Group A) or a 160-mg loading dose followed by an intensified 80-mg daily dose (Group B). High-sensitivity C-reactive protein (hs-CRP) levels were recorded before and after intervention. Evaluation after 6 months included hs-CRP levels, left ventricular systolic function, and major adverse cardiac events. We found no significant difference between the 2 groups in regard to the interventional data. However, blood sampling after coronary intervention, and again 6 months later, revealed a significant decline in mean hs-CRP level among Group B patients (P <0.001). Moreover, patients in Group B manifested a higher left ventricular ejection fraction than did patients in Group A (P <0.05). After 6 months, we found no significant difference between groups in the incidence of major adverse cardiac events. We conclude that intensive atorvastatin therapy in non-ST-segment-elevation acute coronary syndrome patients is associated with lower hs-CRP levels and with higher left ventricular ejection fraction after 6 months, with no significant impact on adverse cardiac events. PMID:26664304

  1. How to take statins

    MedlinePlus

    ... Pravastatin (Pravachol®); Rosuvastatin (Crestor®); Fluvastatin (Lescol®); Hyperlipidemia - statins; Hardening of the arteries statins; Cholesterol - statins; Hypercholesterolemia - statins; ...

  2. Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe

    PubMed Central

    Garcia, Maristela Magnavita Oliveira; Varela, Carolina Garcez; Silva, Patricia Fontes; Lima, Paulo Roberto Passos; Góes, Paulo Meira; Rodrigues, Marilia Galeffi; Silva, Maria de Lourdes Lima Souza e; Ladeia, Ana Marice Teixeira; Guimarães, Armênio Costa; Correia, Luis Claudio Lemos

    2016-01-01

    Background The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms. PMID:27142792

  3. Does short preoperative statin therapy prevent infectious complications in adults undergoing cardiac or non-cardiac surgery?

    PubMed Central

    Li, Hua; Lin, Yuan-Long; Diao, Shu-Ling; Ma, Bao-Xin; Liu, Xian-Liang

    2016-01-01

    Objectives: To evaluate the effect of preoperative statin therapy on the incidence of postoperative infection. Methods: This systematic review of the literature was carried out in August 2015. Studies were retrieved via PubMed, Embase, and the Cochrane Library (1980 to 2015), and the reference files were limited to English-language articles. We used a standardized protocol, and a meta-analysis was performed for data abstraction. Results: Five studies comprising 1,362 patients qualified for the analysis. The incidence of postoperative infections in the statin group (1.1%) was not significantly lower than that in the placebo group (2.4%), with a risk ratio (RR) of 0.56 (95% confidence interval [CI] 0.24-1.33, p=0.19). Patients of 3 studies underwent cardiac surgery. The aggregated results of these studies failed to show significant differences in postoperative infection when a fixed effects model was used (RR: 0.39; 95% CI: 0.08-1.97, p=0.26]. Conclusions: We failed to find sufficient evidence to support the association between statin use and postoperative infectious complications. The absence of any evidence for a beneficial effect in available randomized trials reduces the likelihood of a causal effect as reported in observational studies. PMID:27146610

  4. A Reappraisal of the Safety and Cost-Effectiveness of Statin Therapy in Primary Prevention.

    PubMed

    Bleakley, Caroline; Pumb, Richard; Harbinson, Mark; McVeigh, Gary Eugene

    2015-12-01

    Statins are among the most investigated drugs of all time. There is now a wealth of evidence supporting their use in the primary and secondary prevention arenas. The reduction in event recurrence has since been demonstrated across all levels of risk and in elderly patients. As a result, it is now accepted practice for statins to be prescribed universally in secondary prevention unless contraindicated. The extension of this policy into the primary prevention setting is more problematic, with moral and financial issues arising from the long-term treatment of many young apparently healthy individuals. For these reasons it is necessary to prove not only the financial sustainability of such a strategy but also the long-term safety of statins and the degree of benefit that might be expected. PMID:26386731

  5. Effect of ETC-1002 on Serum Low-Density Lipoprotein Cholesterol in Hypercholesterolemic Patients Receiving Statin Therapy.

    PubMed

    Ballantyne, Christie M; McKenney, James M; MacDougall, Diane E; Margulies, Janice R; Robinson, Paula L; Hanselman, Jeffrey C; Lalwani, Narendra D

    2016-06-15

    ETC-1002 is an oral, once-daily medication that inhibits adenosine triphosphate citrate lyase, an enzyme upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, to reduce cholesterol biosynthesis. ETC-1002 monotherapy has demonstrated significant reduction in low-density lipoprotein cholesterol (LDL-C) compared with placebo in phase 2 studies. The objective of this study was to compare the lipid-lowering efficacy of ETC-1002 versus placebo when added to ongoing statin therapy in patients with hypercholesterolemia. This phase 2b, multicenter, double-blind trial (NCT02072161) randomized 134 hypercholesterolemic patients (LDL-C, 115 to 220 mg/dl) on stable background statin therapy to 12 weeks of add-on treatment with ETC-1002 120 mg, ETC-1002 180 mg, or placebo. The primary efficacy end point was the percent change in calculated LDL-C from baseline to week 12. For LDL-C, the least-squares mean percent change ± standard error from baseline to week 12 was significantly greater with ETC-1002 120 mg (-17 ± 4%, p = 0.0055) and ETC-1002 180 mg (-24 ± 4%, p <0.0001) than placebo (-4 ± 4%). ETC-1002 also dose dependently reduced apolipoprotein B by 15% to 17%, non-high-density lipoprotein cholesterol by 14% to 17%, total cholesterol by 13% to 15%, and LDL particle number by 17% to 21%. All these reductions in ETC-1002-treated cohorts were significantly greater than those with placebo. Rates of adverse events (AEs), muscle-related AEs, and discontinuations for AEs with ETC-1002 were similar to placebo. In conclusion, ETC-1002 120 mg or 180 mg added to stable statin therapy significantly reduced LDL-C compared to placebo and has a similar tolerability profile. PMID:27138185

  6. Impact of statin therapy on plasma levels of plasminogen activator inhibitor-1. A systematic review and meta-analysis of randomised controlled trials.

    PubMed

    Sahebkar, Amirhossein; Catena, Cristiana; Ray, Kausik K; Vallejo-Vaz, Antonio J; Reiner, Željko; Sechi, Leonardo A; Colussi, GianLuca

    2016-07-01

    Elevated plasma levels of the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 (PAI-1) may contribute to the pathogenesis of atherosclerotic cardiovascular disease. Beyond their lipid-lowering effect, statins have been shown to modulate plasma PAI-1 levels but evidence from individual randomised controlled trials (RCTs) is controversial. Therefore, we aimed to assess the potential effects of statin therapy on plasma PAI-1 concentration through a meta-analysis of RCTs. We searched Medline and SCOPUS databases (up to October 3, 2014) to identify RCTs investigating the effect of statin therapy on plasma PAI-1 concentrations. We performed random-effects meta-analysis and assessed heterogeneity (I² test, subgroup and sensitivity analyses) and publication bias (funnel plot, Egger and "trim and fill" tests). Sixteen RCTs (comprising 19 treatment arms) were included and pooled analyses showed a significant effect of statins in reducing plasma PAI-1 concentrations (weighted mean difference WMD: -15.72 ng/ml, 95 % confidence interval [CI]: -25.01, -6.43,). In subgroup analysis, this effect remained significant in with lipophilic statins (atorvastatin and simvastatin) (WMD: -21.32 ng/ml, 95 % CI: -32.73, -9.91, I²=99 %) and particularly atorvastatin (WMD: -20.88 ng/mL, 95 % CI: -28.79, -12.97, I2=97 %). In the meta-regression analysis, the impact of statins on PAI-1 did not correlate with the administered dose, duration of treatment and changes in plasma LDL-cholesterol concentrations. Finally, evidence of publication bias was observed. In conclusion, taking into account the limit of heterogeneity between studies, the present meta-analysis suggests that statin therapy (mainly atorvastatin) significantly lowers plasma PAI-1 concentrations. PMID:27009446

  7. Outcomes of nonsurgical periodontal therapy in severe generalized aggressive periodontitis

    PubMed Central

    2014-01-01

    Purpose Aggressive periodontitis, especially in its severe form, was traditionally considered to have an unfavourable prognosis. It required a complex treatment and its stabilization was often achieved by surgical therapy. The aim of this study was to investigate the results of nonsurgical periodontal treatment in severe generalized forms of aggressive periodontitis. Methods Patients with advanced generalized aggressive periodontitis were included in the study. Probing depth (PD) of pockets ≥7 mm and clinical attachment level (CAL) of sites with attachment loss ≥5 mm were measured at baseline before nonsurgical periodontal treatment, at re-evaluation, and after treatment. The following other parameters were recorded: resolution of inflammation and bone fill. We compared the baseline values with re-evaluation and posttreatment values using the Friedman test. The Wilcoxon test with the Bonferroni correction was used for both re-evaluation and posttreatment values. Results Seven patients with 266 periodontal sites were examined. A significant difference was found between values, reported as medians with interquartile ranges, for PD at baseline (7.94 [7.33-8.19] mm) and both re-evaluation (4.33 [3.63-5.08] mm) and posttreatment (3.54 [3.33-4.11] mm) values (P=0.002). A significant difference was also found between values for CAL at baseline (9.02 [7.5-9.2] mm) and both re-evaluation (6.55 [6.30-6.87] mm) and posttreatment (6.45 [5.70-6.61] mm) (P=0.002). Inflammation was resolved and angular bone defects were repaired in all cases. Conclusions These therapeutic results suggest that this form of periodontitis could have positive outcomes after nonsurgical periodontal treatment. The reparative potential of tissue affected by severe aggressive periodontitis should encourage clinicians to save apparently hopeless teeth in cases of this form of periodontitis. Graphical Abstract PMID:25177522

  8. Statin safety: lessons from new drug applications for marketed statins.

    PubMed

    Jacobson, Terry A

    2006-04-17

    Safety has become a central issue in the management of dyslipidemia with statins. A review of New Drug Applications (NDAs) and the US Food and Drug Administration (FDA) Web site was conducted for all 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, with a major focus on cerivastatin and rosuvastatin. The findings provide insight into the incidence of adverse events for this class of drugs and support the significant benefits of statins relative to associated risks. These data delineate the nature of statin associated liver, muscle, and renal adverse events. Although transaminase levels increase in a dose-related fashion with statins, a definitive correlation between statin therapy and hepatotoxicity is not supported by statin NDA data. Statin-induced myopathy is a relatively rare event (1 in 1,000) and rhabdomyolysis is even rarer (1 in 10,000). The cerivastatin NDA, along with its supplementary NDA, was the first to demonstrate a clear statin dose-response relation with myopathy and a threshold effect above which myotoxicity increases significantly. Proteinuria was identified as a consequence of statin therapy with data from the rosuvastatin NDA, and subsequent analysis suggests a class effect that is dose related but transient. Studies in cell culture suggest the mechanism is a pharmacologic effect on the proximal renal tubule. The available evidence suggests no clear renal toxicity with currently approved statins, because no declines in renal function or glomerular filtration rate have been documented over time. Overall, currently marketed statins have a very favorable benefit-to-risk relation with respect to liver, muscle, and renal issues. PMID:16581328

  9. Effect of preoperative statin therapy on myocardial protection and morbidity endpoints following off-pump coronary bypass surgery in patients with elevated C-reactive protein level

    PubMed Central

    Song, Young; Kwak, Young Lan; Choi, Yong Seon; Kim, Jong Chan; Heo, Sang Baek

    2010-01-01

    Background The aim of this study was to investigate the effects of preoperative statin therapy on myocardial protection and morbidity endpoints following off-pump coronary bypass graft surgery (OPCAB) in patients with elevated serum high-sensitivity C-reactive protein (hs-CRP) levels. Methods Of the 492 patients who underwent multivessel OPCAB from March 2007 to February 2009, the records of 144 patients whose baseline hs-CRP level > 2 mg/L were reviewed. According to the history of preoperative statin therapy for at least one week, patients were classified as either statin group or control group (72 subjects each). Preoperative and operative characteristics and postoperative data including troponin (Tn)-T level and major morbidity endpoints were obtained and compared. Major morbidity endpoints were defined as permanent stroke, renal dysfunction, hemostatic re-exploration, deep sternal wound infection, and the number of patients requiring prolonged ventilation. Results Preoperative and operative characteristics were similar between the two groups. There were no significant differences in the incidence of morbidity endpoints between the two groups, except for the number of patients requiring dialysis, which was significantly lower in the statin group (8 vs. 1, P = 0.033). Tn-T level at 24 h after surgery was also significantly lower in the statin group. Conclusions In this study, we observed beneficial effects of preoperative statin therapy for at least one week in terms of less myocardial enzyme release and fewer patients requiring dialysis following OPCAB in patients whose preoperative hs-CRP was elevated. PMID:20498791

  10. [Pro and contra: aggressive or conservative thrombosis therapy? - Pro aggressive thrombosis therapy].

    PubMed

    Grommes, J

    2014-10-01

    The post-thrombotic syndrome (PTS), long-term sequelae of a deep vein thrombosis (DVT), reduces quality of life and is of great socio-economic importance. Despite conservative treatment which does not directly facilitate recanalization more than 25% of patients develop PTS. Early thrombus removal may decrease the incidence and severity of PTS. Although the evidence for surgical thrombectomy is weak which allows an early and rapid recanalization, this therapy appears to reduce the risk of PTS and iliofemoral thrombosis. Systemic thrombolysis can reduce the incidence of PTS but it is no longer recommended due to serious bleeding complications. Previous studies with new endovascular catheter-guided procedures allowing local application of thrombolysis and thrombus aspiration displayed promising results. However, so far one prospective randomised study (CaVent study) with long-term results has revealed a significant reduction of PTS. The current evidence recommends early thrombus removal for patients at high risk for PTS. New endovascular procedures such as catheter-guided thrombolysis allow rapid thrombus removal but more prospective randomised studies are necessary to ensure the long-term success of this therapy. PMID:25313889

  11. Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis

    PubMed Central

    Wallace, Carol A.; Giannini, Edward H.; Spalding, Steven J.; Hashkes, Philip J.; O’Neil, Kathleen M.; Zeft, Andrew S.; Szer, Ilona S.; Ringold, Sarah; Brunner, Hermine I.; Schanberg, Laura E.; Sundel, Robert P.; Milojevic, Diana; Punaro, Marilynn G.; Chira, Peter; Gottlieb, Beth S.; Higgins, Gloria C.; Ilowite, Norman T.; Kimura, Yukiko; Hamilton, Stephanie; Johnson, Anne; Huang, Bin; Lovell, Daniel J.

    2011-01-01

    OBJECTIVES To determine if aggressive treatment initiated early in the course of rheumatoid factor positive or negative polyarticular juvenile idiopathic arthritis (poly-JIA) can induce clinical inactive disease (CID) within 6 months. METHODS Between May 2007 and October 2010 a multi-center, prospective, double blind, randomized, placebo controlled trial of two aggressive treatments was conducted in 85 children aged 2 to 16 years with polyarticular JIA of less than 12 months duration. Patients received either methotrexate 0.5 mg/kg/wk SQ (40 mg max), etanercept 0.8 mg/kg/wk (50 mg max), prednisolone 0.5 mg/kg/d (60 mg max) tapered to 0 by 17 weeks (Arm 1), or methotrexate (same dose as Arm 1), etanercept placebo, and prednisolone placebo (Arm 2). The primary outcome was CID at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous CID) at 12 months. RESULTS By 6 months, 17 of 42 (40%) of patients in Arm 1 and 10 of 43 (23%) in Arm 2 had achieved CID (X2 = 2.91; p = 0.088). After 12 months, 9 patients in Arm 1 and 3 in Arm 2 achieved clinical remission on medication (p = 0.0534). There were no significant inter-arm differences in adverse events. CONCLUSIONS Although this study did not meet its primary endpoint, early aggressive therapy in this cohort of children with recent onset polyarticular JIA resulted in substantial proportions of patients in both arms achieving CID by 6 months and clinical remission on medication within 12 months of treatment. PMID:22183975

  12. Conceptual Foundations of the UCSD Statin Study

    PubMed Central

    Golomb, Beatrice Alexandra; Criqui, Michael H.; White, Halbert; Dimsdale, Joel E.

    2016-01-01

    Background Statin cholesterol-lowering drugs are among the most prescribed drugs in the United States. Their cardiac benefits are substantial and well supported. However, there has been persistent controversy regarding possible favorable or adverse effects of statins or of cholesterol reduction on cognition, mood, and behavior (including aggressive or violent behavior). Methods The literature pertaining to the relationship of cholesterol or statins to several noncardiac domains was reviewed, including the link between statins (or cholesterol) and cognition, aggression, and serotonin. Results There are reasons to think both favorable and adverse effects of statins and low cholesterol on cognition may pertain; the balance of these factors requires further elucidation. A substantial body of literature links low cholesterol level to aggressive behavior; statin randomized trials have not supported a connection, but they have not been designed to address this issue. A limited number of reports suggest a connection between reduced cholesterol level and reduced serotonin level, but more information is needed with serotonin measures that are practical for clinical use. Whether lipophilic and hydrophilic statins differ in their impact should be assessed. Conclusion There is a strong need for randomized controlled trial data to more clearly establish the impact of hydrophilic and lipophilic statins on cognition, aggression, and serotonin, as well as on other measures relevant to risks and quality-of-life impact in noncardiac domains. PMID:14744838

  13. Lipid-lowering therapy using statins in patients with cardiovascular risk in clinical practice in Thailand

    PubMed Central

    Silaruks, Songkwan; Sriratanasathavorn, Charn; Rawdaree, Petch; Kunjara-Na-Ayudhaya, Rapeephon; Thinkhamrop, Bandit; Sritara, Piyamitr

    2011-01-01

    Background Since the release in Thailand in 2001 of the Third Guidelines by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults or the Adult Treatment Panel (ATP III), there have been no nationwide studies on the proportion of dyslipidaemic patients who have achieved the low-density lipoprotein cholesterol (LDL-C) goals. The authors therefore aimed to estimate the percentage achievement of LDL-C goals based on the modified NCEP ATP III guidelines in intermediate- to high-risk patients. Methods The authors conducted a hospital-based, cross-sectional, epidemiological survey. Patients (1240) were selected consecutively from 50 hospitals across Thailand. Patients were included if they had been treated with statins for at least 3 months. Results Two-thirds were female, and the mean age was 61.7±9.5 years. The median duration of statin treatment was 21 months. Half (633/ 1240) of the patients achieved the LDL-C goal levels as defined by the NCEP guidelines (51.1%, 95% CI 48.3% to 53.8%). The very-high-risk group had the lowest percentage achievement (11.6%; 95% CI 1.6% to 21.6%), compared with 54.2% (95% CI 50.9% to 57.4%) for the high-risk group and 47.0% (95% CI 41.1% to 52.8%) for the moderate-risk group. More males achieved the LDL-C goals than females (55.6% vs 48.9%; p=0.029). Conclusions Overall, 51.1% of the patients with cardiovascular risk, on statins treatment, achieved the NCEP ATP III LDL-C goal levels. PMID:27326004

  14. Lipid dysregulation in hepatitis C virus, and impact of statin therapy upon clinical outcomes

    PubMed Central

    Simon, Tracey G; Butt, Adeel A

    2015-01-01

    The hepatitis C virus (HCV) is one of the most common causes of chronic liver disease and the leading indication for liver transplantation worldwide. Every aspect of the HCV life cycle is closely tied to human lipid metabolism. The virus circulates as a lipid-rich particle, utilizing lipoprotein cell receptors to gain entry into the hepatocyte. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation and circulating hypocholesterolemia. Patients with chronic hepatitis C (CHC) are at increased risk of hepatic steatosis, fibrosis, and cardiovascular disease including accelerated atherosclerosis. HMG CoA Reductase inhibitors, or statins, have been shown to play an important role in the modulation of hepatic steatosis and fibrosis, and recent attention has focused upon their potential therapeutic role in CHC. This article reviews the hepatitis C viral life cycle as it impacts host lipoproteins and lipid metabolism. It then describes the pathogenesis of HCV-related hepatic steatosis, hypocholesterolemia and atherosclerosis, and finally describes the promising anti-viral and anti-fibrotic effects of statins, for the treatment of CHC. PMID:26217081

  15. Biochemistry of Statins.

    PubMed

    Egom, Emmanuel Eroume A; Hafeez, Hafsa

    2016-01-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Elevated blood lipids may be a major risk factor for CVD. Due to consistent and robust association of higher low-density lipoprotein (LDL)-cholesterol levels with CVD across experimental and epidemiologic studies, therapeutic strategies to decrease risk have focused on LDL-cholesterol reduction as the primary goal. Current medication options for lipid-lowering therapy include statins, bile acid sequestrants, a cholesterol-absorption inhibitor, fibrates, nicotinic acid, and omega-3 fatty acids, which all have various mechanisms of action and pharmacokinetic properties. The most widely prescribed lipid-lowering agents are the HMG-CoA reductase inhibitors, or statins. Since their introduction in the 1980s, statins have emerged as the one of the best-selling medication classes to date, with numerous trials demonstrating powerful efficacy in preventing cardiovascular outcomes (Kapur and Musunuru, 2008 [1]). The statins are commonly used in the treatment of hypercholesterolemia and mixed hyperlipidemia. This chapter focuses on the biochemistry of statins including their structures, pharmacokinetics, and mechanism of actions as well as the potential adverse reactions linked to their clinical uses. PMID:26975972

  16. Serum PCSK9 Levels Distinguish Individuals Who Do Not Respond to High-Dose Statin Therapy with the Expected Reduction in LDL-C

    PubMed Central

    Taylor, Beth A.; Panza, Gregory; Pescatello, Linda S.; Chipkin, Stuart; Gipe, Daniel; Shao, Weiping; White, C. Michael; Thompson, Paul D.

    2014-01-01

    The purpose of the present report was to examine whether proprotein convertase subtilisin/kexin type 9 (PCSK9) levels differ in individuals who do not exhibit expected reductions in low density lipoprotein cholesterol (LDL-C) with statin therapy. Eighteen nonresponder subjects treated with 80 mg atorvastatin treatment for 6 months without substantial reductions in LDL-C (ΔLDL-C: 2.6 ± 11.4%) were compared to age- and gender-matched atorvastatin responders (ΔLDL-C: 50.7 ± 8.5%) and placebo-treated subjects (ΔLDL-C: 9.9 ± 21.5%). Free PCSK9 was marginally higher in nonresponders at baseline (P = 0.07) and significantly higher in atorvastatin responders after 6 months of treatment (P = 0.04). The change in free PCSK9 over 6 months with statin treatment was higher (P < 0.01) in atorvastatin responders (134.2 ± 131.5 ng/mL post- versus prestudy) than in either the nonresponders (39.9 ± 87.8 ng/mL) or placebo subjects (27.8 ± 97.6 ng/mL). Drug compliance was not lower in the nonresponders as assessed by pill counts and poststudy plasma atorvastatin levels. Serum PCSK9 levels, both at baseline and in response to statin therapy, may differentiate individuals who do versus those who do not respond to statin treatment. PMID:25136459

  17. Discontinuation of Statins: What Are the Risks?

    PubMed

    Marrs, Joel C; Kostoff, Matthew D

    2016-07-01

    The key benefits of statin therapy have been well established in both primary and secondary prevention cardiovascular patients. Many studies have shown a significant statin discontinuation rate within the first year of initiation whether for primary or secondary prevention. National guidelines for the management of dyslipidemia highlight the lack of benefit seen with statin therapy in patients with chronic kidney disease receiving dialysis, heart failure with reduced ejection fraction, and patients greater than 75 years of age without atherosclerotic cardiovascular disease. Available data outside of these patient populations do not support discontinuation of statin therapy. Recent studies support an association with statin discontinuation and increased risk of myocardial infarction and cardiovascular death. Based on the available data, discontinuation of statin therapy should be carefully considered. PMID:27221503

  18. The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials

    PubMed Central

    Preiss, David; Campbell, Ross T.; Murray, Heather M.; Ford, Ian; Packard, Chris J.; Sattar, Naveed; Rahimi, Kazem; Colhoun, Helen M.; Waters, David D.; LaRosa, John C.; Amarenco, Pierre; Pedersen, Terje R.; Tikkanen, Matti J.; Koren, Michael J.; Poulter, Neil R.; Sever, Peter S.; Ridker, Paul M.; MacFadyen, Jean G.; Solomon, Scott D.; Davis, Barry R.; Simpson, Lara M.; Nakamura, Haruo; Mizuno, Kyoichi; Marfisi, Rosa M.; Marchioli, Roberto; Tognoni, Gianni; Athyros, Vasilios G.; Ray, Kausik K.; Gotto, Antonio M.; Clearfield, Michael B.; Downs, John R.; McMurray, John J.

    2015-01-01

    Aims The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events. Methods and results We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84–0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85–0.99) but not HF death (213/57 734 vs. 220/57 836; RR 0.97, 95% CI 0.80–1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68–1.11) or not (RR 0.91, 95% CI 0.84–0.98). Conclusion In primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not. PMID:25802390

  19. Lower Intensified Target LDL-c Level of Statin Therapy Results in a Higher Risk of Incident Diabetes: A Meta-Analysis

    PubMed Central

    Cai, Rongrong; Yuan, Yang; Zhou, Yi; Xia, Wenqing; Wang, Pin; Sun, Haixia; Yang, Yue; Huang, Rong; Wang, Shaohua

    2014-01-01

    Background A recent meta-analysis has reported that intensive-dose statin drug increases the risk of incident diabetes. However, doubling of the statin dose generates only a further 6% decrease in low-density lipoprotein cholesterol (LDL-c) on average. This study aimed to determine whether statin therapy with lower intensive-target LDL-c level contributes to higher risk of new-onset diabetes. Methods Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled endpoint trials of statins conducted from 1966 to 2012. We included trials with more than 1000 participants who were followed up for at least 2 years. The included trials were stratified by the target LDL-c level. I2 statistic was used to measure heterogeneity between trials. We further calculated risk estimates with random-effect meta-analysis. Meta-regression was used to identify the potential risk factors of statin-induced diabetes. Results Fourteen trials with a total of 95 102 non-diabetic participants were included. The risks elevated by 33% [odds ratio (OR) = 1.33; 95% confidence interval (CI) 1.14–1.56; I2 = 7.7%] and 16% (OR = 1.16; 95% CI 1.06–1.28; I2 = 0.0%) when the intensified target LDL-c levels were ≤1.8 mmol/L and 1.8–2.59 mmol/L, respectively. The risk of incident diabetes did not increase when the target LDL-c level was ≥2.59 mmol/L. Apart from age, female, and baseline level of total cholesterol, meta-regression analysis showed that the target and baseline levels of LDL-c and relative LDL-c reduction were predictors of statin-induced diabetes. Conclusion A lower intensified target LDL-c level of statin therapy resulted in a higher risk of incident diabetes. PMID:25122464

  20. Statin therapy and plasma coenzyme Q10 concentrations--A systematic review and meta-analysis of placebo-controlled trials.

    PubMed

    Banach, Maciej; Serban, Corina; Ursoniu, Sorin; Rysz, Jacek; Muntner, Paul; Toth, Peter P; Jones, Steven R; Rizzo, Manfredi; Glasser, Stephen P; Watts, Gerald F; Blumenthal, Roger S; Lip, Gregory Y H; Mikhailidis, Dimitri P; Sahebkar, Amirhossein

    2015-09-01

    Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin therapy on plasma CoQ10 concentrations through the meta-analysis of available RCTs. The literature search included selected databases up to April 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The data from 8 placebo-controlled treatment arms suggested a significant reduction in plasma CoQ10 concentrations following treatment with statins (WMD: -0.44 μmol/L, 95%CI: -0.52, -0.37, p<0.001). The pooled effect size was robust and remained significant in the leave-one-out sensitivity analysis. Subgroup analysis suggested that the impact of statins on plasma CoQ10 concentrations is significant for all 4 types of statins studied i.e. atorvastatin (WMD: -0.41 μmol/L, 95%CI: -0.53, -0.29, p<0.001), simvastatin (WMD: -0.47 μmol/L, 95% CI: -0.61, -0.33, p<0.001), rosuvastatin (WMD: -0.49 μmol/L, 95%CI: -0.67, -0.31, p<0.001) and pravastatin (WMD: -0.43 μmol/L, 95%CI: -0.69, -0.16, p=0.001). Likewise, there was no differential effect of lipophilic (WMD: -0.43 μmol/L, 95%CI: -0.53, -0.34, p<0.001) and hydrophilic statins (WMD: -0.47 μmol/L, 95%CI: -0.62, -0.32, p<0.001). With respect to treatment duration, a significant effect was observed in both subsets of trials lasting <12 weeks (WMD: -0.51 μmol/L, 95%CI: -0.64, -0.39, p<0.001) and ≥12 weeks (WMD: -0.40 μmol/L, 95%CI: -0.50, -0.30, p<0.001). The meta-analysis showed a significant reduction in plasma CoQ10 concentrations following treatment with statins. Further well-designed trials are required to confirm our findings and elucidate their clinical relevance. PMID:26192349

  1. Statin non-adherence: clinical consequences and proposed solutions.

    PubMed

    Rosenson, Robert S

    2016-01-01

    Large controlled clinical trials have demonstrated reductions with statin therapy in cardiovascular events in patients presenting with acute coronary syndromes and stable coronary heart disease and individuals at high risk of a cardiovascular event. In trials of acute coronary syndromes and stable coronary heart disease, high-intensity statin therapy is more effective in the prevention of recurrent cardiovascular events than low-intensity statin therapy. Thus, evidence-based guidelines recommend in-hospital initiation of high-intensity statin therapy for all acute coronary syndrome patients. Clinical trials report high adherence to and low discontinuation of high-intensity statin therapy; however, in clinical practice, high-intensity statins are prescribed to far fewer patients, who often discontinue their statin after the first refill. A coordinated effort among the patient, provider, pharmacist, health system, and insurer is necessary to improve utilization and persistence of prescribed medications. The major cause for statin discontinuations reported by patients is perceived adverse events. Evaluation of potential adverse events requires validated tools to distinguish between statin-associated adverse events versus non-specific complaints. Treatment options for statin-intolerant patients include the use of a different statin, often at a lower dose or frequency. In order to lower LDL cholesterol, lower doses of statins may be combined with ezetimibe or bile acid sequestrants. Newer treatment options for patients with statin-associated muscle symptoms may include proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors. PMID:27134737

  2. Statin non-adherence: clinical consequences and proposed solutions

    PubMed Central

    Rosenson, Robert S.

    2016-01-01

    Large controlled clinical trials have demonstrated reductions with statin therapy in cardiovascular events in patients presenting with acute coronary syndromes and stable coronary heart disease and individuals at high risk of a cardiovascular event. In trials of acute coronary syndromes and stable coronary heart disease, high-intensity statin therapy is more effective in the prevention of recurrent cardiovascular events than low-intensity statin therapy. Thus, evidence-based guidelines recommend in-hospital initiation of high-intensity statin therapy for all acute coronary syndrome patients. Clinical trials report high adherence to and low discontinuation of high-intensity statin therapy; however, in clinical practice, high-intensity statins are prescribed to far fewer patients, who often discontinue their statin after the first refill. A coordinated effort among the patient, provider, pharmacist, health system, and insurer is necessary to improve utilization and persistence of prescribed medications. The major cause for statin discontinuations reported by patients is perceived adverse events. Evaluation of potential adverse events requires validated tools to distinguish between statin-associated adverse events versus non-specific complaints. Treatment options for statin-intolerant patients include the use of a different statin, often at a lower dose or frequency. In order to lower LDL cholesterol, lower doses of statins may be combined with ezetimibe or bile acid sequestrants. Newer treatment options for patients with statin-associated muscle symptoms may include proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors. PMID:27134737

  3. Statin Therapy and the Development of Cerebral Amyloid Angiopathy—A Rodent in Vivo Approach

    PubMed Central

    Reuter, Björn; Venus, Alexander; Grudzenski, Saskia; Heiler, Patrick; Schad, Lothar; Staufenbiel, Matthias; Hennerici, Michael G.; Fatar, Marc

    2016-01-01

    Background: Cerebral amyloid angiopathy (CAA) is characterized by vascular deposition of amyloid β (Aβ) with a higher incidence of cerebral microbleeds (cMBs) and spontaneous hemorrhage. Since statins are known for their benefit in vascular disease we tested for the effect on CAA. Methods: APP23-transgenic mice received atorvastatin-supplemented food starting at the age of eight months (n = 13), 12 months (n = 7), and 16 months (n = 6), respectively. Controls (n = 16) received standard food only. At 24 months of age cMBs were determined with T2*-weighted 9.4T magnetic resonance imaging and graded by size. Results: Control mice displayed an average of 35 ± 18.5 cMBs (mean ± standard deviation), compared to 29.3 ± 9.8 in mice with eight months (p = 0.49), 24.9 ± 21.3 with 12 months (p = 0.26), and 27.8 ± 15.4 with 16 months of atorvastatin treatment (p = 0.27). In combined analysis treated mice showed lower absolute numbers (27.4 ± 15.6, p = 0.16) compared to controls and also after adjustment for cMB size (p = 0.13). Conclusion: Despite to a non-significant trend towards fewer cMBs our results failed to provide evidence for beneficial effects of long-term atorvastatin treatment in the APP23-transgenic mouse model of CAA. A higher risk for bleeding complications was not observed. PMID:26797603

  4. Statin Therapy for the Prevention of Atrial Fibrillation Trial (SToP AF trial)

    PubMed Central

    Negi, Smita; Shukrullah, Irfan; Veledar, Emir; Bloom, Heather L.; Jones, Dean P.; Dudley, Samuel C.

    2010-01-01

    Background Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti-inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation. (NCT00252967) Methods and Results In a randomized, double-blinded, placebo-controlled trial, patients with atrial fibrillation/flutter (AF) were randomized to receive either atorvastatin 80 mg (n=33) or placebo (n=31) before CV. Treatment was continued for 12 months or until AF recurred. Serum oxidative stress markers (ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, isoprostanes) and inflammatory markers [ high sensitivity C- reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α (TNFα)] were measured at baseline and on follow-up. AF recurred in 22 (66.7%) of atorvastatin and 26 (83.9%) of placebo group (p=0.2). The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 (95% CI: 0.98-1.01, p=0.3). There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates (median (IR): 29 (2-145) days vs. 22 (7-70) days, p=0.9). While no significant effect was seen on oxidative stress, 2 of 4 inflammatory markers, IL-6 (adjusted OR: 0.59, 95% CI: 0.35-0.97, p= 0.04) and hs-CRP (adjusted OR: 0.59, 95% CI: 0.37-0.95, p=0.03) were significantly lowered with atorvastatin. Cholesterol levels significantly decreased with atorvastatin (p=0.03). Conclusions High dose atorvastatin did not reduce the recurrence of AF after CV. It reduced selective markers of inflammation without affecting systemic oxidative stress. Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress. PMID:20946227

  5. Aggression control therapy for violent forensic psychiatric patients: method and clinical practice.

    PubMed

    Hornsveld, Ruud H J; Nijman, Henk L I; Hollin, Clive R; Kraaimaat, Floor W

    2008-04-01

    Aggression control therapy is based on Goldstein, Gibbs, and Glick's aggression replacement training and was developed for violent forensic psychiatric in- and outpatients (adolescents and adults) with a (oppositional-defiant) conduct disorder or an antisocial personality disorder. First, the conditions for promoting "treatment integrity" are examined. Then, target groups, framework, and procedure are described in detail, followed by the most important clinical findings during the period 2002 to 2006. Finally, new programme developments are mentioned, with aggression control therapy as a starting point. PMID:17636205

  6. Reinforcement Behavior Therapy by Kindergarten Teachers on Preschool Children’s Aggression: A Randomized Controlled Trial

    PubMed Central

    Yektatalab, Shahrzad; Alipour, Abdolrasool; Edraki, Mitra; Tavakoli, Pouran

    2016-01-01

    Background: Aggression is a kind of behavior that causes damage or harm to others. The prevalence of aggression is 8–20% in 3–6 years old children. The present study aimed to assess the effect of training kindergarten teachers regarding reinforcement behavior therapy on preschoolers’ aggression. Methods: In this cluster randomized control trial, 14 out of 35 kindergarten and preschool centers of Mohr city, Iran, were chosen using random cluster sampling and then randomly assigned to an intervention and a control group. All 370 kindergarten and preschool children in 14 kindergarten were assessed by preschoolers’ aggression questionnaire and 60 children who obtained a minimum aggression score of 117.48 for girls and 125.77 for boys were randomly selected. The teachers in the intervention group participated in 4 educational sessions on behavior therapy and then practiced this technique under the supervision of the researcher for two months. Preschoolers’ aggression questionnaire was computed in both intervention and control groups before and after a two-month period. Results: The results demonstrated a significant statistical difference in the total aggression score (P=0.01), verbal (P=0.02) and physical (P=0.01) aggression subscales scores in the intervention group in comparison to the control group after the intervention. But the scores of relational aggression (P=0.09) and impulsive anger (P=0.08) subscales were not statistically different in the intervention group compared to the controls. Conclusion: This study highlighted the importance of teaching reinforcement behavior therapy by kindergarten teachers in decreasing verbal and physical aggression in preschoolers. Trial Registration Number: IRCT2014042617436N1 PMID:26793733

  7. Statin tolerability: In defence of placebo-controlled trials

    PubMed Central

    Newman, Connie B

    2015-01-01

    Background Statin intolerance is a barrier to effective lipid-lowering treatment. A significant number of patients stop prescribed statins, or can take only a reduced dose, because of adverse events attributed to the statin, and are then considered statin-intolerant. Methods Examination of differences between statin and placebo in withdrawal rates due to adverse events – a good measure of tolerability – in statin cardiovascular outcome trials in patients with advanced disease and complex medical histories, who may be more vulnerable to adverse effects. The arguments commonly used to dismiss safety and tolerability data in statin clinical trials are examined. Results Rates of withdrawal due to adverse events in trials in patients with advanced disease and complex medical histories are consistently similar in the statin and placebo groups. We find no support for arguments that statin cardiovascular outcome trials do not translate to clinical practice. Conclusions Given the absence of any signal of intolerance in clinical trials, it appears that statin intolerance in the clinic is commonly due to the nocebo effect causing patients to attribute background symptoms to the statin. Consistent with this, over 90% of patients who have stopped treatment because of an adverse event can tolerate a statin if re-challenged. Consequently, new agents, including monoclonal antibodies to proprotein convertase subtilisin/kexin type 9, will be useful when added to statin therapy but should rarely be used as a statin substitute. PMID:26318980

  8. Molecular mechanisms of statin intolerance

    PubMed Central

    Franczyk, Beata; Toth, Peter P.; Rysz, Jacek; Banach, Maciej

    2016-01-01

    Statins reduce cardiovascular morbidity and mortality in primary and secondary prevention. Despite their efficacy, many persons are unable to tolerate statins due to adverse events such as hepatotoxicity and myalgia/myopathy. In the case of most patients, it seems that mild-to-moderate abnormalities in liver and muscle enzymes are not serious adverse effects and do not outweigh the benefits of coronary heart disease risk reduction. The risk for mortality or permanent organ damage ascribed to statin use is very small and limited to cases of myopathy and rhabdomyolysis. Statin-induced muscle-related adverse events comprise a highly heterogeneous clinical disorder with numerous, complex etiologies and a variety of genetic backgrounds. Every patient who presents with statin-related side effects cannot undergo the type of exhaustive molecular characterization that would include all of these mechanisms. Frequently the only solution is to either discontinue statin therapy/reduce the dose or attempt intermittent dosing strategies at a low dose. PMID:27279860

  9. Statins and Nonadherence: Should We RELATE Better?

    PubMed

    Turin, Alexander; Pandit, Jay; Stone, Neil J

    2015-09-01

    Statin nonadherence is a major challenge to optimal management. Patients nonadherent to statin therapy do not receive the expected benefit relative to the degree of low-density lipoprotein cholesterol (LDL-C) lowering obtained. This is important because new evidence guidelines recommend statins as the first-line therapy for those in high-risk groups (secondary prevention, patients with diabetes 40-75 years of age, and LDL-C ≥ 190 mg/dL) and in selected primary prevention patients. Statin assignment in the latter group occurs only in those with an estimated ≥7.5% 10-year atherosclerotic cardiovascular disease risk after shared decision making in a clinician-patient risk discussion. However, in numerous studies, statin nonadherence shows little or no benefit in reducing cardiovascular events or mortality compared to placebo, effectively negating the risk reduction expected from statin use and concomitantly increasing the total cost of health care. The causes and solutions for nonadherence are multifactorial and include patient, clinician, and health system factors. We believe that a clinician-patient partnership that facilitates patients' understanding of the potential for optimal benefit with the least adverse effects is an important first step toward improving adherence. A transtheoretical model of stages of behavior change helps clinicians address many of the common factors limiting adherence to statins. We conclude with a teaching tool emphasizing a structured approach to statin therapy with patient-centered risk discussions. PMID:25827856

  10. Remembering Statins: Do Statins Have Adverse Cognitive Effects?

    PubMed

    Bitzur, Rafael

    2016-08-01

    The issue of statin-associated cognitive impairment has been a hot topic among both patients and health care providers, especially since the U.S. Food and Drug Administration (FDA) issued a statement regarding rare postmarketing reports of ill-defined cognitive impairment associated with statin use. This statement was based on case reports, and no objective measures of cognitive function were used. Nevertheless, many patients at high risk of cardiovascular disease have expressed concerns about possible cognitive decline and may have opted to forgo statin therapy. In this overview, the evidence leading to the statement by the FDA is reviewed. Potential mechanisms of the effect of LDL cholesterol reduction and statin therapy on cognition are discussed. Evidence from observational and prospective randomized trials is summarized, leading to the conclusion that as for now, there is no good evidence that statins cause cognitive impairment to a significant degree. Reported cases seem to be rare, and a causal relationship has not been established. PMID:27440840

  11. Efficacy and tolerability of adding coenzyme A 400 U/d capsule to stable statin therapy for the treatment of patients with mixed dyslipidemia: an 8-week, multicenter, double-Blind, randomized, placebo-controlled study

    PubMed Central

    2014-01-01

    Background Patients with mixed hyperlipidemia usually are in need of combination therapy to achieve low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) target values for reduction of cardiovascular risk. This study investigated the efficacy and safety of adding a new hypolipidemic agent, coenzyme A (CoA) to stable statin therapy in patients with mixed hyperlipidemia. Methods In this multi-center, 8-week, double-blind study, adults who had received ≥8 weeks of stable statin therapy and had hypertriglyceridemia (TG level at 2.3-6.5 mmol/L) were randomized to receive CoA 400 U/d or placebo plus stable dosage of statin. Efficacy was assessed by the changes in the levels and patterns of lipoproteins. Tolerability was assessed by the incidence and severity of adverse events (AEs). Results A total of 304 patients with mixed hyperlipidemia were randomized to receive CoA 400 U/d plus statin or placebo plus statin (n = 152, each group). After treatment for 8 weeks, the mean percent change in TG was significantly greater with CoA plus statin compared with placebo plus statin (-25.9% vs -4.9%, respectively; p = 0.0003). CoA plus statin was associated with significant reductions in TC (-9.1% vs -3.1%; p = 0.0033), LDL-C (-9.9% vs 0.1%; p = 0.003), and non- high-density lipoprotein cholesterol (-13.5% vs -5.7%; p = 0.0039). There was no significant difference in the frequency of AEs between groups. No serious AEs were considered treatment related. Conclusions In these adult patients with persistent hypertriglyceridemia, CoA plus statin therapy improved TG and other lipoprotein parameters to a greater extent than statin alone and has no obviously adverse effect. Trial registration Current Controlled Trials ClinicalTrials.gov ID NCT01928342. PMID:24382338

  12. Growth hormone (GH) replacement decreases serum total and LDL-cholesterol in hypopituitary patients on maintenance HMG CoA reductase inhibitor (statin) therapy

    PubMed Central

    Monson, John P; Jönsson, Peter; Koltowska-Häggström, Maria; Kourides, Ione

    2007-01-01

    Objective Adult onset GH deficiency (GHD) is characterized by abnormalities of serum lipoprotein profiles and GH replacement results in favourable alterations in serum total and low density lipoprotein (LDL)-cholesterol. Preliminary evidence has indicated that the effect of GH replacement in this respect may be additive to that of HMG CoA reductase inhibitor (statin) therapy. We have examined this possibility during prospective follow-up of adult onset hypopituitary patients enrolled in KIMS (Pfizer International Metabolic Database), a pharmacoepidemiological study of GH replacement in adult hypopituitary patients. Design Lipoprotein profiles were measured centrally at baseline and after 12 months GH replacement therapy. Patients Sixty-one hypopituitary patients (30 male, 31 female) on maintenance statin therapy (mean 2·5 ± 2·7 SD years before GH) (statin group – SG) and 1247 (608 male, 639 female) patients not on hypolipidaemic therapy (nonstatin group – NSG) were studied. All patients were naïve or had not received GH replacement during the 6 months prior to study. Patients who developed diabetes mellitus during the first year of GH therapy or in the subsequent year and those with childhood onset GHD were excluded from this analysis. An established diagnosis of diabetes mellitus was present in 18% SG and 4·4% NSG at baseline. Measurements Serum concentrations of total, high density lipoprotein (HDL)-cholesterol, triglycerides and IGF-I were measured centrally in all patients and LDL-cholesterol was estimated using Friedewald's formula. Results The relative frequency of various statin use was simvastatin 52% (15·8 ± 8·1 mg, mean ± SD), atorvastatin 30% (14·4 ± 7·8 mg), pravastatin 9·8% (31·6 mg ± 13·9 mg), lovastatin 6·6% (17·5 ± 5 mg) and fluvastatin 1·6% (40 mg). Baseline serum total and LDL-cholesterol (mean ± SD) were 5·2 ± 1·4 and 3·1 ± 1·3 mmol/l in SG and 5·8 ± 1·2 and 3·7 ± 1·0 mmol/l in NSG, respectively (P < 0·0001

  13. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials

    PubMed Central

    Cholesterol Treatment Trialists' (CTT) Collaborators

    2012-01-01

    Summary Background Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain. Methods This meta-analysis included individual participant data from 22 trials of statin versus control (n=134 537; mean LDL cholesterol difference 1·08 mmol/L; median follow-up 4·8 years) and five trials of more versus less statin (n=39 612; difference 0·51 mmol/L; 5·1 years). Major vascular events were major coronary events (ie, non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%); in each, the rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated. Findings Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0·79, 95% CI 0·77–0·81, per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1·0 mmol/L reduction from lowest to highest risk: 0·62 [99% CI 0·47–0·81], 0·69 [99% CI 0·60–0·79], 0·79 [99% CI 0·74–0·85], 0·81 [99% CI 0·77–0·86], and 0·79 [99% CI 0·74–0·84]; trend p=0·04), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0·57, 99% CI 0·36–0·89, p=0·0012, and 0·61, 99% CI 0·50–0·74, p<0·0001) and in coronary revascularisations (RR 0·52, 99% CI 0·35–0·75, and 0·63, 99% CI 0·51–0·79; both p<0·0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1·0 mmol/L LDL cholesterol

  14. The New Face of Hyperlipidemia Management: Proprotein Convertase Subtilisin/Kexin Inhibitors (PCSK-9) and Their Emergent Role As An Alternative To Statin Therapy.

    PubMed

    Smith, Lillian; Mosley, Juan; Yates, Jarah; Caswell, Luke

    2016-01-01

    This review analyzes Proprotein Convertase Subtilisin/Kexin 9 inhibitors (PCSK-9), a new medication class that has arisen in the last year to combat hypercholesterolemia. They are targeted towards patients who are unable to achieve acceptable low density lipoprotein (LDL) levels despite maximum statin therapy, as well as those who are unable to tolerate maximum statin therapy due to side effects such as myopathy or myalgia. Two of these medications have been released in the last year: alirocumab (Praluent) and evolocumab (Repatha). This article will overview this medication class, describe their pathophysiology, and analyze the clinical data from the numerous studies and trials done on both of these medications for their efficacy and safety outcomes. Data compiled on this new class of medications support the research that PCSK-9 inhibitors are both a safe and effective means of lowering the LDL levels of resistant or otherwise currently unmanaged hypercholesterolemia patients.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID:27096698

  15. Dyslipidemia, Vascular Atheroma and Statins.

    PubMed

    Abuzaid, Ahmed; El-Menyar, Ayman

    2015-01-01

    Dyslipidemia plays an important role in the initiation and progression of atherosclerotic coronary artery disease. However, regression of atherosclerotic atheroma by introducing lipid lowering agents is not fully understood but looks promising. More questions still need to be answered in terms of the modality of assessment, time course of changes and its documentation, whether plaque progression or regression assessed by imaging one arterial tree reflects a uniform effect throughout all arterial territories and whether atheroma regression is a therapeutic goal. Physicians need to define the type of statins, the use of statin as monotherapy or in combination with other agents, and the intensity of statin therapy. Furthermore, the impact of factors like age, gender and ethnicity on the regression process should be of consideration. We still need more randomized controlled studies based on evidence-based diagnostic interventional tools. This narrative review considers this debate. PMID:25360549

  16. Are statins really wonder drugs?

    PubMed

    Grover, Harpreet Singh; Luthra, Shailly; Maroo, Shruti

    2014-12-01

    Statins [3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase], are wonder drugs that have reshaped the treatment of hypercholesterolemia and associated cardiovascular diseases. However, evidence from various studies indicates existence of many statin-induced side effects such as myopathies, rhabdomyolysis, hepatotoxicity, peripheral neuropathy, impaired myocardial contractility, diabetes, autoimmune diseases, and erectile dysfunction (ED). Physician awareness of these side effects is reported to be very low even for the adverse effects (AEs) most widely reported by patients. This can lead to incorrect treatment decisions, compromised patient care, and an increase in patient morbidity. Therefore, the aim of this article is to highlight the AEs of statin therapy as well as rational management of these complications to further improve safety of these excellent drugs. PMID:24231094

  17. Statins and Risk of Diabetes

    PubMed Central

    Danaei, Goodarz; García Rodríguez, Luis A.; Fernandez Cantero, Oscar; Hernán, Miguel A.

    2013-01-01

    OBJECTIVE Two meta-analyses of randomized trials of statins found increased risk of type 2 diabetes. One possible explanation is bias due to differential survival when patients who are at higher risk of diabetes survive longer under statin treatment. RESEARCH DESIGN AND METHODS We used electronic medical records from 500 general practices in the U.K. and included data from 285,864 men and women aged 50–84 years from January 2000 to December 2010. We emulated the design and analysis of a hypothetical randomized trial of statins, estimated the observational analog of the intention-to-treat effect, and adjusted for differential survival bias using inverse-probability weighting. RESULTS During 1.2 million person-years of follow-up, there were 13,455 cases of type 2 diabetes and 8,932 deaths. Statin initiation was associated with increased risk of type 2 diabetes. The hazard ratio (95% CI) of diabetes was 1.45 (1.39–1.50) before adjusting for potential confounders and 1.14 (1.10–1.19) after adjustment. Adjusting for differential survival did not change the estimates. Initiating atorvastatin and simvastatin was associated with increased risk of type 2 diabetes. CONCLUSIONS In this sample of the general population, statin therapy was associated with 14% increased risk of type 2 diabetes. Differential survival did not explain this increased risk. PMID:23248196

  18. Statin-Associated Polymyositis Following Omeprazole Treatment

    PubMed Central

    Kanth, Rajan; Shah, Milind S.; Flores, Rafael Medina

    2013-01-01

    Statins are an extensively used class of drugs, and myopathy is an uncommon, but well-described side effect of statin therapy. Inflammatory myopathies, including polymyositis, dermatomyositis, and necrotizing autoimmune myopathy, are even more rare, but debilitating, side effects of statin therapy that are characterized by the persistence of symptoms even after discontinuation of the drug. It is important to differentiate statin-associated inflammatory myopathies from other self-limited myopathies, as the disease often requires multiple immunosuppressive therapies. Drug interactions increase the risk of statin-associated toxic myopathy, but no risk factors for statin-associated inflammatory myopathies have been established. Here we describe the case of a man, age 59 years, who had been treated with a combination of atorvastatin and gemfibrozil for approximately 5 years and developed polymyositis after treatment with omeprazole for 7 months. Symptoms did not resolve after discontinuation of the atorvastatin, gemfibrozil, and omeprazole. The patient was treated with prednisone and methotrexate followed by intravenous immunoglobulin, which resulted in normalization of creatinine kinase levels and resolution of symptoms after 14 weeks. It is unclear if polymyositis was triggered by interaction of the statin with omeprazole and/or gemfibrozil, or if it developed secondary to long-term use of atorvastatin only. PMID:23580790

  19. Low use of statins and other coronary secondary prevention therapies in primary and secondary care in India

    PubMed Central

    Sharma, Krishna K; Gupta, Rajeev; Agrawal, Aachu; Roy, Sanjeeb; Kasliwal, Atul; Bana, Ajeet; Tongia, Ravindra K; Deedwania, Prakash C

    2009-01-01

    Objective: To determine the frequency of use of pharmacotherapy with aspirin, beta blocker, statin, and angiotensin-converting enzyme (ACE) inhibitor in patients with stable coronary heart disease (CHD) among physicians at different levels of health care in Rajasthan state, India. Methods: Physicians practicing at tertiary hospitals and clinics at tertiary, secondary and primary levels were contacted. Prescriptions of CHD patients were audited and descriptive statistics reported. Results: We evaluated 2,993 prescriptions (tertiary hospital discharge 711, tertiary 688, secondary 1,306, and primary 288). Use of aspirin was in 2,713 (91%) of prescriptions, beta blockers 2,057 (69%), ACE inhibitors or angiotensin receptor blockers (ARBs) 2,471 (82%), and statins 2,059 (69%). Any one of these drugs was prescribed in 2,991 (100%), any two in 2,880 (96%), any three in 1,740 (58%), and all four in 1,062 (35.5%) (P < 0.001). As compared to tertiary hospital, prescriptions at tertiary, secondary, and primary levels were lower: aspirin (96% vs 95%, 91%, 67%), beta blockers (80% vs 62%, 66%, 70%), statins (87% vs 82%, 62%, 21%): two drugs (98% vs 96%, 98%, 85%), three drugs (75% vs 58%, 55%, 28%), or four drugs (54% vs 44%, 28%, 7%) (P < 0.01). Use of ACE inhibitors/ARBs was similar while nitrates (43% vs 23%, 43%, 70%), dihydropyridine calcium channel blockers (12% vs 15%, 30%, 47%), and multivitamins (6% vs 26%, 37%, 47%) use was more in secondary and primary care. Conclusions: There is suboptimal use of various evidence-based drugs (aspirin, beta blockers, ACE inhibitors, and statins) for secondary prevention of CHD in India. PMID:19997570

  20. LDL cholesterol, statins and PCSK 9 inhibitors.

    PubMed

    Gupta, Sanjiv

    2015-01-01

    Reduction of low density lipoprotein cholesterol (LDLc) is of vital importance for the prevention of atherosclerotic cardiovascular disease (ASCVD). Statin is the most effective therapy today to lower LDLc by inhibiting HMG-CoA-reductase. However despite intensive statin therapy, there remains a residual risk of recurrent myocardial infarction in about 20-30% cases. Moreover a few patients develop statin intolerance. For severe hypercholesterolemia, statins alone or in combination of ezetimibe, niacin and fenofibrate have been advocated. For homozygous familial hypercholesterolemia (HOFH), a microsomal triglyceride transfer protein MTP inhibitor (Lopitamide) and antisense oligonucleotide (ASO) (Mipomersen) have recently been approved by FDA, USA through 'Risk evaluation and Mitigation Strategy (REMS)'. Possible future therapies include PCSK-9 inhibitors which have excellent lipid lowering properties. Three monoclonal antibodies (PCSK 9 Inhibitors) alirocumab, evolocumab and Bococizumab are under advanced clinical stage IV trials and awaiting approval by FDA and European Medicines Agency. PMID:26432726

  1. Statin, Calcium Channel Blocker and Beta Blocker Therapy May Decrease the Incidence of Tuberculosis Infection in Elderly Taiwanese Patients with Type 2 Diabetes

    PubMed Central

    Lee, Mei-Yueh; Lin, Kun-Der; Hsu, Wei-Hao; Chang, Hsiu-Ling; Yang, Yi-Hsin; Hsiao, Pi-Jung; Shin, Shyi-Jang

    2015-01-01

    Background: It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether the strong association between tuberculosis and diabetes mellitus is independent from the influence of hypertension and dyslipidemia, and its treatment in elderly Taiwanese patients. Methods: A total of 27,958 patients aged more than 65 years were identified from the National Health Insurance Research Database (NIHRD) in 1997 and were followed from 1998 to 2009. The demographic characteristics between the patients with and without diabetes were analyzed using the χ2 test. A total of 13,981 patients with type 2 diabetes were included in this study. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risk of tuberculosis. Results: After adjusting for age, sex, other co-morbidities and medications, calcium channel blocker, beta blocker and statin users had a lower independent association, with risk ratios of 0.76 (95% CI, 0.58–0.98), 0.72 (95% CI, 0.58–0.91) and 0.76 (95% CI, 0.60–0.97), respectively. Conclusion: Calcium channel blocker, beta blocker and statin therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes. PMID:25993300

  2. Safety of statins.

    PubMed

    Maji, Debasish; Shaikh, Shehla; Solanki, Dharmesh; Gaurav, Kumar

    2013-07-01

    Statins are an established class of drugs with proven efficacy in cardiovascular risk reduction. The concern over statin safety was first raised with the revelation of myopathy and rhabdomyolysis with the use of now withdrawn cerivastatin. Enhanced understanding of the mechanisms behind adverse effects of statins including an insight into the pharmacokinetic properties have minimised fear of statin use among clinicians. Studies reveal that occurrence of myopathy and rhabdomyolysis are rare 1/100000 patient-years. The risk of myopathy/rhabdomyolysis varies between statins due to varying pharmacokinetic profiles. This explains the differing abilities of statins to adverse effects and drug interaction potentials that precipitate adverse effects. Higher dose of rosuvastatin (80 mg/day) was associated with proteinuria and hematuria while lower doses were devoid of such effects. Awareness of drugs interacting with statins and knowledge of certain combinations such as statin and fibrates together with monitoring of altered creatine kinase activity may greatly minimise associated adverse effects. Statins also asymptomatically raise levels of hepatic transaminases but are not correlated with hepatotoxicity. Statins are safe and well tolerated including more recent potent statins such as, rosuvastatin. The benefits of intensive statin use in cardiovascular risk reduction greatly outweigh risks. The present review discusses underlying causes of statin-associated adverse effects including management in high risk groups. PMID:23961479

  3. The role and indications of aggressive locoregional therapy in metastatic inflammatory breast cancer.

    PubMed

    Yan, Yi; Tang, Lili; Tong, Wei; Zhou, Jingyu

    2016-01-01

    We seek to confirm the effect and explore the indications of aggressive locoregional management in patients with metastatic inflammatory breast cancer (IBC). Between 2003 and 2014, we reviewed the records of 156 patients with metastatic IBC from five large centers of Breast Surgery in the region of central south of China. Clinicopathologic data were collected to access overall survival (OS), prognostic factors and the indications for locoregional treatment. 75 (48%) patients underwent aggressive locoregional therapy. Patients in locoregional therapy group had a median OS of 24 months compared with 17 months of those in no locoregional therapy group. 2-year OS rate of these two groups was 52% and 32%, separately. Locoregional therapy (HR = 0.556; 95% CI 0.385-0.803; p = 0.002) was confirmed to be an independent prognostic factor, which could significantly improve OS of patients with metastatic IBC. For locoregional therapy group, statistical differences were observed in all subgroups stratified by the factors that were significant in univariate analysis except in the subgroups of stable disease, Charlson comorbidity index ≥3 and cerebral metastasis. Therefore, systemic therapy efficacy, Charlson comorbidity index and cerebral metastasis status appeared to be important indexes for choice of locoregional therapy in different individuals. PMID:27174789

  4. The role and indications of aggressive locoregional therapy in metastatic inflammatory breast cancer

    PubMed Central

    Yan, Yi; Tang, Lili; Tong, Wei; Zhou, Jingyu

    2016-01-01

    We seek to confirm the effect and explore the indications of aggressive locoregional management in patients with metastatic inflammatory breast cancer (IBC). Between 2003 and 2014, we reviewed the records of 156 patients with metastatic IBC from five large centers of Breast Surgery in the region of central south of China. Clinicopathologic data were collected to access overall survival (OS), prognostic factors and the indications for locoregional treatment. 75 (48%) patients underwent aggressive locoregional therapy. Patients in locoregional therapy group had a median OS of 24 months compared with 17 months of those in no locoregional therapy group. 2-year OS rate of these two groups was 52% and 32%, separately. Locoregional therapy (HR = 0.556; 95% CI 0.385–0.803; p = 0.002) was confirmed to be an independent prognostic factor, which could significantly improve OS of patients with metastatic IBC. For locoregional therapy group, statistical differences were observed in all subgroups stratified by the factors that were significant in univariate analysis except in the subgroups of stable disease, Charlson comorbidity index ≥3 and cerebral metastasis. Therefore, systemic therapy efficacy, Charlson comorbidity index and cerebral metastasis status appeared to be important indexes for choice of locoregional therapy in different individuals. PMID:27174789

  5. Statin-induced diabetes: incidence, mechanisms, and implications

    PubMed Central

    Ganda, Om P.

    2016-01-01

    Persuasive data from many randomized controlled trials and large, long-term observational studies indicate a modestly increased risk for the emergence of new diabetes after statin initiation. Several meta-analyses of many statin trials as well as longitudinal population-based studies suggest that the risk factors for diabetes in statin-treated persons include underlying risk for diabetes at baseline (specifically features of metabolic syndrome), the intensity of statin therapy, certain genetic traits independent of diabetes risk, and adherence to lifestyle factors. Limited data suggest statins modestly worsen hyperglycemia and A1c levels in those with pre-existing diabetes or glucose intolerance. The precise mechanism(s) of diabetogenesis with statin therapy are unclear, but impaired insulin sensitivity and compromised β cell function via enhanced intracellular cholesterol uptake due to inhibition of intracellular cholesterol synthesis by statins, as well as other mechanisms, may be involved. Furthermore, while statins are known to have anti-inflammatory effects, it is hypothesized that, under dysmetabolic conditions, they might have pro-inflammatory effects via induction of certain inflammasomes. This concept requires further elucidation in the human. Finally, it is clear that the risk–benefit ratio for cardiovascular disease events is strongly in favor of statin therapy in those at risk, despite the emergence of new diabetes. Adherence to lifestyle regimen is critical in the prevention of new diabetes on statins. PMID:27408693

  6. Management of intracerebral hemorrhage–use of statins

    PubMed Central

    Van Matre, Edward T; Sherman, Deb S; Kiser, Tyree H

    2016-01-01

    Intracerebral hemorrhage (ICH) is a neurologic injury resulting in significant morbidity and mortality. Statins play a significant role in primary and secondary prevention of cardiovascular and cerebrovascular ischemic events. Despite clear benefits of statins in ischemic stroke, post hoc analyses of some studies suggest there may be a link between statin therapy and development of ICH. Direct pharmacologic effects of decreased serum levels of total cholesterol and low-density lipoproteins in conjunction with pleiotropic effects are thought to be linked to this possible increase in ICH risk. In the face of the potential of statins to increase the risk of ICH, recent evidence suggests that statins may also have beneficial effects on patient outcomes when continued or initiated following an ICH. This discordance in findings and the overall lack of well-designed prospective clinical trials increase the complexity of clinical decision making when utilizing statin therapy in patients with, or at risk for, ICH. This review evaluates the pharmacologic effects of statin therapy and describes how these effects translate to both risks and benefits in ICH. The current literature regarding the effects of statin therapy on clinical outcomes in ICH is evaluated to help guide clinicians with decisions regarding initiation, continuation, or discontinuation of statin therapy in patients with ICH. PMID:27143909

  7. Statins Increase Rifampin Mycobactericidal Effect

    PubMed Central

    Lobato, Lívia Silva; Rosa, Patrícia Sammarco; Ferreira, Jessica da Silva; Neumann, Arthur da Silva; da Silva, Marlei Gomes; do Nascimento, Dejair Caitano; Soares, Cleverson Teixeira; Pedrini, Silvia Cristina Barbosa; de Oliveira, Diego Sá Leal; Monteiro, Cláudia Peres; Pereira, Geraldo Moura Batista; Ribeiro-Alves, Marcelo; Hacker, Mariana Andrea; Moraes, Milton Ozório; Pessolani, Maria Cristina Vidal; Duarte, Rafael Silva

    2014-01-01

    Mycobacterium leprae and Mycobacterium tuberculosis antimicrobial resistance has been followed with great concern during the last years, while the need for new drugs able to control leprosy and tuberculosis, mainly due to extensively drug-resistant tuberculosis (XDR-TB), is pressing. Our group recently showed that M. leprae is able to induce lipid body biogenesis and cholesterol accumulation in macrophages and Schwann cells, facilitating its viability and replication. Considering these previous results, we investigated the efficacies of two statins on the intracellular viability of mycobacteria within the macrophage, as well as the effect of atorvastatin on M. leprae infections in BALB/c mice. We observed that intracellular mycobacteria viability decreased markedly after incubation with both statins, but atorvastatin showed the best inhibitory effect when combined with rifampin. Using Shepard's model, we observed with atorvastatin an efficacy in controlling M. leprae and inflammatory infiltrate in the BALB/c footpad, in a serum cholesterol level-dependent way. We conclude that statins contribute to macrophage-bactericidal activity against Mycobacterium bovis, M. leprae, and M. tuberculosis. It is likely that the association of statins with the actual multidrug therapy effectively reduces mycobacterial viability and tissue lesion in leprosy and tuberculosis patients, although epidemiological studies are still needed for confirmation. PMID:25049257

  8. [PROSPECTS FOR CLINICAL APPLICATION OF STATINS IN GASTROENTEROLOGY].

    PubMed

    Svistunov, A A; Osadchuk, M A; Kireeva, N V

    2016-01-01

    We present the analytical review of non-cardial effects of statins used in gastroenterology with the data illustrating their high antibacterial activity as exemplified by combined therapy of conditions associated with Helicobacter pylori infection. Special emphasis is laid on anti-inflammatory and oncoprotective mechanisms of statin action that are successfully made use of for the treatment of liver, pancreas, gallbladder, and biliary system diseases. Prophylactic aspects of statin application to overcome an addiction to fast food are discussed. PMID:27522720

  9. Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors

    PubMed Central

    Chapman, M. John; Le Goff, Wilfried; Guerin, Maryse; Kontush, Anatol

    2010-01-01

    Subnormal plasma levels of high-density lipoprotein cholesterol (HDL-C) constitute a major cardiovascular risk factor; raising low HDL-C levels may therefore reduce the residual cardiovascular risk that frequently presents in dyslipidaemic subjects despite statin therapy. Cholesteryl ester transfer protein (CETP), a key modulator not only of the intravascular metabolism of HDL and apolipoprotein (apo) A-I but also of triglyceride (TG)-rich particles and low-density lipoprotein (LDL), mediates the transfer of cholesteryl esters from HDL to pro-atherogenic apoB-lipoproteins, with heterotransfer of TG mainly from very low-density lipoprotein to HDL. Cholesteryl ester transfer protein activity is elevated in the dyslipidaemias of metabolic disease involving insulin resistance and moderate to marked hypertriglyceridaemia, and is intimately associated with premature atherosclerosis and high cardiovascular risk. Cholesteryl ester transfer protein inhibition therefore presents a preferential target for elevation of HDL-C and reduction in atherosclerosis. This review appraises recent evidence for a central role of CETP in the action of current lipid-modulating agents with HDL-raising potential, i.e. statins, fibrates, and niacin, and compares their mechanisms of action with those of pharmacological agents under development which directly inhibit CETP. New CETP inhibitors, such as dalcetrapib and anacetrapib, are targeted to normalize HDL/apoA-I levels and anti-atherogenic activities of HDL particles. Further studies of these CETP inhibitors, in particular in long-term, large-scale outcome trials, will provide essential information on their safety and efficacy in reducing residual cardiovascular risk. PMID:19825813

  10. The lower the better? Reviewing the evidence for more aggressive cholesterol reduction and goal attainment.

    PubMed

    Stein, Evan

    2002-04-01

    There is considerable evidence that more aggressive lowering of low-density lipoprotein (LDL) cholesterol is associated with increased benefits in reducing atherosclerotic disease burden, supporting the notion of 'the lower, the better.' However, achievement of currently recommended goals has proven difficult with lipid-lowering agents at the commonly used doses. Current options for achieving greater LDL cholesterol reductions include use of high doses of the most effective of the available statins and use of high or moderate statin doses in combination with agents that work in a complementary manner (e.g. bile acid sequestrants or niacin). Near-term options may include statins with increased LDL cholesterol-lowering effectiveness and better-tolerated secondary agents that can be combined with statin therapy. Rosuvastatin (Crestor, AstraZeneca) is a new statin that may prove to be of considerable utility in achieving greater LDL cholesterol reductions than are currently possible with existing statins. Recent phase III clinical trials have shown that this agent produces significantly greater LDL cholesterol reductions than atorvastatin, simvastatin, or pravastatin in patients with primary hypercholesterolemia and significantly greater reductions than the maximal dose of atorvastatin in patients with familial hypercholesterolemia. PMID:11976073

  11. Statin induced diabetes and its clinical implications

    PubMed Central

    Aiman, Umme; Najmi, Ahmad; Khan, Rahat Ali

    2014-01-01

    Statins are one of the most commonly used drugs in the world based on their potential to prevent adverse cardiovascular events. These cholesterol-lowering drugs received a US Food and Drug Administration warning, in February 2012, regarding increased risk of incident diabetes and impaired glycemic control in patients who already have diabetes. The possible association of diabetes with statin therapy has started a wave of discussion in the medical community. A number of meta-analyses conducted in recent years have demonstrated that the association is real although causality has not been proved yet. Individual statins differ with respect to their diabetogenic property; women and elderly persons appear to be at increased risk. Various aspects of statin's adverse effect on glycemic control remain to be explored. As further research in this area continues, physicians might still take some precautions to make risk benefit ratio more favorable for the patients. PMID:25210397

  12. Statin-induced myopathies.

    PubMed

    Tomaszewski, Michał; Stępień, Karolina M; Tomaszewska, Joanna; Czuczwar, Stanisław J

    2011-01-01

    Statins are considered to be safe, well tolerated and the most efficient drugs for the treatment of hypercholesterolemia, one of the main risk factor for atherosclerosis, and therefore they are frequently prescribed medications. The most severe adverse effect of statins is myotoxicity, in the form of myopathy, myalgia, myositis or rhabdomyolysis. Clinical trials commonly define statin toxicity as myalgia or muscle weakness with creatine kinase (CK) levels greater than 10 times the normal upper limit. Rhabdomyolysis is the most severe adverse effect of statins, which may result in acute renal failure, disseminated intravascular coagulation and death. The exact pathophysiology of statin-induced myopathy is not fully known. Multiple pathophysiological mechanisms may contribute to statin myotoxicity. This review focuses on a number of them. The prevention of statin-related myopathy involves using the lowest statin dose required to achieve therapeutic goals and avoiding polytherapy with drugs known to increase systemic exposure and myopathy risk. Currently, the only effective treatment of statin-induced myopathy is the discontinuation of statin use in patients affected by muscle aches, pains and elevated CK levels. PMID:22001973

  13. PLEIOTROPIC EFFECTS OF STATINS

    PubMed Central

    Liao, James K.; Laufs, Ulrich

    2009-01-01

    Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. Indeed, recent studies indicate that some of the cholesterol-independent or “pleiotropic” effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Furthermore, statins have beneficial extrahepatic effects on the immune system, CNS, and bone. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in mediating the pleiotropic effects of statins. PMID:15822172

  14. [Statins in primary prevention: how to share the decision?].

    PubMed

    Nanchen, David; Vonnez, Jean-Luc; Selby, Kevin; Auer, Reto; Cornuz, Jacques

    2015-11-25

    Long-term treatment of hypercholesterolemia with statins diminishes the risk of cardiovascular events. Statins are recommended in secondary prevention of cardiovascular disease. In the absence of preexisting cardiovascular disease, the decision to start a statin or not is most often made by the general practitioner and his patient. An interactive decision aid, developed by the Mayo Clinic, has just been translated in French and adapted to the Swiss epidemiology of cardiovascular risk factors, with the aim of promoting shared decision-making. This paper reviews the conditions and potential benefits of shared decision-making about statin therapy in primary prevention. PMID:26742352

  15. Cardiovascular Disease, Statins, and HIV.

    PubMed

    Eckard, Allison Ross; Meissner, Eric G; Singh, Inderjit; McComsey, Grace A

    2016-10-01

    Human immunodeficiency virus (HIV)-infected patients are at an increased risk of serious, non-AIDS-defining comorbidities, even in the setting of viral suppression with combination antiretroviral therapy. This increased risk is due in part to immune dysfunction and heightened inflammation and immune activation associated with chronic HIV infection. Statins have wide-reaching immunomodulatory effects, and their use in the HIV-infected population may be of particular benefit. In this article, we review the pathogenesis of increased inflammation during HIV infection and how it contributes to the risk of cardiovascular disease among HIV-infected individuals. We then we review the immunomodulatory effects of statins and how they may attenuate the risk of cardiovascular disease and other comorbidities in this unique patient population. PMID:27625435

  16. Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate.

    PubMed

    Hobbs, F D Richard; Banach, Maciej; Mikhailidis, Dimitri P; Malhotra, Aseem; Capewell, Simon

    2016-01-01

    The most prescribed medications in the world are statins, lipid modifiers that have been available for over 25 years and amongst the most investigated of all drug classes. With over a million patient years of trial data and publications in the most prestigious medical journals, it is remarkable that quite so much debate remains as to their place in healthcare. They have had a bittersweet passage, with vocal concerns over their possible risks, from suicide to cancer, and allegations that they do not work in women or the elderly, to statements that the whole published dataset, on over 200,000 patients consenting to enter trials, was fatally compromised by being industry-funded by and large. On the other side, there have been billions of dollars spent on generating their evidence base followed by promotion which has returned that investment many times over in profits, and a powerful scientific lobby that argue they are wonder drugs and that continued nihilism on their value risks patient lives. So who is right? PMID:26769594

  17. A VOYAGER Meta-Analysis of the Impact of Statin Therapy on Low-Density Lipoprotein Cholesterol and Triglyceride Levels in Patients With Hypertriglyceridemia.

    PubMed

    Karlson, Björn W; Palmer, Michael K; Nicholls, Stephen J; Lundman, Pia; Barter, Philip J

    2016-05-01

    Elevated triglyceride (TG) levels are associated with increased cardiovascular disease risk. In patients with mild-to-moderate hypertriglyceridemia, defined by the European Atherosclerosis Society Consensus Panel as a TG level of 177 to 885 mg/dl (2.0 to 10.0 mmol/L), low-density lipoprotein cholesterol (LDL-C) reduction remains the primary treatment goal. Using data from the indiVidual patient meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin and simvastatin (VOYAGER) meta-analysis, we analyzed LDL-C and TG reductions in patients with baseline TG ≥177 mg/dl (≥2.0 mmol/L). Least squares mean percentage change from baseline in LDL-C and TG was compared using 15,800 patient exposures to rosuvastatin 5 to 40 mg, atorvastatin 10 to 80 mg, and simvastatin 10 to 80 mg in patients with baseline TG ≥177 mg/dl (≥2.0 mmol/L). Comparisons were made using mixed-effects models with data only from studies directly comparing treatments by randomized design. Mean LDL-C reductions ranged from -26.9% to -55.5%. Rosuvastatin 10 to 40 mg resulted in significantly greater LDL-C reductions than equal or double doses of atorvastatin and simvastatin (p <0.05). Mean TG reductions ranged from -15.1% to -31.3%. Rosuvastatin 10 mg resulted in significantly greater TG reductions than atorvastatin 10 mg (p <0.05). Rosuvastatin 20 and 40 mg resulted in TG reductions similar to those with equal doses of atorvastatin. Rosuvastatin 10 to 40 mg resulted in significantly greater TG reductions than equal or double doses of simvastatin (p <0.05). In conclusion, in patients with hypertriglyceridemia, LDL-C reduction was substantial and dependent on the choice and dose of statin. TG reduction was numerically less than for LDL-C, and additional TG-lowering therapy may be considered to further reduce residual cardiovascular risk. PMID:26969416

  18. SAFETY AND UTILITY OF ACUTE ELECTROCONVULSIVE THERAPY FOR AGITATION AND AGGRESSION IN DEMENTIA

    PubMed Central

    Acharya, Deepa; Harper, David G.; Achtyes, Eric D.; Seiner, Stephen J.; Mahdasian, Jack A.; Nykamp, Louis J.; Adkison, Lesley; Van der Schuur White, Lori; McClintock, Shawn M.; Ujkaj, Manjola; Davidoff, Donald A.; Forester, Brent P.

    2015-01-01

    Objective Agitation and aggression are among the most frequent and disruptive behavioral complications of dementia that contribute to increased cost of care, hospitalization, caregiver burden, and risk of premature institutionalization. This current study examined the safety and efficacy of electroconvulsive therapy (ECT) as a treatment for behavioral disturbances in dementia. We hypothesized that ECT would result in reduced agitated and aggressive behaviors between baseline and discharge. Methods Twenty-three participants admitted to McLean Hospital (Belmont, MA) and Pine Rest Christian Mental Health Services (Grand Rapids, MI), with a diagnosis of dementia who were referred for ECT to treat agitation and/or aggression, were enrolled in the study. We administered the Cohen-Mansfield Agitation Inventory (CMAI)-short form, Neuropsychiatric Inventory (NPI)-Nursing Home Version, Cornell Scale for Depression in Dementia (CSDD), and the Clinical Global Impression Scale (CGI) at baseline, during, and after the ECT course. Results Regression analyses revealed a significant decrease from baseline to discharge on the CMAI (F(4, 8) =13.3; p=0.006) and NPI (F(4, 31)= 14.6; p<0.001). There was no statistically significant change in scores on the CSDD. The CGI scores on average changed from a rating of “markedly agitated/aggressive” at baseline to “borderline agitated/aggressive” at discharge. Treatment with ECT was well tolerated by most participants; discontinuation of ECT occurred for two participants due to recurrence of agitation and for three participants due to adverse events. Conclusions ECT may be a safe treatment option to reduce symptoms of agitation and aggression in patients with dementia whose behaviors are refractory to medication management. PMID:24838521

  19. Targeted therapy in uterine serous carcinoma: an aggressive variant of endometrial cancer

    PubMed Central

    Black, Jonathan D; English, Diana P; Roque, Dana M; Santin, Alessandro D

    2014-01-01

    Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial cancer. Although it only represents less than 10% of all cases, it accounts for a disproportionate number of deaths from endometrial cancer. Comprehensive surgical staging followed by carboplatin and paclitaxel chemotherapy represents the mainstay of USC therapy. Vaginal cuff brachytherapy is also of potential benefit in USC. Recent whole-exome sequencing studies have demonstrated gain of function of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and cyclin E/FBXW7 oncogenic pathways in a large number of USCs. These results emphasize the relevance of these novel therapeutic targets for biologic therapy of chemotherapy-resistant recurrent USC. PMID:24328598

  20. Photodynamic therapy in the treatment of aggressive periodontitis: A systematic review

    PubMed Central

    Doufexi, Aikaterini-Ellisavet

    2016-01-01

    Background Aggressive periodontitis (AgP) is a severe form of periodontal diseases with rapid destruction of the supporting bone around teeth. The efficacy of PDT in suppressing periodontal pathogens may be crucial in adopting new protocols for the treatment of AgP. Thus, the aim of this systematic review was to investigate the possible role of PDT in the treatment of AgP as an adjunctive therapy or monotherapy. Material and Methods A systematic search of the literature was performed. Additionally, the references from all the selected full-text studies were searched for relevant articles. Two reviewers screened independently titles and abstracts or full text copies. Quality assessment of all the included studies was held. Results Initial screening of electronic databases yielded 418 potentially relevant publications. After screening of the titles and full-text examination, five studies were included in the systematic review. Four publications evaluated the effects of PDT adjunctive to SRP in patients with AgP: two of them compared the clinical outcomes of SRP and PDT with a control group that received therapy with SRP and antibiotics (metronidazole and amoxicillin); two publications included SRP and PDT in the test group, and SRP alone in the control group. In one study, PDT was tested as a monotherapy compared with SRP alone. Conclusions Within the limitations of this review, PDT may exhibit a beneficial role in the therapy of aggressive periodontitis after repeated applications. In the future, more methodologically sound, long-term randomized clinical trials are needed to be conducted. Key words:Photodynamic therapy, periodontitis, systematic review. PMID:26595837

  1. Statins and cancers.

    PubMed

    Stryjkowska-Góra, Aleksandra; Karczmarek-Borowska, Bożenna; Góra, Tomasz; Krawczak, Katarzyna

    2015-01-01

    Statins (inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) are a group of drugs used to treat lipid disorders. They inhibit cholesterol synthesis at an early stage of the biosynthesis pathway, thus eliminating numerous metabolites involved in the cycle. Numerous studies point to different possible effects of statins on cancer cells. Statins inhibit growth of a tumor, invasion and metastasis formation. They block the production of isoprenoids, which are necessary for post-translational modifications of many proteins, including those involved in normal cell signaling. They also contribute to the reduction in the expression of vascular endothelial growth factor, sensitize tumor cells to NK cell activity, and modify the body inflammatory response. Due to different pharmacokinetic properties of individual statins, they may have opposite effects on the risk of cancer. Currently, most information on the effects of statins on the risk of developing cancer is obtained from observational studies. The studies have different results depending on the location of cancer. The protective effect of statins was observed in the meta-analysis of numerous studies including prostate cancer, stomach cancer, esophagus cancer, and hepatocellular carcinoma; however, it has not yet been confirmed that statins influence the risk of developing colorectal cancer, breast cancer, or lung cancer. The protective effect of statins on the development of many kinds of cancer can be a valuable and easy way to reduce morbidity. However, further research is necessary to thoroughly determine the value of this group of drugs. PMID:26557755

  2. Statin Therapy Is Associated with Improved Survival in Patients with Non-Serous-Papillary Epithelial Ovarian Cancer: A Retrospective Cohort Analysis

    PubMed Central

    Habis, Mohammed; Wroblewski, Kristen; Bradaric, Michael; Ismail, Nadia; Yamada, S. Diane; Litchfield, Lacey; Lengyel, Ernst; Romero, Iris L.

    2014-01-01

    Aim To determine whether statin use is associated with improved epithelial ovarian cancer (OvCa) survival. Methods This is a single-institution retrospective cohort review of patients treated for OvCa between 1992 and 2013. Inclusion criteria were International Federation of Gynecology and Obstetrics (FIGO) stage I–IV OvCa. The primary exposures analyzed were hyperlipidemia and statin use. The primary outcomes were progression-free survival (PFS) and disease-specific survival (DSS). Results 442 patients met inclusion criteria. The cohort was divided into three groups: patients with hyperlipidemia who used statins (n = 68), patients with hyperlipidemia who did not use statins (n = 28), and patients without hyperlipidemia (n = 346). OvCa outcomes were evaluated. When we analyzed the entire cohort, we found no significant differences in PFS or DSS among the groups. The median PFS for hyperlipidemics using statins, hyperlipidemics not using statins, and non-hyperlipidemics was 21.7, 13.6, and 14.7 months, respectively (p = 0.69). Median DSS for hyperlipidemics using statins, hyperlipidemics not using statins, and non-hyperlipidemics was 44.2, 75.7, and 41.5 months, respectively (p = 0.43). These findings did not change after controlling for confounders. However, a secondary analysis revealed that, among patients with non-serous-papillary subtypes of OvCa, statin use was associated with a decrease in hazards of both disease recurrence (adjusted HR = 0.23, p = 0.02) and disease-specific death (adjusted HR = 0.23, p = 0.04). To augment the findings in the retrospective cohort, the histology-specific effects of statins were also evaluated in vitro using proliferation assays. Here, statin treatment of cell lines resulted in a variable level of cytotoxicity. Conclusion Statin use among patients with non-serous-papillary OvCa was associated with improvement in both PFS and DSS. PMID:25118694

  3. Empirical Comparison of Three Treatments for Adolescent Males with Physical and Sexual Aggression: Mode Deactivation Therapy, Cognitive Behavior Therapy and Social Skills Training

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.; Jennings, Jerry L.; Murphy, Christopher J.; Hunter, Linda A.; Siv, Alexander M.

    2005-01-01

    This research study compared the efficacy of three treatment methodologies for adolescent males in residential treatment with conduct disorders and/or personality dysfunctions and documented problems with physical and sexual aggression. The results showed that Mode Deactivation Therapy, an advanced form of cognitive behavioral therapy based on…

  4. Adaptation to statins restricts human tumour growth in Nude mice

    PubMed Central

    2011-01-01

    Background Statins have long been used as anti-hypercholesterolemia drugs, but numerous lines of evidence suggest that they may also bear anti-tumour potential. We have recently demonstrated that it was possible to isolate cancer cells adapted to growth in the continuous presence of lovastatin. These cells grew more slowly than the statin-sensitive cells of origin. In the present study, we compared the ability of both statin-sensitive and statin-resistant cells to give rise to tumours in Nude mice. Methods HGT-1 human gastric cancer cells and L50 statin-resistant derivatives were injected subcutaneously into Nude mice and tumour growth was recorded. At the end of the experiment, tumours were recovered and marker proteins were analyzed by western blotting, RT-PCR and immunohistochemistry. Results L50 tumours grew more slowly, showed a strong decrease in cyclin B1, over-expressed collagen IV, and had reduced laminin 332, VEGF and CD34 levels, which, collectively, may have restricted cell division, cell adhesion and neoangiogenesis. Conclusions Taken together, these results showed that statin-resistant cells developed into smaller tumours than statin-sensitive cells. This may be reflective of the cancer restricting activity of statins in humans, as suggested from several retrospective studies with subjects undergoing statin therapy for several years. PMID:22107808

  5. Maintenance therapy with interferon-alpha 2b, cyclophosphamide, and prednisone in aggressive diffuse large cell lymphoma.

    PubMed

    Avilés, Agustin; Neri, Natividad; Nambo, M Jesús; Castañeda, Claudia; Talavera, Alejandra; Huerta-Guzmán, Judith; Murillo, Edgar

    2004-04-01

    Maintenance therapy in patients with aggressive malignant lymphoma using biological modifiers remains uncertain. We conducted a controlled clinical trial to evaluate the efficacy and toxicity of interferon-alpha 2b, cyclophosphamide, and prednisone as maintenance therapy in patients with aggressive diffuse large B cell lymphomas in complete remission after aggressive chemotherapy. In an intent-to-treat analysis, 169 patients were eligible for this study; the end points were event-free survival (EFS) and overall survival (OS). With a median follow-up of 49.3 months, no statistical differences were observed and actuarial curves at 5 years showed that EFS was 71% (95% confidence interval [CI], 63-79%) for patients who received maintenance compared to 63% (95% CI, 59-71%) for patients in control group (p = 0.05). No statistical differences were observed in OS between maintenance arm: 84% (95% CI, 78-89%) and control group 83% (95% CI, 77-88%) in control group (p = 0.2). All patients received the maintenance therapy as planned and in time, thus dose intensity was considered 1.0 in all cases. Acute toxicity was mild, and no delay or suspension of treatment was necessary. Late toxicity was not evident until now. We conclude that use of maintenance therapy combining interferon-alpha 2b, cyclophosphamide, and prednisone is not useful in patients with aggressive lymphoma if they had been treated with aggressive combined chemotherapy. PMID:15186737

  6. Management of a mixed overdose of calcium channel blockers, β-blockers and statins

    PubMed Central

    Thakrar, Reena; Shulman, Rob; Bellingan, Geoff; Singer, Mervyn

    2014-01-01

    We describe a case of extreme mixed overdose of calcium channel blockers, β-blockers and statins. The patient was successfully treated with aggressive resuscitation including cardiac pacing and multiorgan support, glucagon and high-dose insulin for toxicity related to calcium channel blockade and β-blockade, and ubiquinone for treating severe presumed statin-induced rhabdomyolysis and muscle weakness. PMID:24907219

  7. Prospects of statins in Parkinson disease.

    PubMed

    Roy, Avik; Pahan, Kalipada

    2011-06-01

    Parkinson disease (PD) is second only to Alzheimer disease as the most common neurodegenerative disorder in humans. Despite intense investigations, no effective therapy is available to halt the progression of PD. Although statins are widely used cholesterol-lowering drugs throughout the world, recent studies suggest that these drugs modulate neurodegeneration-related signaling processes and may be beneficial for PD. Simvastatin is the most potent statin in crossing the blood-brain barrier, and this particular statin drug negatively correlates with the incidence of PD and shows efficacy in animal models of PD. However, PD mainly occurs in the aging population, who are more vulnerable to cholesterol or lipid-related disorders, raising questions whether this possible beneficial effect of statins in PD patients is cholesterol dependent or cholesterol independent. This article presents data on the therapeutic efficacy of simvastatin in a chronic MPTP model of PD, reviews recent literature, and discusses the pros and cons of statin therapy in PD. PMID:21252380

  8. Statins for post resuscitation syndrome.

    PubMed

    Kämäräinen, Antti; Virkkunen, Ilkka; Silfvast, Tom; Tenhunen, Jyrki

    2009-07-01

    After sudden cardiac arrest, successful resuscitation and return of spontaneous circulation, a multi-faceted ischaemia/reperfusion related disorder develops. This condition now known as post resuscitation syndrome is characterised by marked increases in the inflammatory response and changes in coagulation profile and vascular reactivity. Additionally, the production of reactive oxygen species and activation of cytotoxic cascades of metabolism add to these injury mechanisms resulting in multiorgan perfusion deficits and dysfunction. Especially in the cerebrum these injuries may be the cause of significant morbidity and mortality. Recent evidence has shown that statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) exert numerous beneficial effects in cardiovascular diseases irrespective of the lipid status. Remarkably, these pleiotropic effects seem to extended beyond cardiovascular diseases such as immunomodulative and antioxidative properties. We hypothesised that administration of statins early in the post resuscitation phase would prove beneficial in the resuscitated patient via several pleiotropic effects. These include inhibition of excessive coagulation and inflammatory response, suppression of oxygen radical production and improved vascular reactivity. The discussed effects are mediated via multiple pathways activated in the cardiac arrest victim, to which statins have been shown to have a beneficial modulating effect in experimental settings and non-cardiac arrest patients. To test this hypothesis in clinical practice, a randomized, controlled trial with sufficient power and standardised post resuscitation treatment would be necessary. The generally good tolerance of statin therapy with minimal adverse effects would support this experiment, although a parenteral form of the drug to ensure adequate dosage might be a prerequisite. PMID:19254829

  9. On-Statin Resistin, Leptin, and Risk of Recurrent Coronary Events After Hospitalization for an Acute Coronary Syndrome (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Study).

    PubMed

    Khera, Amit V; Qamar, Arman; Murphy, Sabina A; Cannon, Christopher P; Sabatine, Marc S; Rader, Daniel J

    2015-09-01

    Resistin is an adipokine secreted by macrophages and inflammatory cells linked to insulin resistance and inflammation. Leptin is an adipokine regulator of appetite and obesity. Although circulating levels of both have been associated with atherosclerosis, few data have reported their relation to coronary events in the context of statin therapy. This study measured on-statin levels of both resistin and leptin through enzyme-linked immunosorbent assay in a nested case-control cohort (n = 176 cases with coronary death, myocardial infarction, or unstable angina pectoris observed in follow-up matched 1:1 to 176 controls) derived from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 study, a randomized controlled trial of atorvastatin 80 mg/day versus pravastatin 40 mg/day in patients with a recent acute coronary syndrome. Resistin demonstrated a moderate association with high-sensitivity C-reactive protein (hsCRP; Spearman rho = 0.25, p <0.0001). On-statin resistin levels were linked to recurrent coronary events in conditional logistic regression analysis adjusted for additional risk factors including hsCRP and history of diabetes (tertile 3 vs 1 adjusted odds ratio 2.08; 95% confidence interval [CI] 1.04 to 4.19). An additive risk was noted when patients were stratified by resistin and glycated hemoglobin levels. In contrast, leptin levels were associated with obesity, diabetes, triglycerides, and hsCRP (p <0.001 for each) but demonstrated no association with recurrent coronary events (tertile 3 vs 1 adjusted odds ratio 0.72; 95% CI 0.28 to 1.83). In conclusion, on-statin resistin, but not leptin, is an independent marker of residual risk for recurrent coronary events in patients after hospitalization for an acute coronary syndrome. PMID:26119654

  10. Unusually Aggressive Primary Testicular Diffuse Large B Cell Lymphoma with Post Therapy Extensive Metastasis

    PubMed Central

    Goel, Shalini; Mohapatra, Ishani; Gajendra, Smeeta; Gupta, Sunil

    2016-01-01

    Primary Testicular Lymphoma (PTL) is a rare intermediate to high grade tumour, diffuse large cell being the most common type. Unlike nodal Diffuse Large B-Cell Lymphoma (DLBCL), testicular DLBCL has a less aggressive course and better prognosis. Metastasis is uncommon in testicular DLBCL. Commonly involved sites are contralateral testes, Waldeyer’s ring, skin, lung, Central Nervous System (CNS) and prostate, however the kidneys, liver, bone marrow, pleura and bones are more rarely involved. We report a case of testicular DLBCL which has metastasized to skin and bone marrow with an aggressive clinical course in a year, in-spite of combined modality of therapy given to the patient. Bone marrow infiltration is common and well documented with nodal DLBCL, however there is no published literature for simultaneous bone marrow and skin infiltration in testicular DLBCL till date. Other large studies done in the west have shown that distinct metastasis is usually common but the median progression-free survival is usually in years. This case stresses on shorter period of progression after standard treatment protocol in this part of the world, thus highlighting the need for other extensive studies to define specific treatment protocol for testicular DLBCL.

  11. Which Patients With Mantle Cell Lymphoma Do Not Need Aggressive Therapy.

    PubMed

    Ruan, Jia; Martin, Peter

    2016-06-01

    Mantle cell lymphoma (MCL) is a heterogeneous disease, and it has been well-established over the last decade that a subset of patients can have indolent presentation. It is therefore important to adopt a risk-stratified approach in order to minimize unnecessary toxicities while maximizing survival and quality of life in selected MCL patients. This review provides an up-to-date assessment of clinical and pathologic entities associated with indolent disease course and delineates available biomarkers with predictive significance. Initial treatment decisions should be guided by risk assessment to discern patients who might do well with deferred therapy, from those who would require treatment with non-aggressive first-line regimens. PMID:27068437

  12. The role of statins in the setting of HIV infection.

    PubMed

    Eckard, Allison Ross; McComsey, Grace A

    2015-09-01

    HIV-infected individuals are at an increased risk of cardiovascular disease (CVD) and other HIV-related co-morbidities. This is due in part to dyslipidemia associated with antiretroviral therapy and increased inflammation and immune activation from chronic HIV infection. Statins not only have potent lipid-lowering properties but are also anti-inflammatory and immunomodulators. Studies suggest that statin therapy in the HIV-infected population may decrease the risk of CVD and other non-AIDS-defining co-morbidities. This review summarizes the recent literature on statin use in the HIV setting. PMID:26126687

  13. Effect of Early Statin Treatment in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction

    PubMed Central

    Sim, Doo Sun; Cho, Kyung Hoon; Ahn, Youngkeun; Kim, Young Jo; Chae, Shung Chull; Hong, Taek Jong; Seong, In Whan; Chae, Jei Keon; Kim, Chong Jin; Cho, Myeong Chan; Rha, Seung-Woon; Bae, Jang Ho; Seung, Ki Bae; Park, Seung Jung

    2013-01-01

    Background and Objectives The benefit of early statin treatment following acute myocardial infarction (MI) complicated with cardiogenic shock (CS) has not been well studied. We sought to assess the effect of early statin therapy in patients with CS complicating acute MI. Subjects and Methods We studied 553 statin-naive patients with acute MI and CS (Killip class IV) who underwent revascularization therapy between November 2005 and January 2008 at 51 hospitals in the Korea Acute Myocardial Infarction Registry. Patients were divided into 2 groups: those who received statins during hospitalization (n=280) and those who did not (n=273). The influence of statin treatment on a 12-month clinical outcome was examined using a matched-pairs analysis (n=200 in each group) based on the propensity for receiving statin therapy during hospitalization. Results Before adjustment, patients receiving statin, compared to those not receiving statin, had a more favorable clinical profile, were less likely to suffer procedural complications, and more likely to receive adequate medical therapy. Patients receiving statin had lower unadjusted in-hospital mortality and composite rate of mortality, MI, and repeat revascularization at 12 months, which remained significantly lower after adjustment for patient risk, procedural characteristics, and treatment propensity. Conclusion In CS patients with acute MI undergoing revascularization therapy, early statin treatment initiated during hospitalization was associated with lower rates of in-hospital death and 12-month adverse cardiac events. PMID:23508129

  14. MedlinePlus: Statins

    MedlinePlus

    ... Clinical Trials. Article: Perioperative Rosuvastatin in Cardiac Surgery. Article: In primary prevention, the ACC/AHA risk-based approach predicted ASCVD better... Statins -- see more articles Find an Expert American Heart Association Food and ...

  15. Statins and breast cancer prognosis: evidence and opportunities

    PubMed Central

    Ahern, Thomas P.; Lash, Timothy L.; Damkier, Per; Christiansen, Peer M.; Cronin-Fenton, Deirdre P.

    2014-01-01

    SUMMARY Much preclinical and epidemiologic evidence supports anticancer effects of HMG-CoA reductase inhibitors (statins). Epidemiologic evidence does not support an association between statin use and reduced breast cancer incidence, but does support a protective effect of statins—particularly simvastatin—on breast cancer prognosis. We argue that the current evidence base is sufficient to justify a clinical trial of breast cancer adjuvant therapy with statins. We advocate for such a trial to be initiated without delay. If a protective effect of statins on breast cancer recurrence is supported by trial evidence, then the indications for a safe, well-tolerated, and in expensive treatment can be expanded to improve outcomes for breast cancer survivors. We discuss several design opportunities—including candidate predictive biomarkers of statin safety and efficacy—and offer solutions to key challenges to enrolment, follow-up, and analysis of such a trial. PMID:25186049

  16. The role of statins in chronic heart failure.

    PubMed

    Szyguła-Jurkiewicz, Bożena; Szczurek, Wioletta; Król, Bogumiła; Zembala, Marian

    2014-09-01

    The efficacy of statins in reducing morbidity and mortality in patients with documented coronary artery disease is unquestionable. However, in chronic heart failure (CHF), evidence regarding the beneficial effects of statin therapy remains contradictory. Although numerous retrospective studies have demonstrated improved prognosis in CHF patients treated with statins, two randomized trials, GISSI-HF and CORONA, have not confirmed the benefit of rosuvastatin in this group of patients. The benefits of using statins in CHF probably result mostly from their pleiotropic action, including the improvement of endothelial function, the inhibition of neurohormonal activation, and the reduction of proinflammatory activation. On the other hand, it has been recognized that low cholesterol is associated with worse morbidity and mortality in patients with CHF. It appears that it is necessary to conduct further randomized clinical trials using different kinds of statins in different populations of patients with CHF. PMID:26336439

  17. Influence of Statins on Influenza Vaccine Response in Elderly Individuals.

    PubMed

    Black, Steven; Nicolay, Uwe; Del Giudice, Giuseppe; Rappuoli, Rino

    2016-04-15

    Influenza vaccination strategies have targeted elderly individuals because they are at high risk of disease complications and mortality. Statins are a class of drugs used to treat hypercholesterolemia and are frequently used in the elderly population to reduce the risk of cardiovascular disease. However, statins are also known to have immunomodulatory effects that could impact influenza vaccine response. In a post hoc analysis, we performed a cross-sectional observational study nested within a comparative immunogenicity clinical trial of adjuvanted versus unadjuvanted influenza vaccine in elderly persons to evaluate the influence of statin therapy on the immune response to vaccination. Overall, data on >5000 trial participants were available for analysis. Comparison of hemagglutination-inhibiting geometric mean titers to influenza A(H1N1), A(H3N2), and B strains revealed that titers were 38% (95% confidence interval [CI], 27%-50%), 67% (95% CI, 54%-80%), and 38% (95% CI, 28%-29%) lower, respectively, in subjects receiving chronic statin therapy, compared with those not receiving chronic statin therapy. This apparent immunosuppressive effect of statins on the vaccine immune response was most dramatic in individuals receiving synthetic statins. These effects were seen in both the adjuvanted and unadjuvanted vaccine groups in the clinical trial. These results, if confirmed, could have implications both for future clinical trials design, as well as for vaccine use recommendations for elderly individuals. PMID:26516142

  18. Relations of Change in Plasma Levels of LDL‐C, Non‐HDL‐C and apoB With Risk Reduction From Statin Therapy: A Meta‐Analysis of Randomized Trials

    PubMed Central

    Thanassoulis, George; Williams, Ken; Ye, Keying; Brook, Robert; Couture, Patrick; Lawler, Patrick R.; de Graaf, Jacqueline; Furberg, Curt D.; Sniderman, Allan

    2014-01-01

    Background Identifying the best markers to judge the adequacy of lipid‐lowering treatment is increasingly important for coronary heart disease (CHD) prevention given that several novel, potent lipid‐lowering therapies are in development. Reductions in LDL‐C, non‐HDL‐C, or apoB can all be used but which most closely relates to benefit, as defined by the reduction in events on statin treatment, is not established. Methods and Results We performed a random‐effects frequentist and Bayesian meta‐analysis of 7 placebo‐controlled statin trials in which LDL‐C, non‐HDL‐C, and apoB values were available at baseline and at 1‐year follow‐up. Summary level data for change in LDL‐C, non‐HDL‐C, and apoB were related to the relative risk reduction from statin therapy in each trial. In frequentist meta‐analyses, the mean CHD risk reduction (95% CI) per standard deviation decrease in each marker across these 7 trials were 20.1% (15.6%, 24.3%) for LDL‐C; 20.0% (15.2%, 24.7%) for non‐HDL‐C; and 24.4% (19.2%, 29.2%) for apoB. Compared within each trial, risk reduction per change in apoB averaged 21.6% (12.0%, 31.2%) greater than changes in LDL‐C (P<0.001) and 24.3% (22.4%, 26.2%) greater than changes in non‐HDL‐C (P<0.001). Similarly, in Bayesian meta‐analyses using various prior distributions, Bayes factors (BFs) favored reduction in apoB as more closely related to risk reduction from statins compared with LDL‐C or non‐HDL‐C (BFs ranging from 484 to 2380). Conclusions Using both a frequentist and Bayesian approach, relative risk reduction across 7 major placebo‐controlled statin trials was more closely related to reductions in apoB than to reductions in either non‐HDL‐C or LDL‐C. PMID:24732920

  19. [Statins and oxidative stress].

    PubMed

    Filip-Ciubotaru, Florina; Foia, Liliana; Manciuc, Carmen

    2009-01-01

    Statins, as inhibitors of the first regulatory enzyme in cholesterol biosynthesis --HMG-CoA reductase--have a special impact in medical practice. Given their therapeutic efficacy, statins are believed to be the strongest class of agents in the treatment of cardiovascular disorders. Moreover, besides decreasing total cholesterol and C-LDL levels, numerous fundamental and clinical researches suggest that statins also have an antiinflammatory effect. Inflammation is closely related to the production of oxygen-derived reactive species (ROS). The antioxidant effects of statins associated with their ability to block the formation and/or action of ROS may add up their therapeutic efficacy. Within this context, the present paper presents data in literature related to the effect of statins on the expression and activity of NAD(P)H oxidase, activity of the enzymes involved in the antioxidative defence (SOD, GPx, catalase, paraoxonase), and their ability to act as free radical scavengers and oxidized-LDL inhibitors. By their antioxidant properties statins may decrease the atherogenic potential of lipoproteins. PMID:21495335

  20. Statin-induced myotoxicity: pharmacokinetic differences among statins and the risk of rhabdomyolysis, with particular reference to pitavastatin.

    PubMed

    Catapano, Alberico L

    2012-03-01

    3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most widely prescribed therapeutic class of drugs worldwide, with established clinical benefits both in terms of improving serum lipid profiles and reducing cardiovascular events and mortality. Although statins have a favorable risk-to-benefit ratio, they have the potential to cause adverse events which can result in muscular inflammation (myositis), muscle breakdown (rhabdomyolysis) and, ultimately, kidney failure. While the incidence of rhabdomyolysis is approximately 3.4 cases per 100,000 person-years with standard-dose statin therapy, the risk of developing the condition increases substantially at higher therapeutic doses. This effect may be exacerbated by prescribing statins in combination with certain other medications because drug � drug interactions increase statin exposure by interacting with enzymes that would normally be involved in their metabolism and clearance. Co-administration of drugs that inhibit the cytochrome P450 (CYP) enzymes responsible for metabolizing statins, or that interact with the organic anion-transporting polypeptides (OATPs) responsible for statin uptake into hepatocytes, substantially increases the risk of developing myotoxicity. Such effects vary among statins according to their metabolic profile. For example, pitavastatin, a novel statin approved for the treatment of hypercholesterolemia and combined (mixed) dyslipidemia, is not catabolized by CYP3A4, unlike other lipophilic statins, and may be less dependent on the OATP1B1 transporter for its uptake into hepatocytes before clearance. Such differences in drug � drug interaction profiles among available statins offer the possibility of reducing the risk of myotoxicity among high-risk patients. PMID:22022768

  1. Statin Lactonization by Uridine 5'-Diphospho-glucuronosyltransferases (UGTs).

    PubMed

    Schirris, Tom J J; Ritschel, Tina; Bilos, Albert; Smeitink, Jan A M; Russel, Frans G M

    2015-11-01

    Statins are cholesterol-lowering drugs that have proven to be effective in lowering the risk of major cardiovascular events. Although well tolerated, statin-induced myopathies are the most common side effects. Compared to their pharmacologically active acid form, statin lactones are more potent inducers of toxicity. They can be formed by glucuronidation mediated by uridine 5'-diphospho-glucuronosyltransferases (UGTs), but a systematic characterization of subtype specificity and kinetics of lactonization is lacking. Here, we demonstrate for six clinically relevant statins that only UGT1A1, 1A3, and 2B7 contribute significantly to their lactonization. UGT1A3 appeared to have the highest lactonization capacity with marked differences in statin conversion rates: pitavastatin ≫ atorvastatin > cerivastatin > lovastatin > rosuvastatin (simvastatin not converted). Using in silico modeling we could identify a probable statin interaction region in the UGT binding pocket. Polymorphisms in these regions of UGT1A1, 1A3, and 2B7 may be a contributing factor in statin-induced myopathies, which could be used in personalization of statin therapy with improved safety. PMID:26412035

  2. Effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) in Reducing Aggression of Individuals at the Juvenile Correction and Rehabilitation Center

    PubMed Central

    Milani, Atefeh; Nikmanesh, Zahra; Farnam, Ali

    2013-01-01

    Background: In the present era, delinquency in children and adolescents is undoubtedly a difficult and upsetting issue attracting the attention of many experts such as psychologists, sociologists, and criminologists. These experts often try to answer why a number of children and adolescents engage in various crimes such as aggressive and anti-social crimes. They also try to find out how these crimes can be prevented. Objectives: The present study investigates the effectiveness of mindfulness-based cognitive therapy training (MBCT) in reducing aggression in a juvenile correction and rehabilitation center of Zahedan province during years 1991 to 1992. Materials and Methods: This experimental study included an experimental and a control group with a pretest, posttest, and follow-up approach. The Buss and Perry aggression questionnaire (1992) was used for data collection. The sample group included 22 (10 experimental and 12 control groups) adolescent males in a juvenile correction and rehabilitation center of Zahedan province who were selected through a census method. Using a matching method based on the pre-test scores of the aggression questionnaire, they were then divided into two equivalent categories and were randomly assigned to the two groups. Mindfulness-based cognitive training took the group training in 8 sessions administered on experimental group. The follow-up test was conducted two weeks after the end of the posttest sessions. The results were analyzed using ANCOVA. Results: The results of ANCOVA showed that mindfulness-based cognitive training could significantly reduce aggression during posttest and follow-up test phases in the experimental group, compared to the control group (P < 0.01). Moreover, the results indicated the effectiveness of this method in significantly reducing anger, physical aggression, and hostility during posttest and follow-up test phases (P < 0.05). However, no significant reduction was observed in the verbal aggression subscale

  3. Statin Intensity or Achieved LDL? Practice-based Evidence for the Evaluation of New Cholesterol Treatment Guidelines

    PubMed Central

    Ross, Elsie Gyang

    2016-01-01

    Background The recently updated American College of Cardiology/American Heart Association cholesterol treatment guidelines outline a paradigm shift in the approach to cardiovascular risk reduction. One major change included a recommendation that practitioners prescribe fixed dose statin regimens rather than focus on specific LDL targets. The goal of this study was to determine whether achieved LDL or statin intensity was more strongly associated with major adverse cardiac events (MACE) using practice-based data from electronic health records (EHR). Methods We analyzed the EHR data of more than 40,000 adult patients on statin therapy between 1995 and 2013. Demographic and clinical variables were extracted from coded data and unstructured clinical text. To account for treatment selection bias we performed propensity score stratification as well as 1:1 propensity score matched analyses. Conditional Cox proportional hazards modeling was used to identify variables associated with MACE. Results We identified 7,373 adults with complete data whose cholesterol appeared to be actively managed. In a stratified propensity score analysis of the entire cohort over 3.3 years of follow-up, achieved LDL was a significant predictor of MACE outcome (Hazard Ratio 1.1; 95% confidence interval, 1.05–1.2; P < 0.0004), while statin intensity was not. In a 1:1 propensity score matched analysis performed to more aggressively control for covariate balance between treatment groups, achieved LDL remained significantly associated with MACE (HR 1.3; 95% CI, 1.03–1.7; P = 0.03) while treatment intensity again was not a significant predictor. Conclusions Using EHR data we found that on-treatment achieved LDL level was a significant predictor of MACE. Statin intensity alone was not associated with outcomes. These findings imply that despite recent guidelines, achieved LDL levels are clinically important and LDL titration strategies warrant further investigation in clinical trials. PMID:27227451

  4. Survival Benefit of Statins in Hemodialysis Patients Awaiting Renal Transplantation.

    PubMed

    Aftab, Waqas; Gazallo, Juliana; Motabar, Ali; Varadrajan, Padmini; Deedwania, Prakash C; Pai, Ramdas G

    2015-06-01

    End-stage renal disease (ESRD) patients have extraordinarily high cardiovascular risk and mortality, yet the benefit of statins in this population remains unclear based on the randomized trials. We investigated the prognostic value of statins in a large, pure cohort of prospectively recruited patients with ESRD awaiting renal transplantation, and being followed up in a dedicated cardiac clinic. We prospectively collected demographic, clinical, laboratory, and pharmacological data on 423 consecutive ESRD patients on hemodialysis awaiting renal transplantation. Survival analysis was performed as a function of statin therapy. The baseline characteristics were as follows: age 57 ± 11 years, males 64%, diabetes mellitus in 68%, known coronary artery disease in 30%, left ventricular (LV) ejection fraction 61 ± 11%. Over a mean follow-up of 2 years, there were 43 deaths. Adjusted for age, gender, hypertension, body mass index, diabetes mellitus, coronary artery disease, smoking, and treatment with angiotensin converting enzyme inhibitor, β blocker, and antiplatelet medications, statin use was a predictor of lower mortality (hazard ratio 0.30, 95% confidence interval 0.11-0.79, p = 0.01). This beneficial effect of statin was supported by propensity score analysis (p = 0.02) and was consistent across all clinical subgroups. The benefit of statins seemed to be greater in those with LV hypertrophy and smoking. Statin therapy in hemodialysis patients awaiting renal transplant is independently associated with better survival supporting its use in this high-risk population. PMID:26060381

  5. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management

    PubMed Central

    Stroes, Erik S.; Thompson, Paul D.; Corsini, Alberto; Vladutiu, Georgirene D.; Raal, Frederick J.; Ray, Kausik K.; Roden, Michael; Stein, Evan; Tokgözoğlu, Lale; Nordestgaard, Børge G.; Bruckert, Eric; De Backer, Guy; Krauss, Ronald M.; Laufs, Ulrich; Santos, Raul D.; Hegele, Robert A.; Hovingh, G. Kees; Leiter, Lawrence A.; Mach, Francois; März, Winfried; Newman, Connie B.; Wiklund, Olov; Jacobson, Terry A.; Catapano, Alberico L.; Chapman, M. John; Ginsberg, Henry N.; Stroes, Erik; Thompson, Paul D.; Corsini, Alberto; Vladutiu, Georgirene D.; Raal, Frederick J.; Ray, Kausik K.; Roden, Michael; Stein, Evan; Tokgözoğlu, Lale; Nordestgaard, Børge G.; Bruckert, Eric; Krauss, Ronald M.; Laufs, Ulrich; Santos, Raul D.; März, Winfried; Newman, Connie B.; John Chapman, M.; Ginsberg, Henry N.; John Chapman, M.; Ginsberg, Henry N.; de Backer, Guy; Catapano, Alberico L.; Hegele, Robert A.; Kees Hovingh, G.; Jacobson, Terry A.; Leiter, Lawrence; Mach, Francois; Wiklund, Olov

    2015-01-01

    Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7–29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential. PMID:25694464

  6. Estimates of Commercial Population at High Risk for Cardiovascular Events: Impact of Aggressive Cholesterol Reduction

    PubMed Central

    Fitch, Kathryn; Goldberg, Sara W.; Iwasaki, Kosuke; Pyenson, Bruce S.; Kuznik, Andreas; Solomon, Henry A.

    2009-01-01

    Objectives To model the financial and health outcomes impact of intensive statin therapy compared with usual care in a high-risk working-age population (actively employed, commercially insured health plan members and their adult dependents). The target population consists of working-age people who are considered high-risk for cardiovascular disease events because of a history of coronary heart disease. Study Design Three-year event forecast for a sample population generated from the National Health and Nutrition Examination Survey data. Methods Using Framingham risk scoring system, the probability of myocardial infarction or stroke events was calculated for a representative sample population, ages 35 to 69 years, of people at high risk for cardiovascular disease, with a history of coronary heart disease. The probability of events for each individual was used to project the number of events expected to be generated for this population. Reductions in cardiovascular and stroke events reported in clinical trials with aggressive statin therapy were applied to these cohorts. We used medical claims data to model the cohorts' event costs. All results are adjusted to reflect the demographics of a typical working-age population. Results The high-risk cohort (those with coronary heart disease) comprises 4% of the 35- to 69-year-old commercially insured population but generates 22% of the risk for coronary heart disease and stroke. Reduced event rates associated with intensive statin therapy yielded a $58 mean medical cost reduction per treated person per month; a typical payer cost for a 30-day supply of intensive statin therapy is approximately $57. Conclusions Aggressive low-density lipoprotein cholesterol–lowering therapy for working-age people at high risk for cardiovascular events and with a history of heart disease appears to have a significant potential to reduce the rate of clinical events and is cost-neutral for payers. PMID:25126293

  7. Statin intolerance - an attempt at a unified definition. Position paper from an International Lipid Expert Panel.

    PubMed

    Banach, Maciej; Rizzo, Manfredi; Toth, Peter P; Farnier, Michel; Davidson, Michael H; Al-Rasadi, Khalid; Aronow, Wilbert S; Athyros, Vasilis; Djuric, Dragan M; Ezhov, Marat V; Greenfield, Robert S; Hovingh, G Kees; Kostner, Karam; Serban, Corina; Lighezan, Daniel; Fras, Zlatko; Moriarty, Patrick M; Muntner, Paul; Goudev, Assen; Ceska, Richard; Nicholls, Stephen J; Broncel, Marlena; Nikolic, Dragana; Pella, Daniel; Puri, Raman; Rysz, Jacek; Wong, Nathan D; Bajnok, Laszlo; Jones, Steven R; Ray, Kausik K; Mikhailidis, Dimitri P

    2015-03-16

    Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term 'statin intolerance'. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10-15% of patients. In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented. PMID:25861286

  8. Pleiotropic effects of statins

    PubMed Central

    Kavalipati, Narasaraju; Shah, Jay; Ramakrishan, Ananthraman; Vasnawala, Hardik

    2015-01-01

    Statins or 3-hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors not only prevents the synthesis of cholesterol biosynthesis but also inhibits the synthesis of essential isoprenoid intermediates such as farnesyl pyrophosphate, geranylgeranyl pyrophosphate, isopentanyl adenosine, dolichols and polyisoprenoid side chains of ubiquinone, heme A, and nuclear lamins. These isoprenoid intermediates are required for activation of various intracellular/signaling proteins- small guanosine triphosphate bound protein Ras and Ras-like proteins like Rho, Rab, Rac, Ral, or Rap which plays an indispensible role in multiple cellular processes. Reduction of circulating isoprenoids intermediates as a result of HMG CoA reductase inhibition by statins prevents activation of these signalling proteins. Hence, the multiple effects of statins such as antiinflammatory effects, antioxidant effects, antiproliferative and immunomodulatory effects, plaque stability, normalization of sympathetic outflow, and prevention of platelet aggregation are due to reduction of circulating isoprenoids and hence inactivation of signalling proteins. These multiple lipid-independent effects of statins termed as statin pleiotropy would potentially open floodgates for research in multiple treatment domains catching attentions of researchers and clinician across the globe. PMID:26425463

  9. Does statin use cause memory decline in the elderly?

    PubMed

    Samaras, Katherine; Brodaty, Henry; Sachdev, Perminder S

    2016-08-01

    Statin therapy has strong evidence supporting health benefits and mortality reduction in cardiovascular disease, stroke, diabetes, renal disease, and genetic lipid disorders. Further, reports that statin therapy might be protective against Alzheimer's disease have subsequently been refuted in randomized trials. Low-level evidence based on case reports suggests that statins may adversely affect memory, a significant consumer concern. In this review, the published evidence on statins and memory in the elderly in randomized controlled trials and prospective observational cohort studies was examined in detail. Overall, there was moderate-strength evidence that statin therapy did not increase the risk of dementia in the elderly and low-strength evidence for no increased risk for Alzheimer's disease. Further, there was moderate-strength evidence that statin therapy in the elderly did not increase the risk for mild cognitive impairment or worsen global cognitive performance in the cognitively intact or impaired. There was moderate-strength evidence for no deterioration of memory function in the elderly. On balance, there was a moderate level of evidence of neither harm nor benefit on memory; however, the published literature contains a number of deficiencies that are detailed in this review, not limited to selection biases and deficiencies of detailed testing. PMID:27177529

  10. Maintenance Therapy with Interferon Alfa 2b Improves Outcome in Aggressive Malignant Lymphoma.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; García, E L; Nambo, M J

    1998-01-01

    To assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with malignant lymphoma on complete response after conventional chemotherapy we start a randomized clinical trial. One hundred and seventy patients were randomized to received either IFN 5.0 MU three time at week by one year or no further treatment, as control group. At a median follow-up of 9.0 years (range 4.3 to 11 years) median freedom from relapse (FFR) has not been reached in patients who received IFN, it is statistically significant to patients in control group with a median FFR of 60 months (p <.001). Actuarial curves show that at 10-years, 58 patients (66%, 95% confidence interval (CI) 53% to 79%) remain in first remission, statistical different to control group 33 patients (40%, 95% Cl: 33% to 57%) (p <.001). Event free survival (EFS) shown that a 10-years 63 patients (71%, 95% CI: 59% to 81%) are alive free of disease in the IFN arm compared to only 38 patients (45%, 95% CI: 37% to 57%) in the control group (p <.001). Toxicity was mild, 81 patients received the planned doses of IFN on time and 6 patients had transitory delay secondary to hematological toxicity (grade 1 or 2) and completed the treatment on 13 months. No late side effects has been observed. After a long term follow-up we confirm that IFN used as maintenance therapy improves outcome in patients with aggressive malignant lymphoma who were in complete remission after conventional chemotherapy without excessive toxicity. We feld that IFN will be consider in controlled clinical trials to define the role of this therapeutic option. PMID:27414082

  11. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.

    PubMed

    Cooper, Odelia; Mamelak, Adam; Bannykh, Serguei; Carmichael, John; Bonert, Vivien; Lim, Stephen; Cook-Wiens, Galen; Ben-Shlomo, Anat

    2014-06-01

    As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors was tested for prolactinoma outcomes and therapy. The objective of this study was to characterize ErbB receptor expression in prolactinomas and then perform a pilot study treating resistant prolactinomas with a targeted tyrosine kinase inhibitor (TKI). Retrospective analysis of prolactinomas and pilot study for dopamine agonist resistant prolactinomas in tertiary referral center. We performed immunofluorescent staining of a tissue array of 29 resected prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical features. Two patients with aggressive resistant prolactinomas enrolled and completed trial. They received lapatinib 1,250 mg daily for 6 months with tumor and hormone assessments. Main outcome measures were positive tumor staining of respective ErbB receptors, therapeutic reduction of prolactin levels and tumor shrinkage. Treated PRL levels and tumor volumes were suppressed in both subjects treated with TKI. EGFR expression was positive in 82 % of adenomas, ErbB2 in 92 %, ErbB3 in 25 %, and ErbB4 in 71 %, with ErbB2 score > EGFR > ErbB4 > ErbB3. Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03), suprasellar extension (p = 0.04), and carotid artery encasement (p = 0.01). Higher DA response rates were observed in tumors with higher ErbB3 expression. Prolactinoma expression of specific ErbB receptors is associated with tumor invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors may be effective therapy in patients with resistant prolactinomas. PMID:24287797

  12. Statins and the Liver.

    PubMed

    Herrick, Cynthia; Bahrainy, Samira; Gill, Edward A

    2016-03-01

    Lipid lowering, particularly with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors ("statins"), reduces the risk of cardiovascular disease. Patients with chronic liver disease present challenges to the use of lipid medications. In the case of most liver disorders, the concern has been one of safety. There is evidence that most lipid-lowering medications can be used safely in many situations, although large outcomes trials are lacking. This review examines lipid physiology and cardiovascular risk in specific liver diseases and reviews the evidence for lipid lowering and the use of statins in chronic liver disease. PMID:26893001

  13. Risk of new-onset diabetes associated with statin use

    PubMed Central

    Beckett, Robert D; Schepers, Sarah M; Gordon, Sarah K

    2015-01-01

    Objective: To identify and assess studies investigating the association between statins and new-onset diabetes and determine the clinical significance of this risk. Data sources: A MEDLINE (1977–April 2015), Google Scholar (1997–April 2015), and International Pharmaceutical Abstracts (1977–April 2015) search was performed using the search terms hydroxymethylglutaryl-CoA reductase inhibitors, hydroxymethylglutaryl-CoA reductase inhibitors/adverse effects, statins, adverse effects, diabetes mellitus, diabetes mellitus/etiology, and drug-induced. Citations of identified articles and clinical practice guidelines were also reviewed. Study selection and data extraction: Articles describing results from original investigations or meta-analyses specifically designed to assess the association between statins and new-onset diabetes and published in English were included. Data synthesis: A total of 13 cohort studies and seven meta-analyses were included. In all, 11 were retrospective cohort studies and reported some degree of increased risk of new-onset diabetes associated with statins. The two prospective cohort studies differed. One identified increased risk of new-onset diabetes, but the other did not. Increased risk was not identified when any statin was compared to placebo alone, individual statins were compared, or in the single meta-analysis that included observational studies. Overall, the meta-analyses suggest that statin therapy is associated with an increased risk of new-onset diabetes when compared to placebo or active control, and when intensive therapy is compared to moderate therapy. Conclusion: Statins have been associated with a small, but statistically significant risk of new-onset diabetes. Patients with risk factors for developing diabetes mellitus may be at higher risk. This risk is likely outweighed by the benefits of reducing cardiovascular risk. PMID:26770803

  14. Grapefruit Juice and Statins.

    PubMed

    Lee, Jonathan W; Morris, Joan K; Wald, Nicholas J

    2016-01-01

    We determined the validity of current medical advice to avoid grapefruit juice consumption while taking 3 widely used statins. A daily glass of grapefruit juice increases blood levels of simvastatin and lovastatin by about 260% if taken at the same time (about 90% if taken 12 hours apart), and atorvastatin by about 80% (whenever taken). Simvastatin 40 mg, lovastatin 40 mg, and atorvastatin 10 mg daily reduce low-density lipoprotein (LDL) cholesterol levels in a 60-year-old man with an LDL cholesterol of 4.8 mmol/L by 37%, reducing ischemic heart disease risk by 61%. When simvastatin or lovastatin are taken at the same time as grapefruit juice, the estimated reduction in LDL cholesterol is 48%, and in heart disease is 70%. If the juice is taken 12 hours before these statins, the reductions are, respectively, 43% and 66%, and for atorvastatin, 42% and 66%. The increased rhabdomyolysis risk from grapefruit juice consumption due to the increased effective statin dose is minimal compared with the greater effect in preventing heart disease. Grapefruit juice should not be contraindicated in people taking statins. PMID:26299317

  15. Antimicrobial photodynamic therapy in the treatment of aggressive periodontitis: a systematic review and meta-analysis.

    PubMed

    Souza, Emmanuel; Medeiros, Ana Cláudia; Gurgel, Bruno César; Sarmento, Carlos

    2016-01-01

    The aim of this systematic review was to investigate whether the use of antimicrobial photodynamic therapy (aPDT) as an adjuvant to scaling and root planning (SRP) yields better results than SRP alone or associated with systemic antibiotics in the treatment of aggressive periodontitis (AgP). A meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statements and Cochrane Collaboration recommendations. The search for relevant studies (earliest record to January 2015) was carried out in seven databases, followed by a manual search. Methodological quality assessment of the studies selected was based on an analysis of the risk of bias. At each time point of follow-up, the existence of significant differences (p < 0.05) in clinical attachment level (CAL) gain and probing depth (PD) reduction (primary outcomes) between groups was assessed with RevMan software 5.0. Heterogeneity between studies was assessed by the Higgin test (I (2)). Four randomized controlled trials (RCTs) satisfied the eligibility criteria of this review. Only one study was found to have a low risk of bias. There were no significant differences in PD reduction (mean difference 0.33, 95 % confidence interval -0.32 to 0.98, p = 0.32) and CAL gain (mean difference 0.20, 95 % confidence interval -0.41 to 0.81, p = 0.53) between the test and control interventions. At present, therefore, when compared to SRP alone or associated with systemic antibiotics, the evidence suggests that the association of aPDT + SRP is of no additional benefit in the nonsurgical treatment of AgP. PMID:26563956

  16. Maintenance periodontal therapy after systemic antibiotic and regenerative therapy of generalized aggressive periodontitis. A case report with 10-year follow-up.

    PubMed

    Siqueira, Sergio Júnior; Ribeiro, Fernanda Vieira; Villalpando, Karina Teixeira; Cirano, Fabiano Ribeiro; Pimentel, Suzana Peres

    2015-05-01

    Aggressive periodontitis (AgP) is an inflammatory disease characterized by rapid attachment loss and bone destruction. This case report presents the 10-year results in a subject with generalized AgP treated by a regenerative periodontal therapeutic approach and the adjunctive use of antibiotics, following a systematic maintenance periodontal therapy. The use of enamel matrix derivatives (EMD) and adjunctive antibiotic therapy to treat AgP yielded improvements in clinical parameters and radiographic bony fill. This combined therapeutic approach following a systematic supportive periodontal therapy supports the long-term maintenance of teeth with previous advanced periodontal defects, demonstrating successful stability after 10-years follow-up. Clinical Relevance: The combined treatment protocol using EMD plus adjunctive antibiotic therapy, associated with a systematic supportive periodontal therapy, benefits the long-term maintenance of teeth with previous advanced periodontal defects in subjects presenting AgP, supporting this approach as an alternative in the treatment of AgP. PMID:26062264

  17. Bilateral patellar tendon rupture associated with statin use.

    PubMed

    Kearns, Marie C; Singh, Vinay K

    2016-01-01

    Patellar tendon rupture is an uncommon clinical presentation, which generally affects the under 40s who are active in sport. Bilateral rupture of both tendons is much rarer. It occurs most frequently in patients with predisposing factors such as corticosteroid use or systemic diseases. The authors present the case of a 56-year-old male on long-term statin therapy who sustained this injury following a fall on ice. He had no known risk factors for tendon rupture. Surgical treatment involved tendon repair using Krakow suture via bony tunnels in the patella. Statins have previously been associated with tendon ruptures at other sites but there have been no published cases of bilateral patellar tendon rupture linked to statin use. We review the literature regarding the association between statins and tendon rupture. PMID:27165749

  18. Bilateral patellar tendon rupture associated with statin use

    PubMed Central

    Kearns, Marie C.; Singh, Vinay K.

    2016-01-01

    Patellar tendon rupture is an uncommon clinical presentation, which generally affects the under 40s who are active in sport. Bilateral rupture of both tendons is much rarer. It occurs most frequently in patients with predisposing factors such as corticosteroid use or systemic diseases. The authors present the case of a 56-year-old male on long-term statin therapy who sustained this injury following a fall on ice. He had no known risk factors for tendon rupture. Surgical treatment involved tendon repair using Krakow suture via bony tunnels in the patella. Statins have previously been associated with tendon ruptures at other sites but there have been no published cases of bilateral patellar tendon rupture linked to statin use. We review the literature regarding the association between statins and tendon rupture. PMID:27165749

  19. [Direct neuronal effects of statins].

    PubMed

    Bösel, J; Endres, M

    2006-03-01

    Statins, i.e. HMG-CoA reductase inhibitors, reduce the risk of stroke and may have therapeutic potential for other neurologic diseases, including multiple sclerosis and Alzheimer's disease. In addition to lowering cholesterol levels, statins exert a number of cholesterol-independent (pleiotropic) effects. While endothelial, anti-thrombotic, anti-inflammatory, and immunomodulatory, i.e. peripheral, effects of statins are well known, little is known about the direct effects on neurons. This may be of clinical relevance because some statins are able to cross the blood-brain barrier. Recent experimental studies demonstrate that statins reduce the activity of neuronal glutamate receptors and protect neurons from excitotoxic insults. At higher doses, however, statins may also inhibit neurite sprouting and even induce neuronal apoptosis. PMID:16028081

  20. Central nervous system recurrence of desmoplastic small round cell tumor following aggressive multimodal therapy: A case report

    PubMed Central

    UMEDA, KATSUTSUGU; SAIDA, SATOSHI; YAMAGUCHI, HIDEKI; OKAMOTO, SHINYA; OKAMOTO, TAKESHI; KATO, ITARU; HIRAMATSU, HIDEFUMI; IMAI, TSUYOSHI; KODAIRA, TAKESHI; HEIKE, TOSHIO; ADACHI, SOUICHI; WATANABE, KEN-ICHIRO

    2016-01-01

    Patients with desmoplastic small round cell tumors (DSRCTs) have an extremely poor outcome despite the use of aggressive therapy. The current study presents the case of 16-year-old male with metastatic DSRCT, in which multimodal therapy, including intensive chemotherapies using frequent autologous stem cell support, gross resection of primary and metastatic lesions, and whole abdominopelvic intensity-modulated radiation therapy, was administered. Subsequent to these treatments, there was no evidence of active disease. However, cerebellar and pineal body lesions, and bone metastasis to the left humerus were detected 1 year and 2 months after the initial diagnosis. Combination chemotherapy with irinotecan and temozolomide was initially effective against the central nervous system (CNS) metastatic lesions; however, the patient succumbed due to progressive CNS disease after seven courses of combination chemotherapy. Additional studies are required to accumulate information regarding CNS recurrence of DSRCT. PMID:26870296

  1. Statins for primary cardiovascular prevention in the elderly

    PubMed Central

    Pedro-Botet, Juan; Climent, Elisenda; Chillarón, Juan J; Toro, Rocio; Benaiges, David; Flores-Le Roux, Juana A

    2015-01-01

    The elderly population is increasing worldwide, with subjects > 65 years of age constituting the fastest-growing age group. Furthermore, the elderly face the greatest risk and burden of cardiovascular disease mortality and morbidity. Although elderly patients, particularly those older > 75, have not been well represented in randomized clinical trials evaluating lipid-lowering therapy, the available evidence supporting the use of statin therapy in primary prevention in older individuals is derived mainly from subgroup analyses and post-hoc data. On the other hand, elderly patients often have multiple co-morbidities that require a high number of concurrent medications; this may increase the risk for drug-drug interactions, thereby reducing the potential benefits of statin therapy. The aim of this review was to present the relevant literature regarding statin use in the elderly for their primary cardiovascular disease, with the associated risks and benefits of treatment. PMID:26345308

  2. Sub-100nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large and highly aggressive triple negative breast tumors.

    PubMed

    Ayala-Orozco, Ciceron; Urban, Cordula; Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-10-10

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or necrotic regions. We report the performance advantages obtained by sub 100nm gold nanomatryushkas, comprising concentric gold-silica-gold layers compared to conventional ~150nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000mm(3)) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5× accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  3. Sub-100 nm Gold Nanomatryoshkas Improve Photo-thermal Therapy Efficacy in Large and Highly Aggressive Triple Negative Breast Tumors

    PubMed Central

    Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-01-01

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or nectrotic regions. We report the performance advantages obtained by sub 100 nm gold nanomatryushkas, comprising of concentric gold-silica-gold layers compared to conventional ~150 nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000 mm3) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5X accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  4. [Prognostic value of markers of inflammation in patients with stable ischemic heart disease after implantation of stents with drug covering at the background of long-term therapy with statins (inhospital period)].

    PubMed

    Karpov, Iu A; Buza, V V

    2012-01-01

    The objective of this study was to examine the prognostic value of C-reactive protein, erythrocyte sedimentation rate (ESR), white blood count, phospholipase A2 in patients with stable ischemic disease on long-term statin therapy undergoing percutaneous coronary intervention (PCI) with drug-eluting stent implantation. In the interim analysis in- hospital outcomes were assessed a total of 602 patients from December 2009 through December 2010 underwent successful PCI with at least one DES implanted. They were prospectively followed before discharge. MACE (death, myocardial infarction [MI], stroke, stent thrombosis [ST] which did not lead to MI) occurred in 10,6% of the patients. There was no death or stroke before discharge. MI (including 0,3% of Q-MI) occurred in 10,3% of the patients. 6 patients had verified ST. Multivariate logistic regression identified ESR level before PCI and total length of stents implanted as independent predictors of MACE. PMID:22839437

  5. The Many Roles of Statins in Ischemic Stroke

    PubMed Central

    Zhao, Jingru; Zhang, Xiangjian; Dong, Lipeng; Wen, Ya; Cui, Lili

    2014-01-01

    Stroke is the third leading cause of human death. Endothelial dysfunction, thrombogenesis, inflammatory and oxidative stress damage, and angiogenesis play an important role in cerebral ischemic pathogenesis and represent a target for prevention and treatment. Statins have been found to improve endothelial function, modulate thrombogenesis, attenuate inflammatory and oxidative stress damage, and facilitate angiogenesis far beyond lowering cholesterol levels. Statins have also been proved to significantly decrease cardiovascular risk and to improve clinical outcome. Could statins be the new candidate agent for the prevention and therapy in ischemic stroke? In recent years, a vast expansion in the understanding of the pathophysiology of ischemic stroke and the pleiotropic effects of statins has occurred and clinical trials involving statins for the prevention and treatment of ischemic stroke have begun. These facts force us to revisit ischemic stroke and consider new strategies for prevention and treatment. Here, we survey the important developments in the non-lipid dependent pleiotropic effects and clinical effects of statins in ischemic stroke. PMID:25977681

  6. The Rosenzweig Picture-Frustration Study "Extra-Aggression" Score as an Indicator in Cognitive Restructuring Therapy for Male Perpetrators of Domestic Violence

    ERIC Educational Resources Information Center

    Norman, Michael; Ryan, Lawrence J.

    2008-01-01

    It was hypothesized that male perpetrators of domestic violence in the early stages of a 1-year process of cognitive restructuring therapy would manifest on the Rosenzweig Picture-Frustration Study higher levels of extra-aggressiveness than in later stages of the therapy process. A sample of male batterers in the process of treatment took the…

  7. Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by scaffolding PP2C to induce hepatic gluconeogenesis.

    PubMed

    Gotoh, Saki; Negishi, Masahiko

    2015-01-01

    Statin therapy is known to increase blood glucose levels in humans. Statins utilize pregnane X receptor (PXR) and serum/glucocorticoid regulated kinase 2 (SGK2) to activate phosphoenolpyruvate carboxykinase 1 (PEPCK1) and glucose-6-phosphatase (G6Pase) genes, thereby increasing glucose production in human liver cells. Here, the novel statin/PXR/SGK2-mediated signaling pathway has now been characterized for hepatic gluconeogenesis. Statin-activated PXR scaffolds the protein phosphatase 2C (PP2C) and SGK2 to stimulate PP2C to dephosphorylate SGK2 at threonine 193. Non-phosphorylated SGK2 co-activates PXR-mediated trans-activation of promoters of gluconeogenic genes in human liver cells, thereby enhancing gluconeogenesis. This gluconeogenic statin-PXR-SGK2 signal is not present in mice, in which statin treatment suppresses hepatic gluconeogenesis. These findings provide the basis for statin-associated side effects such as an increased risk for Type 2 diabetes. PMID:26392083

  8. Cognitive behavioral therapy to reduce overt aggression behavior in Chinese young male violent offenders.

    PubMed

    Chen, Chen; Li, Chun; Wang, Hong; Ou, Jian-Jun; Zhou, Jian-Song; Wang, Xiao-Ping

    2014-01-01

    This 9-week study was designed to determine whether a commercial cognitive-behavioral training program could effectively reduce overt aggression behavior in Chinese young male violent offenders. Sixty-six participants were randomly assigned to receive routine intervention alone (control group) or routine intervention plus Williams LifeSkills Training (WLST group) in a 1:1 ratio. The primary outcome was change scores on the Modified Overt Aggression Scale (MOAS) from baseline to one week following end of training. Secondary outcomes were change scores on the Barratt Impulsiveness Scale-11 (BIS-11) and Cook-Medley Hostility Scale (CMHS). There were significant between-group differences in change of MOAS total score (P < .001) and all sub-scores (Ps < .01) except aggression against property. Between-group differences were also observed in change of BIS-11 and CMHS total score (Ps < 0.05). All results favored the WLST group. These findings suggest WLST has the potential to be an effective intervention to reduce overt aggressive behavior in young male violent offenders. PMID:24375428

  9. Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

    PubMed Central

    Rizzo, Manfredi; Toth, Peter P.; Farnier, Michel; Davidson, Michael H.; Al-Rasadi, Khalid; Aronow, Wilbert S.; Athyros, Vasilis; Djuric, Dragan M.; Ezhov, Marat V.; Greenfield, Robert S.; Hovingh, G. Kees; Kostner, Karam; Serban, Corina; Lighezan, Daniel; Fras, Zlatko; Moriarty, Patrick M.; Muntner, Paul; Goudev, Assen; Ceska, Richard; Nicholls, Stephen J.; Broncel, Marlena; Nikolic, Dragana; Pella, Daniel; Puri, Raman; Rysz, Jacek; Wong, Nathan D.; Bajnok, Laszlo; Jones, Steven R.; Ray, Kausik K.; Mikhailidis, Dimitri P.

    2015-01-01

    Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term ‘statin intolerance’. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10–15% of patients. In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented. PMID:25861286

  10. Cognitive effects of statin medications.

    PubMed

    Kelley, Brendan J; Glasser, Stephen

    2014-05-01

    The demonstrated benefits of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) for cardiovascular and cerebrovascular disease are well established in the medical literature, and this class of medications is among those most commonly prescribed in the USA. In 2012, the US Food and Drug Administration issued updated recommendations regarding statin medications, and the panel's comments regarding memory impairment fostered clinical confusion (in part because of the lay media's amplification). Cognitive data from several large epidemiological studies have not reliably demonstrated a robust association between incident cognitive impairment and statin use, with some studies reporting a protective effect, some reporting an increased risk and others finding no association. Although several interventional studies have evaluated statins as a possible adjunctive treatment for Alzheimer's disease, none have clearly demonstrated a benefit. A small number of case series have reported infrequent memory difficulties associated with statin use. In these series, the patients' cognitive symptoms resolved after statin discontinuation. The existing medical literature does not suggest that cognitive considerations should play a major role in medical decision making to prescribe statins for the large majority of patients. As with any medication prescribed for older adults, careful clinical monitoring for side effects should be exercised. If a patient is suspected of having idiosyncratic memory impairment associated with use of a statin medication, the drug can be discontinued. The patient should then be followed with careful clinical observation for 1-3 months for resolution of the cognitive symptoms. PMID:24504830

  11. Statin-induced Myopathy in Skeletal Muscle: the Role of Exercise.

    PubMed

    Kwak, Hyo-Bum

    2014-09-01

    Statins are widely used drugs to lower cholesterol levels and to reduce the risk of cardiovascular disease. However, it has been reported that statins are associated with adverse side effects of skeletal myopathy. Statin treatment can impair mitochondrial function and induce apoptosis in skeletal muscle in both human and animal models. Ubiquinone plays an essential role in transferring electrons in the mitochondrial electron transfer chain for oxidative phosphorylation. However, statin treatment reduces ubiquinone levels in the cholesterol synthesis pathway, which may be associated with mitochondrial dysfunction. In addition, reactive oxygen species (ROS) production and apoptosis induced by statins may provide cellular and molecular mechanisms in skeletal myopathy. Exercise is the most effective therapy to prevent metabolic and cardiovascular diseases. However, whether exercise provides a benefit to or exacerbation of statin-induced myopathy in skeletal muscle remains poorly investigated. This review will briefly provide a comprehensive summary regarding the effects of statins on skeletal myopathy, and discuss the potential mechanisms of statin-induced myopathy and the role of exercise in statin-induced myopathy in skeletal muscle. PMID:26064857

  12. Statin-induced Myopathy in Skeletal Muscle: the Role of Exercise

    PubMed Central

    Kwak, Hyo-Bum

    2014-01-01

    Statins are widely used drugs to lower cholesterol levels and to reduce the risk of cardiovascular disease. However, it has been reported that statins are associated with adverse side effects of skeletal myopathy. Statin treatment can impair mitochondrial function and induce apoptosis in skeletal muscle in both human and animal models. Ubiquinone plays an essential role in transferring electrons in the mitochondrial electron transfer chain for oxidative phosphorylation. However, statin treatment reduces ubiquinone levels in the cholesterol synthesis pathway, which may be associated with mitochondrial dysfunction. In addition, reactive oxygen species (ROS) production and apoptosis induced by statins may provide cellular and molecular mechanisms in skeletal myopathy. Exercise is the most effective therapy to prevent metabolic and cardiovascular diseases. However, whether exercise provides a benefit to or exacerbation of statin-induced myopathy in skeletal muscle remains poorly investigated. This review will briefly provide a comprehensive summary regarding the effects of statins on skeletal myopathy, and discuss the potential mechanisms of statin-induced myopathy and the role of exercise in statin-induced myopathy in skeletal muscle. PMID:26064857

  13. Development of targeted therapy in uterine serous carcinoma, a biologically aggressive variant of endometrial cancer

    PubMed Central

    El-Sahwi, Karim S; Schwartz, Peter E; Santin, Alessandro D

    2012-01-01

    Endometrial cancer (EC) is the most common female genital malignancy in the USA. Most carcinomas arising from the uterus are estrogen dependent and are associated with obesity and hypertension. They are designated type I ECs and typically, due to their early diagnosis secondary to postmenopausal bleeding, have a good prognosis. By contrast, type II ECs develop in older patients, are not hormone dependent and are responsible for most recurrences and deaths from EC. Uterine serous cancer constitutes up to 10% of all endometrial tumors, and represents the most biologically aggressive variant of type II EC. This article will describe the most salient molecular markers that have been identified in uterine serous cancer, thus far with emphasis on the use of erbB2 (HER2/neu) as the first of a series of therapeutic markers for the treatment of this highly-aggressive subset of ECs. PMID:22149431

  14. Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation.

    PubMed

    Evans, Malkanthi; Rumberger, John A; Azumano, Isao; Napolitano, Joseph J; Citrolo, Danielle; Kamiya, Toshikazu

    2014-01-01

    High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to 16) or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines. PMID:24600231

  15. Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation

    PubMed Central

    Evans, Malkanthi; Rumberger, John A; Azumano, Isao; Napolitano, Joseph J; Citrolo, Danielle; Kamiya, Toshikazu

    2014-01-01

    High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to16) or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines. PMID:24600231

  16. CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi

    PubMed Central

    Gopal, Satish; Fedoriw, Yuri; Kaimila, Bongani; Montgomery, Nathan D.; Kasonkanji, Edwards; Moses, Agnes; Nyasosela, Richard; Mzumara, Suzgo; Varela, Carlos; Chikasema, Maria; Makwakwa, Victor; Itimu, Salama; Tomoka, Tamiwe; Kamiza, Steve; Dhungel, Bal M.; Chimzimu, Fred; Kampani, Coxcilly; Krysiak, Robert; Richards, Kristy L.; Shea, Thomas C.; Liomba, N. George

    2016-01-01

    There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV. PMID:26934054

  17. CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi.

    PubMed

    Gopal, Satish; Fedoriw, Yuri; Kaimila, Bongani; Montgomery, Nathan D; Kasonkanji, Edwards; Moses, Agnes; Nyasosela, Richard; Mzumara, Suzgo; Varela, Carlos; Chikasema, Maria; Makwakwa, Victor; Itimu, Salama; Tomoka, Tamiwe; Kamiza, Steve; Dhungel, Bal M; Chimzimu, Fred; Kampani, Coxcilly; Krysiak, Robert; Richards, Kristy L; Shea, Thomas C; Liomba, N George

    2016-01-01

    There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39-56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥ 2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1-31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61-244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31-57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV. PMID:26934054

  18. Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma

    SciTech Connect

    Tseng, Yolanda D.; Chen, Yu-Hui; Catalano, Paul J.; Ng, Andrea

    2015-01-01

    Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treated with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a shorter

  19. Drug interactions and the statins

    PubMed Central

    Herman, R J

    1999-01-01

    Drug interactions commonly occur in patients receiving treatment with multiple medications. Most interactions remain unrecognized because drugs, in general, have a wide margin of safety or because the extent of change in drug levels is small when compared with the variation normally seen in clinical therapy. All drug interactions have a pharmacokinetic or pharmacodynamic basis and are predictable given an understanding of the pharmacology of the drugs involved. Drugs most liable to pose problems are those having concentration-dependent toxicity within, or close to, the therapeutic range; those with steep dose-response curves; those having high first-pass metabolism or those with a single, inhibitable route of elimination. Knowing which drugs possess these intrinsic characteristics, together with a knowledge of hepatic P-450 metabolism and common enzyme-inducing and enzyme-inhibiting drugs, can greatly assist physicians in predicting interactions that may be clinically relevant. This article reviews the pharmacology of drug interactions that can occur with hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) to illustrate the scope of the problem and the ways in which physicians may manage this important therapeutic class of drugs. PMID:10584091

  20. Statin Use Is Associated With Incident Diabetes Mellitus Among Patients in the HIV Outpatient Study

    PubMed Central

    Lichtenstein, Kenneth A.; Hart, Rachel L. D.; Wood, Kathleen C.; Bozzette, Samuel; Buchacz, Kate; Brooks, John T.

    2015-01-01

    Introduction Statin therapy is effective in the prevention of cardiovascular disease in the general population but has been shown to modestly increase the risk for incident diabetes mellitus (DM). Methods We analyzed incident DM in HIV Outpatient Study (HOPS) participants followed at 8 HIV clinic sites during 2002–2011, comparing rates among those who initiated statin therapy during that period with those who did not. Using Cox proportional hazards models, we examined the association between cumulative years of statin exposure and the risk of developing DM, after controlling for age, sex, race/ethnicity, antiretroviral history, prevalent hepatitis C, body mass index, and cumulative exposure to protease inhibitor therapy. We also adjusted for propensity scores to account for residual confounding by indication. Results Of 4692 patients analyzed, 590 (12.6%) initiated statin therapy and 355 (7.2%) developed DM. Incident DM was independently associated with statin therapy (adjusted hazard ratio, 1.14 per year of statin use), as well as older age, Hispanic/Latino ethnicity, non-Hispanic/Latino black race, antiretroviral-naive status, prevalent hepatitis C, and body mass index ≥30 kg/m2 (P < 0.05 for all). The association of statin use with incident DM was similar in the model adjusted for propensity score. Conclusions Statin use was associated with a modestly increased risk of incident DM in an HIV-infected population, similar to existing data for the general population. HIV-infected patients should be monitored for glucose intolerance, but statins should not be withheld if clinically indicated for cardiovascular disease risk reduction. PMID:26181706

  1. Statins and percutaneous coronary intervention: a complementary synergy.

    PubMed

    Echeverri, Darío; Cabrales, Jaime

    2013-01-01

    The inclusion of statins and stents in coronary disease management during the 1980s has marked a dramatic change in the natural history of the disease. Separately, each of these therapies have progressed rapidly and have achieved a prime position in the current armamentarium. The simultaneous use of statins in patients undergoing percutaneous coronary revascularization procedures with stent implantation has shown a significant beneficial synergistic effect by reducing ischemia and necrosis, and improving coronary blood flow in patients with stable coronary disease, as well as in acute coronary syndromes. The use of high dose statins in conjunction with coronary angioplasty with stent implantation has shown great efficacy and safety in patients with severe coronary disease. PMID:24079365

  2. [Statins diabetogenicity: are all the same? state of art].

    PubMed

    Rius Tarruella, Joan; Millán Núñez-Cortés, Jesús; Pedro-Botet, Juan; Pintó Sala, Xavier

    2015-01-01

    Statins are the cornerstone of cardiovascular prevention for general population, and in patients with type 2 diabetes mellitus (T2DM). However, statin therapy predisposes to type 2 diabetes, particularly in patients with predisposition to this condition. Some statins have been associated with increases in blood glucose in patients with or without DM2, and others have shown to have neutral effects, varying from one another their glucose or diabetogenic capacity. In many statin trials the incidence of DM2 has not been systematically evaluated and others the power to detect differences between statins is lacking. Evidence highest quality available comes from the meta-analysis of controlled clinical trials. The only controlled clinical trial to evaluate the incidence of new-onset T2DM is the J-PREDICT conducted with pitavastatin in patients with abnormal glucose tolerance. Preliminary results of this study show that pitavastatin is associated with a significant decrease in the incidence of de novo T2DM compared to only modification lifestyle. Therefore, pitavastatin may be an appropriate therapeutic alternative of choice to reduce vascular risk in patients with T2DM or at risk of presenting it. PMID:25835612

  3. Dialectical behavior therapy deployed: an aggressive alternative to traditional mental health on the noncontiguous battlefield.

    PubMed

    Parrish, Brian D

    2008-01-01

    This paper provides a description of the Witmer Wellness Center, the first successful military application of dialectical behavior therapy in a theater of war. Dialectical behavior therapy is a dynamic and provocative evidenced-based modification of cognitive behavioral treatment developed by Dr Marsha Linehan for patients with severe emotional dysregulation. One of the primary concepts of dialectical behavior therapy is that self-harming behaviors are learned, and provide evidence of maladaptive coping that is reinforced in an invalidating environment. Dialectical behavior therapy recommends a hierarchy of goals to effectively address the behaviors associated with dysregulation. Chief among these goals is reducing risk of violence to self or others. Dialectical behavior therapy is especially well-suited for the complex and dynamic environment of the noncontiguous battlefield with its chronic threat of ultraviolence, strain of nonresponse, shifting rules of engagement, and extended duration and frequency of combat deployments. The Witmer Wellness Center program uses an intensive outpatient organizational structure and minimal, but innovative, modifications to standard dialectical behavior therapy designed to meet the special requirements of Warriors in a combat zone. The Wellness Center program was designed and implemented during Operation Iraqi Freedom 07-09, at a time during the troop surge when suicide rates among US forces had reached an unprecedented level. PMID:20088061

  4. Pharmacogenetics of Response to Statins

    PubMed Central

    Zineh, Issam

    2016-01-01

    The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) are among the most commonly prescribed drugs worldwide. On average, statins improve lipid profiles and have been shown to have ancillary beneficial effects on inflammation, platelet activity, and endothelial function. However, variability in drug response exists regardless of the measured phenotype, and genetic variability may be a contributing factor. Recently, there has been an interesting shift in statin pharmacogenetic studies. Novel study designs have been employed and nontraditional candidate genes have been investigated in relation to both lipid and nonlipid responses to statins. This review outlines earlier pharmacogenetic studies and highlights newly published findings that expand on previous work. Furthermore, a framework is provided in which the necessary next steps in research are described, with the ultimate goal of translating pharmacogenetic findings into clinically meaningful changes in patient care. PMID:18241612

  5. Diagnosis, Prevention, and Management of Statin Adverse Effects and Intolerance: Canadian Consensus Working Group Update (2016).

    PubMed

    Mancini, G B John; Baker, Steven; Bergeron, Jean; Fitchett, David; Frohlich, Jiri; Genest, Jacques; Gupta, Milan; Hegele, Robert A; Ng, Dominic; Pearson, Glen J; Pope, Janet; Tashakkor, A Yashar

    2016-07-01

    The Canadian Consensus Working Group has updated its evaluation of the literature pertaining to statin intolerance and adverse effects. This overview introduces a pragmatic definition of statin intolerance (goal-inhibiting statin intolerance) that emphasizes the effects of symptoms on achieving nationally vetted goals in patients fulfilling indications for lipid-lowering therapy and cardiovascular risk reduction. The Canadian Consensus Working Group provides a structured framework for avoiding, evaluating and managing goal-inhibiting statin intolerance. Particularly difficult practice situations are reviewed, including management in young and elderly individuals, and in athletes and labourers. Finally, targeted at specialty practitioners, more detailed analyses of specific but more unusual adverse effects ascribed to statins are updated including evidence regarding new-onset diabetes, cognitive dysfunction, cataracts, and the rare but important immune-mediated necrotizing myopathy. PMID:27342697

  6. Major diet-drug interactions affecting the kinetic characteristics and hypolipidaemic properties of statins.

    PubMed

    Vaquero, M P; Sánchez Muniz, F J; Jiménez Redondo, S; Prats Oliván, P; Higueras, F J; Bastida, S

    2010-01-01

    Concomitant administration of statins with food may alter statin pharmacokinetics or pharmacodynamics, increasing the risk of adverse reactions such as myopathy or rhabdomyolysis or reducing their pharmacological action. This paper reviews major interactions between statins and dietary compounds. Consumption of pectin or oat bran together with Lovastatin reduces absorption of the drug, while alcohol intake does not appear to affect the efficacy and safety of Fluvastatin treatment. Grapefruit juice components inhibit cytochrome P-4503A4, reducing the presystemic metabolism of drugs such as Simvastatin, Lovastatin and Atorvastatin. Follow-up studies on the therapeutic effect of statins in patients consuming a Mediterranean-style diet are necessary to assure the correct prescription because the oil-statin and minor oil compound-statin possible interactions have been only briefly studied. Preliminary study suggests that olive oil can increase the hypolipaemiant effect of Simvastatin with respect sunflower oil. The consumption of polyunsaturated rich oils, throughout the cytochrome P- 450 activation could decrease the half-life of some statins and therefore their hypolipaemic effects. The statins and n-3 fatty acids combined therapy gives rise to pharmacodinamic interaction that improves the lipid profile and leads greater cardioprotection. Although statins are more effective in high endogenous cholesterol production subjects and plant sterols are more effective in high cholesterol absorption efficacy subjects, plant esterols-statins combined therapy generates very positive complementary effects. This review ends suggesting possible diet-stain interactions that require further investigations (e.g. types of olive oils, fruit juices other than grapefruit, fibre or consumption of alcoholic beverages rich in polyphenols or ethanol). PMID:20449528

  7. A Case of Recalcitrant Plantar Warts Associated with Statin Use

    PubMed Central

    Wernham, Aaron G.; Velangi, Shireen S.

    2015-01-01

    Background. Plantar warts are a common presenting skin complaint caused by the human papillomavirus. 1st line therapies include cryotherapy and topical salicylic acid. Where there is resistance to these treatments, consideration is made for 2nd line therapies, including intralesional bleomycin, imiquimod, 5-fluorouracil, and photodynamic therapy. We present a case of bilateral persistent plantar warts, resistant to treatment with repeated cryotherapy and topical salicylic acid over a 6-year period. Following a patient initiated decision to discontinue their statin medication, we observed rapid clearance of plantar warts without change to standard therapy or their environment. This case correlates with emerging literature demonstrating a link between statin medication and proliferation of HPV through increased levels of FOXP3+ regulatory T cells. PMID:25789179

  8. Statin Use and Its Facility-Level Variation in Patients With Diabetes: Insight From the Veterans Affairs National Database.

    PubMed

    Pokharel, Yashashwi; Akeroyd, Julia M; Ramsey, David J; Hira, Ravi S; Nambi, Vijay; Shah, Tina; Woodard, LeChauncy D; Winchester, David E; Ballantyne, Christie M; Petersen, Laura A; Virani, Salim S

    2016-04-01

    We sought to determine use of any and at least moderate-intensity statin therapy in a national sample of patients with diabetes mellitus (DM), with the hypothesis that nationwide frequency and facility-level variation in statin therapy are suboptimal. We sampled patients with DM age 40 to 75 years receiving primary care between October 1, 2012, and September 30, 2013, at 130 parent facilities and associated community-based outpatient clinics in the Veterans Affairs Health Care System. We examined frequency and facility-level variation in use of any or at least moderate-intensity statin therapy (mean daily dose associated with ≥30% low-density lipoprotein cholesterol lowering). In 911 444 patients with DM, 68.3% and 58.4% were receiving any and moderate- to high-intensity statin therapy, respectively. Patients receiving statin had higher burden of cardiovascular disease, were more likely to be on nonstatin lipid-lowering therapy and to receive care at a teaching facility, and had more frequent primary-care visits. Median facility-level uses of any and at least moderate-intensity statin therapy were 68.7% (interquartile range, 65.9%-70.8%) and 58.6% (interquartile range, 55.8%-61.4%), respectively. After adjusting for several patient-related and some facility-related characteristics, the median rate ratios for any and moderate- to high-intensity statin therapy were 1.20 (95% confidence interval: 1.18-1.22) and 1.29 (95% confidence interval: 1.24-1.33) respectively, indicating 20% to 29% variation in statin use between 2 identical patients receiving care at 2 random facilities. Statin use was suboptimal in a national sample of patients with DM with modest facility-level variation, likely indicating differences in statin-prescribing patterns. PMID:27059708

  9. Lifestyle intervention and/or statins for the reduction of C-reactive protein in type 2 diabetes: From the Look AHEAD Study

    PubMed Central

    Belalcazar, L.M.; Haffner, S.M.; Lang, W.; Hoogeveen, R.C.; Rushing, J.; Schwenke, D.C.; Tracy, R.P.; Pi-Sunyer, F.X.; Kriska, A.M.; Ballantyne, C.M.

    2013-01-01

    Objective Cardiovascular risk remains high despite statin use. Overweight/obese diabetic persons usually have normal/low LDL-cholesterol but high C-reactive protein (CRP) levels. We aimed to examine the effects of intensive lifestyle intervention for weight loss (ILI) on CRP levels in overweight/obese diabetic individuals by statin use. Design and Methods Look AHEAD was a randomized trial in overweight/obese type 2 diabetic individuals testing whether ILI would reduce cardiovascular mortality, when compared to usual care. We evaluated CRP changes in 1,431 participants with biomarker levels, who remained on or off statin treatment for 1-year. Results The reduction in CRP levels with ILI at 1 year in men and women on statins was −44.9 and −42.3 %, respectively, compared to −13.7 and −21.0 % for those on statins and usual care (p<0.0001). At 1 year, median CRP levels were: 1.8 mg/L in participants randomized to ILI on statin therapy; 2.6 mg/L for those on statins randomized to usual care and 2.9 mg/L for participants not on statins but randomized to ILI. Weight loss was associated with 1-year CRP reduction (p<0.0001) in statin and non-statin users. Conclusions Our findings suggest that in overweight/obese diabetic persons, ILI and statin therapy may have substantial additive anti-inflammatory benefits. PMID:23512860

  10. Is Impact of Statin Therapy on All-Cause Mortality Different in HIV-Infected Individuals Compared to General Population? Results from the FHDH-ANRS CO4 Cohort

    PubMed Central

    Lang, Sylvie; Lacombe, Jean-Marc; Mary-Krause, Murielle; Partisani, Marialuisa; Bidegain, Frédéric; Cotte, Laurent; Aslangul, Elisabeth; Chéret, Antoine; Boccara, Franck; Meynard, Jean-Luc; Pradier, Christian; Roger, Pierre-Marie; Tattevin, Pierre; Costagliola, Dominique; Molina, Jean-Michel

    2015-01-01

    Background The effect of statins on all-cause mortality in the general population has been estimated as 0.86 (95%CI 0.79-0.94) for primary prevention. Reported values in HIV-infected individuals have been discordant. We assessed the impact of statin-based primary prevention on all-cause mortality among HIV-infected individuals. Methods Patients were selected among controls from a multicentre nested case-control study on the risk of myocardial infarction. Patients with prior cardiovascular or cerebrovascular disorders were not eligible. Potential confounders, including variables that were associated either with statin use and/or death occurrence and statin use were evaluated within the last 3 months prior to inclusion in the case-control study. Using an intention to continue approach, multiple imputation of missing data, Cox’s proportional hazard models or propensity based weighting, the impact of statins on the 7-year all-cause mortality was evaluated. Results Among 1,776 HIV-infected individuals, 138 (8%) were statins users. During a median follow-up of 53 months, 76 deaths occurred, including 6 in statin users. Statin users had more cardiovascular risk factors and a lower CD4 T cell nadir than statin non-users. In univariable analysis, the death rate was higher in statins users (11% vs 7%, HR 1.22, 95%CI 0.53-2.82). The confounders accounted for were age, HIV transmission group, current CD4 T cell count, haemoglobin level, body mass index, smoking status, anti-HCV antibodies positivity, HBs antigen positivity, diabetes and hypertension. In the Cox multivariable model the estimated hazard ratio of statin on all-cause mortality was estimated as 0.86 (95%CI 0.34-2.19) and it was 0.83 (95%CI 0.51-1.35) using inverse probability treatment weights. Conclusion The impact of statin for primary prevention appears similar in HIV-infected individuals and in the general population. PMID:26200661

  11. Statins in therapy: understanding their hydrophilicity, lipophilicity, binding to 3-hydroxy-3-methylglutaryl-CoA reductase, ability to cross the blood brain barrier and metabolic stability based on electrostatic molecular orbital studies.

    PubMed

    Fong, Clifford W

    2014-10-01

    The atomic electrostatic potentials calculated by the CHELPG method have been shown to be sensitive indicators of the gas phase and solution properties of the statins. Solvation free energies in water, n-octanol and n-octane have been determined using the SMD solvent model. The percentage hydrophilicity and hydrophobicity (or lipophilicity) of the statins in solution have been determined using (a) the differences in solvation free energies between n-octanol and n-octane as a measure of hydrophilicity, and the solvation energy in octane as a measure of hydrophobicity (b) the sum of the atomic electrostatic charges on the hydrogen bonding and polar bonding nuclei of the common pharmacophore combined with a solvent measure of hydrophobicity, and (c) using the buried surface areas after statin binding to HMGCR to calculate the hydrophobicity of the bound statins. The data suggests that clinical definitions of statins as either "hydrophilic" or "lipophilic" based on experimental partition coefficients are misleading. An estimate of the binding energy between rosuvastatin and HMGCR has been made using: (a) a coulombic electrostatic interaction model, (b) the calculated desolvation and resolvation of the statin in water, and (c) the first shell transfer solvation energy as a proxy for the restructuring of the water molecules immediately adjacent to the active binding site of HMGCR prior to binding. Desolvation and resolvation of the statins before and after binding to HMGCR are major determinants of the energetics of the binding process. An analysis of the amphiphilic nature of lovastatin anion, acid and lactone and fluvastatin anion and their abilities to cross the blood brain barrier has indicated that this process may be dominated by desolvation and resolvation effects, rather than the statin molecular size or statin-lipid interactions within the bilayer. The ionization energy and electron affinity of the statins are sensitive physical indicators of the ease that the

  12. Association of statin use and stress-induced hyperglycemia in patients with acute ST-elevation myocardial infarction

    PubMed Central

    Yan, Chen; Qin, Ma; Juan, Yang S; Tao, Li Y; dong, Gao M; Zechun, Zeng; Chun, Yang X; Liang, Cong H; Yin, Liu

    2016-01-01

    Background Only a few information is available on the risk of stress hyperglycemia following acute myocardial infarction after statin use. We investigate the association of stress-induced hyperglycemia following statin use in patients with acute myocardial infarction. Methods An observational analysis of 476 consecutive patients who suffered acute myocardial infarction was carried out. All selected patients were divided into diabetes mellitus and non-diabetes based on the presence or absence of diabetes. The cardiac incidence of in-hospital and stress-induced hyperglycemia was recorded. Results Among patients with stress hyperglycemia in non-diabetes mellitus subgroups, the average fasting plasma glucose values in statin users were higher than in non-statin users (P < 0.05). But in diabetes mellitus subgroups, the average fasting plasma glucose did not have a significant difference between statin users and non-statin users (P > 0.05). In non-diabetes mellitus patients, the incidence of stress hyperglycemia with statin therapy was significantly higher than with non-statin therapy (P = 0.003). But in diabetes mellitus patients group, there is no significant difference in incidence of stress hyperglycemia between patients with statin therapy and patients without statin therapy (P = 0.902).The incidence of heart failure and in-hospital mortality of acute myocardial infarction in patients with stress-induced hyperglycemia was significantly higher than in non-hyperglycemia patients (P < 0.05). Conclusion Statins are related to higher stress hyperglycemia and cardiac incidences after acute myocardial infarction. PMID:27158481

  13. Role of Maintenance Therapy after High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Aggressive Lymphomas: A Systematic Review.

    PubMed

    Taverna, Josephine A; Yun, Seongseok; Jonnadula, Jayasree; Saleh, Ahlam; Riaz, Irbaz Bin; Abraham, Ivo; Yeager, Andrew M; Persky, Daniel O; McBride, Ali; Haldar, Subrata; Anwer, Faiz

    2016-07-01

    Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas. PMID:26899562

  14. Heterogeneity in statin indications within the 2013 american college of cardiology/american heart association guidelines.

    PubMed

    Shah, Ravi V; Rubenfire, Melvyn; Brook, Robert D; Lima, João A C; Nallamothu, Brahmajee; Murthy, Venkatesh L

    2015-01-01

    A standard ("core") implementation of American College of Cardiology/American Heart Association 2013 lipid guidelines (based on 10-year risk) dramatically increases the statin-eligible population in older Americans, raising controversy in the cardiovascular community. The guidelines also endorse a more "comprehensive" risk approach based in part on lifetime risk. The impact of this broader approach on statin eligibility remains unclear. We studied the impact of 2 different implementations of the new guidelines ("core" and "comprehensive") using the National Health and Nutrition Examination Survey. Although "core" guidelines led to 72.0 million subjects qualifying for statin therapy, the broader "comprehensive" application led to nearly a twofold greater estimate for statin-eligible subjects (121.2 million), with the greatest impact among those aged 21 to 45 years. Subjects indicated for statin therapy under comprehensive guidelines had a greater burden of cardiovascular risk factors and a higher lifetime risk of cardiovascular disease than those not indicated for statins. In particular, men aged 21 to 45 years had a 3.13-fold increased odds of being eligible for statin therapy only under the "comprehensive" guidelines (vs standard "core" guidelines; 95% confidence interval 2.82 to 3.47, p <0.0001). There were no racial differences. In conclusion, the "comprehensive" approach to statin eligibility espoused by the American College of Cardiology/American Heart Association 2013 guidelines would increase the statin-eligible population to over 120 million Americans, particularly targeting younger men with high-risk factor burden. PMID:25456869

  15. Identification of targeted therapy for an aggressive subgroup of muscle-invasive bladder cancers.

    PubMed

    Lebret, Thierry; Neuzillet, Yann; Houede, Nadine; Rebouissou, Sandra; Bernard-Pierrot, Isabelle; De Reynies, Aurélien; Benhamou, Simone; Allory, Yves; Radvanyi, François

    2015-01-01

    Rebouissou et al. recently provided preclinical evidence that a subset of patients with muscle-invasive bladder cancer might benefit from anti-epidermal growth factor receptor (EGFR) therapy and reported diagnostic tools for identifying these patients in the clinical setting. This work also identified relevant experimental models that may be useful for future basic and clinical research on this subgroup of tumors. PMID:27308521

  16. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

    NASA Astrophysics Data System (ADS)

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

  17. An Unusual Case of Statin-Induced Myopathy: Anti-HMGCoA Necrotizing Autoimmune Myopathy.

    PubMed

    Nichols, Laura; Pfeifer, Kurt; Mammen, Andrew L; Shahnoor, Nazima; Konersman, Chamindra G

    2015-12-01

    Statins are some of the most widely prescribed medications, and though generally well tolerated, can lead to a self-limited myopathy in a minority of patients. Recently, these medications have been associated with a necrotizing autoimmune myopathy (NAM). Statin-associated NAM is characterized by irritable myopathy on electromyography (EMG) and muscle necrosis with minimal inflammation on muscle biopsy. The case presented is a 63-year-old woman who has continued elevation of creatine kinase (CK) after discontinuation of statin therapy. She has irritable myopathy on EMG and NAM is confirmed by muscle biopsy. She subsequently tests positive for an experimental anti-3-hydroxy-3-methylglutaryl-coenzyme A (anti-HMGCoA) antibody that is found to be present in patients with statin-associated NAM. Though statin-associated NAM is a relatively rare entity, it is an important consideration for the general internist in patients who continue to have CK elevation and weakness after discontinuation of statin therapy. Continued research is necessary to better define statin-specific and dose-dependent risk, as well as optimal treatment for this condition. PMID:25855481

  18. A Statin-Loaded Reconstituted High-Density Lipoprotein Nanoparticle Inhibits Atherosclerotic Plaque Inflammation

    PubMed Central

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S.G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J.M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show this effect is mediated through inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show they accumulate in atherosclerotic lesions where they directly affect plaque macrophages. Finally we demonstrate that a three-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a one-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation. PMID:24445279

  19. Statins, Mood, Sleep, and Physical Function: A Systematic Review

    PubMed Central

    Swiger, Kristopher J.; Manalac, Raoul J.; Blaha, Michael J.; Blumenthal, Roger S.; Martin, Seth S.

    2014-01-01

    Purpose We aimed to evaluate the effects of statins on mood, sleep, and physical function. Methods We performed a systematic computer-aided search of MEDLINE/PubMed, EMBASE, and the Cochrane Central Register and augmented this search by scrutinizing reference lists, and making inquiries among colleagues and experts in the field. All patient populations and study types were considered. We selected studies of statin therapy compared with no statin or placebo. Outcome measures included mood, sleep, and physical function. Results Thirty four studies were included in qualitative synthesis. Seven of 8 (88%) observational studies, 4/6 (66%) randomized trials with mood as a primary endpoint (487 total participants; exposure 4 weeks to 1 year), and 3/3 (100%) randomized trials with mood as a secondary endpoint (2,851 total participants; exposure 1–4 years) were not compatible with a negative mood effect of statins. Comparatively fewer studies examined statin effects on sleep and physical function. Studies reporting negative effects contained potential sources of bias, including multiple testing or lack of adjustment for confounders in observational studies, and failure to pre-specify outcomes or report blinding in trials. Conclusions A limited body of available evidence is most compatible with no adverse effect of statins on quality of life measures, namely mood, sleep, and physical function. Studies suggesting such effects suffer from an increased risk of bias. High-quality, prospective, and adequately powered studies are needed, especially in the domains of sleep and physical function, with careful attention to patients who may be most vulnerable to adverse effects. PMID:25291991

  20. Effects of HMG-CoA reductase inhibitors on skeletal muscle: are all statins the same?

    PubMed

    Evans, Marc; Rees, Alan

    2002-01-01

    The 3-hydroxy-3-methyl coenzyme A (HMG-CoA) reductase inhibitors or statins, specifically inhibit the enzyme HMG-CoA in the liver, thereby inhibiting the rate limiting step in cholesterol biosynthesis and so reducing plasma cholesterol levels. Numerous studies have consistently demonstrated that cholesterol lowering with statin therapy reduces morbidity and mortality from coronary heart disease, whilst recent evidence has demonstrated that benefits of statin therapy may also extend into stroke prevention. Since hypercholesterolaemia is a chronic condition, the long-term safety and tolerability of these agents is an important issue. Numerous large-scale clinical trials have consistently demonstrated a positive safety and tolerability profile for statins. Hepatic, renal and muscular systems are rarely affected during statin therapy, with adverse reactions involving skeletal muscle being the most common, ranging from mild myopathy to myositis and occasionally to rhabdomyolysis and death. Postmarketing data supports the positive safety and tolerability profile of statins, with an overall adverse event frequency of less than 0.5% and a myotoxicity event rate of less than 0.1%. The recent withdrawal of cerivastatin from the world market due to deaths from rhabdomyolysis has, however, focused attention on the risk of adverse events and in particular myotoxicity associated with statins. Indeed, initial clinical trial data supports postmarketing data, demonstrating a higher incidence of myotoxicity associated with cerivastatin, particularly when used in combination with fibrates. The potential mechanisms underlying statin-induced myotoxicity are complex with no clear consensus of opinion. Candidate mechanisms include intracellular depletion of essential metabolites and destabilisation of cell membranes, resulting in increased cytotoxicity. Cytochrome P450 3A4 is the main isoenzyme involved in statin metabolism. Reduced activity of this enzyme due to either reduced

  1. Laboratory Medicine in the Clinical Decision Support for Treatment of Hypercholesterolemia: Pharmacogenetics of Statins.

    PubMed

    Ruaño, Gualberto; Seip, Richard; Windemuth, Andreas; Wu, Alan H B; Thompson, Paul D

    2016-09-01

    Statin responsiveness is an area of great research interest given the success of the drug class in the treatment of hypercholesterolemia and in primary and secondary prevention of cardiovascular disease. Interrogation of the patient's genome for gene variants will eventually guide anti-hyperlipidemic intervention. In this review, we discuss methodological approaches to discover genetic markers predictive of class-wide and drug-specific statin efficacy and safety. Notable pharmacogenetic findings are summarized from hypothesis-free genome wide and hypothesis-led candidate gene association studies. Physiogenomic models and clinical decision support systems will be required for DNA-guided statin therapy to reach practical use in medicine. PMID:27514463

  2. Statins are Associated with Reduced Use of Steroids in Inflammatory Bowel Disease: a Retrospective Cohort Study

    PubMed Central

    Crockett, Seth D.; Hansen, Richard A.; Stürmer, Til; Schectman, Robin; Darter, Jane; Sandler, Robert S.; Kappelman, Michael D.

    2011-01-01

    Introduction Statin medications have anti-inflammatory effects. We sought to determine whether statin use in persons with inflammatory bowel disease (IBD) was associated with reduced rates of steroid use or other markers of disease activity. Methods We performed a retrospective cohort study using administrative data. Statin users with IBD were compared to statin-unexposed IBD subjects. The primary outcome was an oral steroid prescription; secondary outcomes included anti-TNF initiation, hospitalization, or abdominal surgery. Cox proportional hazard models were used to estimate hazard ratios (HR) adjusted for potential confounders. Results The study cohort included 1,986 statin-exposed and 9,871 unexposed subjects. Statin use was associated with an 18% reduction in the rate of steroid initiation [HR 0.82 (95% CI 0.71, 0.94)]. A statistically significant result was seen with atorvastatin only [HR 0.76 (95% CI 0.60, 0.96)]. Statins were associated with a reduced rate of steroids in ulcerative colitis [HRs 0.75 (95% CI 0.62, 0.91)], but not in Crohn’s disease [HR 0.91 (95% CI 0.74, 1.12)]. Statin use was associated with reduced hazard of anti-TNF use [HR 0.72 (95% CI 0.46, 1.11)], abdominal surgery [HR 0.80 (95% CI 0.63, 1.02)], and hospitalization [HR 0.88 (95% CI 0.74, 1.05)], but these results did not reach statistical significance. Conclusion In this large retrospective cohort study, statin use amongst persons with IBD was associated with reduced use of oral steroids, particularly for UC. Prospective clinical trials are needed to confirm whether adjuvant treatment of IBD with statin drugs may spare immunosuppressant therapy or ameliorate flares. PMID:21826766

  3. Age-Varying Association Between Statin Use and Incident Alzheimer Disease

    PubMed Central

    Li, Ge; Shofer, Jane B.; Rhew, Isaac C.; Kukull, Walter A.; Peskind, Elaine R.; McCormick, Wayne; Bowen, James D.; Schellenberg, Gerard D.; Crane, Paul K.; Breitner, John C.S.; Larson, Eric B.

    2011-01-01

    Objectives Our earlier post hoc analysis suggested possible benefits of statins in reducing risk of Alzheimer’s disease (AD) in younger participants (< age 80 years) with the APOE ε4 allele. We further investigated these findings with more follow-up time and more recently enrolled participants. Design A cohort of cognitively intact elderly was assessed biennially for dementia and AD. Setting Community based. Participants 3,392 non-demented member of a health maintenance organization (HMO) aged ≥ 65 years. Measurements We identified statin use from the HMO pharmacy database and applied proportional hazards models with statin use as a time-dependent covariate to assess the statin-AD association and the modifying effects of age and the APOE ε4 allele. Results Over an average of 6.1 years of follow-up of 3099 participants, 263 participants developed probable AD. The adjusted hazard ratio (aHR) for statin use was 0.62 (95% confidence interval [CI], 0.40 – 0.97) for AD in models including demographic characteristics and vascular risk factors as covariates. The strength of the statin-AD association diminished with age (statin × age-at-entry interaction p = 0.04); the aHR in those younger than 80 was 0.44 (CI 0.25 – 0.78) vs. 1.22 (CI 0.61 – 2.42) for those older than 80. The interaction term for statin use × APOE ε4 was not significant (p = 0.65). Conclusion This enlarged study confirms earlier findings that statin therapy in early old age, but not in late age, may be associated with reduced risk of AD. The relationship between statin use and AD was consistent across APOE genotypes. PMID:20533968

  4. Statins and morbidity and mortality in COPD in the COMIC study: a prospective COPD cohort study

    PubMed Central

    Citgez, Emanuel; van der Palen, Job; Koehorst-ter Huurne, Kirsten; Movig, Kris; van der Valk, Paul; Brusse-Keizer, Marjolein

    2016-01-01

    Background Both chronic inflammation and cardiovascular comorbidity play an important role in the morbidity and mortality of patients with chronic obstructive pulmonary disease (COPD). Statins could be a potential adjunct therapy. The additional effects of statins in COPD are, however, still under discussion. The aim of this study is to further investigate the association of statin use with clinical outcomes in a well-described COPD cohort. Methods 795 patients of the Cohort of Mortality and Inflammation in COPD (COMIC) study were divided into statin users or not. Statin use was defined as having a statin for at least 90 consecutive days after inclusion. Outcome parameters were 3-year survival, based on all-cause mortality, time until first hospitalisation for an acute exacerbation of COPD (AECOPD) and time until first community-acquired pneumonia (CAP). A sensitivity analysis was performed without patients who started a statin 3 months or more after inclusion to exclude immortal time bias. Results Statin use resulted in a better overall survival (corrected HR 0.70 (95% CI 0.51 to 0.96) in multivariate analysis), but in the sensitivity analysis this association disappeared. Statin use was not associated with time until first hospitalisation for an AECOPD (cHR 0.95, 95% CI 0.74 to 1.22) or time until first CAP (cHR 1.1, 95% CI 0.83 to 1.47). Conclusions In the COMIC study, statin use is not associated with a reduced risk of all-cause mortality, time until first hospitalisation for an AECOPD or time until first CAP in patients with COPD. PMID:27403321

  5. How do we manage high-grade T1 bladder cancer? Conservative or aggressive therapy?

    PubMed Central

    Kim, Seon-Kyu; Kim, Wun-Jae

    2016-01-01

    High-grade T1 bladder cancer has a poor prognosis due to a higher incidence of recurrence and progression than other nonmuscle invasive bladder cancer; thus patients with high-grade T1 have to be carefully monitored and managed. If patients are diagnosed with high-grade T1 at initial transurethral resection (TUR), a second TUR is strongly recommended regardless of whether muscle layer is present in the specimen because of the possibility of understating due to incomplete resection. Since high-grade T1 disease shows diverse clinical courses, individual approaches are recommended for treatment. In cases with low risk of progression, cystectomy could represent overtreatment and deteriorate quality of life irreversibly, while, in those with high risk, bacillus Calmette-Guérin (BCG) therapy may worsen survival by delaying definitive therapy. Therefore, a strategy for predicting prognosis based on the risk of progression is needed for managing high-grade T1 disease. Molecular risk classifiers predicting the risk of progression and response to BCG may help identify the optimal management of high-grade T1 disease for each individual. PMID:27326407

  6. The Relationship Between the Level of Program Integrity and Pre- and Post-Test Changes of Responsive-Aggression Regulation Therapy (Re-ART) Outpatient: A Pilot Study.

    PubMed

    Hoogsteder, Larissa M; van Horn, Joan E; Stams, Geert Jan J M; Wissink, Inge B; Hendriks, Jan

    2016-03-01

    Responsive-Aggression Regulation Therapy (Re-ART) Outpatient is a cognitive behavioral-based intervention for adolescents and young adults (16-24 years) with severe aggressive behavioral problems. This pilot study (N = 26) examined the level of program integrity (PI; that is, the delivery of the intervention as it is originally intended) of Re-ART. We also investigated the pre- and post-test changes in several outcome variables, and the relation between the level of PI and these changes. Participants were recruited from three different outpatient forensic settings. Results showed that the PI of half of the treatments was not sufficient (e.g., the intensity of the program was too low and some standard modules were not offered). In addition, this pilot study demonstrated that sufficient PI was related to positive changes in aggression, cognitive distortions, social support, coping (reported by therapist), and distrust (responsiveness to treatment). PMID:25326466

  7. Cholesterol confusion and statin controversy.

    PubMed

    DuBroff, Robert; de Lorgeril, Michel

    2015-07-26

    The role of blood cholesterol levels in coronary heart disease (CHD) and the true effect of cholesterol-lowering statin drugs are debatable. In particular, whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently, the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes, cancer, and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary, we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD. PMID:26225201

  8. Cholesterol confusion and statin controversy

    PubMed Central

    DuBroff, Robert; de Lorgeril, Michel

    2015-01-01

    The role of blood cholesterol levels in coronary heart disease (CHD) and the true effect of cholesterol-lowering statin drugs are debatable. In particular, whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently, the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes, cancer, and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary, we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD. PMID:26225201

  9. The large social value resulting from use of statins warrants steps to improve adherence and broaden treatment.

    PubMed

    Grabowski, David C; Lakdawalla, Darius N; Goldman, Dana P; Eber, Michael; Liu, Larry Z; Abdelgawad, Tamer; Kuznik, Andreas; Chernew, Michael E; Philipson, Tomas

    2012-10-01

    Statins are considered a clinically important breakthrough for the treatment of cardiovascular disease. However, their social value at the US population level has not previously been studied. From an economic perspective, social value measures the quantity of resources--in monetary terms--that society would be willing to give up in order to retain the survival gains resulting from statin therapy. Using combined population and clinical data, this article calculates statins' social value to consumers, or the value of survival benefits above actual payments for the drug, and to producers, or drug revenues, for the period 1987-2008. National survey data suggest that statin therapy reduced low-density lipoprotein levels by 18.8 percent, which translated into roughly 40,000 fewer deaths, 60,000 fewer hospitalizations for heart attacks, and 22,000 fewer hospitalizations for strokes in 2008. For people starting statin therapy in 1987-2008, consumers captured $947.4 billion (76 percent) of the total social value of the survival gains. Even greater consumer benefits could be achieved in the future if statins were prescribed in full compliance with cholesterol guidelines and patients adhered to prescribed regimens. In addition, statin costs are declining because of patent expirations. Policy makers should consider interventions at the patient and provider levels to encourage both therapy for untreated patients with high cholesterol and greater adherence after therapy is initiated. PMID:23048109

  10. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    PubMed Central

    Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  11. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer.

    PubMed

    Dal Pra, Alan; Locke, Jennifer A; Borst, Gerben; Supiot, Stephane; Bristow, Robert G

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  12. [Adherence to statins: updates and practical proposals].

    PubMed

    Bauwens, Marine; Schneider, Marie-paule; Nanchen, David

    2016-03-01

    Statins are an established treatment for dyslipidemia, because they were shown to decrease the cardiovascular risk by 25%. However, one third of patients using statins don't take them regularly. Statin intolerance is an important risk factor for nonadherence, but health literacy and lack of education regarding the cardiovascular benefits are also important triggers for poor adherence to statins. A better communication between the caregiver and his patient, by taking patient's perspectives into account could help find effective solutions. This article reviews the issue of statins adherence and suggests solutions to improve it. PMID:27089601

  13. The use of statins in people at risk of developing diabetes mellitus: evidence and guidance for clinical practice.

    PubMed

    Sattar, Naveed A; Ginsberg, Henry; Ray, Kausik; Chapman, M John; Arca, Marcello; Averna, Maurizio; Betteridge, D John; Bhatnagar, Deepak; Bilianou, Elena; Carmena, Rafael; Ceška, Richard; Corsini, Alberto; Erbel, Raimund; Flynn, Paul D; Garcia-Moll, Xavier; Gumprecht, Janusz; Ishibashi, Shun; Jambart, Selim; Kastelein, John J P; Maher, Vincent; da Silva, Pedro Marques; Masana, Luis; Odawara, Masato; Pedersen, Terje R; Rotella, Carlo Maria; Salti, Ibrahim; Teramoto, Tamio; Tokgozoglu, Lale; Toth, Peter P; Valensi, Paul; Vergès, Bruno

    2014-06-01

    Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines. PMID:24840509

  14. The Effects of Aggression on Symptom Severity and Treatment Response in a Trial of Cognitive Behavioral Therapy for Panic Disorder

    PubMed Central

    Cassiello-Robbins, Clair; Conklin, Laren R.; Anakwenze, Ujunwa; Gorman, Jack M.; Woods, Scott W.; Shear, M. Katherine; Barlow, David H.

    2015-01-01

    Background Previous research suggests that patients with panic disorder exhibit higher levels of aggression than patients with other anxiety disorders. This aggression is associated with more severe symptomatology and interpersonal problems. However, few studies have examined whether higher levels of aggression are associated with a worse treatment response in this population. Methods The present study sought to examine the association of aggression with panic disorder symptom severity in a sample of 379 patients who participated in a trial examining long-term strategies for the treatment of panic disorder. Results We found that aggression was significantly associated with higher baseline levels of panic disorder symptoms, anxiety, depression, and functional impairment. Further, we found that patients higher in aggression did not achieve the same level of improvement in general anxiety symptoms during treatment compared to patients lower in aggression, even when controlling for baseline anxiety symptom severity. Conclusion These results suggest that more research is needed concerning patients with anxiety disorders with higher aggression, as they may be a group in need of additional treatment considerations. PMID:25987198

  15. Efficacy of Photodynamic Therapy and Lasers as an Adjunct to Scaling and Root Planing in the Treatment of Aggressive Periodontitis – A Clinical and Microbiologic Short Term Study

    PubMed Central

    Sarkar, Indranil; Rajan, Padma; Pai, Jagdish; Malagi, Sachin; Bharmappa, Radhika; Kamath, Vinesh

    2016-01-01

    Introduction Aggressive periodontitis comprises a group of rare, severe, rapidly progressive form of periodontitis. Conventional treatment includes mechanical debridement augmented with adjunctive antimicrobial therapy. Development of antibiotic resistance has led to use of lasers. Photodynamic therapy (PDT) is a novel non-invasive therapeutic approach with increased site and pathogen specificity. This study compares PDT and Lasers as an adjunct to conventional Scaling in the treatment of patients with aggressive periodontitis. Materials and Methods Fifteen untreated aggressive periodo-ntitis patients were randomly assigned in a split mouth design for one of the following treatment modalities: 1) SRP alone; (2) SRP + Diode Laser irradiation with 810 nm at 1W, continuous mode for 30 sec per tooth; (3) SRP + PDT on “0” day; (4) SRP + PDT on “0”, 7th and 21st day. The clinical parameters included PI, BOP, PPD, CAL recorded at the baseline & 3rd month. The site with greatest probing pocket depth (PPD) was selected from each quadrant for bacterial sampling and cultured for Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis & Prevotella intermedia. Results Statistically significant reduction in clinical & microbial parameters was seen. Sites 4 showed a greater reduction compared to other groups. Conclusion Photodynamic therapy is a valuable treatment modality adjunctive to conventional scaling and root planing. PMID:27042576

  16. Adherence to Drug Label Recommendations for Avoiding Drug Interactions Causing Statin-Induced Myopathy–A Nationwide Register Study

    PubMed Central

    Settergren, Jennifer; Eiermann, Birgit; Mannheimer, Buster

    2013-01-01

    Purpose To investigate the extent to which clinicians avoid well-established drug-drug interactions that cause statin-induced myopathy. We hypothesised that clinicians would avoid combining erythromycin or verapamil/diltiazem respectively with atorvastatin or simvastatin. In patients with statin-fibrate combination therapy, we hypothesised that gemfibrozil was avoided to the preference of bezafibrate or fenofibrate. When combined with verapamil/diltiazem or fibrates, we hypothesized that the dispensed doses of atorvastatin/simvastatin would be decreased. Methods Cross-sectional analysis of nationwide dispensing data. Odds ratios of interacting erythromycin, verapamil/diltiazem versus respective prevalence of comparator drugs doxycycline, amlodipine/felodipine in patients co-dispensed interacting statins simvastatin/atorvastatin versus patients unexposed (pravastatin/fluvastatin/rosuvastatin) was calculated. For fibrates, OR of gemfibrozil versus fenofibrate/bezafibrate in patients co-dispensed any statin was assessed. Results OR of interacting erythromycin versus comparator doxycycline did not differ between patients on interacting and comparator statins either in patients dispensed high or low statin doses (adjusted OR 0.87; 95% CI 0.60–1.25 and 0.92; 95% CI 0.69–1.23). Interacting statins were less common among patients dispensed verapamil/diltiazem as compared to patients on amlodipine/felodipine (OR high dose 0.62; CI 0.56–0.68 and low dose 0.63; CI 0.58–0.68). Patients on any statin were to a lesser extent dispensed gemfibrozil compared to patients not dispensed a statin (OR high dose 0.65; CI 0.55–0.76 and low dose 0.70; CI 0.63–0.78). Mean DDD (SD) for any statin was substantially higher in patients co-dispensed gemfibrozil 178 (149) compared to patients on statin monotherapy 127 (93), (p<0.001). Conclusions Prescribers may to some extent avoid co-prescription of statins with calcium blockers and fibrates with an increased risk of myopathy. We

  17. Effects of Coenzyme Q10 on Skeletal Muscle Oxidative Metabolism in Statin Users Assessed Using 31P Magnetic Resonance Spectroscopy: a Randomized Controlled Study

    PubMed Central

    Buettner, Catherine; Greenman, Robert L.; Ngo, Long H.; Wu, Jim S.

    2016-01-01

    Objectives Statins partially block the production of coenzyme Q10 (CoQ10), an essential component for mitochondrial function. Reduced skeletal muscle mitochondrial oxidative capacity has been proposed to be a cause of statin myalgia and can be measured using 31phosphorus magnetic resonance spectroscopy (31P-MRS). The purpose of this study is to assess the effect of CoQ10 oral supplementation on mitochondrial function in statin users using 31P-MRS. Design/Setting In this randomized, double-blind, placebo-controlled pilot study, 21 adults aged 47–73 were randomized to statin+placebo (n=9) or statin+CoQ10 (n=12). Phosphocreatine (PCr) recovery kinetics of calf muscles were assessed at baseline (off statin and CoQ10) and 4 weeks after randomization to either statin+CoQ10 or statin+placebo. Results Baseline and post-treatment PCr recovery kinetics were assessed for 19 participants. After 4 weeks of statin+ CoQ10 or statin+placebo, the overall relative percentage change (100*(baseline−follow up)/baseline) in PCr recovery time was −15.1% compared with baseline among all participants, (p-value=0.258). Participants randomized to statin+placebo (n=9) had a relative percentage change in PCr recovery time of −18.9%, compared to −7.7% among participants (n=10) receiving statin+CoQ10 (p-value=0.448). Conclusions In this pilot study, there was no significant change in mitochondrial function in patients receiving 4 weeks of statin+CoQ10 oral therapy when compared to patients on statin+placebo. PMID:27610419

  18. Therapeutic Management of Familial Hypercholesterolemia: Current and Emerging Drug Therapies.

    PubMed

    Patel, Roshni S; Scopelliti, Emily M; Savelloni, Julie

    2015-12-01

    Familial hypercholesterolemia (FH) is a genetic disorder characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) concentrations that result from mutations of the LDL receptor, apolipoprotein B (apo B-100), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Early and aggressive treatment can prevent premature atherosclerotic cardiovascular disease in these high-risk patients. Given that the cardiovascular consequences of FH are similar to typical hypercholesterolemia, traditional therapies are utilized to decrease LDL-C levels. Patients with FH should receive statins as first-line treatment; high-potency statins at high doses are often required. Despite the use of statins, additional treatments are often necessary to achieve appropriate LDL-C lowering in this patient population. Novel drug therapies that target the pathophysiologic defects of the condition are continuously emerging. Contemporary therapies including mipomersen (Kynamro, Genzyme), an oligonucleotide inhibitor of apo B-100 synthesis; lomitapide (Juxtapid, Aegerion), a microsomal triglyceride transfer protein inhibitor; and alirocumab (Praluent, Sanofi-Aventis/Regeneron) and evolocumab (Repatha, Amgen), PCSK9 inhibitors, are currently approved by the U.S. Food and Drug Administration for use in FH. This review highlights traditional as well as emerging contemporary therapies with supporting clinical data to evaluate current recommendations and discuss the future direction of FH management. PMID:26684558

  19. Effect of statins on the clinical outcomes of patients with sepsis.

    PubMed

    Goodin, J; Manrique, C; Dulohery, M; Sampson, J; Saettele, M; Dabbagh, O

    2011-11-01

    Despite numerous attempts at novel intervention and tests to aid in earlier diagnosis and improved treatment, there has been an increased incidence of overall mortality related to sepsis, despite improvements in in-hospital mortality. Statins have emerged as potential immunomodulatory and antioxidant agents that might impact on sepsis outcomes. Definitive evidence to support the routine use of statins in patients with sepsis has not yet been elicited. We retrospectively analysed data from patients who presented with sepsis, severe sepsis or septic shock, stratifiying them according to statin use into two groups (statin and no statin). Sequential Organ Failure Assessment was used to evaluate severity of illness. The primary outcome was hospital mortality. Secondary outcomes included intensive care unit (ICU) mortality, hospital and ICU length of stay, and mechanical ventilation and vasopressor therapy duration. Five hundred and sixty-eight patients were included. Patients with prior statin use (statin group) were older; more obese and had higher prevalence of smoking, diabetes and ischaemic heart disease. There was no difference in Sequential Organ Failure Assessment scores and mortality did not vary between the two groups (19.6 vs. 16.9%). Furthermore, secondary outcomes including ICU mortality, hospital and ICU length of stay, mechanical ventilation and vasopressor duration did not differ Multivariate analysis revealed age and Sequential Organ Failure Assessment score were independent predictors of survival, while history of statin use was not (p = 0.403). This current retrospective study did not find any benefit of statin use on primary and secondary outcomes of the patients admitted to an academic hospital with sepsis. PMID:22165357

  20. Targeting intratumoral androgens: statins and beyond.

    PubMed

    Schweizer, Michael T; Yu, Evan Y

    2016-09-01

    While initially effective, androgen deprivation therapy (ADT) is not curative, and nearly all men with advanced prostate cancer will eventually progress to the more resistant, and ultimately lethal form of the disease, so called castration-resistant prostate cancer (CRPC). The maintenance of androgens within the prostate cancer microenvironment likely represents one of the key mechanisms by which this transition from hormone-sensitive to CRPC occurs. This can be accomplished either through intratumoral androgen biosynthesis or the active transport of androgens and androgenic precursors into the tumor microenvironment. More recently, preclinical and clinical data supported therapeutic strategies that seek to target these two mechanisms, either through the use of drugs that impair androgen biosynthesis (e.g. inhibiting the steroidogenic enzymes CYP17 and AKR1C3 with abiraterone and indomethacin, respectively) or drugs that inhibit the SLCO transporters responsible for importing androgens (e.g. statins). PMID:27583031

  1. Effect of Statins on Venous Thromboembolic Events: A Meta-analysis of Published and Unpublished Evidence from Randomised Controlled Trials

    PubMed Central

    Rahimi, Kazem; Bhala, Neeraj; Kamphuisen, Pieter; Emberson, Jonathan; Biere-Rafi, Sara; Krane, Vera; Robertson, Michele; Wikstrand, John; McMurray, John

    2012-01-01

    Background It has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins. Methods and Findings We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9%] statin versus 521 [1.0%] control, odds ratio [OR] = 0.89, 95% CI 0.78–1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95% CI 0.72–1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95% CI 0.76–1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9%] versus 461 [1.0%], OR = 0.93 [95% CI 0.82–1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0%] versus 202 [1.0%], OR = 0.98, 95% CI 0.80–1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out. Please see later in the article for the Editors' Summary. Conclusions The findings from this meta-analysis do not support the

  2. BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy.

    PubMed

    Zheng, Hua-chuan; Li, Jing; Shen, Dao-fu; Yang, Xue-feng; Zhao, Shuang; Wu, Ya-zhou; Takano, Yasuo; Sun, Hong-zhi; Su, Rong-jian; Luo, Jun-sheng; Gou, Wen-feng

    2015-08-14

    Here, we found that BTG1 overexpression inhibited proliferation, migration and invasion, induced G2/M arrest, differentiation, senescence and apoptosis in BGC-823 and MKN28 cells (p < 0.05). BTG1 transfectants showed a higher mRNA expression of Cyclin D1 and Bax, but a lower mRNA expression of cdc2, p21, mTOR and MMP-9 than the control and mock (p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG1 transfectants showed lower mRNA viability and higher apoptosis than the control in both time- and dose-dependent manners (p < 0.05) with the hypoexpression of chemoresistance-related genes (slug, CD147, GRP78, GRP94, FBXW7 TOP1, TOP2 and GST-π). BTG1 expression was restored after 5-aza-2'-deoxycytidine treatment in gastric cancer cells. BTG1 expression was statistically lower in gastric cancer than non-neoplastic mucosa and metastatic cancer in lymph node (p < 0.05). BTG1 expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, TNM staging and worse prognosis (p < 0.05). The diffuse-type carcinoma showed less BTG1 expression than intestinal- and mixed-type ones (p < 0.05). BTG1 overexpression suppressed tumor growth and lung metastasis of gastric cancer cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that down-regulated BTG1 expression might promote gastric carcinogenesis partially due to its promoter methylation. BTG1 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer. PMID:26050197

  3. Inhibition of xanthine oxidase to prevent statin-induced myalgia and rhabdomiolysis.

    PubMed

    Alis, Rafael; Sanchis-Gomar, Fabian; Risso-Ballester, Jennifer; Perez-Quilis, Carme; Cortell-Ballester, Jose; Romagnoli, Marco; Blesa, Jose R; Emanuele, Enzo

    2015-03-01

    Although statins remain the cornerstone of lipid-lowering therapy for reducing the burden of atherosclerotic vascular disease, their administration has been associated with muscle-related adverse effects, including myalgia and rhabdomyolysis. Such adverse events are probably due to reduced antioxidant defenses associated with fewer intermediate metabolites in the cholesterol synthesis pathway. We hypothesize that the concomitant inhibition of xanthine oxidase via coadministration of allopurinol with statins could diminish reactive oxygen species (ROS)-related muscle damage, which would have in turn have positive effects on both the incidence of muscle-related adverse events and cardiovascular outcomes. Accordingly, inhibition of xanthine oxidase has been previously shown to be effective for reducing biomarkers of muscle damage following exercise in professional athletes. Because of the widespread statin utilization and increasing trends in their therapeutic use in atherosclerotic vascular diseases, the proposed strategy could have important clinical implications for reducing statin-induced myalgia and rhabdomyolysis. PMID:25568951

  4. Cholesterol suppresses antimicrobial effect of statins

    PubMed Central

    Haeri, Mohammad Reza; White, Kenneth; Qharebeglou, Mohammad; Ansar, Malek Moein

    2015-01-01

    Objective(s): Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. Materials and Methods: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria using gel diffusion assay. Results: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. Conclusion: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol. PMID:26877857

  5. Statin use and mortality of patients with prostate cancer: a meta-analysis

    PubMed Central

    Meng, Yang; Liao, Yan-Biao; Xu, Peng; Wei, Wu-Ran; Wang, Jia

    2016-01-01

    Objective The aim of this meta-analysis was to investigate the effect of statin use on the mortality of patients with prostate cancer (PCa). Methods An electronic search of PubMed, Embase, and CENTRAL databases from inception to August 2015 was performed to find eligible studies. Articles investigating the association between statin use and mortality of PCa were identified. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Results In total, 13 studies that enrolled 100,536 participants were included in this meta-analysis. Results showed that prediagnostic statin use had a significantly lower risk of both all-cause mortality (ACM; HR, 0.56; 95% CI, 0.38–0.83) and PCa-specific mortality (PCSM; HR, 0.53; 95% CI, 0.36–0.77). Similarly, postdiagnostic statin use was correlated with reductions in both ACM (HR, 0.77; 95% CI, 0.69–0.87) and PCSM (HR, 0.64; 95% CI, 0.52–0.79). When stratified by primary treatment, postdiagnostic use of statins had a 0.4-fold lower risk of ACM in patients with PCa who were treated with local therapy; both pre- and postdiagnostic use of statins was correlated with a significantly lower risk of PCSM in patients who were treated with androgen deprivation therapy. Conclusion Both pre- and postdiagnostic use of statins is associated with better overall survival and PCa-specific survival. This suggests a need for randomized controlled trials of statins in patients with PCa. PMID:27051303

  6. A review of trials evaluating nonstatin lipid-lowering therapies.

    PubMed

    Ansell, Benjamin J

    2009-01-01

    Recently reported clinical trials raise doubts on the effectiveness of nonstatin lipid-lowering therapies in reducing the residual risk of cardiovascular events after statin monotherapy. Addition of -torcetrapib to statin therapy increased overall mortality in coronary patients despite a marked increase in high-density lipoprotein cholesterol. Combining ezetimibe with statin therapy neither further reduces carotid atherosclerosis nor slows aortic stenosis, and it has not been shown to be superior to statin monotherapy in reducing cardiovascular events. Clinical trials currently in progress will more clearly delineate the cardiovascular effects of adding either ezetimibe or extended-release niacin/laropiprant to statin therapy. PMID:19080730

  7. Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase

    PubMed Central

    Würtz, Peter; Wang, Qin; Soininen, Pasi; Kangas, Antti J.; Fatemifar, Ghazaleh; Tynkkynen, Tuulia; Tiainen, Mika; Perola, Markus; Tillin, Therese; Hughes, Alun D.; Mäntyselkä, Pekka; Kähönen, Mika; Lehtimäki, Terho; Sattar, Naveed; Hingorani, Aroon D.; Casas, Juan-Pablo; Salomaa, Veikko; Kivimäki, Mika; Järvelin, Marjo-Riitta; Davey Smith, George; Vanhala, Mauno; Lawlor, Debbie A.; Raitakari, Olli T.; Chaturvedi, Nish; Kettunen, Johannes; Ala-Korpela, Mika

    2016-01-01

    Background Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized. Objectives This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. Methods Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. Results Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol [LDL-C]), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene (R2 = 0.94, slope 1.00 ± 0.03). Conclusions Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug

  8. Unmet Needs in LDL-C Lowering: When Statins Won't Do!

    PubMed

    Krähenbühl, Stephan; Pavik-Mezzour, Ivana; von Eckardstein, Arnold

    2016-08-01

    The use of low-density lipoprotein cholesterol (LDL-C)-lowering medications has led to a significant reduction of cardiovascular risk in both primary and secondary prevention. Statin therapy, one of the cornerstones for the prevention and treatment of cardiovascular disease (CVD), has been demonstrated to be effective in lowering LDL-C levels and in reducing the risk for CVD and is generally well-tolerated. However, compliance with statins remains suboptimal. One of the main reasons is limitations by adverse events, notably myopathies, which can lead to non-compliance with the prescribed statin regimen. Reducing the burden of elevated LDL-C levels is critical in patients with CVD as well as in patients with very high baseline levels of LDL-C (e.g. patients with familial hypercholesterolaemia), as statin therapy is insufficient for optimally reducing LDL-C below target values. In this review, we discuss alternative treatment options after maximally tolerated doses of statin therapy, including ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and cholesteryl ester transfer protein (CETP) inhibitors. Difficult-to-treat patients may benefit from combination therapy with ezetimibe or a PCSK9 inhibitor (evolocumab or alirocumab, which are now available). Updates of treatment guidelines are needed to guide the management of patients who will best benefit from these new treatments. PMID:27456066

  9. Disentangling the Association between Statins, Cholesterol, and Colorectal Cancer: A Nested Case-Control Study

    PubMed Central

    Mamtani, Ronac; Lewis, James D.; Scott, Frank I.; Ahmad, Tariq; Goldberg, David S.; Datta, Jashodeep; Yang, Yu-Xiao; Boursi, Ben

    2016-01-01

    Background Several prior studies have found an association between statin use and reduced risk of colorectal cancer. We hypothesized that these findings may be due to systematic bias and examined the independent association of colorectal cancer risk with statin use, serum cholesterol, and change in cholesterol concentration. Methods and Findings 22,163 colorectal cancer cases and 86,538 matched controls between 1995 and 2013 were identified within The Health Improvement Network (THIN) a population-representative database. Conditional logistic regression models estimated colorectal cancer risk with statin use, serum total cholesterol (mmol/L), and change in total cholesterol level. We confirmed a decreased risk of colorectal cancer with statin use (long-term: odds ratio [OR], 0.95; 95% confidence interval [CI], 0.91–0.99; short-term: OR, 0.92; 95% CI, 0.85–0.99). However, to assess whether the observed association may result from indication bias, a subgroup analysis was conducted among patients prescribed a statin. In this subgroup (n = 5,102 cases, n = 19,032 controls), 3.1% of case subjects and 3.1% of controls discontinued therapy. The risk of colorectal cancer was not significantly different among those who continued statin therapy and those who discontinued (OR, 0.98; 95% CI, 0.79–1.22). Increased serum cholesterol was independently associated with decreased risk of colorectal cancer (OR, 0.89 per mmol/L increase; 95% CI, 0.87–0.91); the association was only present if serum cholesterol was measured near the cancer diagnosis (<6 mo: OR, 0.76; 95% CI, 0.47–0.61; >24 mo: OR, 0.98; 95% CI, 0.93–1.03). Decreases in serum total cholesterol >1 mmol/L ≥1 year prior to cancer diagnosis were associated with subsequent colorectal cancer (statin users: OR, 1.25; 95 CI%, 1.03–1.53; nonusers: OR, 2.36; 95 CI%, 1.78–3.12). As an observational study, limitations included incomplete data and residual confounding. Conclusions Although the risk of colorectal

  10. Despite increased use and sales of statins in India, per capita prescription rates remain far below high-income countries.

    PubMed

    Choudhry, Niteesh K; Dugani, Sagar; Shrank, William H; Polinski, Jennifer M; Stark, Christina E; Gupta, Rajeev; Prabhakaran, Dorairaj; Brill, Gregory; Jha, Prabhat

    2014-02-01

    Statin use has increased substantially in North America and Europe, with resultant reductions in cardiovascular mortality. However, little is known about statin use in lower-income countries. India is of interest because of its burden of cardiovascular disease, the unique nature of its prescription drug market, and the growing globalization of drug sales. We conducted an observational study using IMS Health data for the period February 2006-January 2010. During the period, monthly statin prescriptions increased from 45.8 to 84.1 per 1,000 patients with coronary heart disease-an increase of 0.80 prescriptions per month. The proportion of the Indian population receiving a defined daily statin dose increased from 3.35 percent to 7.78 percent. Nevertheless, only a fraction of those eligible for a statin appeared to receive the therapy, even though there were 259 distinct statin products available to Indian consumers in January 2010. Low rates of statin use in India may reflect problems with access to health care, affordability, underdiagnosis, and cultural beliefs. Because of the growing burden of cardiovascular disease in lower-income countries such as India, there is an urgent need to increase statin use and ensure access to safe products whose use is based on evidence. Policies are needed to expand insurance, increase medications' affordability, educate physicians and patients, and improve regulatory oversight. PMID:24493771

  11. Pharmacological actions of statins: potential utility in COPD.

    PubMed

    Young, R P; Hopkins, R; Eaton, T E

    2009-12-01

    Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-κB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-α, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD. PMID:20956147

  12. Statin Use in Prostate Cancer: An Update.

    PubMed

    Babcook, Melissa A; Joshi, Aditya; Montellano, Jeniece A; Shankar, Eswar; Gupta, Sanjay

    2016-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are commonly prescribed for the treatment of hypercholesterolemia and cardiovascular disease. A systematic review was conducted using the keywords "statin and prostate cancer" within the title search engines including PubMed, Web of Science, and the Cochrane Library for relevant research work published between 2004 and December 2015. Although still premature, accumulating clinical evidence suggests that statin use may be beneficial in the prevention and/or treatment of prostate cancer. These human studies consist of meta-analyses of secondary endpoints obtained from randomized, controlled cardiovascular disease clinical trials of statins, patient database, observational studies, and a few, small case-control studies, directly addressing statin use on prostate cancer pathology and recurrence. This review summarizes and discusses the recent clinical literature on statins and prostate cancer with a recommendation to move forward with randomized, placebo-controlled clinical trials, investigating the use of statins. Additional preclinical testing of statins on prostate cancer cell lines and in vivo models is needed to elucidate pathways and determine its efficacy for prevention and/or treatment of prostate cancer, more specifically, the difference in the effectiveness of lipophilic versus hydrophilic statins in prostate cancer. PMID:27441003

  13. Statin use and risk of diabetes mellitus.

    PubMed

    Chogtu, Bharti; Magazine, Rahul; Bairy, K L

    2015-03-15

    The 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used in the primary and secondary prevention of cardiovascular diseases to lower serum cholesterol levels. As type 2 diabetes mellitus is accompanied by dyslipidemia, statins have a major role in preventing the long term complications in diabetes and are recommended for diabetics with normal low density lipoprotein levels as well. In 2012, United States Food and Drug Administration released changes to statin safety label to include that statins have been found to increase glycosylated haemoglobin and fasting serum glucose levels. Many studies done on patients with cardiovascular risk factors have shown that statins have diabetogenic potential and the effect varies as per the dosage and type used. The various mechanisms for this effect have been proposed and one of them is downregulation of glucose transporters by the statins. The recommendations by the investigators are that though statins can have diabetogenic risk, they have more long term benefits which can outweigh the risk. In elderly patients and those with metabolic syndrome, as the risk of diabetes increase, the statins should be used cautiously. Other than a subset of population with risk for diabetes; statins still have long term survival benefits in most of the patients. PMID:25789118

  14. Statins and transcriptional regulation: The FXR connection

    SciTech Connect

    Habeos, Ioannis; Ziros, Panos G.; Psyrogiannis, Agathoklis; Vagenakis, Apostolos G.; Papavassiliou, Athanasios G. . E-mail: papavas@med.upatras.gr

    2005-08-26

    Farnesoid X receptor (FXR) is a nuclear receptor involved in lipoprotein as well as glucose metabolism. Statins are widely used hypolipidemic agents with many pleiotropic actions. It is known that statins affect other nuclear hormone receptors, but no reports are available on the effect of these drugs on FXR. Employing an animal model (Syrian hamsters), we hereby present evidence to demonstrate that Simvastatin, a broadly prescribed statin, decreases the expression of FXR at both the RNA and protein levels and down-regulates its DNA-binding activity. This novel property may have important implications on the mode statins influence on lipoprotein and carbohydrate homeostasis in the organism.

  15. Statin Use in Prostate Cancer: An Update

    PubMed Central

    Babcook, Melissa A.; Joshi, Aditya; Montellano, Jeniece A.; Shankar, Eswar; Gupta, Sanjay

    2016-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are commonly prescribed for the treatment of hypercholesterolemia and cardiovascular disease. A systematic review was conducted using the keywords “statin and prostate cancer” within the title search engines including PubMed, Web of Science, and the Cochrane Library for relevant research work published between 2004 and December 2015. Although still premature, accumulating clinical evidence suggests that statin use may be beneficial in the prevention and/or treatment of prostate cancer. These human studies consist of meta-analyses of secondary endpoints obtained from randomized, controlled cardiovascular disease clinical trials of statins, patient database, observational studies, and a few, small case–control studies, directly addressing statin use on prostate cancer pathology and recurrence. This review summarizes and discusses the recent clinical literature on statins and prostate cancer with a recommendation to move forward with randomized, placebo-controlled clinical trials, investigating the use of statins. Additional preclinical testing of statins on prostate cancer cell lines and in vivo models is needed to elucidate pathways and determine its efficacy for prevention and/or treatment of prostate cancer, more specifically, the difference in the effectiveness of lipophilic versus hydrophilic statins in prostate cancer. PMID:27441003

  16. Differential Lipid Response to Statins is Associated with Variants in the BUD13-APOA5 Gene Region

    PubMed Central

    O'Brien, Sarah E; Schrodi, Steven J; Ye, Zhan; Brilliant, Murray H; Virani, Salim S.; Brautbar, Ariel

    2016-01-01

    Genetic variants within the BUD13-APOA5 gene region are known to be associated with high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels. Recent studies suggest that single-nucleotide polymorphisms (SNPs) within this region affect HDL-C response to statin-fibrate combination therapy and low-density lipoprotein cholesterol (LDL-C) response to statin therapy. We hypothesized that SNPs within the BUD13-APOA5 region are associated with TG, HDL-C, and LDL-C response to statin therapy. We examined 1520 observations for 1086 patients from the Personalized Medicine Research Project, a large biorepository at the Marshfield Clinic Research Foundation, who had received statin therapy and been previously genotyped for polymorphisms in the 11q23 chromosomal region. A significant differential response to statin therapy was observed for three SNPs. The minor allele at rs11605293 significantly attenuated TG-lowering response to pravastatin (P=1.59E-04) while the minor allele at rs12806755 was associated with a similar response to lovastatin (P=1.92E-04). Genotypes at rs947990 significantly attenuated LDL-C reduction to atorvastatin therapy (P=6.68E-04) with some patients with the minor allele having LDL-C increase following therapy. No SNPs within the BUD13-APOA5 region were associated with a significant effect on HDL-C reduction in response to statin therapy. In conclusion, this study suggests that common SNPs within the BUD13-APOA5 can affect TG and LDL-C response to statin therapy in a North American population. PMID:25900265

  17. Statins and breast cancer: a smoking gun or guilt by association?

    PubMed

    Ahmed, Mohamed H; Osman, Meissa M; Alokail, Majed S

    2006-09-01

    Statins are widely prescribed, effective cholesterol-lowering drugs. Indeed, atorvastatin and simvastatin were the most commonly prescribed drugs in the US in 2004, with > 70 million prescriptions written for atorvastatin alone. Statins are pleiotropic agents and, after an early study of patients with coronary heart disease showed a lower than expected incidence of cancers, preclinical studies were carried out that have supported the potential anticancer activity of these compounds. However, clinical reports on the relationship between statin use and breast cancer risk have yielded mixed results, with no association and both positive and negative associations being observed. Because breast cancer is the most frequent cancer in women, any link between statin use and breast cancer risk would have major public health implications. The current evidence suggests that statins are safe and effective agents in treating hyperlipidaemia and no evidence of increase or decrease risk of breast cancer. Indeed, more research is needed to define whether long-term statin therapy may decrease or increase the risk of breast cancer. PMID:16907648

  18. Clinical Factors Influencing the Efficacy of Systemic Moxifloxacin in the Therapy of Patients With Generalized Aggressive Periodontitis: A Multilevel Analysis From a Clinical Trial

    PubMed Central

    Ardila, Carlos M.; Guzmán, Isabel C.

    2016-01-01

    Background: It has been reported that clinical results of mechanical periodontal treatment could differ between subjects and among different sites of the tooth in the patient. The objective of this multilevel analysis is to investigate clinical factors at subject and sites of the tooth that influence variations in clinical attachment (CAL) increase and probing depth (PD) diminution of adjunctive moxifloxacin (MOX) at six months post-treatment in generalized aggressive periodontitis. Methods: This clinical trial included 40 patients randomly distributed to two therapy protocols: scaling and root planing alone or combined with MOX. Multilevel linear models for continuous variables were formulated to evaluate the clinical impact of the hierarchical configuration of periodontal data. Results: Six months following therapy, the divergences between both protocols were statistically significant in PD diminution and CAL increase, favouring the MOX therapy (p<0.001). Besides, the multilevel analysis revealed that adjunctive MOX at the subject level, non-molar and the interaction non-molar x MOX at the tooth level, interproximal sites and the interaction interproximal sites x MOX at the site level, were statistically significant factors in determining CAL increase and PD diminution. Conclusions: The main cause of variability in CAL gain and PD reduction following adjunctive MOX was attributable to the tooth level. Adjunctive MOX and their interactions with non-molar and interproximal sites showed higher clinical benefits at the tooth and site levels which could be essential for PD reduction and CAL gain in generalized aggressive periodontitis subjects. PMID:26493435

  19. Statins improve outcomes of nonsurgical curative treatments in hepatocellular carcinoma patients.

    PubMed

    Wu, Li-Li; Hsieh, Mao-Chih; Chow, Jyh-Ming; Liu, Shing-Hwa; Chang, Chia-Lun; Wu, Szu-Yuan

    2016-09-01

    Statins are associated with a reduced risk of hepatocellular carcinoma (HCC) and have the potential to be an adjuvant agent for HCC. In this study, we examined whether statin use is associated with additional benefits among patients who received curative treatments (CTs) such as surgery, percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA).We conducted a cohort study using the Taiwan National Health Insurance Research Data linked to the Taiwan Cancer Registry in 2001 to 2012. The patient cohort consisted of those who received different treatments, and we compared patients who received statins with those who did not. Statin users were defined as patients who received >28 cumulative defined daily doses after their HCC diagnosis. We used a time-dependent Cox proportional method to model the time from the HCC diagnosis to any death and HCC death between men who received statins and those who did not after adjusting for confounders. Data on statin prescriptions were collected every 6 months to define the user status.In total, 18,892 patients were included, and the mean follow-up duration was 1.74 years. The adjusted hazard ratio (aHR) of all-cause deaths increased in HCC patients who received RFA/PEI compared to those who received surgery (P < 0.0001 and P < 0.05, with aHRs of 1.81 and 1.16, respectively, for hepatitis B virus [HBV] or non-HBV HCC). However, with the addition of statin use to RFA or PEI, the overall survival was statistically equal.Surgical resection is still superior over other therapies. If HCC patients cannot meet the criteria for surgery, the addition of statin use to RFA or PEI might improve HCC survival. PMID:27603355

  20. Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?

    PubMed

    Ferenczi, Emily A; Asaria, Perviz; Hughes, Alun D; Chaturvedi, Nishi; Francis, Darrel P

    2010-08-15

    The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive

  1. Perihematoma cerebral blood flow is unaffected by statin use in acute intracerebral hemorrhage patients.

    PubMed

    Gioia, Laura C; Kate, Mahesh; McCourt, Rebecca; Gould, Bronwen; Coutts, Shelagh B; Dowlatshahi, Dariush; Asdaghi, Negar; Jeerakathil, Thomas; Hill, Michael D; Demchuk, Andrew M; Buck, Brian; Emery, Derek; Shuaib, Ashfaq; Butcher, Kenneth

    2015-07-01

    Statin therapy has been associated with improved cerebral blood flow (CBF) and decreased perihematoma edema in animal models of intracerebral hemorrhage (ICH). We aimed to assess the relationship between statin use and cerebral hemodynamics in ICH patients. A post hoc analysis of 73 ICH patients enrolled in the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT). Patients presenting <24 hours from ICH onset were randomized to a systolic blood pressure target <150 or <180 mm Hg with computed tomography perfusion imaging 2 hours after randomization. Cerebral blood flow maps were calculated. Hematoma and edema volumes were measured planimetrically. Regression models were used to assess the relationship between statin use, perihematoma edema and cerebral hemodynamics. Fourteen patients (19%) were taking statins at the time of ICH. Statin-treated patients had similar median (IQR Q25 to 75) hematoma volumes (21.1 (9.5 to 38.3) mL versus 14.5 (5.6 to 27.7) mL, P=0.25), but larger median (IQR Q25 to 75) perihematoma edema volumes (2.9 (1.7 to 9.0) mL versus 2.2 (0.8 to 3.5) mL, P=0.02) compared with nontreated patients. Perihematoma and ipsilateral hemispheric CBF were similar in both groups. A multivariate linear regression model revealed that statin use and hematoma volumes were independent predictors of acute edema volumes. Statin use does not affect CBF in ICH patients. Statin use, along with hematoma volume, are independently associated with increased perihematoma edema volume. PMID:25757757

  2. Perihematoma cerebral blood flow is unaffected by statin use in acute intracerebral hemorrhage patients

    PubMed Central

    Gioia, Laura C; Kate, Mahesh; McCourt, Rebecca; Gould, Bronwen; Coutts, Shelagh B; Dowlatshahi, Dariush; Asdaghi, Negar; Jeerakathil, Thomas; Hill, Michael D; Demchuk, Andrew M; Buck, Brian; Emery, Derek; Shuaib, Ashfaq; Butcher, Kenneth

    2015-01-01

    Statin therapy has been associated with improved cerebral blood flow (CBF) and decreased perihematoma edema in animal models of intracerebral hemorrhage (ICH). We aimed to assess the relationship between statin use and cerebral hemodynamics in ICH patients. A post hoc analysis of 73 ICH patients enrolled in the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT). Patients presenting <24 hours from ICH onset were randomized to a systolic blood pressure target <150 or <180 mm Hg with computed tomography perfusion imaging 2 hours after randomization. Cerebral blood flow maps were calculated. Hematoma and edema volumes were measured planimetrically. Regression models were used to assess the relationship between statin use, perihematoma edema and cerebral hemodynamics. Fourteen patients (19%) were taking statins at the time of ICH. Statin-treated patients had similar median (IQR Q25 to 75) hematoma volumes (21.1 (9.5 to 38.3) mL versus 14.5 (5.6 to 27.7) mL, P=0.25), but larger median (IQR Q25 to 75) perihematoma edema volumes (2.9 (1.7 to 9.0) mL versus 2.2 (0.8 to 3.5) mL, P=0.02) compared with nontreated patients. Perihematoma and ipsilateral hemispheric CBF were similar in both groups. A multivariate linear regression model revealed that statin use and hematoma volumes were independent predictors of acute edema volumes. Statin use does not affect CBF in ICH patients. Statin use, along with hematoma volume, are independently associated with increased perihematoma edema volume. PMID:25757757

  3. Statin Use and Markers of Immunity in the Doetinchem Cohort Study

    PubMed Central

    De Jong, Hilda J.I.; Damoiseaux, Jan G.M.C.; Vandebriel, Rob J.; Souverein, Patrick C.; Gremmer, Eric R.; Wolfs, Mia; Klungel, Olaf H.; Van Loveren, Henk; Cohen Tervaert, Jan Willem; Verschuren, W.M. Monique

    2013-01-01

    It has been suggested that statins can both stimulate and suppress the immune system, and thereby, may influence autoimmune diseases. Therefore, we studied effects of statins on innate and adaptive immunity, and self-tolerance by measuring serological levels of C-reactive protein (CRP), neopterin, immunoglobulin E (IgE) antibodies and the presence of autoantibodies (antinuclear antibodies (ANA) and IgM rheumatoid factor (RF)) in the general population. We conducted a nested case-control study within the population-based Doetinchem cohort. Data from health questionnaires, serological measurements and information on medication from linkage to pharmacy-dispensing records were available. We selected 332 statin users (cases) and 331 non-users (controls), matched by age, sex, date of serum collection, history of cardiovascular diseases, diabetes mellitus type II and stroke. Multivariate regression analyses were performed to estimate effect of statins on the immune system. The median level of CRP in statin users (1.28 mg/L, interquartile range (IQR): 0.59-2.79) was lower than in non-users (1.62 mg/L, IQR: 0.79-3.35), which after adjustment was estimated to be a 28% lower level. We observed an inverse association between duration of statin use and CRP levels. Elevated levels of IgE (>100 IU/mL) were more prevalent in statin users compared to non-users. A trend towards increased levels of IgE antibodies in statin users was observed, whereas no associations were found between statin use and levels of neopterin or the presence of autoantibodies. In this general population sub-sample, we observed an anti-inflammatory effect of statin use and a trend towards an increase of IgE levels, an surrogate marker for Th (helper) 2 responses without a decrease in neopterin levels, a surrogate marker for Th1 response and/or self-tolerance. We postulate that the observed decreased inflammatory response during statin therapy may be important but is insufficient to induce loss of self

  4. Non-cardiovascular effects associated with statins

    PubMed Central

    Martin, Seth S; Blumenthal, Roger S

    2014-01-01

    Statins form the pharmacologic cornerstone of the primary and secondary prevention of atherosclerotic cardiovascular disease. In addition to beneficial cardiovascular effects, statins seem to have multiple non-cardiovascular effects. Although early concerns about statin induced hepatotoxicity and cancer have subsided owing to reassuring evidence, two of the most common concerns that clinicians have are myopathy and diabetes. Randomized controlled trials suggest that statins are associated with a modest increase in the risk of myositis but not the risk of myalgia. Severe myopathy (rhabdomyolysis) is rare and often linked to a statin regimen that is no longer recommended (simvastatin 80 mg). Randomized controlled trials and meta-analyses suggest an increase in the risk of diabetes with statins, particularly with higher intensity regimens in people with two or more components of the metabolic syndrome. Other non-cardiovascular effects covered in this review are contrast induced nephropathy, cognition, cataracts, erectile dysfunction, and venous thromboembolism. Currently, systematic reviews and clinical practice guidelines indicate that the cardiovascular benefits of statins generally outweigh non-cardiovascular harms in patients above a certain threshold of cardiovascular risk. Literature is also accumulating on the potential non-cardiovascular benefits of statins, which could lead to novel applications of this class of drug in the future. PMID:25035309

  5. Non-cardiovascular effects associated with statins.

    PubMed

    Desai, Chintan S; Martin, Seth S; Blumenthal, Roger S

    2014-01-01

    Statins form the pharmacologic cornerstone of the primary and secondary prevention of atherosclerotic cardiovascular disease. In addition to beneficial cardiovascular effects, statins seem to have multiple non-cardiovascular effects. Although early concerns about statin induced hepatotoxicity and cancer have subsided owing to reassuring evidence, two of the most common concerns that clinicians have are myopathy and diabetes. Randomized controlled trials suggest that statins are associated with a modest increase in the risk of myositis but not the risk of myalgia. Severe myopathy (rhabdomyolysis) is rare and often linked to a statin regimen that is no longer recommended (simvastatin 80 mg). Randomized controlled trials and meta-analyses suggest an increase in the risk of diabetes with statins, particularly with higher intensity regimens in people with two or more components of the metabolic syndrome. Other non-cardiovascular effects covered in this review are contrast induced nephropathy, cognition, cataracts, erectile dysfunction, and venous thromboembolism. Currently, systematic reviews and clinical practice guidelines indicate that the cardiovascular benefits of statins generally outweigh non-cardiovascular harms in patients above a certain threshold of cardiovascular risk. Literature is also accumulating on the potential non-cardiovascular benefits of statins, which could lead to novel applications of this class of drug in the future. PMID:25035309

  6. Statins impair glucose uptake in human cells

    PubMed Central

    Nowis, Dominika; Malenda, Agata; Furs, Karolina; Oleszczak, Bozenna; Sadowski, Radoslaw; Chlebowska, Justyna; Firczuk, Malgorzata; Bujnicki, Janusz M; Staruch, Adam D; Zagozdzon, Radoslaw; Glodkowska-Mrowka, Eliza; Szablewski, Leszek; Golab, Jakub

    2014-01-01

    Objective Considering the increasing number of clinical observations indicating hyperglycemic effects of statins, this study was designed to measure the influence of statins on the uptake of glucose analogs by human cells derived from liver, adipose tissue, and skeletal muscle. Design Flow cytometry and scintillation counting were used to measure the uptake of fluorescently labeled or tritiated glucose analogs by differentiated visceral preadipocytes, skeletal muscle cells, skeletal muscle myoblasts, and contact-inhibited human hepatocellular carcinoma cells. A bioinformatics approach was used to predict the structure of human glucose transporter 1 (GLUT1) and to identify the presence of putative cholesterol-binding (cholesterol recognition/interaction amino acid consensus (CRAC)) motifs within this transporter. Mutagenesis of CRAC motifs in SLC2A1 gene and limited proteolysis of membrane GLUT1 were used to determine the molecular effects of statins. Results Statins significantly inhibit the uptake of glucose analogs in all cell types. Similar effects are induced by methyl-β-cyclodextrin, which removes membrane cholesterol. Statin effects can be rescued by addition of mevalonic acid, or supplementation with exogenous cholesterol. Limited proteolysis of GLUT1 and mutagenesis of CRAC motifs revealed that statins induce conformational changes in GLUTs. Conclusions Statins impair glucose uptake by cells involved in regulation of glucose homeostasis by inducing cholesterol-dependent conformational changes in GLUTs. This molecular mechanism might explain hyperglycemic effects of statins observed in clinical trials. PMID:25452863

  7. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

    SciTech Connect

    Katz, Matthew S.; Minsky, Bruce D. . E-mail: minskyb@mskcc.org; Saltz, Leonard B.; Riedel, Elyn; Chessin, David B.; Guillem, Jose G.

    2005-08-01

    Purpose: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. Methods and Materials: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-flurouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. Results: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. Conclusion: In multivariate analysis, statin use is associated with an improved p

  8. An overview of statin-associated proteinuria.

    PubMed

    Tiwari, Atul

    2006-05-01

    Statins are an established therapeutic modality for the treatment of hypercholesterolemia. Although they generally exhibit a good efficacy and tolerability profile, their reputation has been tarnished as a result of reports of myotoxicity and, more recently, observations of proteinuria. The increased incidence of proteinuria with rosuvastatin was of particular concern, and raised questions about the renoprotective actions of statins. Different hypotheses have been put forward to explain the mechanisms of statin-induced proteinuria. The multifarious effects of statins, independent of their effects on cholesterol-lowering, form the basis of such hypotheses. However, rosuvastatin-associated proteinuria is transient and reversible and even at the highest dose did not affect renal function after prolonged treatment. It would appear that clinically relevant proteinuria is not associated solely with rosuvastatin and might represent a minor class effect of statins with a fairly low incidence. However, definitive proof of this assertion will need to be provided by rigorous testing. PMID:16635810

  9. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08.

    PubMed

    Hitz, Felicitas; Zucca, Emanuele; Pabst, Thomas; Fischer, Natalie; Cairoli, Anne; Samaras, Panagiotis; Caspar, Clemens B; Mach, Nicolas; Krasniqi, Fatime; Schmidt, Adrian; Rothermundt, Christian; Enoiu, Milica; Eckhardt, Katrin; Berardi Vilei, Simona; Rondeau, Stephanie; Mey, Ulrich

    2016-07-01

    An increasing number of older patients are suffering from aggressive lymphoma. Effective and more tolerable treatment regimens are urgently needed for this growing patient population. Patients with aggressive lymphoma not eligible for anthracycline-based first-line therapy or intensive salvage regimens were treated with the rituximab-bendamustine-lenalidomide (R-BL) regimen (rituximab 375 mg/m(2)  day 1, bendamustine 70 mg/m(2)  d 1, 2, lenalidomide 10 mg d 1-21) for six cycles every 4 weeks. Forty-one patients with a median age of 75 (range 40-94) years were enrolled: 33 patients had substantial co-morbidities. 13 patients were not eligible for anthracycline-based first-line chemotherapy, 28 patients had relapsed/refractory disease. The primary endpoint, overall response, was achieved by 25 (61%) patients (95% confidence interval 45-76%). Grade ≥ 3 toxicity comprised haematological (59%), skin (15%), constitutional (15%) and neurological (12%) events. 9 patients died during trial treatment: 5 from lymphoma progression, 2 from toxicity, 2 with sudden death. After a median follow-up of 25·9 (interquartile range 20·4-31·6) months, 13 patients were still alive. Median overall survival was 14·5 months. In conclusion, R-BL can be considered a treatment option for elderly patients with treatment naïve or relapsed/refractory aggressive lymphoma not eligible for standard aggressive regimens. PMID:27018242

  10. Very low levels of atherogenic lipoproteins and risk of cardiovascular events; a meta-analysis of statin trials

    PubMed Central

    Boekholdt, S. Matthijs; Hovingh, G. Kees; Mora, Samia; Arsenault, Benoit J.; Amarenco, Pierre; Pedersen, Terje R.; LaRosa, John C.; Waters, David D.; DeMicco, David A.; Simes, R. John; Keech, Antony C.; Colquhoun, David; Hitman, Graham A.; Betteridge, D. John; Clearfield, Michael B.; Downs, John R.; Colhoun, Helen M.; Gotto, Antonio M.; Ridker, Paul M.; Grundy, Scott M.; Kastelein, John J.P.

    2015-01-01

    Objectives To evaluate (1) the inter-individual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein B (apoB) levels achieved with statin therapy, (2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy, and (3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and CVD risk. Background Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease (CVD) risk is not well documented. Methods Meta-analysis of individual patient data from 8 randomized controlled statin trials in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Results Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large inter-individual variability in the reductions of LDL-C, non-HDL-C and apoB achieved with a fixed statin dose. Over 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target below 70 mg/dL. Compared to patients who achieved an LDL-C > 175 mg/dL, those who reached an LDL-C 75-100 mg/dL, 50-75 mg/dL and < 50 mg/dL had adjusted hazard ratios for major cardiovascular events of 0.56 (95%CI 0.46-0.67), 0.51 (95%CI 0.42-0,62) and 0.44 (95%CI 0.35-0.55), respectively. Similar associations were observed for non-HDL-C and apoB. Conclusions The reduction of LDL-C, non-HDL-C and apoB levels achieved with statin therapy displays large inter-individual variation. Among trial participants treated with high-dose statin therapy, over 40% do not reach an LDL-C target <70 mg/dL. Patients who achieve very low LDL-C levels have a lower risk of major cardiovascular events than those achieving moderately low levels

  11. A novel therapeutic effect of statins on nephrogenic diabetes insipidus

    PubMed Central

    Bonfrate, Leonilde; Procino, Giuseppe; Wang, David Q-H; Svelto, Maria; Portincasa, Piero

    2015-01-01

    Statins competitively inhibit hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase, resulting in reduced plasma total and low-density lipoprotein cholesterol levels. Recently, it has been shown that statins exert additional ‘pleiotropic’ effects by increasing expression levels of the membrane water channels aquaporin 2 (AQP2). AQP2 is localized mainly in the kidney and plays a critical role in determining cellular water content. This additional effect is independent of cholesterol homoeostasis, and depends on depletion of mevalonate-derived intermediates of sterol synthetic pathways, i.e. farnesylpyrophosphate and geranylgeranylpyrophosphate. By up-regulating the expression levels of AQP2, statins increase water reabsorption by the kidney, thus opening up a new avenue in treating patients with nephrogenic diabetes insipidus (NDI), a hereditary disease that yet lacks high-powered and limited side effects therapy. Aspects related to water balance determined by AQP2 in the kidney, as well as standard and novel therapeutic strategies of NDI are discussed. PMID:25594563

  12. Controversies Regarding Lipid Management and Statin Use for Cardiovascular Risk Reduction in Patients With CKD.

    PubMed

    Markossian, Talar; Burge, Nicholas; Ling, Benjamin; Schneider, Julia; Pacold, Ivan; Bansal, Vinod; Leehey, David; Stroupe, Kevin; Chang, Alex; Kramer, Holly

    2016-06-01

    Adults with chronic kidney disease (CKD) are at heightened risk for dying of cardiovascular disease. Results from randomized clinical trials of statin drugs versus placebo demonstrate that statin drugs or statin plus ezetimibe reduce the absolute risk for coronary heart disease and mortality among adults with non-dialysis-dependent CKD. The Kidney Disease: Improving Global Outcomes 2013 clinical practice guideline for lipid management in CKD recommends that adults 50 years or older with non-dialysis-dependent CKD be treated with a statin or statin plus ezetimibe regardless of low-density lipoprotein cholesterol levels. However, at least 9 guidelines published during the last 5 years address lipid management for primary and secondary prevention of atherosclerotic cardiovascular disease, and not all guidelines address the utility of lipid-lowering therapy in adults with CKD. Because most patients with CKD receive most of their clinical care from non-nephrologists, differences in recommendations for lipid-lowering therapy for cardiovascular disease prevention may negatively affect the clinical care of adults with CKD and cause confusion for both patients and providers. This review addresses the identification and management of lipid levels in patients with CKD and discusses the existing controversies regarding testing and treatment of lipid levels in the CKD population. PMID:26943983

  13. Novel applications of statins for bone regeneration

    PubMed Central

    Shah, Sarita R.; Werlang, Caroline A.; Kasper, F. Kurtis; Mikos, Antonios G.

    2015-01-01

    The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering. PMID:26543666

  14. Statins and angiogenesis: Is it about connections?

    SciTech Connect

    Khaidakov, Magomed; Wang, Wenze; Khan, Junaid A.; Kang, Bum-Yong; Hermonat, Paul L.; Mehta, Jawahar L.

    2009-09-25

    Statins, inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, have been shown to induce both angiogenic and angiostatic responses. We attempted to resolve this controversy by studying the effects of two different statins, rosuvastatin and simvastatin, in two different assay systems. In the matrigel angiogenesis assay, both statins enhanced tube formation by human umbilical vein endothelial cells (HUVECs, p < 0.01 vs. control). In the ex vivo mouse aortic ring sprouting assay, both statins virtually abolished new vessel formation (p < 0.01). As a basic difference between the two models of angiogenesis is dispersed state of endothelial cells vs. compact monolayer, we analyzed influence of statins on endothelial junction proteins. RT-PCR analysis and cytoimmunostaining of HUVECs treated with simvastatin revealed increased expression of VE-cadherin (p < 0.05). The blockade of VE-cadherin with a specific antibody reversed simvastatin-induced tube formation (p < 0.002). These data suggest that statins through VE-cadherin stimulation modulate cell-cell adhesion and diminish the ability of cells to proliferate and migrate. The observations of reduced angiogenesis in the intact vessel may relate to anti-atherosclerotic and anti-cancer effects of statins, and provide a feasible explanation for conflicting data under different experimental conditions.

  15. Proton-Beam, Intensity-Modulated, and/or Intraoperative Electron Radiation Therapy Combined with Aggressive Anterior Surgical Resection for Retroperitoneal Sarcomas

    PubMed Central

    Yoon, Sam S.; Chen, Yen-Lin; Kirsch, David G.; Maduekwe, Ugwuji N.; Rosenberg, Andrew E.; Nielsen, G. Petur; Sahani, Dushyant V.; Choy, Edwin; Harmon, David C.; DeLaney, Thomas F.

    2010-01-01

    Background We sought to reduce local recurrence for retroperitoneal sarcomas by using a coordinated strategy of advanced radiation techniques and aggressive en-bloc surgical resection. Methods Proton-beam radiation therapy (PBRT) and/or intensity-modulated radiation therapy (IMRT) were delivered to improve tumor target coverage and spare selected adjacent organs. Surgical resection of tumor and adjacent organs was performed to obtain a disease-free anterior margin. Intraoperative electron radiation therapy (IOERT) was delivered to any close posterior margin. Results Twenty patients had primary tumors and eight had recurrent tumors. Tumors were large (median size 9.75 cm), primarily liposarcomas and leiomyosarcomas (71%), and were mostly of intermediate or high grade (81%). PBRT and/or IMRT were delivered to all patients, preferably preoperatively (75%), to a median dose of 50 Gy. Surgical resection included up to five adjacent organs, most commonly the colon (n = 7) and kidney (n = 7). Margins were positive for disease, usually posteriorly, in 15 patients (54%). IOERT was delivered to the posterior margin in 12 patients (43%) to a median dose of 11 Gy. Surgical complications occurred in eight patients (28.6%), and radiation-related complications occurred in four patients (14%). After a median follow-up of 33 months, only two patients (10%) with primary disease experienced local recurrence, while three patients (37.5%) with recurrent disease experienced local recurrence. Conclusions Aggressive resection of retroperitoneal sarcomas can achieve a disease-negative anterior margin. PBRT and/or IMRT with IOERT may possibly deliver sufficient radiation dose to the posterior margin to control microscopic residual disease. This strategy may minimize radiation-related morbidity and reduce local recurrence, especially in patients with primary disease. PMID:20151216

  16. Statin Effects to Reduce Hepatosteatosis as Measured by Computed Tomography in Patients With Human Immunodeficiency Virus

    PubMed Central

    Lo, Janet; Lu, Michael T.; Kim, Elli A.; Nou, Eric; Hallett, Travis R.; Park, Jakob; Hoffmann, Udo; Grinspoon, Steven K.

    2016-01-01

    Hepatosteatosis is highly prevalent among patients living with human immunodeficiency virus. In a 1-year, randomized, double-blind trial of atorvastatin or placebo, atorvastatin increased liver/spleen ratio among patients with nonalcoholic fatty liver disease, indicating a reduction in hepatosteatosis. This reduction in hepatosteatosis is associated with reduction in low-density lipoprotein cholesterol with statin therapy. PMID:27419149

  17. Statin Effects to Reduce Hepatosteatosis as Measured by Computed Tomography in Patients With Human Immunodeficiency Virus.

    PubMed

    Lo, Janet; Lu, Michael T; Kim, Elli A; Nou, Eric; Hallett, Travis R; Park, Jakob; Hoffmann, Udo; Grinspoon, Steven K

    2016-04-01

    Hepatosteatosis is highly prevalent among patients living with human immunodeficiency virus. In a 1-year, randomized, double-blind trial of atorvastatin or placebo, atorvastatin increased liver/spleen ratio among patients with nonalcoholic fatty liver disease, indicating a reduction in hepatosteatosis. This reduction in hepatosteatosis is associated with reduction in low-density lipoprotein cholesterol with statin therapy. PMID:27419149

  18. Statins and myotoxicity: a therapeutic limitation.

    PubMed

    Tiwari, Atul; Bansal, Vinay; Chugh, Anita; Mookhtiar, Kasim

    2006-09-01

    Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors represent the most successful class of drugs for the treatment of hypercholesterolaemia and dyslipidaemia implicated in the pathogenesis of coronary heart disease and atherosclerosis. However, the popular profile of statins in terms of efficacy has been maligned by its adverse events. The myotoxicity, ranging from mild myopathy to serious rhabdomyolysis, associated with HMG-CoA reductase inhibitors, during treatment of hypercholesterolaemia is of paramount importance. Rhabdomyolysis is a rare but idiosyncratic muscle wasting disorder of different etiologies. Statin-associated rhabdomyolysis causes skeletal muscle injury by self-perpetuating events leading to fatal irreversible renal damage through a series of biochemical reactions. Preferential distribution and action of statins in liver could be the key to minimise myotoxicity concerns. Hepato-specific distribution of statins is governed by various factors such as physicochemical properties, pharmacokinetic properties and selective transporter-mediated uptake in liver rather in extrahepatic cells. The interactions of statins with concomitant drugs of different classes merit attention for their safety profile. Although pharmacokinetic as well as pharmacodynamic interactions have been implicated in pathophysiology of statin-induced muscle wasting, the underlying mechanism is not clearly understood. Besides, pharmacokinetic and phramcodynamic factors, statin-associated myotoxcity may also implicate pharmacogenomic factors. The pharmacogenomics characterised by CYP polymorphism and other genetic factors is responsible for inter-individual variations to efficacy and tolerability of statins. The pathophysiological mechanisms may include statin-induced differences in cholesterol:phospholipid ratio, isoprenoid levels, small GTP binding proteins and apoptosis. However, the present understanding of pathophysiological mechanisms, does not offer a reliable

  19. Statins in pneumonia--magic versus science?

    PubMed

    Kruger, Peter S; Thomas, Robert M

    2012-01-01

    Several studies have investigated the use of statins as an adjunct in the treatment of pneumonia, some with conflicting conclusions. The most recent of these large observational studies again suggests statin use is associated with an improved outcome for patients with pneumonia. How best to incorporate these findings into current practice is of great interest. Hidden confounders plague database interrogation and so cast doubt on the real or causal nature of observed associations. Data from large, observational studies must be complemented by smaller biological studies and randomised controlled trials in an effort to complete missing pieces in the biological puzzle of the use of statins in patients with pneumonia. PMID:23025797

  20. Translational insight into statin-induced muscle toxicity: from cell culture to clinical studies.

    PubMed

    Taha, Dhiaa A; De Moor, Cornelia H; Barrett, David A; Gershkovich, Pavel

    2014-08-01

    Statins are lipid-lowering drugs used widely to prevent and treat cardiovascular and coronary heart diseases. These drugs are among the most commonly prescribed medicines intended for long-term use. In general, statins are well tolerated. However, muscular adverse effects appear to be the most common obstacle that limits their use, resulting in poor patient compliance or even drug discontinuation. In addition, rare but potentially fatal cases of rhabdomyolysis have been reported with the use of these drugs, especially in the presence of certain risk factors. Previous reports have investigated statin-induced myotoxicity in vivo and in vitro using a number of cell lines, muscle tissues, and laboratory animals, in addition to randomized clinical trials, observational studies, and case reports. None of them have compared directly results from laboratory investigations with clinical observations of statin-related muscular adverse effects. To the best of our knowledge this is the first review article that combines laboratory investigation with clinical aspects of statin-induced myotoxicity. By reviewing published literature of in vivo, in vitro, and clinically relevant studies of statin myotoxicity, we aim to translate this important drug-related problem to establish a clear picture of proposed mechanisms that explain the risk factors and describe the diagnostic approaches currently used for evaluating the degree of muscle damage induced by these agents. This review provides baseline novel translational insight that can be used to enhance the safety profile, to minimize the chance of progression of these adverse effects to more severe and potentially fatal rhabdomyolysis, and to improve the overall patient compliance and adherence to long-term statin therapy. PMID:24530275

  1. Effect of Statins on the Progression of Coronary Calcification in Kidney Transplant Recipients

    PubMed Central

    Yazbek, Daniel Constantino; de Carvalho, Aluizio Barbosa; Barros, Cinara Sá; Medina Pestana, Jose Osmar; Canziani, Maria Eugênia F.

    2016-01-01

    Background Coronary calcification (CAC) is highly prevalent in kidney transplant recipients (KTRs) and has been associated with cardiovascular morbidity and mortality. Some studies have shown a reduction in CAC progression with statin therapy in the general and chronic kidney disease (CKD) populations. Objectives and Methods The aim of the present study was to evaluate the effect of statins on CAC progression in incident kidney transplant recipients. Patients were randomly assigned to the statin (n = 61, 10 mg daily) and control group (n = 59). CAC and biochemical analyses were performed at baseline and 12 months. Results At baseline, CAC was observed in 30% and 21% of patients in the statin and control groups, respectively (p = 0.39). The calcium score at baseline and its absolute and relative changes over 12 months of follow up were similar among the groups. In the statin group, total cholesterol (p < 0.001), low density lipoprotein cholesterol (p < 0.001) and triglycerides (p = 0.005) decreased, and the estimated glomerular function rate increased (p<0.001) significantly. CRP levels remained stable (p = 0.52) in the statin group but increased in the control group (p = 0.01). In the multivariate model, there was no difference in CAC progression between the groups (group effect p = 0.034; time-effect p = 0.23; interaction p = 0.74). Similar results were obtained when only patients with ≥ 10AU calcium score (calcified) were analyzed (group effect p = 0.051; time-effect p = 0.58; interaction p = 0.99). Conclusion Although statins reduce the levels of cholesterol, triglycerides, inflammation and improve graft function, the dose adopted in the current study did not delay CAC progression within 12 months of follow up. Trial Registration Brazilian Clinical Trials Registry RBR-32RFMB PMID:27100788

  2. The Effect of Statins Use on the Risk and Outcome of Acute Bacterial Infections in Adult Patients

    PubMed Central

    Ghorbani, Raheb; Afshar, Reza Kiaee

    2015-01-01

    Background Beyond their lipid-lowering abilities, statins have anti-inflammatory and immunomodulatory properties. In view of these effects, a growing interest has emerged in the possible role of statins, in preventing or decreasing morbidity and mortality from infection. Objectives The aim of this study was to determine whether previous statin use is associated with reduced risk of acute bacterial infections and better outcome of these infections. Materials and Methods In this historical cohort study, consecutive adult patients admitted with acute bacterial infection were enrolled. Control group were selected from adult outpatient and without history of acute bacterial infections. Acute bacterial infections included in this study were; pneumonia, acute pyelonephritis, cellulitis and sepsis with unknown origin. Data about baseline characteristics, co-morbidities and statins use of two groups was obtained. Results Finally 144 patients met inclusion criteria and were enrolled. Same numbers of controls were selected. Two groups were matched based on most baseline characteristics and co-morbidities. The patients’ categories were as follows: pneumonia 42.3%, acute pyelonephritis 23.6%, cellulitis 16% and sepsis 18%. From all participants 29.9% of patients and 45.8% controls were statin users. There was significant association between previous statin use and reduced risk of acute bacterial infections (Mantel Haenszel Weighted Odds Ratio=0.51, 95% CI: 0.30-0.85, p=0.009). Duration of hospitalization was significantly shorter in statin users (p=0.002). Hospital mortality rate was lower (14.6%) in statins users when compared with non-users (18.8%) with significant difference (p=0.028). Conclusion Prior therapy with statins is associated with considerably reduced onset of acute bacterial infections and better outcome in adult patients. PMID:26676277

  3. Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley; Yamada, Yoshiya; Feder, David J.; Zhang Zhigang; Jia Xiaoyu; Shi Weiji; Zelefsky, Michael J.

    2011-03-01

    Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years. Results: The 5- and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p = 0.002). In a multivariate analysis, statin use (hazard ratio [HR]0.69, p = 0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p = 0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p = 0.51). On multivariate analysis, lower NCCN risk group (p = 0.01) and ADT use (p = 0.005) predicted improved DMFS. Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer.

  4. Co-medication of statins and CYP3A4 inhibitors before and after introduction of new reimbursement policy

    PubMed Central

    Devold, Helene M; Molden, Espen; Skurtveit, Svetlana; Furu, Kari

    2009-01-01

    AIMS To assess the prevalence of co-medication of statins and CYP3A4 inhibitors before and after introduction of a new Norwegian reimbursement policy, which states that all patients should be prescribed simvastatin as first-line lipid-lowering therapy. METHODS Data from patients receiving simvastatin, lovastatin, pravastatin, fluvastatin or atorvastatin in 2004 and 2006, including co-medication of potent CYP3A4 inhibitors, were retrieved from the Norwegian Prescription Database covering the total population of Norway. Key measurements were prevalence of continuous statin use (two or more prescriptions on one statin) and proportions of different statin types among all patients and those co-medicated with CYP3A4 inhibitors. RESULTS In 2004, 5.9% (n = 272 342) of the Norwegian population received two or more prescriptions on one statin compared with 7.0% (n = 324 267) in 2006. The relative number of simvastatin users increased from 39.7% (n = 112 122) in 2004 to 63.1% (n = 226 672) in 2006. A parallel increase was observed within the subpopulation co-medicated with statins and CYP3A4 inhibitors, i.e. from 42.9% (n = 7706) in 2004 to 63.6% (n = 13 367) in 2006. For all other statins the number of overall users decreased to a similar extent to those co-medicated with CYP3A4 inhibitors. CONCLUSIONS In both 2004 and 2006, the choice of statin type did not depend on whether the patient used a CYP3A4 inhibitor or not. Considering the pronounced interaction potential of simvastatin with CYP3A4 inhibitors, a negative influence of the new policy on overall statin safety seems likely. PMID:19220274

  5. Statins Enhance Clonal Growth of Late Outgrowth Endothelial Progenitors and Increase Myocardial Capillary Density in the Chronically Ischemic Heart

    PubMed Central

    Wang, Wen; Lang, Jennifer K.; Suzuki, Gen; Canty, John M.; Cimato, Thomas

    2011-01-01

    Background Coronary artery disease and ischemic heart disease are leading causes of heart failure and death. Reduced blood flow to heart tissue leads to decreased heart function and symptoms of heart failure. Therapies to improve heart function in chronic coronary artery disease are important to identify. HMG-CoA reductase inhibitors (statins) are an important therapy for prevention of coronary artery disease, but also have non-cholesterol lowering effects. Our prior work showed that pravastatin improves contractile function in the chronically ischemic heart in pigs. Endothelial progenitor cells are a potential source of new blood vessels in ischemic tissues. While statins are known to increase the number of early outgrowth endothelial progenitor cells, their effects on late outgrowth endothelial progenitor cells (LOEPCs) and capillary density in ischemic heart tissue are not known. We hypothesized that statins exert positive effects on the mobilization and growth of late outgrowth EPCs, and capillary density in ischemic heart tissue. Methodology/Principal Findings We determined the effects of statins on the mobilization and growth of late outgrowth endothelial progenitor cells from pigs. We also determined the density of capillaries in myocardial tissue in pigs with chronic myocardial ischemia with or without treatment with pravastatin. Pravastatin therapy resulted in greater than two-fold increase in CD31+ LOEPCs versus untreated animals. Addition of pravastatin or simvastatin to blood mononuclear cells increased the number of LOEPCs greater than three fold in culture. Finally, in animals with chronic myocardial ischemia, pravastatin increased capillary density 46%. Conclusions Statins promote the derivation, mobilization, and clonal growth of LOEPCs. Pravastatin therapy in vivo increases myocardial capillary density in chronically ischemic myocardium, providing an in vivo correlate for the effects of statins on LOEPC growth in vitro. Our findings provide

  6. A statin-dependent QTL for GATM expression is associated with statin-induced myopathy.

    PubMed

    Mangravite, Lara M; Engelhardt, Barbara E; Medina, Marisa W; Smith, Joshua D; Brown, Christopher D; Chasman, Daniel I; Mecham, Brigham H; Howie, Bryan; Shim, Heejung; Naidoo, Devesh; Feng, QiPing; Rieder, Mark J; Chen, Yii-Der I; Rotter, Jerome I; Ridker, Paul M; Hopewell, Jemma C; Parish, Sarah; Armitage, Jane; Collins, Rory; Wilke, Russell A; Nickerson, Deborah A; Stephens, Matthew; Krauss, Ronald M

    2013-10-17

    Statins are prescribed widely to lower plasma low-density lipoprotein (LDL) concentrations and cardiovascular disease risk and have been shown to have beneficial effects in a broad range of patients. However, statins are associated with an increased risk, albeit small, of clinical myopathy and type 2 diabetes. Despite evidence for substantial genetic influence on LDL concentrations, pharmacogenomic trials have failed to identify genetic variations with large effects on either statin efficacy or toxicity, and have produced little information regarding mechanisms that modulate statin response. Here we identify a downstream target of statin treatment by screening for the effects of in vitro statin exposure on genetic associations with gene expression levels in lymphoblastoid cell lines derived from 480 participants of a clinical trial of simvastatin treatment. This analysis identified six expression quantitative trait loci (eQTLs) that interacted with simvastatin exposure, including rs9806699, a cis-eQTL for the gene glycine amidinotransferase (GATM) that encodes the rate-limiting enzyme in creatine synthesis. We found this locus to be associated with incidence of statin-induced myotoxicity in two separate populations (meta-analysis odds ratio = 0.60). Furthermore, we found that GATM knockdown in hepatocyte-derived cell lines attenuated transcriptional response to sterol depletion, demonstrating that GATM may act as a functional link between statin-mediated lowering of cholesterol and susceptibility to statin-induced myopathy. PMID:23995691

  7. Are statin trials in diabetes representative of real-world diabetes care: a population-based study on statin initiators in Finland

    PubMed Central

    Ruokoniemi, Päivi; Sund, Reijo; Arffman, Martti; Helin-Salmivaara, Arja; Huupponen, Risto; Keskimäki, Ilmo; Vehko, Tuulikki; Korhonen, Maarit Jaana

    2014-01-01

    Objective To assess the representativeness of the Heart Protection Study (HPS) and the Collaborative Atorvastatin Diabetes Study (CARDS) for incident statin users. Design A population-based analysis with linked register data. Setting Finland. Population 56 963 patients with diabetes initiating statin use from 2005 to 2008. Main outcome measures We determined the proportions of real-world patients who fulfilled the eligibility criteria for HPS and CARDS trials and assessed the cardiovascular disease (CVD) event rates, assumed to reflect the background CVD risk, for those eligible and ineligible. We used descriptive statistics to identify the patient characteristics, lipid-lowering interventions and adherence to statin therapy. Results Of the real-world patients, 57% (N=32 582) fulfilled the eligibility criteria for HPS (DM) and 49% (N=20 499) of those without CVD for CARDS. The patients ineligible for HPS (DM) had a higher cumulative risk for CVD events than those eligible, whereas regarding CARDS the cumulative risks were of similar magnitude. The overall CVD event rates seemed to be comparable to those in the reviewed trials. Both trials were under-representative of women and users of antihypertensive agents and metformin. 27% and 29% of real-world patients had an initial statin dose corresponding to <20 mg of simvastatin. The proportions of patients who were deemed adherent were 57% in the real world and 85% in both trials. Conclusions Only half of the real-world patients would have qualified for the HPS (DM) and CARDS, limiting their representativeness for clinical practice. Women and users of antihypertensive agents and metformin were under-represented in both trials. These deviations reflect the changes in diabetes treatment over the years and are not expected to modify the average treatment effects of statins on CVD. Prescribing of lower statin doses in clinical practice than used in the trials and lower adherence may, however, attenuate the benefits

  8. Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients

    PubMed Central

    Klein Hesselink, E.N.; Links, T.P.

    2015-01-01

    Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine. PMID:26279993

  9. A review on the use of statins and tocotrienols, individually or in combination for the treatment of osteoporosis.

    PubMed

    Abdul-Majeed, Saif; Mohamed, Norazlina; Soelaiman, Ima-Nirwana

    2013-12-01

    Skeletal tissue undergoes continuous remodeling which makes it unique among other body tissues. Osteoporosis is a common bone metabolic disorder affecting both men and women. Osteoporosis and its complications mainly osteoporotic fractures, have a high impact on health and economy. Current approved medications are associated with numerous side effects, which limit their use. Identification of a new and safe therapy is mandatory. Statins, also known as HMGCoA reductase inhibitors, are frequently used for the treatment of hypercholesterolemia and for the prevention of morbidity and mortality associated with cardiovascular disease. Statins improved bone health status in intact and ovariectomised rodents following high clinically intolerable oral doses. However, this beneficial effect of statins could not be significantly demonstrated in humans. The reason behind this discrepancy might be due to the safety and bioavailability of the currently used oral statins. Vitamin E, especially the tocotrienols at the dose 60 mg/kg/day provided significant antiosteoporotic effects in different animal models of osteoporosis. The use of the aforementioned dose of tocotrienols was shown to be safe in both humans and animals. Enhancement of bone formation and reduction of bone resorption were achieved more effectively by a combination of tocotrienols and statins than by either treatment when supplemented separately at clinically tolerable doses. Therefore, the adverse effects associated with high statin doses might be avoided with the coadministration of tocotrienols. Moreover, the combination therapy strategy might be useful for patients who are at high risk of osteoporosis, cardiovascular events and hypercholesterolaemia. PMID:23848479

  10. Anticoagulants and Statins As Pharmacological Agents in Free Flap Surgery: Current Rationale

    PubMed Central

    Pršić, Adnan; Kiwanuka, Elizabeth; Caterson, Stephanie A.

    2015-01-01

    Microvascular free flaps are key components of reconstructive surgery, but despite their common use and usual reliability, flap failures still occur. Many pharmacological agents have been utilized to minimize risk of flap failure caused by thrombosis. However, the challenge of most antithrombotic therapy lies in providing patients with optimal antithrombotic prophylaxis without adverse bleeding effects. There is a limited but growing body of evidence suggesting that the vasoprotective and anti-inflammatory actions of statins can be beneficial for free flap survival. By inhibiting mevalonic acid, the downstream effects of statins include reduction of inflammation, reduced thrombogenicity, and improved vasodilation. This review provides a summary of the pathophysiology of thrombus formation and the current evidence of anticoagulation practices with aspirin, heparin, and dextran. In addition, the potential benefits of statins in the perioperative management of free flaps are highlighted. PMID:26617953

  11. The role of PCSK9 in intestinal lipoprotein metabolism: synergism of statin and ezetimibe.

    PubMed

    Fazio, Sergio

    2015-02-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role in the regulation of lipoprotein metabolism, mostly through control of low-density lipoprotein receptor degradation. Depletion of cellular cholesterol causes a compensatory increase in plasma PCSK9 levels, which can diminish the cholesterol-lowering power of statins and may lead to the overproduction of intestinal lipoproteins, mainly thorough the up regulation of microsomal triglyceride transfer protein and the Niemann-Pick C1-like 1 protein, the target of ezetimibe. Thus, ezetimibe therapy may counter this unwanted effect of statins, providing an additional theoretical rationale for combining the effect of ezetimibe on intestinal cholesterol absorption and that of statins on cholesterol synthesis. PMID:25659873

  12. Structural and biomechanical changes in the Achilles tendon after chronic treatment with statins.

    PubMed

    de Oliveira, L P; Vieira, C P; Guerra, F D; Almeida, M S; Pimentel, E R

    2015-03-01

    Cases of tendinopathy and tendon ruptures have been reported as side effects associated with statin therapy. This work assessed possible changes in the structural and biomechanical properties of the tendons after chronic treatment with statins. Wistar rats were divided into the following groups: treated with atorvastatin (A-20 and A-80), simvastatin (S-20 and S-80) and the group that received no treatment (C). The doses of statins were calculated using allometric scaling, based on the doses of 80 mg/day and 20 mg/day recommended for humans. The morphological aspect of the tendons in A-20, S-20 and S-80 presented signals consistent with degeneration. Both the groups A-80 and S-80 showed a less pronounced metachromasia in the compression region of the tendons. Measurements of birefringence showed that A-20, A-80 and S-80 groups had a lower degree of organization of the collagen fibers. In all of the groups treated with statins, the thickness of the epitenon was thinner when compared to the C group. In the biomechanical tests the tendons of the groups A-20, A-80 and S-20 were less resistant to rupture. Therefore, statins affected the organization of the collagen fibers and decreased the biomechanical strength of the tendons, making them more predisposed to ruptures. PMID:25544391

  13. Simulated Value Based Insurance Design Applied to Statin Use by Medicare Beneficiaries with Diabetes

    PubMed Central

    Davidoff, Amy; Lopert, Ruth; Stuart, Bruce; Shaffer, Thomas; Lloyd, Jennifer; Shoemaker, J. Samantha

    2013-01-01

    Objective To examine cost responsiveness and total costs associated with a simulated “value based” insurance design (VBID) for statin therapy in a Medicare population with diabetes. Methods Four-year panels constructed from the 1997–2005 Medicare Current Beneficiary Survey selected by self-report or claims-based diagnoses of diabetes in Year 1, and use of statins in Year 2 (N= 899). We computed number of 30-day statin prescription fills, out-of-pocket (OOP) and third party drug costs, and Medicare Part A and B spending. Methods Multivariate ordinary least squares regression models predicted statins fills as a function of OOP costs, and a generalized linear model with log link predicted Medicare spending as a function of number of fills, controlling for baseline characteristics. Estimated coefficients were used to simulate changes in fills associated with copayment caps from $25 to $1, and to compute changes in 3rd-party payments and Medicare cost offsets associated with incremental fills. Analyses were stratified by patient cardiovascular event risk. Results A simulated OOP price of $25[$1] increased plan drug spending by $340[$794], and generated Medicare Part A/B savings of $262[$531]. Medicare Part A/B savings were greater for higher risk patients, generating a net savings for the plans. Conclusions Reducing statin copayments for Medicare beneficiaries with diabetes resulted in modestly increased use, and reduced medical spending. The VBID simulation strategy met financial feasibility criteria, but only for higher risk patients. PMID:22583449

  14. [Statin intolerance and associated muscular dysfunctions].

    PubMed

    Boulanger-Piette, Antoine; Bergeron, Jean; Desgreniers, Joël; Côté-Levesque, Michèle; Brassard, Dominic; Joanisse, Denis R; Frenette, Jérôme

    2015-12-01

    Hypercholesterolemia is a major risk factor for cardiovascular diseases. The 2012-2013 survey of Canada's public health measures revealed that dyslipidemia was present in 38% of the respondents aged between 18 and 79 years. According to the American College of Cardiology, the American Heart Association, the Canadian Cardiovascular Society and the Canadian Working Group Consensus, statins remain the treatment of choice for dyslipidemia and the reduction of cardiovascular risk. However, concerns and questions persist regarding statins use and safety, potential and harmful muscular side-effects, interactions with exercise, and molecular mechanisms of myotoxicity. The goal of the present review is to provide a clear picture of the clinical situation and to investigate possible mechanisms of statin-induced myopathy. A better understanding of muscle pathology in statin users is absolutely essential to minimize their muscle symptoms and to provide a sound clinical basis for the management of cardiovascular risk. PMID:26672664

  15. FDA Expands Advice on Statin Risks

    MedlinePlus

    ... of liver damage. back to top Reports of Memory Loss FDA has been investigating reports of cognitive ... included assessments of cognitive function. The reports about memory loss, forgetfulness and confusion span all statin products ...

  16. Phenotype Standardization for Statin-Induced Myotoxicity

    PubMed Central

    Alfirevic, A; Neely, D; Armitage, J; Chinoy, H; Cooper, R G; Laaksonen, R; Carr, D F; Bloch, K M; Fahy, J; Hanson, A; Yue, Q-Y; Wadelius, M; Maitland-van Der Zee, A H; Voora, D; Psaty, B M; Palmer, C N A; Pirmohamed, M

    2014-01-01

    Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy. PMID:24897241

  17. Effect of Surgical Periodontal Therapy on Serum C-reactive Protein Levels Using ELISA in Both Chronic and Aggressive Periodontitis Patient

    PubMed Central

    Gupta, Bharat; Patil, Neha; Yadav, Manoj; Tripathi, Shashank; Sinha, Saurabh; Sharma, Saurabh; Gupta, Saurabh

    2015-01-01

    Background Periodontitis can be defined as a local inflammatory process which mediates destruction of periodontal tissues & is triggered by bacterial insult. In periodontal infections, the levels of C reactive proteins are elevated as compared to the levels in a periodontally healthy individual. The study was done to determine the relative levels of serum CRP in aggressive, chronic and periodontally healthy subjects and to evaluate the effect of surgical periodontal therapy on serum C-reactive protein levels. Materials and Methods Serum samples were collected from 150 participants (50 healthy control patients (non-periodontitis), 50 patients with chronic periodontitis and aggressive periodontitis. Serum C- reactive protein levels were assessed by means of immunoturbidimetric assay at baseline for subjects in all the 3 groups and 3 months after completion of surgical therapy. Results The mean baseline C-reactive protein (CRP) concentrations in the Groups I, II and III were 1.65±0.57 mg/L, 3.03±2.14 mg/L and 3.09±2.27 mg/L respectively. After treatment, the mean C-reactive protein (CRP) levels in Groups II and III reduced from 3.03±1.67 mg/L to 1.46±1.67 mg/L and from 3.09±1.21 to 1.43±1.21 mg/L respectively. Similar results were found for probing depth and all indexes in Group II and III after treatment. Also, the mean attachment loss in Groups II and III reduced, so the results were highly significant. Conclusion Successful periodontal treatment results in significant decrease in serum C-reactive protein (CRP) levels in otherwise healthy subjects. PMID:26557605

  18. Effects of plant stanol or sterol-enriched diets on lipid profiles in patients treated with statins: systematic review and meta-analysis.

    PubMed

    Han, Shufen; Jiao, Jun; Xu, Jiaying; Zimmermann, Diane; Actis-Goretta, Lucas; Guan, Lei; Zhao, Youyou; Qin, Liqiang

    2016-01-01

    Efficacy and safety data from trials with suitable endpoints have shown that non-statin medication in combination with a statin is a potential strategy to further reduce cardiovascular events. We aimed to evaluate the overall effect of stanol- or sterol-enriched diets on serum lipid profiles in patients treated with statins by conducting a meta-analysis of randomized controlled trials (RCTs). We used the PubMed, Cochrane library and ClinicalTrials.gov databases to search for literature published up to December 2015. Trials were included in the analysis if they were RCTs evaluating the effect of plant stanols or sterols in patients under statin therapy that reported corresponding data on serum lipid profiles. We included 15 RCTs involving a total of 500 participants. Stanol- or sterol-enriched diets in combination with statins, compared with statins alone, produced significant reductions in total cholesterol of 0.30 mmol/L (95% CI -0.36 to -0.25) and low-density lipoprotein (LDL) cholesterol of 0.30 mmol/L (95% CI -0.35 to -0.25), but not in high-density lipoprotein cholesterol or triglycerides. These results persisted in the subgroup analysis. Our meta-analysis provides further evidence that stanol- or sterol-enriched diets additionally lower total cholesterol and LDL-cholesterol levels in patients treated with statins beyond that achieved by statins alone. PMID:27539156

  19. Effects of plant stanol or sterol-enriched diets on lipid profiles in patients treated with statins: systematic review and meta-analysis

    PubMed Central

    Han, Shufen; Jiao, Jun; Xu, Jiaying; Zimmermann, Diane; Actis-Goretta, Lucas; Guan, Lei; Zhao, Youyou; Qin, Liqiang

    2016-01-01

    Efficacy and safety data from trials with suitable endpoints have shown that non-statin medication in combination with a statin is a potential strategy to further reduce cardiovascular events. We aimed to evaluate the overall effect of stanol- or sterol-enriched diets on serum lipid profiles in patients treated with statins by conducting a meta-analysis of randomized controlled trials (RCTs). We used the PubMed, Cochrane library and ClinicalTrials.gov databases to search for literature published up to December 2015. Trials were included in the analysis if they were RCTs evaluating the effect of plant stanols or sterols in patients under statin therapy that reported corresponding data on serum lipid profiles. We included 15 RCTs involving a total of 500 participants. Stanol- or sterol-enriched diets in combination with statins, compared with statins alone, produced significant reductions in total cholesterol of 0.30 mmol/L (95% CI −0.36 to −0.25) and low-density lipoprotein (LDL) cholesterol of 0.30 mmol/L (95% CI −0.35 to −0.25), but not in high-density lipoprotein cholesterol or triglycerides. These results persisted in the subgroup analysis. Our meta-analysis provides further evidence that stanol- or sterol-enriched diets additionally lower total cholesterol and LDL-cholesterol levels in patients treated with statins beyond that achieved by statins alone. PMID:27539156

  20. A statin-dependent QTL for GATM expression is associated with statin-induced myopathy

    PubMed Central

    Mangravite, Lara M.; Engelhardt, Barbara E.; Medina, Marisa W.; Smith, Joshua D.; Brown, Christopher D.; Chasman, Daniel I.; Mecham, Brigham H.; Howie, Bryan; Shim, Heejung; Naidoo, Devesh; Feng, QiPing; Rieder, Mark J.; Chen, Y-D I.; Rotter, Jerome I.; Ridker, Paul M.; Hopewell, Jemma C.; Parish, Sarah; Armitage, Jane; Collins, Rory; Wilke, Russell A.; Nickerson, Deborah A.; Stephens, Matthew; Krauss, Ronald M.

    2013-01-01

    Statins are widely prescribed for lowering plasma low-density lipoprotein (LDL) concentrations and cardiovascular disease risk1, but there is considerable interindividual variation in treatment response2,3 and increasing concern regarding the potential for adverse effects, including myopathy4 and type 2 diabetes5. Despite evidence for substantial genetic influence on LDL concentrations6, pharmacogenomic trials have failed to identify genetic variations with large effects on either statin efficacy7-9 or toxicity10, and have yielded little information regarding mechanisms that modulate statin response. Here we identify a downstream target of statin treatment by screening for the effects of in vitro statin exposure on genetic associations with gene expression levels in lymphoblastoid cell lines derived from 480 participants of a clinical trial of simvastatin treatment7. This analysis identified six expression quantitative trait loci (eQTLs) that interacted with simvastatin exposure including rs9806699, a cis-eQTL for the gene GATM that encodes glycine amidinotransferase, a rate-limiting enzyme in creatine synthesis. We found this locus to be associated with incidence of statin-induced myotoxicity in two separate populations (meta-analysis odds ratio = 0.60, 95% confidence interval = 0.45-0.81, P=6.0×10-4). Furthermore, we found that GATM knockdown in hepatocyte-derived cell lines attenuated transcriptional response to sterol depletion, demonstrating that GATM may act as a functional link between statin-mediated cholesterol lowering and susceptibility to statin-induced myopathy. PMID:23995691

  1. Statin-centric versus low-density lipoprotein-centric approach for atherosclerotic cardiovascular disease prevention: a Singapore perspective

    PubMed Central

    Yan, Peter; Tan, Eng Kiat Kevin; Choo, Jason Chon Jun; Liew, Choon Fong Stanley; Lau, Titus; Waters, David D

    2016-01-01

    The link between cholesterol levels and atherosclerotic cardiovascular disease (ASCVD) is well-established. In Singapore, there is an increasing prevalence of risk factors for ASCVD. Like many Asian countries, Singapore’s population is rapidly ageing and increasingly sedentary, which predisposes individuals to chronic health problems. Current international and local guidelines recommend statin therapy for the primary and secondary prevention of ASCVD. However, despite the effectiveness of statin therapy, some studies have highlighted that Asian patients with cardiovascular disease are not achieving target lipid goals. Furthermore, it is widely believed that the responses of Asians (both patients and physicians) to statin therapy are different from those of their Western counterparts. Experts convened in 2014 to determine the impact of current guidelines on clinical practice in Singapore. This review summarises the key findings and recommendations of these guidelines, and presents key principles to aid clinicians to manage the cardiovascular risk of their patients more effectively. PMID:27439304

  2. Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a

    PubMed Central

    Rudick, R A.; Pace, A; Rani, M R.S.; Hyde, R; Panzara, M; Appachi, S; Shrock, J; Maurer, S L.; Calabresi, P A.; Confavreux, C; Galetta, S L.; Lublin, F D.; Radue, E -W.; Ransohoff, R M.

    2009-01-01

    Background: Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNβ) in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNβ-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNβ. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri®, Biogen Idec, Inc., Cambridge, MA) plus IM IFNβ-1a (Avonex®, Biogen Idec, Inc.) 30 μg compared with placebo plus IM IFNβ-1a 30 μg. Clinical and MRI outcomes in patients treated with IM IFNβ-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNβ-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). Results: No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. Conclusions: Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment. GLOSSARY ANCOVA = analysis of covariance; CI = confidence interval; EDSS = Expanded Disability Status Scale; GAPDH = glyceraldehyde-3-phosphate dehydrogenase; Gd+ = gadolinium-enhancing; IFNβ = interferon beta; ISG = IFN-stimulated gene; RRMS = relapsing-remitting multiple sclerosis; SENTINEL = Safety and Efficacy of

  3. Exploring response signals and targets in aggressive unresectable hepatocellular carcinoma: an analysis of targeted therapy phase 1 trials

    PubMed Central

    Subbiah, Ishwaria M.; Falchook, Gerald S.; Kaseb, Ahmed O.; Hess, Kenneth R.; Tsimberidou, Apostolia M.; Fu, Siqing; Subbiah, Vivek; Hong, David S.; Naing, Aung; Sarina, A. Piha-Paul; Akmal, Owais; Janku, Filip; Kurzrock, Razelle

    2015-01-01

    PURPOSE Patients with advanced hepatocellular carcinoma (HCC) have limited effective therapeutic options. Given the rapid advanced in drug development and emergence of novel agents, we analyzed the characteristics and outcomes of HCC patients treated on early phase trials with an emphasis on targeted therapies. METHODS We reviewed the records of consecutive HCC patients evaluated in the Phase I Clinical Trials Program at MD Anderson from March 2004. RESULTS Thirty-nine patients were not treated due to poor performance status (n = 22, 56%) and decision to pursue alternate therapies (n = 10, 27%). Of 61 treated patients (median age, 60 years; median prior therapies, 3), eight patients (13%) attained stable disease lasting ≥6 months; four (7%) had a partial response, mainly with anti-angiogenic or multikinase inhibitors. Median Phase I progression-free survival (PFS) was 2.6 months versus 4.4 months (p 0.019) and 4.1 months (p 0.27) for their first-, and second-line FDA-approved therapy. Molecular analysis showed frequent PTEN loss (10/19 patients, 53%) and P53 mutation (4/4 patients tested). On multivariate analysis, independent factors predicting shorter survival were white ethnicity/race (p 0.031), cirrhosis (p 0.016), and serum sodium (p 0.0013). CONCLUSIONS In our heavily-pretreated HCC patients, the phase I PFS was comparable to that of 2nd-line therapy, highlighting a potential role for clinical trials after progression on first-line therapy. The response rate (SD>6 months/PR) of 20% was observed with early signals of activity in regimens combining inhibitors of angiogenesis, multiple kinases and mTOR with preliminary molecular analysis revealing prevalence of PTEN loss. PMID:26164085

  4. Low-Density Lipoprotein Cholesterol Levels and Statin Treatment by HIV Status Among Multicenter AIDS Cohort Study Men

    PubMed Central

    Fu, Wei; Zikusoka, Michelle N.; Jacobson, Lisa P.; Witt, Mallory D.; Palella, Frank J.; Kingsley, Lawrence A.; Post, Wendy S.; Brown, Todd T.

    2015-01-01

    Abstract Treating cardiovascular disease (CVD) risk factors, including dyslipidemia, is important in HIV care. Low-density lipoprotein cholesterol (LDL-c) target achievement is a readily available benchmark for dyslipidemia control, although use of this target is not uniformly endorsed by professional societies. We examined whether HIV serostatus is associated with not achieving LDL-c target. Among Multicenter AIDS Cohort Study (MACS) participants completing visit 56 (10/1/2011–3/31/2012), we categorized each man as on or off statin therapy and used NCEP ATP III guidelines to determine if each man was at LDL-c target or not at target. We compared proportions of men not at target and determined predictors using multivariate logistic regression. Sixty of 543 (11.1%) HIV-infected men and 87 of 585 (14.9%) HIV-uninfected men not receiving statin therapy were not at target (p=0.07), while 31 of 230 (13.5%) HIV-infected and 29 of 204 (14.2%) HIV-uninfected men receiving statin therapy were not at target (p=0.82). Factors associated with not being at target (among men not receiving statin therapy) included current smoking (OR=2.31, 95% CI 1.31, 4.06) and a diagnosis of hypertension (OR=4.69, 95% CI 2.68, 8.21). Factors associated with not being at target (among men receiving statin therapy) included current smoking (OR=2.72, 95% CI 1.30, 5.67) and diabetes (OR=5.31, 95% CI 2.47, 11.42). HIV-infected and HIV-uninfected men receiving statin therapy demonstrated similar nonachievement of LDL-c targets. Comorbidities (e.g., diabetes) lowered targets and may explain why goals were less likely to be met. PMID:25664922

  5. Statins and congenital malformations: cohort study

    PubMed Central

    Hernandez-Diaz, Sonia; Fischer, Michael A; Seely, Ellen W; Ecker, Jeffrey L; Franklin, Jessica M; Desai, Rishi J; Allen-Coleman, Cora; Mogun, Helen; Avorn, Jerry; Huybrechts, Krista F

    2015-01-01

    Objective To examine the teratogenic potential of statins. Design Cohort study. Setting United States. Participants A cohort of 886 996 completed pregnancies linked to liveborn infants of women enrolled in Medicaid from 2000 to 2007. Methods We examined the risk of major congenital malformations and organ specific malformations in offspring associated with maternal use of a statin in the first trimester. Propensity score based methods were used to control for potential confounders, including maternal demographic characteristics, obstetric and medical conditions, and use of other drugs. Results 1152 (0.13%) women used a statin during the first trimester. In unadjusted analyses, the prevalence of malformations in the offspring of these women was 6.34% compared with 3.55% in those of women who did not use a statin in the first trimester (relative risk 1.79, 95% confidence interval 1.43 to 2.23). Controlling for confounders, particularly pre-existing diabetes, accounted for this increase in risk (1.07, 0.85 to 1.37). There were also no statistically significant increases in any of the organ specific malformations assessed after accounting for confounders. Results were similar across a range of sensitivity analyses. Conclusions Our analysis did not find a significant teratogenic effect from maternal use of statins in the first trimester. However, these findings need to be replicated in other large studies, and the long term effects of in utero exposure to statins needs to be assessed, before use of statins in pregnancy can be considered safe. PMID:25784688

  6. IL12 and IL27 sequential gene therapy via intramuscular electroporation delivery for eliminating distal aggressive tumors1

    PubMed Central

    Zhu, Shiguo; Lee, Dean Anthony; Li, Shulin

    2010-01-01

    Eradication of residual malignancies and metastatic tumors via a systemic approach is the key for successfully treating cancer and increasing the cancer patient survival. Systemic administration of IL12 protein in an acute large dose is effective but toxic. Systemic administration of IL12 gene by persistently expressing a low level of IL12 protein may reduce the systemic toxicity, but only eradicates IL12 sensitive tumors. Here, we discovered that sequential administration of IL12 and IL27 encoding DNA, referred to as sequential IL12-IL27 gene therapy, not only eradicated IL12 sensitive tumors from 100% of mice but also eradicated the highly malignant 4T1 tumors from 33% of treated mice in multiple independent experiments. This IL12-IL27 sequential gene therapy is not only superior to IL12-IL12 sequential gene therapy for eliminating tumors, but also for inducing CTL activity, increasing T cell infiltration into tumors, and yielding a large number of tumor-specific IFNγ positive CD8 T cells. Notably, depletion of either T- or NK-cells during the IL27 treatment phase reverses tumor eradication, suggesting an NK-cell requirement for this sequential gene therapy-mediated tumor eradication. Both reversal of the administration sequence and co-administration of IL12 and IL27 impaired the tumor eradication in 4T1 tumor bearing mice. This IL12-IL27 sequential gene therapy, via sequential administration of IL12 and IL27 encoding plasmid DNA into tumor-bearing mice through intramuscular electroporation, provides a simple but effective approach for eliminating inaccessible residual tumors. PMID:20139275

  7. Sequential therapy combining clofarabine and T-cell-replete HLA-haploidentical haematopoietic SCT is feasible and shows efficacy in the treatment of refractory or relapsed aggressive lymphoma.

    PubMed

    Zoellner, A-K; Fritsch, S; Prevalsek, D; Engel, N; Hubmann, M; Reibke, R; Rieger, C T; Hellmuth, J C; Haas, M; Mumm, F; Herold, T; Ledderose, G; Hiddemann, W; Dreyling, M; Hausmann, A; Tischer, J

    2015-05-01

    Prognosis is poor for patients with biologically aggressive Non-Hodgkin lymphoma (NHL), refractory to chemotherapy or relapsed after autologous transplantation, especially when no disease control before allogeneic transplantation is achieved. In 16 patients (median age 53, median prior regimes 5) with relapsed or refractory non-remission NHL, we analysed retrospectively the efficacy of a sequential therapy comprising clofarabine re-induction followed by a reduced-intensity conditioning with fludarabine, CY and melphalan, and T-cell-replete HLA-haploidentical transplantation. High-dose CY was utilized post-transplantation. All patients engrafted. Early response (day +30) was achieved in 94%. Treatment-related grade III-IV toxicity occurred in 56%, most commonly transient elevation of transaminases (36%), while there was a low incidence of infections (19% CMV reactivation, 19% invasive fungal infection) and GVHD (GVHD: acute III-IV: 6%; mild chronic: 25%). One-year non-relapse mortality was 19%. After a median follow-up of 21 months, estimated 1- and 2-year PFS was 56 and 50%, respectively, with 11 patients (69%) still alive after 2 years. In summary, sequential therapy is feasible and effective and provides an acceptable toxicity profile in high-risk non-remission NHL. Presumably, cytotoxic reinduction with clofarabine provides enough remission time for the graft-versus lymphoma effect of HLA-haploidentical transplantation to kick in, even in lymphomas that are otherwise chemo-refractory. PMID:25642765

  8. Statin Use and the Risk of Kidney Disease With Long-Term Follow-Up (8.4-Year Study).

    PubMed

    Acharya, Tushar; Huang, Jian; Tringali, Steven; Frei, Christopher R; Mortensen, Eric M; Mansi, Ishak A

    2016-02-15

    Few studies have examined long-term effects of statin therapy on kidney diseases. The objective of this study was to determine the association of statin use with incidence of acute and chronic kidney diseases after prolonged follow-up. In this retrospective cohort study, we analyzed data from the San Antonio area military health care system from October 2003 through March 2012. Statin users were propensity score matched to nonusers using 82 baseline characteristics including demographics, co-morbidities, medications, and health care utilization. Study outcomes were acute kidney injury, chronic kidney disease (CKD), and nephritis/nephrosis/renal sclerosis. Of the 43,438 subjects included, we propensity score matched 6,342 statin users with 6,342 nonusers. Statin users had greater odds of acute kidney injury (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.14 to 1.48), CKD (OR 1.36, 95% CI 1.22 to 1.52), and nephritis/nephrosis/renal sclerosis (OR 1.35, 95% CI 1.05 to 1.73). In a subset of patients without co-morbidities, the association of statin use with CKD remained significant (OR 1.53, 95% CI 1.27 to 1.85). In a secondary analysis, adjusting for diseases/conditions that developed during follow-up weakened this association. In conclusion, statin use is associated with increased incidence of acute and chronic kidney disease. These findings are cautionary and suggest that long-term effects of statins in real-life patients may differ from shorter term effects in selected clinical trial populations. PMID:26742473

  9. How Do PCSK9 Inhibitors Stack Up to Statins for Low-Density Lipoprotein Cholesterol Control?

    PubMed

    Zimmerman, Marj P

    2015-11-01

    Despite advances in the approach toward treating hypercholesterolemia and widespread access to statin medications, not all people are able to reach target low-density lipoprotein cholesterol (LDL-C) levels to reduce their cardiovascular risk. Some of the reasons include the inability to tolerate statin therapy, LDL-C levels that remain high even in the presence of statin therapy, and a familial disorder that is characterized by extremely high levels of LDL-C. A new therapeutic class, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, represents a novel and promising approach to reducing LDL-C levels using a mechanism at the LDL receptor level. The recent approval of the first 2 PCSK9 inhibitors and the anticipated approval of the third agent in this class within approximately 1 year may provide clinicians powerful new weapons to lower LDL-C levels in patients who are not satisfactorily managed with statins. However, the results of long-term studies of the ability of these new medications to influence cardiovascular outcomes will not be known for several years. PMID:26702335

  10. How Do PCSK9 Inhibitors Stack Up to Statins for Low-Density Lipoprotein Cholesterol Control?

    PubMed Central

    Zimmerman, Marj P.

    2015-01-01

    Despite advances in the approach toward treating hypercholesterolemia and widespread access to statin medications, not all people are able to reach target low-density lipoprotein cholesterol (LDL-C) levels to reduce their cardiovascular risk. Some of the reasons include the inability to tolerate statin therapy, LDL-C levels that remain high even in the presence of statin therapy, and a familial disorder that is characterized by extremely high levels of LDL-C. A new therapeutic class, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, represents a novel and promising approach to reducing LDL-C levels using a mechanism at the LDL receptor level. The recent approval of the first 2 PCSK9 inhibitors and the anticipated approval of the third agent in this class within approximately 1 year may provide clinicians powerful new weapons to lower LDL-C levels in patients who are not satisfactorily managed with statins. However, the results of long-term studies of the ability of these new medications to influence cardiovascular outcomes will not be known for several years. PMID:26702335

  11. Muscular effects of statins in the elderly female: a review

    PubMed Central

    Bhardwaj, Shilpa; Selvarajah, Shalini; Schneider, Eric B

    2013-01-01

    Statins have demonstrated substantial benefits in supporting cardiovascular health. Older individuals are more likely to experience the well-known muscle-related side effects of statins compared with younger individuals. Elderly females may be especially vulnerable to statin-related muscle disorder. This review will collate and discuss statin-related muscular effects, examine their molecular and genetic basis, and how these apply specifically to elderly women. Developing strategies to reduce the incidence of statin-induced myopathy in older adult women could contribute to a significant reduction in the overall incidence of statin-induced muscle disorder in this vulnerable group of patients. Reducing statin-related muscle disorder would likely improve overall patient compliance, thereby leading to an increase in improved short- and long-term outcomes associated with appropriate use of statins. PMID:23355775

  12. Research Finds Link Between Statin Use and Progressive Muscle Disease

    MedlinePlus

    ... Research Finds Link Between Statin Use and Progressive Muscle Disease Each year, millions of Americans take statins, ... people these benefits come at a cost: widespread muscle pain that persists as long as the drugs ...

  13. Statins Might Protect People with Narrowed Leg Arteries

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158707.html Statins Might Protect People With Narrowed Leg Arteries Study ... FRIDAY, May 6, 2016 (HealthDay News) -- Cholesterol-lowering statins may spare people with narrowed leg arteries from ...

  14. Statins Might Not Lower Colon Cancer Risk: Study

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158506.html Statins Might Not Lower Colon Cancer Risk: Study But ... HealthDay News) -- Long-term use of cholesterol-lowering statins does not appear to reduce the risk of ...

  15. Rituximab-CHOP-ESHAP vs CHOP-ESHAP-high-dose therapy vs conventional CHOP chemotherapy in high-intermediate and high-risk aggressive non-Hodgkin's lymphoma.

    PubMed

    Intragumtornchai, Tanin; Bunworasate, Udomsak; Nakorn, Thanyaphong Na; Rojnuckarin, Ponlapat

    2006-07-01

    With currently available combination chemotherapy regimens, the outcome of the patients newly diagnosed with aggressive non-Hodgkin's lymphoma (NHL) identified as 'high' and 'high-intermediate' risk groups according to the international prognostic index (IPI) is still unsatisfactory and a more innovative therapy is urgently required to improve the survival of the patients. The purpose of this study was to compare the efficacy of rituximab given in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and ESHAP (etoposide, methylprednisolone, high-dose Ara-C, cisplatin) vs CHOP-ESHAP and upfront high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) vs standard CHOP in patients aged < or = 65 years old newly diagnosed with 'high' and 'high-intermediate' risk aggressive lymphoma enrolled onto two consecutive treatment trials at the institute. Between May 1995 - July 2002, 84 patients, aged 15 - 65 years old, with newly diagnosed aggressive NHL and an age-adjusted IPI of 2 or 3 were enrolled. The median age of the patients was 38 years (range 15 - 65). The baseline demographic features, in particular the major prognostic variables, were similar between the treatment groups. Patients treated with rituximab-CHOP-ESHAP received eight cycles of rituximab (375 mg m(-2) on day 1 of cycles 1 - 6 and days 21 and 28 of cycle 7) plus CHOP (day 3 of cycles 1, 3 and 5) and ESHAP (day 3 of cycles 2, 4 and 6 and day 1 of cycle 7) at 21-day intervals. Patients enrolled onto the CHOP-ESHAP-HDT arm (n = 23) were treated with three courses of CHOP and then switched to two or four cycles of ESHAP followed by HDT. Patients treated with CHOP alone (n = 25) were treated with the standard eight cycles of CHOP. The rate of complete remission was significantly improved with rituximab-CHOP-ESHAP compared with either CHOP-ESHAP-HDT or CHOP alone (67% compared with 44% and 36%, respectively; p = 0.043). With a median follow-up time of 53 months, the 5

  16. Lipid-lowering update 2001. Aggressive new goals.

    PubMed Central

    Fenske, T. K.

    2001-01-01

    OBJECTIVE: To review the central role of cholesterol in coronary artery disease (CAD), underscore the need for identifying patients at high risk of CAD, and discuss treatment of dyslipidemias. QUALITY OF EVIDENCE: Current literature (1995-2000) was searched via MEDLINE using the MeSH headings "cholesterol," "risk reduction," and "statins." Recommendations in this paper are based mainly on the results of large randomized controlled trials. Preference was given to more recent articles, clinically relevant articles, and landmark clinical trials. MAIN MESSAGE: Lipid lowering, and specifically low-density lipoprotein lowering, has been repeatedly shown in large clinical trials to improve survival dramatically and reduce cardiac events in both primary and secondary prevention. Identifying those at highest risk for future cardiac events is critical because these patients will benefit most from aggressive modification of risk factors. The definition of high risk has been expanded to include patients with diabetes mellitus and peripheral vascular disease, as well as those with established CAD. A full lipid profile is required for these patients to assess risk and develop a lipid-lowering strategy with proven effectiveness. CONCLUSION: With the advent of powerful, efficacious, and well tolerated cholesterol-modifying therapies, lipid normalization should be a mandate for all physicians caring for patients with established CAD and patients at risk of developing CAD. PMID:11228031

  17. Statins and PPAR{alpha} agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment

    SciTech Connect

    Johnson, Timothy E. . E-mail: Timothy_Johnson@merck.com; Zhang, Xiaohua; Shi, Shu; Umbenhauer, Diane R.

    2005-11-01

    Statins and fibrates (weak PPAR{alpha} agonists) are prescribed for the treatment of lipid disorders. Both drugs cause myopathy, but with a low incidence, 0.1-0.5%. However, combined statin and fibrate therapy can enhance myopathy risk. We tested the myotoxic potential of PPAR subtype selective agonists alone and in combination with statins in a differentiated rat myotube model. A pharmacologically potent experimental PPAR{alpha} agonist, Compound A, induced myotoxicity as assessed by TUNEL staining at a minimum concentration of 1 nM, while other weaker PPAR{alpha} compounds, for example, WY-14643, Gemfibrozil and Bezafibrate increased the percentage of TUNEL-positive nuclei at micromolar concentrations. In contrast, the PPAR{gamma} agonist Rosiglitazone caused little or no cell death at up to 10 {mu}M and the PPAR{delta} ligand GW-501516 exhibited comparatively less myotoxicity than that seen with Compound A. An experimental statin (Compound B) and Atorvastatin also increased the percentage of TUNEL-positive nuclei and co-treatment with WY-14643, Gemfibrozil or Bezafibrate had less than a full additive effect on statin-induced cell killing. The mechanism of PPAR{alpha} agonist-induced cell death was different from that of statins. Unlike statins, Compound A and WY-14643 did not activate caspase 3/7. In addition, mevalonate and geranylgeraniol reversed the toxicity caused by statins, but did not prevent the cell killing induced by WY-14643. Furthermore, unlike statins, Compound A did not inhibit the isoprenylation of rab4 or rap1a. Interestingly, Compound A and Compound B had differential effects on ATP levels. Taken together, these observations support the hypothesis that in rat myotube cultures, PPAR{alpha} agonism mediates in part the toxicity response to PPAR{alpha} compounds. Furthermore, PPAR{alpha} agonists and statins cause myotoxicity through distinct and independent pathways.

  18. Statin Intolerance Because of Myalgia, Myositis, Myopathy, or Myonecrosis Can in Most Cases be Safely Resolved by Vitamin D Supplementation

    PubMed Central

    Khayznikov, Maksim; Hemachrandra, Kallish; Pandit, Ramesh; Kumar, Ashwin; Wang, Ping; Glueck, Charles J

    2015-01-01

    Background: Low serum vitamin D can cause myalgia, myositis, myopathy, and myonecrosis. Statin-induced myalgia is a major and common cause of statin intolerance. Low serum vitamin D and statins, additively or synergistically, cause myalgia, myositis, myopathy, and/or myonecrosis. Statin-induced myalgia in vitamin D deficient patients can often be resolved by vitamin D supplementation, normalizing serum vitamin D levels. Aims: In 74 men and 72 women (age 59 ± 14 years) intolerant to ≥2 statins because of myalgia, myositis, myopathy, or myonecrosis and found to have low (<32 ng/mL) serum vitamin D, we prospectively assessed whether vitamin D supplementation (vitamin D2: 50,000-100,000 units/week) to normalize serum vitamin D would allow successful rechallenge therapy with statins. Materials and Methods: Follow-up evaluation on vitamin D supplementation was done on 134 patients at 6 months (median 5.3), 103 patients at 12 months (median 12.2), and 82 patients at 24 months (median 24). Results: Median entry serum vitamin D (22 ng/mL, 23 ng/mL, and 23 ng/mL) rose at 6 months, 12 months, and 24 months follow-up to 53 ng/mL, 53 ng/mL, and 55 ng/mL, respectively, (P < .0001 for all) on vitamin D therapy (50,000-100,000 units/week). On vitamin D supplementation, serum vitamin D normalized at 6 months, 12 months, and 24 months follow-up in 90%, 86%, and 91% of the patients, respectively. On rechallenge with statins while on vitamin D supplementation, median low-density lipoprotein cholesterol (LDLC) fell from the study entry (167 mg/dL, 164 mg/dL, and 158 mg/dL) to 90 mg/dL, 91 mg/dL, and 84 mg/dL, respectively, (P < .0001 for all). On follow-up at median 6 months, 12 months, and 24 months on statins and vitamin D, 88%, 91%, and 95% of the previously statin-intolerant patients, respectively, were free of myalgia, myositis, myopathy, and/or myonecrosis. Conclusions: Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis associated with low serum vitamin

  19. Efficacy of Statin Monotherapy or in Combination With Coenzyme A Capsule in Patients With Metabolic Syndrome and Mixed Dyslipidemia

    PubMed Central

    Lai, Jiangtao; Wu, Bifeng; Xuan, Tianming; Xia, Shudong; Liu, Zhong; Chen, Junzhu

    2015-01-01

    Background Patients with metabolic syndrome are at increased risk for cardiovascular disease. Combination lipid-lowering therapy is often needed in patients with metabolic syndrome and mixed dyslipidemia. The aim of this study was to compare the effect of statin combined with a new hypolipidemic agent, coenzyme A (CoA) with moderate-dose statin monotherapy in subjects with metabolic syndrome and mixed dyslipidemia by evaluating data from a subgroup of patients with metabolic syndrome and mixed dyslipidemia from a previously conducted randomized study. Methods In the present post hoc analysis, 212 patients were included, receiving statin monotherapy (n = 94) or statin combined with CoA 400 U/day (n = 118) for 8 weeks. The lipoprotein profile was determined at baseline and week 8 visits. Attainment of low-density lipoprotein-cholesterol (LDL-C) < 100 mg/dL, non-high-density lipoprotein-cholesterol (HDL-C) < 130 mg/dL, and the combined goal of these two parameters was also evaluated. Results The mean percent change was more prominent with CoA plus statin compared with placebo plus statin in triglyceride (TG) (-32.5% vs. -8.7%, respectively; P = 0.0002), total cholesterol (-9.6% vs. -3.6%, P = 0.013), LDL-C (-7.5% vs. 2.1%, P = 0.033), and non-HDL-C (-14.3% vs. -6.4%, P = 0.011). Treatment with CoA plus statin resulted in larger percentages of participants attaining lipid goals for LDL-C (70.3% vs. 56.4%, P = 0.044), non-HDL-C (60.2% vs. 45.7%, P = 0.039), and the combined goal of LDL-C and non-HDL-C (57.6% vs. 42.6%, P = 0.038) than statin monotherapy. Conclusion These results demonstrate that CoA plus statin therapy was more effective in improving lipoprotein parameters than statin alone in patients with metabolic syndrome and mixed hyperlipidemia. PMID:25883708

  20. Mechanisms of bone anabolism regulated by statins

    PubMed Central

    Ruan, Feng; Zheng, Qiang; Wang, Jinfu

    2012-01-01

    Osteoporosis is a common disease in the elderly population. The progress of this disease results in the reduction of bone mass and can increase the incidence of fractures. Drugs presently used clinically can block the aggravation of this disease. However, these drugs cannot increase the bone mass and may result in certain side effects. Statins, also known as HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, have been widely prescribed for CVD (cardiovascular disease) for decades. Nonetheless, several studies have demonstrated that statins exert bone anabolic effect and may be helpful for the treatment of osteoporosis. Several experiments have analysed the mechanisms of bone anabolism regulated by statins. In the present paper, we review the mechanisms of promoting osteogenesis, suppressing osteoblast apoptosis and inhibiting osteoclastogenesis. PMID:22799752

  1. Pharmacogenetics of Statin-Induced Myopathy: A Focused Review of the Clinical Translation of Pharmacokinetic Genetic Variants

    PubMed Central

    Talameh, Jasmine A; Kitzmiller, Joseph P

    2014-01-01

    Statins are the most commonly prescribed drugs in the United States and are extremely effective in reducing major cardiovascular events in the millions of Americans with hyperlipidemia. However, many patients (up to 25%) cannot tolerate or discontinue statin therapy due to statin-induced myopathy (SIM). Patients will continue to experience SIM at unacceptably high rates or experience unnecessary cardiovascular events (as a result of discontinuing or decreasing their statin therapy) until strategies for predicting or mitigating SIM are identified. A promising strategy for predicting or mitigating SIM is pharmacogenetic testing, particularly of pharmacokinetic genetic variants as SIM is related to statin exposure. Data is emerging on the association between pharmacokinetic genetic variants and SIM. A current, critical evaluation of the literature on pharmacokinetic genetic variants and SIM for potential translation to clinical practice is lacking. This review focuses specifically on pharmacokinetic genetic variants and their association with SIM clinical outcomes. We also discuss future directions, specific to the research on pharmacokinetic genetic variants, which could speed the translation into clinical practice. For simvastatin, we did not find sufficient evidence to support the clinical translation of pharmacokinetic genetic variants other than SLCO1B1. However, SLCO1B1 may also be clinically relevant for pravastatin- and pitavastatin-induced myopathy, but additional studies assessing SIM clinical outcome are needed. CYP2D6*4 may be clinically relevant for atorvastatin-induced myopathy, but mechanistic studies are needed. Future research efforts need to incorporate statin-specific analyses, multi-variant analyses, and a standard definition of SIM. As the use of statins is extremely common and SIM continues to occur in a significant number of patients, future research investments in pharmacokinetic genetic variants have the potential to make a profound impact on

  2. Low serum docosahexaenoic acid is associated with progression of coronary atherosclerosis in statin-treated patients with diabetes mellitus: results of the treatment with statin on atheroma regression evaluated by intravascular ultrasound with virtual histology (TRUTH) study

    PubMed Central

    2014-01-01

    Background Diabetes mellitus (DM) accelerates plaque progression despite the use of statin therapy. The purpose of the present study was to evaluate the determinants of atheroma progression in statin-treated patients with DM. Methods Coronary atherosclerosis in nonculprit lesions in a vessel undergoing percutaneous coronary intervention (PCI) was evaluated using virtual histology intravascular ultrasound. The study included 50 patients with DM who had been taking statin therapy for 8 months at the time of PCI. Results Twenty-six patients (52%) showed atheroma progression (progressors) and the remaining 24 patients (48%) showed atheroma regression (regressors) after 8 months of follow-up. Fewer progressors than regressors received intensive lipid-lowering therapy with pitavastatin (31% vs. 50%, p = 0.17) and the frequency of insulin use was higher in progressors (31% vs. 13%, p = 0.18). However, neither of these differences reached statistical significance. Risk factor control at baseline and at the 8-month follow-up did not differ between the 2 groups except for serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Univariate regression analysis showed that serum EPA (r = -0.317, p = 0.03) and DHA (r = -0.353, p = 0.02) negatively correlated with atheroma progression. Multivariate stepwise regression analysis showed that low serum DHA and pravastatin use were significant independent predictors for atheroma progression during statin therapy (DHA: β = -0.414, type of statin: β = -0.287, p = 0.001). Conclusions Low serum DHA is associated with progression of coronary atherosclerosis in statin-treated patients with DM. Trial registration UMIN Clinical Trials Registry, UMIN ID: C000000311. PMID:24410834

  3. Statins: An undesirable class of aquatic contaminants?

    PubMed

    Santos, Miguel M; Ruivo, Raquel; Lopes-Marques, Mónica; Torres, Tiago; de Los Santos, Carmen B; Castro, L Filipe C; Neuparth, Teresa

    2016-05-01

    Emerging pollutants, such as pharmaceuticals, may pose a considerable environment risk. Hypocholesterolaemic drugs such as statins are among the most prescribed human pharmaceuticals in western European countries. In vertebrates, this therapeutic class disrupts the cholesterol synthesis by inhibiting the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), responsible for the limiting step in the mevalonate pathway. Recently, functional studies have shown that statins competitively inhibit HMGR in vertebrates and arthropods, two taxa that have diverged over 450 million years ago. Importantly, chronic simvastatin exposure disrupts crustacean reproduction and development at environmentally relevant concentrations. Hence, a fundamental question emerges: what is the taxonomic scope of statins-induced HMGR inhibition across metazoans? Here, we address this central question in a large sampling of metazoans using comparative genomics, homology modelling and molecular docking. Sequence alignment of metazoan HMGRs allowed the annotation of highly conserved catalytic, co-factor and substrate binding sites, including residues highjacked for statin binding. Furthermore, molecular docking shows that the catalytic domains of metazoan HMGRs are highly conserved regarding interactions, not only with HMG-CoA, but also with both simvastatin and atorvastatin, the top prescribed statins in Europe and USA. Hence, the data indicates that both statins are expected to competitively inhibit metazoan's HMGRs, and therefore all metazoan taxa might be at risk. The environmental relevance of these findings are discussed and research priorities established. We believe that the conceptual framework used in this study can be applied to other emerging pollutants and assist in the design of toxicity testing and risk assessment. PMID:26896816

  4. Gemfibrozil in Combination with Statins-Is It Really Contraindicated?

    PubMed

    Wiggins, Barbara S; Saseen, Joseph J; Morris, Pamela B

    2016-04-01

    Gemfibrozil is a lipid-modifying agent that belongs to the fibric acid derivative class. Fibric acid derivatives activate peroxisome proliferator activated receptor α (PPAR-α). The primary role of these agents in clinical practice is for the management of hypertriglyceridemia. Triglycerides may be reduced by as much as 74 % in some patients. In addition to lowering triglycerides, these agents can also decrease very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as raise high-density lipoprotein cholesterol (HDL-C). Based on the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults and the National Lipid Association, pharmacologic therapy to reduce triglycerides should be considered when triglyceride levels are ≥500 mg/dL. While the use of gemfibrozil has decreased over the years for a variety of reasons, muscle-associated adverse effects is the predominant reason and the one that is most clinically relevant. However, despite these concerns, there are situations in which the use of gemfibrozil in combination with a statin may be necessary. Understanding the metabolism of gemfibrozil and the degree of interaction with the various statins will assist health-care providers to optimize safety when this combination is clinically indicated. PMID:26932225

  5. Prescribing statins for cardiovascular disease prevention in the old: an absence of evidence and an absence of guidelines.

    PubMed

    Noaman, Samer; Ibrahim, Joseph E; Grenfell, Robert

    2014-07-01

    Australia's oldest old are potentially being harmed by the under- and over- use of statins. Variations in prescription of statins are in part due to the vacuum of clinical research trial evidence and paucity of contemporary guidelines that are needed to address the use of lipid lowering therapy in the oldest old. There are a few randomised placebo-controlled trials that recruited an older population. Therefore evidence of statins efficacy in the oldest old is based on an extrapolation of results from those studies. The extensive exclusion criteria of those studies, the relative youth of the study participants, the low levels of comorbidity and functional impairment limit the external validity and the generalisability of the findings. Current guidelines are silent or generally non-specific about statin therapy for the oldest old deferring decisions to individual medical practitioners. Life expectancy, time to benefit, functional status and medication related adverse events, polypharmacy, adherence to treatment are factors that need to be considered when forming appropriate guidelines for statin prescription in the very old. Well-designed clinical trials that account for the heterogeneity of this population are needed. While waiting for this research evidence better clinical guidelines are needed to address this issue. PMID:24704467

  6. Effect of n-3 Polyunsaturated Fatty Acids on Regression of Coronary Atherosclerosis in Statin Treated Patients Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Ahn, Jinhee; Park, Seo Kwang; Park, Tae Sik; Kim, Jin Hee; Yun, Eunyoung; Kim, Sang-Pil; Lee, Hye Won; Oh, Jun-Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Lee, Sang Yeoup

    2016-01-01

    Background and Objectives Statins remain the mainstay of secondary coronary artery disease (CAD) prevention, but n-3 polyunsaturated fatty acids (ω-3 PUFA) display biological effects that may also reduce the risk of atherosclerosis and CAD. However, data on the possible antiatherosclerotic benefits of adding ω-3 PUFA to statin therapy are limited. This study aimed to investigate the potential additive effects of ω-3 PUFA on regression of atherosclerosis in CAD patients receiving statin therapy and stent implantation. Subjects and Methods Seventy-four CAD patients undergoing percutaneous coronary intervention (PCI) with stent implantation were enrolled, prescribed statins, and randomly assigned to two groups: n-3 group (ω-3 PUFA 3 g/day, n=38) or placebo group (placebo, n=36). All patients completed the study follow-up consisting of an intravascular ultrasound at baseline and at 12 months. Results There was no difference in the baseline characteristics and distribution of other medications. No significant differences were observed in primary endpoints, including changes in atheroma volume index (−12.65% vs. −8.51%, p=0.768) and percent atheroma volume (−4.36% vs. −9.98%, p=0.526), and in secondary endpoints including a change in neointimal volume index (7.84 vs. 4.94 mm3/mm, p=0.087). Conclusion ω-3 PUFA had no definite additional effect on the regression of coronary atherosclerosis when added to statin in CAD patients undergoing PCI. PMID:27482256

  7. Management of Lipid Levels and Cardiovascular Disease in HIV-Infected Individuals: Just Give Them a Statin?

    PubMed

    Stein, James H

    Current guidelines for managing cholesterol to reduce cardiovascular disease (CVD) risk focus on providing the appropriate intensity of statin therapy to reduce low-density lipoprotein cholesterol (LDL-C) level. There is very little evidence supporting the use of treatments aimed at raising high-density lipoprotein cholesterol level or reducing triglyceride levels. HIV-infected persons have excess risk of CVD compared with the general population. Statins are less effective at reducing LDL-C levels in HIV-infected persons who are also at greater risk for adverse effects from statin treatment. When selecting a statin to achieve desired lowering of LDL-C level, the potential for drug interactions with antiretroviral therapy must be considered. Information from ongoing research is expected to help identify optimal strategies for use of statin treatment in this population. This article summarizes a presentation by James H. Stein, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Chicago, Illinois, in May 201. PMID:27398770

  8. The chondroprotective effects of intraarticular application of statin in osteoarthritis: An experimental study

    PubMed Central

    Bayyurt, Sarp; Küçükalp, Abdullah; Bilgen, Muhammed Sadik; Bilgen, Ömer Faruk; Çavuşoğlu, İlkin; Yalçınkaya, Ulviye

    2015-01-01

    Background: Osteoarthritis (OA) is the most frequent chronic joint disease causing pain and disability. Recent reports have shown that statin may have the potential to inhibit osteoarthritis. This study of early stage OA developed in an experimental rabbit model, aimed to evaluate the chondroprotective effects of intraarticularly applied atorvastatin on cartilage tissue macroscopically and histopathologically by examining intracellular and extracellular changes by light and electron microscope. Materials and Methods: The experimental knee OA model was created by cutting the anterior cruciate ligament of the 20 mature New Zealand rabbits. The rabbits were randomly allocated into two groups of 10. Study group: The group that received intraarticular statin therapy; Control group: The group that did not receive any intraarticular statin therapy. The control group received an intraarticular administration of saline and the study group atorvastatin from the 1st week postoperatively, once a week for 3 weeks. The knee joints were removed including the femoral and tibial joint surfaces for light and electron microscopic studies of articular cartilages. Results: The mean total points obtained from the evaluation of the lesions that developed in the medial femoral condyle were 11.33 ± 0.667 for the control group and 1.5 ± 0.687 for the study group. The mean total points obtained from the evaluation of the lesions that developed in medial tibial plateau cartilage tissue were 11.56 ± 0.709 for the control group and 1.40 ± 0.618 for the study group. Electron microscopic evaluation revealed healthy cartilage tissue with appropriate chondrocyte and matrix structure in study group and impaired cartilage tissue in control group. Conclusion: Chondroprotective effect of statin on cartilage tissue was determined in this experimental OA model evaluated macroscopically and by light and electron microscope. There are some evidences to believe that the chondroprotective effect of the

  9. Protective effects of a squalene synthase inhibitor, lapaquistat acetate (TAK-475), on statin-induced myotoxicity in guinea pigs.

    PubMed

    Nishimoto, Tomoyuki; Ishikawa, Eiichiro; Anayama, Hisashi; Hamajyo, Hitomi; Nagai, Hirofumi; Hirakata, Masao; Tozawa, Ryuichi

    2007-08-15

    High-dose statin treatment has been recommended as a primary strategy for aggressive reduction of LDL cholesterol levels and protection against coronary artery disease. The effectiveness of high-dose statins may be limited by their potential for myotoxic side effects. There is currently little known about the molecular mechanisms of statin-induced myotoxicity. Previously we showed that T-91485, an active metabolite of the squalene synthase inhibitor lapaquistat acetate (lapaquistat: a previous name is TAK-475), attenuated statin-induced cytotoxicity in human skeletal muscle cells [Nishimoto, T., Tozawa, R., Amano, Y., Wada, T., Imura, Y., Sugiyama, Y., 2003a. Comparing myotoxic effects of squalene synthase inhibitor, T-91485, and 3-hydroxy-3-methylglutaryl coenzyme A. Biochem. Pharmacol. 66, 2133-2139]. In the current study, we investigated the effects of lapaquistat administration on statin-induced myotoxicity in vivo. Guinea pigs were treated with either high-dose cerivastatin (1 mg/kg) or cerivastatin together with lapaquistat (30 mg/kg) for 14 days. Treatment with cerivastatin alone decreased plasma cholesterol levels by 45% and increased creatine kinase (CK) levels by more than 10-fold (a marker of myotoxicity). The plasma CK levels positively correlated with the severity of skeletal muscle lesions as assessed by histopathology. Co-administration of lapaquistat almost completely prevented the cerivastatin-induced myotoxicity. Administration of mevalonolactone (100 mg/kg b.i.d.) prevented the cerivastatin-induced myotoxicity, confirming that this effect is directly related to HMG-CoA reductase inhibition. These results strongly suggest that cerivastatin-induced myotoxicity is due to depletion of mevalonate derived isoprenoids. In addition, squalene synthase inhibition could potentially be used clinically to prevent statin-induced myopathy. PMID:17599378

  10. A Systems Biology Strategy Reveals Biological Pathways and Plasma Biomarker Candidates for Potentially Toxic Statin-Induced Changes in Muscle

    PubMed Central

    Laaksonen, Reijo; Katajamaa, Mikko; Päivä, Hannu; Sysi-Aho, Marko; Saarinen, Lilli; Junni, Päivi; Lütjohann, Dieter; Smet, Joél; Van Coster, Rudy; Seppänen-Laakso, Tuulikki; Lehtimäki, Terho; Soini, Juhani; Orešič, Matej

    2006-01-01

    Background Aggressive lipid lowering with high doses of statins increases the risk of statin-induced myopathy. However, the cellular mechanisms leading to muscle damage are not known and sensitive biomarkers are needed to identify patients at risk of developing statin-induced serious side effects. Methodology We performed bioinformatics analysis of whole genome expression profiling of muscle specimens and UPLC/MS based lipidomics analyses of plasma samples obtained in an earlier randomized trial from patients either on high dose simvastatin (80 mg), atorvastatin (40 mg), or placebo. Principal Findings High dose simvastatin treatment resulted in 111 differentially expressed genes (1.5-fold change and p-value<0.05), while expression of only one and five genes was altered in the placebo and atorvastatin groups, respectively. The Gene Set Enrichment Analysis identified several affected pathways (23 gene lists with False Discovery Rate q-value<0.1) in muscle following high dose simvastatin, including eicosanoid synthesis and Phospholipase C pathways. Using lipidomic analysis we identified previously uncharacterized drug-specific changes in the plasma lipid profile despite similar statin-induced changes in plasma LDL-cholesterol. We also found that the plasma lipidomic changes following simvastatin treatment correlate with the muscle expression of the arachidonate 5-lipoxygenase-activating protein. Conclusions High dose simvastatin affects multiple metabolic and signaling pathways in skeletal muscle, including the pro-inflammatory pathways. Thus, our results demonstrate that clinically used high statin dosages may lead to unexpected metabolic effects in non-hepatic tissues. The lipidomic profiles may serve as highly sensitive biomarkers of statin-induced metabolic alterations in muscle and may thus allow us to identify patients who should be treated with a lower dose to prevent a possible toxicity. PMID:17183729

  11. Protective effects of a squalene synthase inhibitor, lapaquistat acetate (TAK-475), on statin-induced myotoxicity in guinea pigs

    SciTech Connect

    Nishimoto, Tomoyuki; Ishikawa, Eiichiro; Anayama, Hisashi; Hamajyo, Hitomi; Nagai, Hirofumi; Hirakata, Masao; Tozawa, Ryuichi

    2007-08-15

    High-dose statin treatment has been recommended as a primary strategy for aggressive reduction of LDL cholesterol levels and protection against coronary artery disease. The effectiveness of high-dose statins may be limited by their potential for myotoxic side effects. There is currently little known about the molecular mechanisms of statin-induced myotoxicity. Previously we showed that T-91485, an active metabolite of the squalene synthase inhibitor lapaquistat acetate (lapaquistat: a previous name is TAK-475), attenuated statin-induced cytotoxicity in human skeletal muscle cells [Nishimoto, T., Tozawa, R., Amano, Y., Wada, T., Imura, Y., Sugiyama, Y., 2003a. Comparing myotoxic effects of squalene synthase inhibitor, T-91485, and 3-hydroxy-3-methylglutaryl coenzyme A. Biochem. Pharmacol. 66, 2133-2139]. In the current study, we investigated the effects of lapaquistat administration on statin-induced myotoxicity in vivo. Guinea pigs were treated with either high-dose cerivastatin (1 mg/kg) or cerivastatin together with lapaquistat (30 mg/kg) for 14 days. Treatment with cerivastatin alone decreased plasma cholesterol levels by 45% and increased creatine kinase (CK) levels by more than 10-fold (a marker of myotoxicity). The plasma CK levels positively correlated with the severity of skeletal muscle lesions as assessed by histopathology. Co-administration of lapaquistat almost completely prevented the cerivastatin-induced myotoxicity. Administration of mevalonolactone (100 mg/kg b.i.d.) prevented the cerivastatin-induced myotoxicity, confirming that this effect is directly related to HMG-CoA reductase inhibition. These results strongly suggest that cerivastatin-induced myotoxicity is due to depletion of mevalonate derived isoprenoids. In addition, squalene synthase inhibition could potentially be used clinically to prevent statin-induced myopathy.

  12. [Prevention of coronary heart disease with statins. Which patients profit?].

    PubMed

    Adam, O; Forth, W

    2003-06-19

    Statins are generally considered as safe drugs with a very favorable cost-efficacy-ratio. Calculation of health expenses limits the prescription of statins in primary prevention to persons on high risk (i.e. 20% risk of a coronary infarction within the next 10 years). Prescription of statins in secondary prevention of atherosclerosis is mandatory. Advanced age, impairment of renal function or polypharmacotherapy increase the incidence of severe side-effects, especially myopathy and rhabdomyolysis. These patients should be given statins with lesser risk of these side-effects. Combination of statins with fibrates has attracted public concern, but may be indicated in persons with otherwise not treatable hyperlipidemia. These patients need intensive monitoring, just as patients on other drugs that are metabolized via the enzyme CYP3A4. Patients on statins should get dietary counseling, as an appropriate diet increases the effect of statins. PMID:12891851

  13. Statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor)-based therapy for hepatitis C virus (HCV) infection-related diseases in the era of direct-acting antiviral agents.

    PubMed

    Kishta, Sara; Ei-Shenawy, Reem; Kishta, Sobhy

    2016-01-01

    Recent improvements have been made in the treatment of hepatitis C virus (HCV) infection with the introduction of direct-acting antiviral agents (DAAs). However, despite successful viral clearance, many patients continue to have HCV-related disease progression. Therefore, new treatments must be developed to achieve viral clearance and prevent the risk of HCV-related diseases. In particular, the use of pitavastatin together with DAAs may improve the antiviral efficacy as well as decrease the progression of liver fibrosis and the incidence of HCV-related hepatocellular carcinoma. To investigate the management methods for HCV-related diseases using pitavastatin and DAAs, clinical trials should be undertaken. However, concerns have been raised about potential drug interactions between statins and DAAs. Therefore, pre-clinical trials using a replicon system, human hepatocyte-like cells, human neurons and human cardiomyocytes from human-induced pluripotent stem cells should be conducted. Based on these pre-clinical trials, an optimal direct-acting antiviral agent could be selected for combination with pitavastatin and DAAs. Following the pre-clinical trial, the combination of pitavastatin and the optimal direct-acting antiviral agent should be compared to other combinations of DAAs ( e.g., sofosbuvir and velpatasvir) according to the antiviral effect on HCV infection, HCV-related diseases and cost-effectiveness. PMID:27583130

  14. Statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor)-based therapy for hepatitis C virus (HCV) infection-related diseases in the era of direct-acting antiviral agents

    PubMed Central

    Kishta, Sara; EI-Shenawy, Reem; Kishta, Sobhy

    2016-01-01

    Recent improvements have been made in the treatment of hepatitis C virus (HCV) infection with the introduction of direct-acting antiviral agents (DAAs). However, despite successful viral clearance, many patients continue to have HCV-related disease progression. Therefore, new treatments must be developed to achieve viral clearance and prevent the risk of HCV-related diseases. In particular, the use of pitavastatin together with DAAs may improve the antiviral efficacy as well as decrease the progression of liver fibrosis and the incidence of HCV-related hepatocellular carcinoma. To investigate the management methods for HCV-related diseases using pitavastatin and DAAs, clinical trials should be undertaken. However, concerns have been raised about potential drug interactions between statins and DAAs. Therefore, pre-clinical trials using a replicon system, human hepatocyte-like cells, human neurons and human cardiomyocytes from human-induced pluripotent stem cells should be conducted. Based on these pre-clinical trials, an optimal direct-acting antiviral agent could be selected for combination with pitavastatin and DAAs. Following the pre-clinical trial, the combination of pitavastatin and the optimal direct-acting antiviral agent should be compared to other combinations of DAAs ( e.g., sofosbuvir and velpatasvir) according to the antiviral effect on HCV infection, HCV-related diseases and cost-effectiveness.

  15. Statins stimulate the production of a soluble form of the receptor for advanced glycation end products

    PubMed Central

    Quade-Lyssy, Patricia; Kanarek, Anna Maria; Baiersdörfer, Markus; Postina, Rolf; Kojro, Elzbieta

    2013-01-01

    The beneficial effects of statin therapy in the reduction of cardiovascular pathogenesis, atherosclerosis, and diabetic complications are well known. The receptor for advanced glycation end products (RAGE) plays an important role in the progression of these diseases. In contrast, soluble forms of RAGE act as decoys for RAGE ligands and may prevent the development of RAGE-mediated disorders. Soluble forms of RAGE are either produced by alternative splicing [endogenous secretory RAGE (esRAGE)] or by proteolytic shedding mediated by metalloproteinases [shed RAGE (sRAGE)]. Therefore we analyzed whether statins influence the production of soluble RAGE. Lovastatin treatment of either mouse alveolar epithelial cells endogenously expressing RAGE or HEK cells overexpressing RAGE caused induction of RAGE shedding, but did not influence secretion of esRAGE from HEK cells overexpressing esRAGE. Lovastatin-induced secretion of sRAGE was also evident after restoration of the isoprenylation pathway, demonstrating a correlation of sterol biosynthesis and activation of RAGE shedding. Lovastatin-stimulated induction of RAGE shedding was completely abolished by a metalloproteinase ADAM10 inhibitor. We also demonstrate that statins stimulate RAGE shedding at low physiologically relevant concentrations. Our results show that statins, due to their cholesterol-lowering effects, increase the soluble RAGE level by inducing RAGE shedding, and by doing this, might prevent the development of RAGE-mediated pathogenesis. PMID:23966666

  16. Statins for the prevention of contrast-induced acute kidney injury.

    PubMed

    Ball, Timothy; McCullough, Peter A

    2014-01-01

    Acute kidney injury (AKI) is a common medical problem, especially in patients undergoing cardiovascular procedures. The risk of kidney damage has multiple determinants and is often related to or exacerbated by intravenous or intra-arterial iodinated contrast. Contrast-induced AKI (CI-AKI) has been associated with an increased risk of subsequent myocardial infarction, stroke, the development of heart failure, rehospitalization, progression of chronic kidney disease, end-stage renal disease, and death. Statins have been studied extensively in the setting of chronic kidney disease and they have been shown to reduce albuminuria, but they have had no effect on the progressive reduction of glomerular filtration or the need for renal replacement therapy. Several meta-analyses have shown a protective effect of short-term statin administration on CI-AKI and led to two large randomized controlled trials evaluating the role of rosuvastatin in the prevention of CI-AKI in high-risk patients with acute coronary syndrome and diabetes mellitus. Both trials showed a benefit of rosuvastatin prior to contrast administration in a statin-naive patient population. In aggregate, these studies support the short-term use of statins specifically for the prevention of CI-AKI in patients undergoing coronary angiography with or without percutaneous coronary intervention. PMID:25343843

  17. Myopathy induced by statin-ezetimibe combination: Evaluation of potential risk factors

    PubMed Central

    Brahmachari, Ballari; Chatterjee, Suparna

    2015-01-01

    Although both atorvastatin and ezetimibe may cause myopathy, statin-induced myopathy is less likely at low doses, and ezetimibe is only rarely reported to induce myopathy. Also, ezetimibe is not usually known to potentiate statin-induced myopathy. We report a case of myalgia with elevated serum creatinine phosphokinase in a patient after 2 months of therapy with fixed dose combination of atorvastatin and ezetimibe (10 mg each). At the time of the event, patient was undertaking moderate physical exertion in the form of brisk walking for 30–40 min a day and was detected to have low serum Vitamin D levels. The adverse event resolved after stopping atorvastatin-ezetimibe combination therapy. Potential risk factors, such as physical exertion and Vitamin D deficiency, co-existent in dyslipidemic patients, may exacerbate myopathy potential of these drugs, and precipitate muscular symptoms even at a low-dose. PMID:26600650

  18. Myopathy induced by statin-ezetimibe combination: Evaluation of potential risk factors.

    PubMed

    Brahmachari, Ballari; Chatterjee, Suparna

    2015-01-01

    Although both atorvastatin and ezetimibe may cause myopathy, statin-induced myopathy is less likely at low doses, and ezetimibe is only rarely reported to induce myopathy. Also, ezetimibe is not usually known to potentiate statin-induced myopathy. We report a case of myalgia with elevated serum creatinine phosphokinase in a patient after 2 months of therapy with fixed dose combination of atorvastatin and ezetimibe (10 mg each). At the time of the event, patient was undertaking moderate physical exertion in the form of brisk walking for 30-40 min a day and was detected to have low serum Vitamin D levels. The adverse event resolved after stopping atorvastatin-ezetimibe combination therapy. Potential risk factors, such as physical exertion and Vitamin D deficiency, co-existent in dyslipidemic patients, may exacerbate myopathy potential of these drugs, and precipitate muscular symptoms even at a low-dose. PMID:26600650

  19. Statins: Cholesterol guidelines and Indian perspective

    PubMed Central

    Menon, Anil S.; Kotwal, Narendra; Singh, Yashpal; Girish, R.

    2015-01-01

    Statins have become an important drug in preventing the occurrence of atherosclerotic cardiovascular disease (ASCVD). The effectiveness of statins in reducing ASCVD has been established in large-scale clinical trials. The lipid management guidelines have been periodically modified due to accumulating evidence about the proportionate benefit achieved with a progressive reduction in cholesterol levels with higher doses of statins and even in those at low risk of development of ASCVD. The current American College of Cardiology/American Heart Association guidelines have based its recommendations from data gathered exclusively from randomized controlled trials. It has simplified the use of statins, but also raised questions regarding the validity of its cardiovascular event risk prediction tool. Epidemiology of cardiovascular disease in India differs from the western population; there is an increased the prevalence of metabolic syndrome and atherogenic dyslipidemia phenotype a group not addressed in the current guidelines. The guidelines are based on trials, which do not have a representative South Asian population. This article reviews the relevant literature, and examines the issues involved in adopting the guidelines to the Indian population. PMID:26425462

  20. Emerging approaches in fermentative production of statins.

    PubMed

    Singh, Sudheer Kumar; Pandey, Ashok

    2013-10-01

    Microbial metabolites have many important applications in pharmaceutical and health-care industry. The products of microbial origin are usually produced by submerged fermentation. The solid-state fermentation represents an alternative mode of fermentation, which is increasingly being employed as an alternative to submerged fermentation for metabolite production. The prospect of producing high-value product using low-value raw material offers a substantial premium to switch to these technologies. The cost of statins being one major factor, solid-state fermentation with agro-industrial residues as carbon, nitrogen and support matrix, promises to substantially lower the cost of production. Hence, newer approaches are required to exploit the agro-industrial residues for statin production. The development of these technologies offers an opportunity to exploit low-cost substrates without substantial investment in newer production methodologies. The emerging evidence of beneficial effect of statins in applications other than lipid lowering such as in Alzheimer disease, HIV, age-related dementia, and cancer chemotherapy makes it very important to develop methods for economic production of statins. PMID:23912209

  1. Statins and Cardiovascular Primary Prevention in CKD: A Meta-Analysis

    PubMed Central

    Cheung, Chee Kay; Gray, Laura J.; Brunskill, Nigel J.

    2015-01-01

    Background and objectives Multiple meta-analyses of lipid-lowering therapies for cardiovascular primary prevention in the general population have been performed. Other meta-analyses of lipid-lowering therapies in CKD have also been performed, but not for primary prevention. This meta-analysis assesses lipid-lowering therapies for cardiovascular primary prevention in CKD. Design, setting, participants, & measurements A systematic review and meta-analysis using a random-effects model was performed. MEDLINE was searched between January 2012 and September 2013 for new studies using predefined search criteria without language restrictions. A number of other sources including previously published meta-analyses were also reviewed. Inclusion criteria were randomized control trials of primary prevention with lipid-lowering therapy in non–end stage CKD. Results Six trials were identified, five including patients with stage 3 CKD only. These studies included 8834 participants and 32,846 person-years of follow-up. All trials were post hoc subgroup analyses of statins in the general population. Statins reduced the risk of cardiovascular disease (the prespecified primary outcome) by 41% in stages 1–3 CKD compared with placebo (pooled risk ratio, 0.59; 95% confidence interval [95% CI], 0.48 to 0.72). For the secondary outcomes, the risk ratios were 0.66 (95% CI, 0.49 to 0.88) for total mortality, 0.55 (95% CI, 0.42 to 0.72) for coronary heart disease events, and 0.56 (95% CI, 0.28 to 1.13) for stroke. In study participants with stage 3 CKD specifically, the results were similar. Conclusions This meta-analysis suggests that the use of statins in CKD for primary prevention of cardiovascular disease is effective. These findings are consistent with recent guidance for the use of statins in all patients with CKD. PMID:25833405

  2. New Drugs for Treating Dyslipidemia: Beyond Statins

    PubMed Central

    Ahn, Chang Ho

    2015-01-01

    Statins have been shown to be very effective and safe in numerous randomized clinical trials, and became the implacable first-line treatment against atherogenic dyslipidemia. However, even with optimal statin treatment, 60% to 80% of residual cardiovascular risk still exists. The patients with familial hypercholesterolemia which results in extremely high level of low density lipoprotein cholesterol (LDL-C) level and the patients who are intolerant or unresponsive to statins are the other hurdles of statin treatment. Recently, new classes of lipid-lowering drugs have been developed and some of them are available for the clinical practice. The pro-protein convertase subtilisin/kexintype 9 (PCSK9) inhibitor increases the expression of low density lipoprotein (LDL) receptor in hepatocytes by enhancing LDL receptor recycling. The microsomal triglyceride transport protein (MTP) inhibitor and antisense oligonucleotide against apolipoprotein B (ApoB) reduce the ApoB containing lipoprotein by blocking the hepatic very low density lipoprotein synthesis pathway. The apolipoprotein A1 (ApoA1) mimetics pursuing the beneficial effect of high density lipoprotein cholesterol and can reverse the course of atherosclerosis. ApoA1 mimetics had many controversial clinical data and need more validation in humans. The PCSK9 inhibitor recently showed promising results of significant LDL-C lowering in familial hypercholesterolemia (FH) patients from the long-term phase III trials. The MTP inhibitor and antisesnse oligonucleotide against ApoB were approved for the treatment of homozygous FH but still needs more consolidated evidences about hepatic safety such as hepatosteatosis. We would discuss the benefits and concerns of these new lipid-lowering drugs anticipating additional benefits beyond statin treatment. PMID:25922802

  3. Aggression in borderline personality disorder.

    PubMed

    Látalová, K; Prasko, J

    2010-09-01

    This review examined aggressive behavior in Borderline Personality Disorder (BPD) and its management in adults. Aggression against self or against others is a core component of BPD. Impulsiveness is a clinical hallmark (as well as a DSM-IV-TR diagnostic criterion) of BPD, and aggressive acts by BPD patients are largely of the impulsive type. BPD has high comorbidity rates with substance use disorders, Bipolar Disorder, and Antisocial Personality Disorder; these conditions further elevate the risk for violence. Treatment of BDP includes psychodynamic, cognitive behavioral, schema therapy, dialectic behavioral, group and pharmacological interventions. Recent studies indicate that many medications, particularly atypical antipsychotics and anticonvulsants, may reduce impulsivity, affective lability as well as irritability and aggressive behavior. But there is still a lack of large, double blind, placebo controlled studies in this area. PMID:20390357

  4. Predictors of long-term mortality in new start statin users

    PubMed Central

    Kazerooni, Rashid; Lim, Jane

    2015-01-01

    Background Cardiovascular diseases are among the leading causes of death worldwide and studies have found a direct relationship between levels of low-density lipoprotein cholesterol and coronary heart disease. Statins are the most commonly prescribed medications to lower cholesterol, a major controllable risk factor for coronary heart disease. Objective This study aims to find what factors in the first year of statin therapy are predictive of long-term all-cause mortality. Methods Data for this retrospective cohort study were collected on patients identified as new statin users between December 1, 2006 and November 30, 2007 at five Veterans Affairs Healthcare Systems from Southern California and Nevada. Multiple independent variables were assessed utilizing a logistic regression model assessing for all cause mortality at 6 years follow-up. The independent variables included race, age, ethnicity, body mass index, socioeconomic status, and baseline comorbidities. Secondary analysis analyzed high-density lipoprotein levels, adherence, total cholesterol, and triglycerides. Results Increased age, increased medication count, hypertension, diabetes, tobacco use, chronic obstructive pulmonary disease, and congestive heart failure were all associated with an increased risk of mortality. Hispanic ethnicity, Asian race, and increased body mass index were associated with decreased risk of mortality. There were no significant associations between mortality and race, LDL outcomes at 1 year, or annual income level. Conclusion There is clear evidence that statin use is associated with decreased events in cardiovascular disease and total mortality. This study found multiple independent variables as predictors of mortality in new start statin users after a 6 year follow-up, but differences in lipid groups after 1 year were not predictive of long-term mortality in the cohort studied.

  5. Abnormal splicing of NEDD4 in myotonic dystrophy type 2: possible link to statin adverse reactions.

    PubMed

    Screen, Mark; Jonson, Per Harald; Raheem, Olayinka; Palmio, Johanna; Laaksonen, Reijo; Lehtimäki, Terho; Sirito, Mario; Krahe, Ralf; Hackman, Peter; Udd, Bjarne

    2014-08-01

    Myotonic dystrophy type 2 (DM2) is a multisystemic disorder caused by a (CCTG)n repeat expansion in intron 1 of CNBP. Transcription of the repeats causes a toxic RNA gain of function involving their accumulation in ribonuclear foci. This leads to sequestration of splicing factors and alters pre-mRNA splicing in a range of downstream effector genes, which is thought to contribute to the diverse DM2 clinical features. Hyperlipidemia is frequent in DM2 patients, but the treatment is problematic because of an increased risk of statin-induced adverse reactions. Hypothesizing that shared pathways lead to the increased risk, we compared the skeletal muscle expression profiles of DM2 patients and controls with patients with hyperlipidemia on statin therapy. Neural precursor cell expressed, developmentally downregulated-4 (NEDD4), an ubiquitin ligase, was one of the dysregulated genes identified in DM2 patients and patients with statin-treated hyperlipidemia. In DM2 muscle, NEDD4 mRNA was abnormally spliced, leading to aberrant NEDD4 proteins. NEDD4 was down-regulated in persons taking statins, and simvastatin treatment of C2C12 cells suppressed NEDD4 transcription. Phosphatase and tensin homologue (PTEN), an established NEDD4 target, was increased and accumulated in highly atrophic DM2 muscle fibers. PTEN ubiquitination was reduced in DM2 myofibers, suggesting that the NEDD4-PTEN pathway is dysregulated in DM2 skeletal muscle. Thus, this pathway may contribute to the increased risk of statin-adverse reactions in patients with DM2. PMID:24907641

  6. The role of acid-base imbalance in statin-induced myotoxicity.

    PubMed

    Taha, Dhiaa A; De Moor, Cornelia H; Barrett, David A; Lee, Jong Bong; Gandhi, Raj D; Hoo, Chee Wei; Gershkovich, Pavel

    2016-08-01

    Disturbances in acid-base balance, such as acidosis and alkalosis, have potential to alter the pharmacologic and toxicologic outcomes of statin therapy. Statins are commonly prescribed for elderly patients who have multiple comorbidities such as diabetes mellitus, cardiovascular, and renal diseases. These patients are at risk of developing acid-base imbalance. In the present study, the effect of disturbances in acid-base balance on the interconversion of simvastatin and pravastatin between lactone and hydroxy acid forms have been investigated in physiological buffers, human plasma, and cell culture medium over pH ranging from 6.8-7.8. The effects of such interconversion on cellular uptake and myotoxicity of statins were assessed in vitro using C2C12 skeletal muscle cells under conditions relevant to acidosis, alkalosis, and physiological pH. Results indicate that the conversion of the lactone forms of simvastatin and pravastatin to the corresponding hydroxy acid is strongly pH dependent. At physiological and alkaline pH, substantial proportions of simvastatin lactone (SVL; ∼87% and 99%, respectively) and pravastatin lactone (PVL; ∼98% and 99%, respectively) were converted to the active hydroxy acid forms after 24 hours of incubation at 37°C. At acidic pH, conversion occurs to a lower extent, resulting in greater proportion of statin remaining in the more lipophilic lactone form. However, pH alteration did not influence the conversion of the hydroxy acid forms of simvastatin and pravastatin to the corresponding lactones. Furthermore, acidosis has been shown to hinder the metabolism of the lactone form of statins by inhibiting hepatic microsomal enzyme activities. Lipophilic SVL was found to be more cytotoxic to undifferentiated and differentiated skeletal muscle cells compared with more hydrophilic simvastatin hydroxy acid, PVL, and pravastatin hydroxy acid. Enhanced cytotoxicity of statins was observed under acidic conditions and is attributed to increased

  7. Effects of niacin, statin, and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 levels in patients with dyslipidemia.

    PubMed

    Khera, Amit V; Qamar, Arman; Reilly, Muredach P; Dunbar, Richard L; Rader, Daniel J

    2015-01-15

    Recent trials demonstrated substantial improvement in lipid parameters with inhibition of proprotein convertase subtilisin-like/kexin type 9 (PCSK9). Although statins and fibrates have been reported to increase plasma PCSK9 levels, the effect of niacin on PCSK9 is unknown. We investigated the impact of niacin, atorvastatin, and fenofibrate on PCSK9 levels in 3 distinct studies. A statin-only study randomized 74 hypercholesterolemic patients to placebo, atorvastatin 10 mg/day, or atorvastatin 80 mg/day for 16 weeks. A dose-related increase in PCSK9 was noted such that atorvastatin 80 mg increased PCSK9 by a mean +27% (95% confidence interval [CI] +12 to +42), confirming the effect of statin therapy on raising PCSK9. A second study randomized 70 patients with carotid atherosclerosis to simvastatin 20 mg/day, simvastatin 80 mg/day, or simvastatin 20 mg/extended-release (ER) niacin 2 g/day. PCSK9 levels were increased with statin therapy, but decreased with the simvastatin 20 mg/ER niacin combination (mean -13%, CI -3 to -23). A final study involved 19 dyslipidemic participants on atorvastatin 10 mg with serial addition of fenofibric acid 135 mg followed by ER niacin 2 g/day. Fenofibric acid led to a +23% (CI +10 to +36, p = 0.001) increase in PCSK9; the addition of niacin resulted in a subsequent -17% decrease (CI -19 to -5, p = 0.004). A positive association was noted between change in PCSK9 and low-density lipoprotein cholesterol levels (r = 0.62, p = 0.006) with the addition of niacin. In conclusion, niacin therapy offsets the increase in PCSK9 levels noted with statin and fibrate therapy. A portion of the low-density lipoprotein cholesterol reduction seen with niacin therapy may be due to reduction in PCSK9. PMID:25432415

  8. Statin Effects on Exacerbation Rates, Mortality, and Inflammatory Markers in Patients with Chronic Obstructive Pulmonary Disease: A Review of Prospective Studies.

    PubMed

    Howard, Meredith L; Vincent, Ashley H

    2016-05-01

    Chronic obstructive pulmonary disease (COPD) is a debilitating, irreversible disease with currently available therapies targeting symptom control and exacerbation reduction. A need for alternative disease-modifying therapies remains, specifically those that may have antiinflammatory and immunomodulatory properties that impact the pathophysiologic components of COPD. Statin drugs, the current gold standard for the treatment of dyslipidemia and prevention of cardiovascular disease (CVD), contain properties that affect the inflammatory disease processes seen in COPD. Several retrospective studies have demonstrated that statins may have a benefit in the reduction of morbidity and mortality in patients with COPD. This has led to prospective trials evaluating the impact of statins on various COPD-related outcomes. This article reviews the current body of prospective evidence for use of statins in patients with COPD. A search of the PubMed/Medline database of English-language articles was conducted from 1964 through November 2015; references of relevant articles were also reviewed for qualifying studies. Prospective studies of all types relating to statin use in patients with COPD were included if they had COPD- or respiratory-related outcomes; ultimately, eight studies were identified for this review. Statin effects on exacerbation rates, mortality, and inflammatory markers in patients with COPD are discussed. Strong prospective evidence does not currently exist to suggest that statins provide a clinical benefit in patients with COPD who do not have other CVD risk factors. Benefits from statins that have been illustrated are likely explained by their impact on underlying CVD risk factors rather than the COPD disease process. An opportunity exists for unanswered questions to be addressed in future studies. PMID:26990316

  9. Hydrophobic statins induce autophagy in cultured human rhabdomyosarcoma cells.

    PubMed

    Araki, Makoto; Motojima, Kiyoto

    2008-03-01

    Statins are widely used to treat hypercholesterolemia, but they are associated with muscle-related adverse events, by as yet, inadequately resolved mechanisms. In this study, we report that statins induced autophagy in cultured human rhabdomyosarcoma A204 cells. Potency differed widely among the statins: cerivastatin induced autophagy at 0.1muM, simvastatin at 10muM but none was induced by pravastatin. Addition of mevalonate, but not cholesterol, blocked induction of autophagy by cerivastatin, suggesting that this induction is dependent on modulation of isoprenoid metabolic pathways. The statin-induced autophagy was not observed in other types of cells, such as human hepatoma HepG2 or embryonic kidney HEK293 cells. Muscle-specific abortive induction of autophagy by hydrophobic statins is a possible mechanism for statin-induced muscle-related side effects. PMID:18178158

  10. Statins in skin: research and rediscovery, from psoriasis to sclerosis.

    PubMed

    Egesi, Adaeze; Sun, Grace; Khachemoune, Amor; Rashid, Rashid M

    2010-08-01

    Statins, initially developed as antimicrobials, are primarily considered cholesterol-lowering agents. Recently, researchers discovered anti-inflammatory properties of statins. Studies on the effects of statins and the alterations noted include: bench work that supported a Th1/Th2 skew to Th1, altered lymphocyte migration, inhibition of MHC-II induction and cytokine release on antigen-presenting cells, inhibition of mast cell degranulation and inhibition of Th17 cells and IL-17 production. In addition to the anti-inflammatory properties, statins have been found to induce apoptosis in melanoma models. The potential therapeutic value of statins is illustrated in the management of alopecia areata, atopic dermatitis, psoriasis, systemic lupus erythematosus, cutaneous T-cell lymphomas, cutaneous melanoma, mastocytosis and more. This manuscript presents a comprehensive review of statins and their potential dermatologic application. PMID:20684142

  11. Persisting weakness after withdrawal of a statin.

    PubMed

    Mygland, Åse; Ljøstad, Unn; Krossnes, Bård Kronen

    2014-01-01

    An 81-year-old woman treated with simvastatin for several years followed by atorvastatin for about 1 year presented with fatigue, weakness and unsteady gait. The finding of elevated creatine kinase (CK) and symmetric muscle weakness around shoulders and hips led to suspicion of a toxic statin-associated myopathy. Atorvastatin was withdrawn, but her weakness persisted. Owing to persisting weakness, an autoimmune myopathy (myositis) was suspected, but initially disregarded since a muscle biopsy showed necrotic muscle fibres without inflammatory cell infiltrates and myositis-specific autoantibodies were absent. After 18 months with slowly progressive weakness and increasing CK values, awareness of new knowledge about autoimmunity as a cause of necrotic myopathy, led to a successful treatment trial with intravenous immunoglobulines, followed by steroids and metothrexate. Antibodies to the target enzyme of statins (HMGCR (3-hydroksy-3-methylglutaryl-coenzyme A reductase)) were detected in her serum, and she was diagnosed with autoimmune necrotic myositis probably triggered by atorvastatin. PMID:24713712

  12. Tendon, tendon healing, hyperlipidemia and statins

    PubMed Central

    Esenkaya, Irfan; Unay, Koray

    2011-01-01

    Summary Both hyperlipidemia and metabolic syndrome have adverse effect on tendon structure. Atorvastatin is most widely used antihyperlipidemic drug. Statins have adverse effects on the tendon. Many studies have analyzed the relationship between atorvastatin and skeletal muscles. Atorvastatin administered after the surgical repair of a ruptured tendon appears to affect revascularization, collagenization, inflammatory cell infiltration, and collagen construction. Therefore, further investigations on the effects of atorvastatin on tendon healing are needed. PMID:23738266

  13. Green analytical method development for statin analysis.

    PubMed

    Assassi, Amira Louiza; Roy, Claude-Eric; Perovitch, Philippe; Auzerie, Jack; Hamon, Tiphaine; Gaudin, Karen

    2015-02-01

    Green analytical chemistry method was developed for pravastatin, fluvastatin and atorvastatin analysis. HPLC/DAD method using ethanol-based mobile phase with octadecyl-grafted silica with various grafting and related-column parameters such as particle sizes, core-shell and monolith was studied. Retention, efficiency and detector linearity were optimized. Even for column with particle size under 2 μm, the benefit of keeping efficiency within a large range of flow rate was not obtained with ethanol based mobile phase compared to acetonitrile one. Therefore the strategy to shorten analysis by increasing the flow rate induced decrease of efficiency with ethanol based mobile phase. An ODS-AQ YMC column, 50 mm × 4.6 mm, 3 μm was selected which showed the best compromise between analysis time, statin separation, and efficiency. HPLC conditions were at 1 mL/min, ethanol/formic acid (pH 2.5, 25 mM) (50:50, v/v) and thermostated at 40°C. To reduce solvent consumption for sample preparation, 0.5mg/mL concentration of each statin was found the highest which respected detector linearity. These conditions were validated for each statin for content determination in high concentrated hydro-alcoholic solutions. Solubility higher than 100mg/mL was found for pravastatin and fluvastatin, whereas for atorvastatin calcium salt the maximum concentration was 2mg/mL for hydro-alcoholic binary mixtures between 35% and 55% of ethanol in water. Using atorvastatin instead of its calcium salt, solubility was improved. Highly concentrated solution of statins offered potential fluid for per Buccal Per-Mucous(®) administration with the advantages of rapid and easy passage of drugs. PMID:25582487

  14. Adlerian Therapy with Aggressive Children.

    ERIC Educational Resources Information Center

    Kizer, Betty

    Alfred Adler devised a theory that was holistic, social, teleological, and phenomenological. Adler believed that the basis of problems with children originated in the child's inability to cooperate with society, feelings of inferiority, and a lack of a goal in life. Adler felt the child's life should be examined through the child's eyes.…

  15. Prevalence of dyslipidemia in statin-treated patients in Canada: Results of the DYSlipidemia International Study (DYSIS)

    PubMed Central

    Goodman, Shaun G; Langer, Anatoly; Bastien, Natacha R; McPherson, Ruth; Francis, Gordon A; Genest, Jacques J; Leiter, Lawrence A

    2010-01-01

    BACKGROUND Despite clear guideline recommendations, there is a growing body of evidence that there is suboptimal use of lipid-lowering treatment in Canadians. OBJECTIVE To assess the prevalence and types of persistent lipid abnormalities in Canadian patients receiving statin therapy. METHODS The present cross-sectional study recruited 2436 outpatients 45 years of age or older who were treated with statins by 232 physicians from 10 provinces; all underwent clinical examination and had their latest fasting lipid values while on statin therapy recorded. RESULTS The median patient age was 66 years (interquartile range [IQR] 58 to 74 years), 60% were men and 80% were in the high 10-year risk category. The median low-density lipoprotein cholesterol level was 2.0 mmol/L (IQR 1.6 mmol/L to 2.5 mmol/L) and the median total cholesterol/high-density lipoprotein cholesterol ratio was 3.4 mmol/L (IQR 2.8 mmol/L to 4.1 mmol/L). However, based on the 2006 Canadian Cardiovascular Society recommendations, 37% of all patients did not have a low-density lipoprotein cholesterol level at goal or intervention target level, including 45% of high-risk category patients. The majority of patients received atorvastatin (50%) or rosuvastatin (37%) but primarily at low-to-medium doses, and a minority (14%) received additional lipid-modifying therapies. CONCLUSIONS The present observational study highlights the need for more intensive treatment of lipid abnormalities, particularly among high-risk patients. Recognizing several important limitations related to the observational nature of the study, the findings suggest the possibility that, in addition to optimizing adherence, there remains an important need to titrate current statin therapy to higher doses and potentially use a combination of lipid-modifying treatments (once the statin dose has been truly maximized) to further bridge the gap between evidence-based medicine and current Canadian practice. PMID:21076724

  16. [Statins in the secondary prevention of stroke: New evidence from the SPARCL Study].

    PubMed

    Castilla-Guerra, Luis; Fernández-Moreno, María Del Carmen; López-Chozas, José Manuel

    2016-01-01

    Until recently there was little evidence that statin therapy reduced the risk of stroke recurrence. The SPARCL trial, published in 2006, was the first trial to show the benefits of statin therapy in preventing recurrent stroke. The SPARCL trial showed that treatment with atorvastatin 80mg/day reduced recurrent stroke in patients with a recent stroke or transient ischemic attack (TIA). Several post hoc analyses of different subgroups followed the SPARCL trial. They have not revealed any significant differences when patients were grouped by age, sex or type of stroke. The SPARCL trial has also helped to identify patients who may have a greater benefit from statins: Patients with carotid stenosis, with more intense lipid lowering, and those who achieve optimal levels of LDL-C, HDL-C, triglycerides, and blood pressure. The trial has also helped to identify individuals at high risk of new vascular events. Clearly there is a before and after in stroke prevention since the SPARCL trial was published. PMID:26150172

  17. Is immunity a mechanism contributing to statin-induced diabetes?

    PubMed Central

    Henriksbo, Brandyn D; Schertzer, Jonathan D

    2015-01-01

    Statins lower cholesterol and are commonly prescribed for prevention and treatment of cardiovascular disease risk. Statins have pleotropic actions beyond cholesterol lowering, including decreased protein prenylation, which can alter immune function. The general anti-inflammatory effect of statins may be a key pleiotropic effect that improves cardiovascular disease risk. However, a series of findings have shown that statins increase the pro-inflammatory cytokine, IL-1β, via decreased protein prenylation in immune cells. IL-1β can be regulated by the NLRP3 inflammasome containing caspase-1. Statins have been associated with an increased risk of new onset diabetes. Inflammation can promote ineffective insulin action (insulin resistance), which often precedes diabetes. This review highlights the links between statins, insulin resistance and immunity via the NLRP3 inflammasome. We propose that statin-induced changes in immunity should be investigated as a mechanism underlying increased risk of diabetes. It is possible that statin-related insulin resistance occurs through a separate pathway from various mechanisms that confer cardiovascular benefits. Therefore, understanding the potential mechanisms that segregate statin-induced cardiovascular effects from those that cause dysglycemia may lead to improvements in this drugs class. PMID:26451278

  18. STATINS AND NEUROPROTECTION: A PRESCRIPTION TO MOVE THE FIELD FORWARD

    PubMed Central

    Wood, W. Gibson; Eckert, Gunter P.; Igbavboa, Urule; Müller, Walter E.

    2009-01-01

    There is growing interest in the use of statins, HMG-CoA reductase inhibitors, for treating specific neurodegenerative diseases (cerebrovascular disease, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis) and possibly traumatic brain injury. Neither is there is a consensus on the efficacy of statins in treating the aforementioned diseases nor are the mechanisms of the purported statin-induced neuroprotection well-understood. Part of the support for statin-induced neuroprotection comes from studies using animal models and cell culture. Important information has resulted from that work but there continues to be a lack of progress on basic issues pertaining to statins and brain which impedes advancement in understanding how statins alter brain function. For example, there are scant data on the pharmacokinetics of lipophilic and hydrophilic statins in brain, statin-induced neuroprotection versus cell death and statins and brain isoprenoids. The purpose of this mini-review will be to examine those aforementioned issues and to identify directions of future research. PMID:20633110

  19. [The combinations of statins and fibrates: pharmacokinetic and clinical implications].

    PubMed

    González Santos, Pedro

    2014-07-01

    With mixed dyslipidemia of the atherogenic dyslipidemia type, once the LDL-c objectives have been achieved through statin treatment, there is often a residual risk, for which the addition of a fibrate is recommended. The combination of statins and fibrates has been limited by the possibility of drug interactions, which mostly result in myopathy. Interactions between statins and other drugs are caused by pharmacokinetic mechanisms, mainly by changing the metabolism of statins in the CYP450 enzyme system, in the hepatic glucuronidation pathway or in the transporters responsible for statin distribution in tissues. The most significant adverse eff ect of statins is myopathy, which can also be induced by fibrates and is more frequent when the 2 drugs (statins and fibrates) are combined. This adverse eff ect manifests clinically as myalgia, muscle weakness, increased CK levels and, in its most severe form, rhabdomyolysis. This interaction mainly aff ects gemfibrozil due to its specific action on the CYP450 enzyme system and that interferes with the hepatic glucuronidation of statins by using the same isoenzymes and with organic anion transporters in the liver. When combining statins, we should use other fibric acid derivatives, preferably fenofibrate. PMID:25043540

  20. Statins and prevention of venous thromboembolism: Myth or reality?

    PubMed

    Gaertner, Sébastien; Cordeanu, Eléna-Mihaela; Nouri, Salah; Mirea, Corina; Stephan, Dominique

    2016-03-01

    The pleiotropic effects of statins, beyond their cholesterol-lowering properties, are much debated. In primary prevention, several observational cohort and case-control studies appear to show that statins reduce the incidence of venous thromboembolism by about 30%. In a single randomized placebo-controlled clinical trial (JUPITER), which included 17,000 patients, rosuvastatin 20mg/day reduced the risk of venous thromboembolism by 43%. However, these patients were at low risk of venous thromboembolism, and the frequency of the event was, in principle, low. In secondary prevention, several observational studies and post-hoc analyses of randomized clinical trials have suggested that statins may prevent recurrence of venous thromboembolism. However, none of these studies had enough scientific weight to form the basis of a recommendation to use statins for secondary prevention. The putative preventive effect of statins appears to be independent of plasma cholesterol concentration and could be a pharmacological property of the statin class, although a dose-effect relationship has not been demonstrated. The mechanism through which statins might prevent venous thrombosis is thought to involve their anti-inflammatory and antioxidant effects or perhaps a more specific action, by blocking the degradation of antithrombotic proteins. A mechanism involving the action of statins on interactions between risk factors for atherosclerosis and venous thromboembolism is supported by some studies, but not all. In the absence of firm evidence, statins cannot currently be recommended for primary or secondary prevention of venous thromboembolism. PMID:26778087

  1. Pleiotropic effects of statins: new therapeutic targets in drug design.

    PubMed

    Bedi, Onkar; Dhawan, Veena; Sharma, P L; Kumar, Puneet

    2016-07-01

    The HMG Co-enzyme inhibitors and new lipid-modifying agents expand their new therapeutic target options in the field of medical profession. Statins have been described as the most effective class of drugs to reduce serum cholesterol levels. Since the discovery of the first statin nearly 30 years ago, these drugs have become the main therapeutic approach to lower cholesterol levels. The present scientific research demonstrates numerous non-lipid modifiable effects of statins termed as pleiotropic effects of statins, which could be beneficial for the treatment of various devastating disorders. The most important positive effects of statins are anti-inflammatory, anti-proliferative, antioxidant, immunomodulatory, neuroprotective, anti-diabetes, and antithrombotic, improving endothelial dysfunction and attenuating vascular remodeling besides many others which are discussed under the scope of this review. In particular, inhibition of Rho and its downstream target, Rho-associated coiled-coil-containing protein kinase (ROCK), and their agonistic action on peroxisome proliferator-activated receptors (PPARs) can be viewed as the principle mechanisms underlying the pleiotropic effects of statins. With gradually increasing knowledge of new therapeutic targets of statins, their use has also been advocated in chronic inflammatory disorders for example rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE). In the scope of review, we highlight statins and their pleiotropic effects with reference to their harmful and beneficial effects as a novel approach for their use in the treatment of devastating disorders. Graphical abstract Pleiotropic effect of statins. PMID:27146293

  2. Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation

    PubMed Central

    Spindler, Stephen R.; Li, Rui; Dhahbi, Joseph M.; Yamakawa, Amy; Mote, Patricia; Bodmer, Rolf; Ocorr, Karen; Williams, Renee T.; Wang, Yinsheng; Ablao, Kenneth P.

    2012-01-01

    Statins such as simvastatin are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and standard therapy for the prevention and treatment of cardiovascular diseases in mammals. Here we show that simvastatin significantly increased the mean and maximum lifespan of Drosophila melanogaster (Drosophila) and enhanced cardiac function in aging flies by significantly reducing heart arrhythmias and increasing the contraction proportion of the contraction/relaxation cycle. These results appeared independent of internal changes in ubiquinone or juvenile hormone levels. Rather, they appeared to involve decreased protein prenylation. Simvastatin decreased the membrane association (prenylation) of specific small Ras GTPases in mice. Both farnesyl (L744832) and type 1 geranylgeranyl transferase (GGTI-298) inhibitors increased Drosophila lifespan. These data are the most direct evidence to date that decreased protein prenylation can increase cardiac health and lifespan in any metazoan species, and may explain the pleiotropic (non-cholesterol related) health effects of statins. PMID:22737247

  3. CONCEPT ANALYSIS: AGGRESSION

    PubMed Central

    Liu, Jianghong

    2006-01-01

    The concept of aggression is important to nursing because further knowledge of aggression can help generate a better theoretical model to drive more effective intervention and prevention approaches. This paper outlines a conceptual analysis of aggression. First, the different forms of aggression are reviewed, including the clinical classification and the stimulus-based classification. Then the manifestations and measurement of aggression are described. Finally, the causes and consequences of aggression are outlined. It is argued that a better understanding of aggression and the causal factors underlying it are essential for learning how to prevent negative aggression in the future. PMID:15371137

  4. Concept analysis: aggression.

    PubMed

    Liu, Jianghong

    2004-01-01

    The concept of aggression is important to nursing because further knowledge of aggression can help generate a better theoretical model to drive more effective intervention and prevention approaches. This paper outlines a conceptual analysis of aggression. First, the different forms of aggression are reviewed, including the clinical classification and the stimulus-based classification. Then the manifestations and measurement of aggression are described. Finally, the causes and consequences of aggression are outlined. It is argued that a better understanding of aggression and the causal factors underlying it are essential for learning how to prevent negative aggression in the future. PMID:15371137

  5. Statins, antidiabetic medications and liver histology in patients with diabetes with non-alcoholic fatty liver disease

    PubMed Central

    Nascimbeni, Fabio; Aron-Wisnewsky, Judith; Pais, Raluca; Tordjman, Joan; Poitou, Christine; Charlotte, Frederic; Bedossa, Pierre; Poynard, Thierry; Clément, Karine; Ratziu, Vlad

    2016-01-01

    Background Type-2 diabetes mellitus (T2DM) is a risk factor for progressive non-alcoholic fatty liver disease (NAFLD). Drugs commonly prescribed in patients with T2DM may affect liver histology by interfering with lipid metabolism and insulin resistance/secretion. Aim We studied if statins or antidiabetic agents were associated with non-alcoholic steatohepatitis (NASH) and significant fibrosis (SF). Methods We performed a cross-sectional study of 346 diabetics with biopsy-proven NAFLD. T2DM was defined as fasting glucose ≥7 mmol/L or glycated haemoglobin ≥6.5% and/or use of antidiabetics. NASH was defined according to the FLIP algorithm and SF as F2–4 Kleiner's stages. Results 84% of patients were on antidiabetic therapy and 45% on statins. NASH and SF were present in 57% and 48% of patients. Statin-treated patients were older, more frequently male and with poorer glycaemic control despite more frequent antidiabetic therapy than those without statins; however, the prevalence of NASH (57%vs56%, p=0.868) and SF (48%vs48%, p=0.943) was not different between statin users and non-users. NASH was more common in patients on metformin or insulin than in those not treated with these drugs (60%vs47%, p=0.026; 68%vs53%, p=0.017). SF was more common in those treated with sulfonylureas (57%vs44%, p=0.030). Multivariate analyses confirmed that use of statins was independently and negatively associated with both NASH (OR (95% CI) 0.57 (0.32 to 1.01), p=0.055) and SF (OR (95% CI) 0.47 (0.26 to 0.84), p=0.011). Moreover, we found independent associations between insulin use and NASH (OR (95% CI) 2.24 (1.11 to 4.54), p=0.025) and sulfonylureas use and SF (OR (95% CI) 2.04 (1.11 to 3.74), p=0.022). Conclusions Several medications used in patients with diabetes are differently associated with NAFLD histology. Statin use is negatively associated, while insulin and sulfonylureas are positively associated with NASH and SF. A wider use of statins may be warranted in this high

  6. Time trends in the prescription of statins for the primary prevention of cardiovascular disease in the United Kingdom: a cohort study using The Health Improvement Network primary care data

    PubMed Central

    O’Keeffe, Aidan G; Nazareth, Irwin; Petersen, Irene

    2016-01-01

    Background Statins are widely prescribed for the primary prevention of cardiovascular disease. Guidelines exist for statin prescriptions, but there is little recent analysis concerning prescription trends over time and how these vary with respect to demographic variables. Methods and results Using The Health Improvement Network primary care database, statin therapy initiation and statin prescription prevalence rates were calculated using data from 7,027,711 individuals across the UK for the years 1995 to 2013, overall and stratified by sex, age group, and socioeconomic deprivation level (Townsend score). Statin therapy initiation rates rose sharply from 1995 (0.51 per 1,000 person-years) up to 2006 (19.83 per 1,000 person-years) and thereafter declined (10.76 per 1,000 person-years in 2013). Males had higher initiation rates than females and individuals aged 60–85 years had higher initiation rates than younger or more elderly age groups. Initiation rates were slightly higher as social deprivation level increased, after accounting for age and sex. Prescription prevalence increased sharply from 1995 (2.36 per 1,000 person-years) to 2013 (128.03 per 1,000 person-years) with males generally having a higher prevalence rate, over time, than females. Prevalence rates over time were generally higher for older age groups but were similar with respect to social deprivation level. Conclusion The uptake of statins within UK primary care has increased greatly over time with statins being more commonly prescribed to older patients in general and, in recent years, males appear to have been prescribed statins at higher rates than females. After accounting for age and sex, the statin therapy initiation rate increases with the level of social deprivation. PMID:27313477

  7. Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins

    PubMed Central

    Tenenbaum, Alexander; Fisman, Enrique Z; Motro, Michael; Adler, Yehuda

    2006-01-01

    Lowering of low-density lipoprotein cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is clearly efficacious in the treatment and prevention of coronary artery disease. However, despite increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is being paid now to combined atherogenic dyslipidemia which typically presents in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or "lipid quartet"): hypertriglyceridemia, low high-density lipoprotein cholesterol levels, a preponderance of small, dense low-density lipoprotein particles and an accumulation of cholesterol-rich remnant particles (e.g. high levels of apolipoprotein B) – emerged as the greatest "competitor" of low-density lipoprotein-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP – Bezafibrate Infarction Prevention study, HHS – Helsinki Heart Study, VAHIT – Veterans Affairs High-density lipoprotein cholesterol Intervention Trial and FIELD – Fenofibrate Intervention and Event Lowering in Diabetes) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants and cholesteryl ester transfer protein inhibition. In addition, bezafibrate as pan-peroxisome proliferator activated receptor activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism and insulin sensitivity. Because fibrates, niacin, ezetimibe and statins each regulate serum lipids by different mechanisms, combination therapy

  8. Perspective of synaptic protection after post-infarction treatment with statins.

    PubMed

    Gutiérrez-Vargas, Johanna Andrea; Cespedes-Rubio, Angel; Cardona-Gómez, Gloria Patricia

    2015-01-01

    Stroke is the second most common cause of death in people over 45 years of age in Colombia and is the leading cause of permanent disability worldwide. Cerebral ischemia is a stroke characterized by decreased blood flow due to the occlusion of one or more cerebral arteries, which can cause memory problems and hemiplegia or paralysis, among other impairments. The literature contains hundreds of therapies (invasive and noninvasive) that exhibit a neuroprotective effect when evaluated in animal models. However, in clinical trials, most of these drugs do not reproduce the previously demonstrated neuroprotective property, and some even have adverse effects that had not previously been detected in animal experimentation.Statins are drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis. Several studies have shown that statin therapy in an animal model of focal cerebral ischemia reduces infarct volume, as well as markers of neurodegeneration, activates neuronal survival pathways, and improves performance on learning and memory tests. Given the implied therapeutic benefit and the limited understanding of the mechanism of action of statins in brain repair, it is necessary to address the biochemical and tissue effects of these drugs on synaptic proteins, such as NMDA receptors, synaptic adhesion proteins, and cytoskeletal proteins; these proteins are highly relevant therapeutic targets, which, in addition to giving a structural account of synaptic connectivity and function, are also indicators of cellular communication and the integrity of the blood-brain barrier, which are widely affected in the long term post-cerebral infarct but, interestingly, are protected by statins when administered during the acute phase. PMID:25884826

  9. Statins inhibited the MIP-1α expression via inhibition of Ras/ERK and Ras/Akt pathways in myeloma cells.

    PubMed

    Tsubaki, Masanobu; Mashimo, Kenji; Takeda, Tomoya; Kino, Toshiki; Fujita, Arisa; Itoh, Tatsuki; Imano, Motohiro; Sakaguchi, Katsuhiko; Satou, Takao; Nishida, Shozo

    2016-03-01

    Macrophage inflammatory protein-1alpha (MIP-1α) is detected at high concentrations in patients with multiple myeloma. It is thought to play an important role in the etiology of multiple myeloma and osteolysis. Thus, inhibiting MIP-1α expression may be useful in developing therapeutic treatments for multiple myeloma-induced osteolysis. In this study, we investigated the potential of statins to inhibit mRNA expression and secretion of MIP-1α in mouse myeloma cells (MOPC-31C). We found that statins inhibited the lipopolysaccharide (LPS)-induced MIP-1α mRNA expression and protein secretion in MOPC-31C cells. This inhibition was reversed when farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), intermediates of the mevalonate pathway, were combined with statins. Furthermore, statins reduced the GTP form of Ras, a phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphorylated Akt. Our results indicate that statins inhibit biosynthesis of FPP and GGPP and thereby down regulate signal transduction of Ras/ERK and Ras/Akt pathways. The net effect suppresses LPS-induced MIP-1α mRNA expression and protein secretion in MOPC-31C cells. Thus, statins hold great promise for developing effective therapies against myeloma-induced osteolysis. PMID:26898421

  10. Differential Benefit of Statin in Secondary Prevention of Acute Myocardial Infarction according to the Level of Triglyceride and High Density Lipoprotein Cholesterol

    PubMed Central

    Kim, Kyung Hwan; Kim, Cheol Hwan; Ahn, Youngkeun; Kim, Young Jo; Cho, Myeong Chan; Kim, Wan; Kim, Jong Jin

    2016-01-01

    Background and Objectives The differential benefit of statin according to the state of dyslipidemia has been sparsely investigated. We sought to address the efficacy of statin in secondary prevention of myocardial infarction (MI) according to the level of triglyceride and high density lipoprotein cholesterol (HDL-C) on admission. Subjects and Methods Acute MI patients (24653) were enrolled and the total patients were divided according to level of triglyceride and HDL-C on admission: group A (HDL-C≥40 mg/dL and triglyceride<150 mg/dL; n=11819), group B (HDL-C≥40 mg/dL and triglyceride≥150 mg/dL; n=3329), group C (HDL-C<40 mg/dL and triglyceride<150 mg/dL; n=6062), and group D (HDL-C<40 mg/dL & triglyceride≥150 mg/dL; n=3443). We evaluated the differential efficacy of statin according to the presence or absence of component of dyslipidemia. The primary end points were major adverse cardiac events (MACE) for 2 years. Results Statin therapy significantly reduced the risk of MACE in group A (hazard ratio=0.676; 95% confidence interval: 0.582-0.785; p<0.001). However, the efficacy of statin was not prominent in groups B, C, or D. In a propensity-matched population, the result was similar. In particular, the benefit of statin in group A was different compared with group D (interaction p=0.042) Conclusion The benefit of statin in patients with MI was different according to the presence or absence of dyslipidemia. In particular, because of the insufficient benefit of statin in patients with MI and dyslipidemia, a different lipid-lowering strategy is necessary in these patients. PMID:27275169

  11. Pleiotropic effects of statins in the diseases of the liver.

    PubMed

    Janicko, Martin; Drazilova, Sylvia; Pella, Daniel; Fedacko, Jan; Jarcuska, Peter

    2016-07-21

    Statins are a class of molecules that inhibit HMG CoA reductase. They are usually prescribed as a lipid lowering medication. However, there is accumulating evidence that statins have multiple secondary effects both related and unrelated to their lipid-lowering effect. This narrative review of the literature aims to provide the reader with information from clinical studies related to the effect of statin and statins' potential use in patients with liver diseases. In patients with advanced liver disease due to any etiology, statins exhibit an antifibrotic effect possibly through the prevention of hepatic sinusoidal microthrombosis. Two randomized controlled trials confirmed that statins decrease hepatic vein pressure gradient in patients with portal hypertension and improve the survival of patients after variceal bleeding. Lower rates of infections were observed in patients with cirrhosis who received statin treatment. Statins decrease the risk of hepatocellular carcinoma (HCC) in patients with advanced liver disease in general but particularly in patients with chronic hepatitis B and C. Statins in patients with chronic hepatitis C likely increase the virological response to the treatment with pegylated interferon and ribavirin and have the potential to decrease the rate of fibrosis. Finally, data from randomized controlled trials also confirmed that the addition of statin prolongs the survival of patients with advanced HCC even more than sorafenib. Statins are a very promising group of drugs especially in patients with liver disease, where therapeutic options can often be limited. Some indications, such as the prevention of re-bleeding from esophageal varices and the palliative treatment of HCC have been proven through randomized controlled trials, while additional indications still need to be confirmed through prospective studies. PMID:27468210

  12. Statin Use Reduces Prostate Cancer All-Cause Mortality

    PubMed Central

    Sun, Li-Min; Lin, Ming-Chia; Lin, Cheng-Li; Chang, Shih-Ni; Liang, Ji-An; Lin, I-Ching; Kao, Chia-Hung

    2015-01-01

    Abstract Studies have suggested that statin use is related to cancer risk and prostate cancer mortality. We conducted a population-based cohort study to determine whether using statins in prostate cancer patients is associated with reduced all-cause mortality rates. Data were obtained from the Taiwan National Health Insurance Research Database. The study cohort comprised 5179 patients diagnosed with prostate cancer who used statins for at least 6 months between January 1, 1998 and December 31, 2010. To form a comparison group, each patient was randomly frequency-matched (according to age and index date) with a prostate cancer patient who did not use any type of statin-based drugs during the study period. The study endpoint was mortality. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox regression models. Among prostate cancer patients, statin use was associated with significantly decreased all-cause mortality (adjusted HR = 0.65; 95% CI = 0.60–0.71). This phenomenon was observed among various types of statin, age groups, and treatment methods. Analyzing the defined daily dose of statins indicated that both low- and high-dose groups exhibited significantly decreased death rates compared with nonusers, suggesting a dose–response relationship. The results of this population-based cohort study suggest that using statins reduces all-cause mortality among prostate cancer patients, and a dose–response relationship may exist. PMID:26426656

  13. New insights into mechanisms of statin-associated myotoxicity.

    PubMed

    Sirvent, Pascal; Mercier, Jacques; Lacampagne, Alain

    2008-06-01

    Statin drugs represent a major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Besides the tremendous beneficial effects of statins, various forms of muscular toxicity (myalgia, cramp, exercise intolerance, fatigability) occur frequently. Many hypotheses were proposed to explain statin myotoxicity. The goal of this review is to highlight some of the most recent findings that can account for interpreting the pathophysiological mechanisms for statin-induced myotoxicity. Statin-induced myotoxicity appears multifactorial. Apart from the deleterious effect due to a reduction in cholesterol biosynthesis, statins have a direct effect on the respiratory chain of the mitochondria. It is proposed that mitochondrial impairment leads to a mitochondrial calcium leak that directly interferes with the regulation of sarcoplasmic reticulum calcium cycling without excluding a direct effect of statin on the sarcoplasmic reticulum. Both mitochondrial and calcium impairments may account for apoptosis process, oxidative stress, and muscle remodeling and degeneration that have been extensively reported to explain statin myotoxicity and functional symptoms described by treated patients. PMID:18243052

  14. Statins Reduce the Risks of Relapse to Addiction in Rats.

    PubMed

    Chauvet, Claudia; Nicolas, Celine; Lafay-Chebassier, Claire; Jaber, Mohamed; Thiriet, Nathalie; Solinas, Marcello

    2016-05-01

    Statins are drugs that have been used for decades in humans for the treatment of hypercholesterolemia. More recently, several lines of evidence demonstrate that statins, in addition to their peripheral effects, produce a wide variety of effects in the brain and may be beneficial in neurological and psychiatric conditions. In this study, we allowed rats to self-administer cocaine for several weeks and, at the end of self-administration training, we treated them with low doses of statins daily for a 21-day period of abstinence. Chronic administration of brain-penetrating statins, simvastatin (1 mg/kg) and atorvastatin (1 mg/kg), reduced cocaine seeking compared with vehicle, whereas administration of pravastatin (2 mg/kg), a statin with low brain penetrability, did not. Importantly, the effects of brain-penetrating statins persisted even after discontinuation of the treatment and were specific for drug seeking because drug taking was not altered by simvastatin treatment. Finally, the effects of simvastatin were found to generalize to another drug of abuse such as nicotine, but not to food reward, and to reinstatement of cocaine seeking induced by stress. These results demonstrate that brain-penetrating statins can reduce risks of relapse to addiction. Given their well-known safety profile in humans, statins could be a novel effective treatment for relapse to cocaine and nicotine addiction and their use could be implemented in clinical settings without major health risks. PMID:26466819

  15. Antithrombotic actions of statins involve PECAM-1 signaling.

    PubMed

    Moraes, Leonardo A; Vaiyapuri, Sakthivel; Sasikumar, Parvathy; Ali, Marfoua S; Kriek, Neline; Sage, Tanya; Gibbins, Jonathan M

    2013-10-31

    Statins are widely prescribed cholesterol-lowering drugs that are a first-line treatment of coronary artery disease and atherosclerosis, reducing the incidence of thrombotic events such as myocardial infarction and stroke. Statins have been shown to reduce platelet activation, although the mechanism(s) through which this occurs is unclear. Because several of the characteristic effects of statins on platelets are shared with those elicited by the inhibitory platelet adhesion receptor PECAM-1 (platelet endothelial cell adhesion molecule-1), we investigated a potential connection between the influence of statins on platelet function and PECAM-1 signaling. Statins were found to inhibit a range of platelet functional responses and thrombus formation in vitro and in vivo. Notably, these effects of statins on platelet function in vitro and in vivo were diminished in PECAM-1(-/-) platelets. Activation of PECAM-1 signaling results in its tyrosine phosphorylation, the recruitment and activation of tyrosine phosphatase SHP-2, the subsequent binding of phosphoinositol 3-kinase (PI3K), and diminished PI3K signaling. Statins resulted in the stimulation of these events, leading to the inhibition of Akt activation. Together, these data provide evidence for a fundamental role of PECAM-1 in the inhibitory effects of statins on platelet activation, which may explain some of the pleiotropic actions of these drugs. PMID:24030383

  16. Statin drug-drug interactions in a Romanian community pharmacy

    PubMed Central

    BADIU, RALUCA; BUCSA, CAMELIA; MOGOSAN, CRISTINA; DUMITRASCU, DAN

    2016-01-01

    Background and aim Statins are frequently prescribed for patients with dyslipidemia and have a well-established safety profile. However, when associated with interacting dugs, the risk of adverse effects, especially muscular toxicity, is increased. The objective of this study was to identify, characterize and quantify the prevalence of the potential drug-drug interactions (pDDIs) of statins in reimbursed prescriptions from a community pharmacy in Bucharest. Methods We analyzed the reimbursed prescriptions including statins collected during one month in a community pharmacy. The online program Medscape Drug Interaction Checker was used for checking the drug interactions and their classification based on severity: Serious – Use alternative, Significant – Monitor closely and Minor. Results 132 prescriptions pertaining to 125 patients were included in the analysis. Our study showed that 25% of the patients who were prescribed statins were exposed to pDDIs: 37 Serious and Significant interactions in 31 of the statins prescriptions. The statins involved were atorvastatin, simvastatin and rosuvastatin. Conclusions Statin pDDIs have a high prevalence and patients should be monitored closely in order to prevent the development of adverse effects that result from statin interactions. PMID:27152080

  17. Statins Impair Glucose Uptake in Tumor Cells1

    PubMed Central

    Malenda, Agata; Skrobanska, Anna; Issat, Tadeusz; Winiarska, Magdalena; Bil, Jacek; Oleszczak, Bozenna; Sinski, Maciej; Firczuk, Małgorzata; Bujnicki, Janusz M; Chlebowska, Justyna; Staruch, Adam D; Glodkowska-Mrowka, Eliza; Kunikowska, Jolanta; Krolicki, Leszek; Szablewski, Leszek; Gaciong, Zbigniew; Koziak, Katarzyna; Jakobisiak, Marek; Golab, Jakub; Nowis, Dominika A

    2012-01-01

    Statins, HMG-CoA reductase inhibitors, are used in the prevention and treatment of cardiovascular diseases owing to their lipid-lowering effects. Previous studies revealed that, by modulating membrane cholesterol content, statins could induce conformational changes in cluster of differentiation 20 (CD20) tetraspanin. The aim of the presented study was to investigate the influence of statins on glucose transporter 1 (GLUT1)-mediated glucose uptake in tumor cells. We observed a significant concentration- and time-dependent decrease in glucose analogs' uptake in several tumor cell lines incubated with statins. This effect was reversible with restitution of cholesterol synthesis pathway with mevalonic acid as well as with supplementation of plasma membrane with exogenous cholesterol. Statins did not change overall GLUT1 expression at either transcriptional or protein levels. An exploratory clinical trial revealed that statin treatment decreased glucose uptake in peripheral blood leukocytes and lowered 18F-fluorodeoxyglucose (18F-FDG) uptake by tumor masses in a mantle cell lymphoma patient. A bioinformatics analysis was used to predict the structure of human GLUT1 and to identify putative cholesterol-binding motifs in its juxtamembrane fragment. Altogether, the influence of statins on glucose uptake seems to be of clinical significance. By inhibiting 18F-FDG uptake, statins can negatively affect the sensitivity of positron emission tomography, a diagnostic procedure frequently used in oncology. PMID:22577346

  18. Antithrombotic actions of statins involve PECAM-1 signaling

    PubMed Central

    Vaiyapuri, Sakthivel; Sasikumar, Parvathy; Ali, Marfoua S.; Kriek, Neline; Sage, Tanya; Gibbins, Jonathan M.

    2013-01-01

    Statins are widely prescribed cholesterol-lowering drugs that are a first-line treatment of coronary artery disease and atherosclerosis, reducing the incidence of thrombotic events such as myocardial infarction and stroke. Statins have been shown to reduce platelet activation, although the mechanism(s) through which this occurs is unclear. Because several of the characteristic effects of statins on platelets are shared with those elicited by the inhibitory platelet adhesion receptor PECAM-1 (platelet endothelial cell adhesion molecule-1), we investigated a potential connection between the influence of statins on platelet function and PECAM-1 signaling. Statins were found to inhibit a range of platelet functional responses and thrombus formation in vitro and in vivo. Notably, these effects of statins on platelet function in vitro and in vivo were diminished in PECAM-1−/− platelets. Activation of PECAM-1 signaling results in its tyrosine phosphorylation, the recruitment and activation of tyrosine phosphatase SHP-2, the subsequent binding of phosphoinositol 3-kinase (PI3K), and diminished PI3K signaling. Statins resulted in the stimulation of these events, leading to the inhibition of Akt activation. Together, these data provide evidence for a fundamental role of PECAM-1 in the inhibitory effects of statins on platelet activation, which may explain some of the pleiotropic actions of these drugs. PMID:24030383

  19. Thrombotic thrombocytopenic purpura associated with statin treatment

    PubMed Central

    Sundram, F; Roberts, P; Kennedy, B; Pavord, S

    2004-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare condition but associated with 90% mortality if left untreated. The diagnosis is usually made when there is thrombocytopenia and microangiopathic haemolytic anaemia, although the full pentad also includes fever, renal impairment, and neurological dysfunction. A variety of underlying causes have been implicated in acquired TTP including bacterial and viral infections, bone marrow and organ transplantation, pregnancy, immune disorders, and certain drugs. To date there is just one case report of TTP associated with statin treatment. The clinical course of a patient who presented with TTP after being started on simvastatin, a HMG-CoA inhibitor, is described. PMID:15356359

  20. Statins and atherosclerosis: the role of epigenetics.

    PubMed

    Storino Farina, Marcelo; Rojano Rada, Jairo; Molina Garrido, Antony; Martínez, Xiomara; Pulgar, Alfredo; Paniagua, Roxanna; Garrido, Jorge

    2015-01-01

    Atherosclerosis is an immune-inflammatory disease, in which pathophysiological mechanisms include inflammation patterns and epigenetic changes that alter gene expression of several inflammatory and non-inflammatory mediators. Epigenetics is offering explanations on how diet, environmental factors and lifestyle can influence the onset and progression of the disease, and how these alterations can be transmitted to the following generations without any changes in DNA sequences. Statins, through their pleiotropic effects, provide a useful tool in controlling the progression of plaques and their subsequent impact. PMID:26639162

  1. Pleiotropic effects of statins in the diseases of the liver

    PubMed Central

    Janicko, Martin; Drazilova, Sylvia; Pella, Daniel; Fedacko, Jan; Jarcuska, Peter

    2016-01-01

    Statins are a class of molecules that inhibit HMG CoA reductase. They are usually prescribed as a lipid lowering medication. However, there is accumulating evidence that statins have multiple secondary effects both related and unrelated to their lipid-lowering effect. This narrative review of the literature aims to provide the reader with information from clinical studies related to the effect of statin and statins’ potential use in patients with liver diseases. In patients with advanced liver disease due to any etiology, statins exhibit an antifibrotic effect possibly through the prevention of hepatic sinusoidal microthrombosis. Two randomized controlled trials confirmed that statins decrease hepatic vein pressure gradient in patients with portal hypertension and improve the survival of patients after variceal bleeding. Lower rates of infections were observed in patients with cirrhosis who received statin treatment. Statins decrease the risk of hepatocellular carcinoma (HCC) in patients with advanced liver disease in general but particularly in patients with chronic hepatitis B and C. Statins in patients with chronic hepatitis C likely increase the virological response to the treatment with pegylated interferon and ribavirin and have the potential to decrease the rate of fibrosis. Finally, data from randomized controlled trials also confirmed that the addition of statin prolongs the survival of patients with advanced HCC even more than sorafenib. Statins are a very promising group of drugs especially in patients with liver disease, where therapeutic options can often be limited. Some indications, such as the prevention of re-bleeding from esophageal varices and the palliative treatment of HCC have been proven through randomized controlled trials, while additional indications still need to be confirmed through prospective studies. PMID:27468210

  2. Statins in Acute Ischemic Stroke: A Systematic Review

    PubMed Central

    Hong, Keun-Sik; Lee, Ji Sung

    2015-01-01

    Background and Purpose Statins have pleiotropic effects of potential neuroprotection. However, because of lack of large randomized clinical trials, current guidelines do not provide specific recommendations on statin initiation in acute ischemic stroke (AIS). The current study aims to systematically review the statin effect in AIS. Methods From literature review, we identified articles exploring prestroke and immediate post-stroke statin effect on imaging surrogate markers, initial stroke severity, functional outcome, and short-term mortality in human AIS. We summarized descriptive overview. In addition, for subjects with available data from publications, we conducted meta-analysis to provide pooled estimates. Results In total, we identified 70 relevant articles including 6 meta-analyses. Surrogate imaging marker studies suggested that statin might enhance collaterals and reperfusion. Our updated meta-analysis indicated that prestroke statin use was associated with milder initial stroke severity (odds ratio [OR] [95% confidence interval], 1.24 [1.05-1.48]; P=0.013), good functional outcome (1.50 [1.29-1.75]; P<0.001), and lower mortality (0.42 [0.21-0.82]; P=0.0108). In-hospital statin use was associated with good functional outcome (1.31 [1.12-1.53]; P=0.001), and lower mortality (0.41 [0.29-0.58]; P<0.001). In contrast, statin withdrawal was associated with poor functional outcome (1.83 [1.01-3.30]; P=0.045). In patients treated with thrombolysis, statin was associated with good functional outcome (1.44 [1.10-1.89]; P=0.001), despite an increased risk of symptomatic hemorrhagic transformation (1.63 [1.04-2.56]; P=0.035). Conclusions The current study findings support the use of statin in AIS. However, the findings were mostly driven by observational studies at risk of bias, and thereby large randomized clinical trials would provide confirmatory evidence. PMID:26437994

  3. Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency.

    PubMed

    Jung, Hae Hyun; Lee, Soo-Hyeon; Kim, Ji-Yeon; Ahn, Jin Seok; Park, Yeon Hee; Im, Young-Hyuck

    2016-01-01

    We investigated the molecular mechanisms underlying statin-induced growth suppression of triple-negative breast cancer (TNBC) that overexpress the transcription factor ets proto-oncogene 1(ets-1) and downregulate dual specific protein phosphatase 4(dusp4) expression. We examined the gene expression of BC cell lines using the nCounter expression assay, MTT viability assay, cell proliferation assay and Western blot to evaluate the effects of simvastatin. Finally, we performed cell viability testing in TNBC cell line-transfected DUSP4. We demonstrated that ETS1 mRNA and protein were overexpressed in TNBC cells compared with other BC cell lines (P = <0.001) and DUSP4 mRNA was downregulated (P = <0.001). MTT viability assay showed that simvastatin had significant antitumor activity (P = 0.002 in 0.1 μM). In addition, simvastatin could restore dusp4 deficiency and suppress ets-1 expression in TNBC. Lastly, we found that si-DUSP4 RNA transfection overcame the antitumor activity of statins. MAPK pathway inhibitor, U0126 and PI3KCA inhibitor LY294002 also decreased levels of ets-1, phosphor-ERK and phosphor-AKT on Western blot assay. Accordingly, our study indicates that simvastatin potentially affects the activity of transcriptional factors such as ets-1 and dusp4 through the MAPK pathway. In conclusion, statins might be potential candidates for TNBC therapy reducing ets-1 expression via overexpression of dusp4. PMID:27604655

  4. Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency

    PubMed Central

    Jung, Hae Hyun; Lee, Soo-Hyeon; Kim, Ji-Yeon; Ahn, Jin Seok; Park, Yeon Hee; Im, Young-Hyuck

    2016-01-01

    We investigated the molecular mechanisms underlying statin-induced growth suppression of triple-negative breast cancer (TNBC) that overexpress the transcription factor ets proto-oncogene 1(ets-1) and downregulate dual specific protein phosphatase 4(dusp4) expression. We examined the gene expression of BC cell lines using the nCounter expression assay, MTT viability assay, cell proliferation assay and Western blot to evaluate the effects of simvastatin. Finally, we performed cell viability testing in TNBC cell line-transfected DUSP4. We demonstrated that ETS1 mRNA and protein were overexpressed in TNBC cells compared with other BC cell lines (P = <0.001) and DUSP4 mRNA was downregulated (P = <0.001). MTT viability assay showed that simvastatin had significant antitumor activity (P = 0.002 in 0.1 μM). In addition, simvastatin could restore dusp4 deficiency and suppress ets-1 expression in TNBC. Lastly, we found that si-DUSP4 RNA transfection overcame the antitumor activity of statins. MAPK pathway inhibitor, U0126 and PI3KCA inhibitor LY294002 also decreased levels of ets-1, phosphor-ERK and phosphor-AKT on Western blot assay. Accordingly, our study indicates that simvastatin potentially affects the activity of transcriptional factors such as ets-1 and dusp4 through the MAPK pathway. In conclusion, statins might be potential candidates for TNBC therapy reducing ets-1 expression via overexpression of dusp4. PMID:27604655

  5. Inhibition of prenyltransferase activity by statins in both liver and muscle cell lines is not causative of cytotoxicity.

    PubMed

    Gee, Rowena H; Spinks, Jenny N; Malia, Jason M; Johnston, Jonathan D; Plant, Nick J; Plant, Kathryn E

    2015-03-01

    As inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, statins are an important first-line treatment for hypercholesterolemia. However, a recognized side-effect of statin therapy is myopathy, which in severe cases can present as potentially fatal rhabdomyolysis. This represents an important impediment to successful statin therapy, and despite decades of research the molecular mechanisms underlying this side-effect remain unclear. Current evidence supports a role for reduced levels of mevalonate pathway intermediates, with the most accepted hypothesis being a reduction in isoprenoids formation, leading to faulty post-translational modifications of membrane-associated proteins. We have undertaken a comprehensive analysis of the impact of nine statins on two human cell lines; Huh7 hepatoma and RD rhabdomyosarcoma. In both cell lines, concentration-dependent inhibition of prenylation was observed for cerivastatin and simvastatin, which could be rescued with the pathway intermediate mevalonate; in general, muscle cells were more sensitive to this effect, as measured by the levels of unprenylated Rap1A, a marker for prenylation by geranylgeranyl transferase I. Concentration-dependent toxicity was observed in both cell lines, with muscle cells again being more sensitive. Importantly, there was no correlation between inhibition of prenylation and cell toxicity, suggesting they are not causally linked. The lack of a causal relationship was confirmed by the absence of cytotoxicity in all cell lines following exposure to specific inhibitors of geranylgeranyl transferases I and II, and farnesyl transferase. As such, we provide strong evidence against the commonly accepted hypothesis linking inhibition of prenylation and statin-mediated toxicity, with the two processes likely to be simultaneous but independent. PMID:25578243

  6. An investigation into the therapeutic effects of statins with metformin on polycystic ovary syndrome: a meta-analysis of randomised controlled trials

    PubMed Central

    Sun, Jie; Yuan, Yang; Cai, Rongrong; Sun, Haixia; Zhou, Yi; Wang, Pin; Huang, Rong; Xia, Wenqing; Wang, Shaohua

    2015-01-01

    Objectives To investigate the therapeutic effects of statins with metformin on polycystic ovary syndrome (PCOS). Settings Endocrinology department. Participants MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched until October 2014. Studies comparing statins and placebo, as well as the combination of statins and metformin and metformin alone, were included in the analysis. Interventions Data were independently extracted by two researchers; any convergence was resolved by a third reviewer. Primary and secondary outcome measures The following properties were extracted from the qualified trials to identify the effects of statins: clinical variables, metabolic characteristics, hormone outcomes, sign of inflammation, glucose parameters and insulin outcomes. Results Data from four trials comparing statin and metformin with metformin alone were analysed. The combination of statins and metformin decreases the levels of C reactive protein (standardised mean difference (SMD) −0.91; 95% CI −1.81 to −0.02; p=0.046), triglyceride (SMD −1.37; 95% CI −2.46 to −0.28; p=0.014), total cholesterol (SMD −1.28; 95% CI −1.59 to −0.97; p=0.000) and low-density lipoprotein (LDL) cholesterol (SMD −0.74; 95% CI −1.03 to −0.44; p=0.000). However, the combined therapy fails to reduce fasting insulin (SMD −0.92; 95% CI −2.07 to 0.24; p=0.120), homeostasis model assessment of insulin resistance (SMD −1.15; 95% CI −3.36 to 1.06; p=0.309) and total testosterone (SMD −1.12; 95% CI −2.29 to 0.05; p=0.061). Analysis of the five trials comparing statin with placebo shows that statin monotherapy reduces LDL-cholesterol, triglyceride and total cholesterol. Conclusions Combined statin and metformin therapy can improve lipid and inflammation parameters, but cannot effectively improve insulin sensitivity and reduce hyperandrogenism in women with PCOS. A large-scale randomised controlled study must be conducted to ascertain the long

  7. Anti-cancer potential of MAPK pathway inhibition in paragangliomas-effect of different statins on mouse pheochromocytoma cells.

    PubMed

    Fliedner, Stephanie M J; Engel, Tobias; Lendvai, Nikoletta K; Shankavaram, Uma; Nölting, Svenja; Wesley, Robert; Elkahloun, Abdel G; Ungefroren, Hendrik; Oldoerp, Angela; Lampert, Gary; Lehnert, Hendrik; Timmers, Henri; Pacak, Karel

    2014-01-01

    To date, malignant pheochromocytomas and paragangliomas (PHEOs/PGLs) cannot be effectively cured and thus novel treatment strategies are urgently needed. Lovastatin has been shown to effectively induce apoptosis in mouse PHEO cells (MPC) and the more aggressive mouse tumor tissue-derived cells (MTT), which was accompanied by decreased phosphorylation of mitogen-activated kinase (MAPK) pathway players. The MAPK pathway plays a role in numerous aggressive tumors and has been associated with a subgroup of PHEOs/PGLs, including K-RAS-, RET-, and NF1-mutated tumors. Our aim was to establish whether MAPK signaling may also play a role in aggressive, succinate dehydrogenase (SDH) B mutation-derived PHEOs/PGLs. Expression profiling and western blot analysis indicated that specific aspects of MAPK-signaling are active in SDHB PHEOs/PGLs, suggesting that inhibition by statin treatment could be beneficial. Moreover, we aimed to assess whether the anti-proliferative effect of lovastatin on MPC and MTT differed from that exerted by fluvastatin, simvastatin, atorvastatin, pravastatin, or rosuvastatin. Simvastatin and fluvastatin decreased cell proliferation most effectively and the more aggressive MTT cells appeared more sensitive in this respect. Inhibition of MAPK1 and 3 phosphorylation following treatment with fluvastatin, simvastatin, and lovastatin was confirmed by western blot. Increased levels of CASP-3 and PARP cleavage confirmed induction of apoptosis following the treatment. At a concentration low enough not to affect cell proliferation, spontaneous migration of MPC and MTT was significantly inhibited within 24 hours of treatment. In conclusion, lipophilic statins may present a promising therapeutic option for treatment of aggressive human paragangliomas by inducing apoptosis and inhibiting tumor spread. PMID:24846270

  8. Anti-Cancer Potential of MAPK Pathway Inhibition in Paragangliomas–Effect of Different Statins on Mouse Pheochromocytoma Cells

    PubMed Central

    Lendvai, Nikoletta K.; Shankavaram, Uma; Nölting, Svenja; Wesley, Robert; Elkahloun, Abdel G.; Ungefroren, Hendrik; Oldoerp, Angela; Lampert, Gary; Lehnert, Hendrik; Timmers, Henri; Pacak, Karel

    2014-01-01

    To date, malignant pheochromocytomas and paragangliomas (PHEOs/PGLs) cannot be effectively cured and thus novel treatment strategies are urgently needed. Lovastatin has been shown to effectively induce apoptosis in mouse PHEO cells (MPC) and the more aggressive mouse tumor tissue-derived cells (MTT), which was accompanied by decreased phosphorylation of mitogen-activated kinase (MAPK) pathway players. The MAPK pathway plays a role in numerous aggressive tumors and has been associated with a subgroup of PHEOs/PGLs, including K-RAS-, RET-, and NF1-mutated tumors. Our aim was to establish whether MAPK signaling may also play a role in aggressive, succinate dehydrogenase (SDH) B mutation-derived PHEOs/PGLs. Expression profiling and western blot analysis indicated that specific aspects of MAPK-signaling are active in SDHB PHEOs/PGLs, suggesting that inhibition by statin treatment could be beneficial. Moreover, we aimed to assess whether the anti-proliferative effect of lovastatin on MPC and MTT differed from that exerted by fluvastatin, simvastatin, atorvastatin, pravastatin, or rosuvastatin. Simvastatin and fluvastatin decreased cell proliferation most effectively and the more aggressive MTT cells appeared more sensitive in this respect. Inhibition of MAPK1 and 3 phosphorylation following treatment with fluvastatin, simvastatin, and lovastatin was confirmed by western blot. Increased levels of CASP-3 and PARP cleavage confirmed induction of apoptosis following the treatment. At a concentration low enough not to affect cell proliferation, spontaneous migration of MPC and MTT was significantly inhibited within 24 hours of treatment. In conclusion, lipophilic statins may present a promising therapeutic option for treatment of aggressive human paragangliomas by inducing apoptosis and inhibiting tumor spread. PMID:24846270

  9. Persisting weakness after withdrawal of a statin

    PubMed Central

    Mygland, Åse; Ljøstad, Unn; Krossnes, Bård Kronen

    2014-01-01

    An 81-year-old woman treated with simvastatin for several years followed by atorvastatin for about 1 year presented with fatigue, weakness and unsteady gait. The finding of elevated creatine kinase (CK) and symmetric muscle weakness around shoulders and hips led to suspicion of a toxic statin-associated myopathy. Atorvastatin was withdrawn, but her weakness persisted. Owing to persisting weakness, an autoimmune myopathy (myositis) was suspected, but initially disregarded since a muscle biopsy showed necrotic muscle fibres without inflammatory cell infiltrates and myositis-specific autoantibodies were absent. After 18 months with slowly progressive weakness and increasing CK values, awareness of new knowledge about autoimmunity as a cause of necrotic myopathy, led to a successful treatment trial with intravenous immunoglobulines, followed by steroids and metothrexate. Antibodies to the target enzyme of statins (HMGCR (3-hydroksy-3-methylglutaryl-coenzyme A reductase)) were detected in her serum, and she was diagnosed with autoimmune necrotic myositis probably triggered by atorvastatin. PMID:24713712

  10. Role of integrin-linked kinase in vascular smooth muscle cells: Regulation by statins and angiotensin II

    SciTech Connect

    Friedrich, Erik B. . E-mail: efriedrich@med-in.uni-sb.de; Clever, Yvonne P.; Wassmann, Sven; Werner, Nikos; Boehm, Michael; Nickenig, Georg

    2006-10-27

    Our goal was to characterize the role of integrin-linked kinase (ILK) in vascular smooth muscle cells (VSMC), which play a crucial role in atherogenesis. Transfection of VSMC with wild-type and dominant-negative ILK cDNA constructs revealed that ILK mediates migration and proliferation of VSMC but has no effect on VSMC survival. The pro-atherogenic mediator angiotensin II increases ILK protein expression and kinase activity while statin treatment down-regulates ILK in VSMC. Functionally, ILK is necessary for angiotensin II-mediated VSMC migration and proliferation. In VSMC transduced with dominant-negative ILK, statins mediate an additive inhibition of VSMC migration and proliferation, while transfection with wild-type ILK is sufficient to overcome the inhibitory effects of statin treatment on VSMC migration and proliferation. In vivo, ILK is expressed in VSMC of aortic sections from wild-type mice where it is down-regulated following statin treatment and up-regulated following induction of atherosclerosis in apoE-/- mice. These data identify ILK as a novel target in VSMC for anti-atherosclerotic therapy.

  11. Molecular mechanism of statin-mediated LOX-1 inhibition.

    PubMed

    Biocca, Silvia; Iacovelli, Federico; Matarazzo, Sara; Vindigni, Giulia; Oteri, Francesco; Desideri, Alessandro; Falconi, Mattia

    2015-01-01

    Statins are largely used in clinics in the treatment of patients with cardiovascular diseases for their effect on lowering circulating cholesterol. Lectin-like oxidized low-density lipoprotein (LOX-1), the primary receptor for ox-LDL, plays a central role in the pathogenesis of atherosclerosis and cardiovascular disorders. We have recently shown that chronic exposure of cells to lovastatin disrupts LOX-1 receptor cluster distribution in plasma membranes, leading to a marked loss of LOX-1 function. Here we investigated the molecular mechanism of statin-mediated LOX-1 inhibition and we demonstrate that all tested statins are able to displace the binding of fluorescent ox-LDL to LOX-1 by a direct interaction with LOX-1 receptors in a cell-based binding assay. Molecular docking simulations confirm the interaction and indicate that statins completely fill the hydrophobic tunnel that crosses the C-type lectin-like (CTLD) recognition domain of LOX-1. Classical molecular dynamics simulation technique applied to the LOX-1 CTLD, considered in the entire receptor structure with or without a statin ligand inside the tunnel, indicates that the presence of a ligand largely increases the dimer stability. Electrophoretic separation and western blot confirm that different statins binding stabilize the dimer assembly of LOX-1 receptors in vivo. The simulative and experimental results allow us to propose a CTLD clamp motion, which enables the receptor-substrate coupling. These findings reveal a novel and significant functional effect of statins. PMID:25950192

  12. Statins, cognition, and dementia—systematic review and methodological commentary

    PubMed Central

    Power, Melinda C.; Weuve, Jennifer; Sharrett, A. Richey; Blacker, Deborah

    2015-01-01

    Firm conclusions about whether mid-life or long-term statin use has an impact on cognitive decline and dementia remain elusive. Here, our objective was to systematically review, synthesize and critique the epidemiological literature that examines the relationship between statin use and cognition, so as to assess the current state of knowledge, identify gaps in our understanding, and make recommendations for future research. We summarize the findings of randomized controlled trials (RCTs) and observational studies, grouped according to study design. We discuss the methods for each, and consider likely sources of bias, such as reverse causation and confounding. Although observational studies that considered statin use at or near the time of dementia diagnosis suggest a protective effect of statins, these findings could be attributable to reverse causation. RCTs and well-conducted observational studies of baseline statin use and subsequent cognition over several years of follow-up do not support a causal preventative effect of late-life statin use on cognitive decline or dementia. Given that much of the human research on statins and cognition in the future will be observational, careful study design and analysis will be essential. PMID:25799928

  13. Statins and Cardiovascular Diseases: From Cholesterol Lowering to Pleiotropy

    PubMed Central

    Zhou, Qian; Liao, James K.

    2010-01-01

    Statins are 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which are prescribed extensively for cholesterol lowering in the primary and secondary prevention of cardiovascular disease. Recent compelling evidence suggests that the beneficial effects of statins may not only be due to their cholesterol lowering effects, but also, to their cholesterol-independent or pleiotropic effects. Through these so-called pleiotropic effects, statins are directly involved in restoring or improving endothelial function, attenuating vascular remodeling, inhibiting vascular inflammatory response, and perhaps, stabilizing atherosclerotic plaques. These cholesterol-independent effects of statins are due predominantly to their ability to inhibit isoprenoid synthesis, the products of which are important lipid attachments for intracellular signaling molecules, such as Rho, Rac and Cdc42. In particular, inhibition of Rho and its downstream target, Rho-associated coiled-coil containing protein kinase (ROCK), has emerged as the principle mechanisms underlying the pleiotropic effects of statins. This review provides an update of statin-mediated vascular effects beyond cholesterol lowering and highlights recent findings from bench to bedside to support the concept of statin pleiotropy. PMID:19199975

  14. Molecular mechanism of statin-mediated LOX-1 inhibition

    PubMed Central

    Biocca, Silvia; Iacovelli, Federico; Matarazzo, Sara; Vindigni, Giulia; Oteri, Francesco; Desideri, Alessandro; Falconi, Mattia

    2015-01-01

    Statins are largely used in clinics in the treatment of patients with cardiovascular diseases for their effect on lowering circulating cholesterol. Lectin-like oxidized low-density lipoprotein (LOX-1), the primary receptor for ox-LDL, plays a central role in the pathogenesis of atherosclerosis and cardiovascular disorders. We have recently shown that chronic exposure of cells to lovastatin disrupts LOX-1 receptor cluster distribution in plasma membranes, leading to a marked loss of LOX-1 function. Here we investigated the molecular mechanism of statin-mediated LOX-1 inhibition and we demonstrate that all tested statins are able to displace the binding of fluorescent ox-LDL to LOX-1 by a direct interaction with LOX-1 receptors in a cell-based binding assay. Molecular docking simulations confirm the interaction and indicate that statins completely fill the hydrophobic tunnel that crosses the C-type lectin-like (CTLD) recognition domain of LOX-1. Classical molecular dynamics simulation technique applied to the LOX-1 CTLD, considered in the entire receptor structure with or without a statin ligand inside the tunnel, indicates that the presence of a ligand largely increases the dimer stability. Electrophoretic separation and western blot confirm that different statins binding stabilize the dimer assembly of LOX-1 receptors in vivo. The simulative and experimental results allow us to propose a CTLD clamp motion, which enables the receptor-substrate coupling. These findings reveal a novel and significant functional effect of statins. PMID:25950192

  15. Selective serotonin reuptake inhibitor drug interactions in patients receiving statins.

    PubMed

    Andrade, Chittaranjan

    2014-02-01

    Elderly patients commonly receive statin drugs for the primary or secondary prevention of cardiovascular and cerebrovascular events. Elderly patients also commonly receive antidepressant drugs, usually selective serotonin reuptake inhibitors (SSRIs), for the treatment of depression, anxiety, or other conditions. SSRIs are associated with many pharmacokinetic drug interactions related to the inhibition of the cytochrome P450 (CYP) metabolic pathways. There is concern that drugs that inhibit statin metabolism can trigger statin adverse effects, especially myopathy (which can be potentially serious, if rhabdomyolysis occurs). However, a detailed literature review of statin metabolism and of SSRI effects on CYP enzymes suggests that escitalopram, citalopram, and paroxetine are almost certain to be safe with all statins, and rosuvastatin, pitavastatin, and pravastatin are almost certain to be safe with all SSRIs. Even though other SSRI-statin combinations may theoretically be associated with risks, the magnitude of the pharmacokinetic interaction is likely to be below the threshold for clinical significance. Risk, if at all, lies in combining fluvoxamine with atorvastatin, simvastatin, or lovastatin, and even this risk can be minimized by using lower statin doses and monitoring the patient. PMID:24602259

  16. Statins, cognition, and dementia—systematic review and methodological commentary.

    PubMed

    Power, Melinda C; Weuve, Jennifer; Sharrett, A Richey; Blacker, Deborah; Gottesman, Rebecca F

    2015-04-01

    Firm conclusions about whether mid-life or long-term statin use has an impact on cognitive decline and dementia remain elusive. Here, our objective was to systematically review, synthesize and critique the epidemiological literature that examines the relationship between statin use and cognition, so as to assess the current state of knowledge, identify gaps in our understanding, and make recommendations for future research. We summarize the findings of randomized controlled trials (RCTs) and observational studies, grouped according to study design. We discuss the methods for each, and consider likely sources of bias, such as reverse causation and confounding. Although observational studies that considered statin use at or near the time of dementia diagnosis suggest a protective effect of statins, these findings could be attributable to reverse causation. RCTs and well-conducted observational studies of baseline statin use and subsequent cognition over several years of follow-up do not support a causal preventative effect of late-life statin use on cognitive decline or dementia. Given that much of the human research on statins and cognition in the future will be observational, careful study design and analysis will be essential. PMID:25799928

  17. Cholesterol and Statins in Alzheimer’s Disease

    PubMed Central

    Shepardson, Nina E.; Shankar, Ganesh M.; Selkoe, Dennis J.

    2011-01-01

    Substantial evidence has accumulated in support of the hypothesis that elevated cholesterol levels increase the risk of developing Alzheimer’s disease (AD). As a result, much work has been done investigating the potential use of lipid-lowering agents (LLAs), particularly statins, as preventive or therapeutic agents for AD. While epidemiology and preclinical statin research (described in Part 1 of this review) have generally supported an adverse role of high cholesterol regarding AD, human studies of statins (reviewed here) show highly variable outcomes, making it difficult to draw firm conclusions. We identify several confounding factors among the human studies, including differing blood-brain barrier permeabilities among statins, the stage in AD at which statins were administered, and the drugs’ pleiotropic metabolic effects, all of which contribute to the substantial variability observed to date. We recommend that future human studies of this important therapeutic topic 1) take the blood-brain barrier permeabilities of statins into account when analyzing results, 2) include specific analyses of effects on low-density and high-density lipoprotein cholesterol, and most importantly, 3) conduct statin treatment trials solely in mild AD patients, who have the best chance for disease modification. PMID:22084122

  18. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update.

    PubMed

    Schachter, Michael

    2005-02-01

    Statins are the treatment of choice for the management of hypercholesterolaemia because of their proven efficacy and safety profile. They also have an increasing role in managing cardiovascular risk in patients with relatively normal levels of plasma cholesterol. Although all statins share a common mechanism of action, they differ in terms of their chemical structures, pharmacokinetic profiles, and lipid-modifying efficacy. The chemical structures of statins govern their water solubility, which in turn influences their absorption, distribution, metabolism and excretion. Lovastatin, pravastatin and simvastatin are derived from fungal metabolites and have elimination half-lives of 1-3 h. Atorvastatin, cerivastatin (withdrawn from clinical use in 2001), fluvastatin, pitavastatin and rosuvastatin are fully synthetic compounds, with elimination half-lives ranging from 1 h for fluvastatin to 19 h for rosuvastatin. Atorvastatin, simvastatin, lovastatin, fluvastatin, cerivastatin and pitavastatin are relatively lipophilic compounds. Lipophilic statins are more susceptible to metabolism by the cytochrome P(450) system, except for pitavastatin, which undergoes limited metabolism via this pathway. Pravastatin and rosuvastatin are relatively hydrophilic and not significantly metabolized by cytochrome P(450) enzymes. All statins are selective for effect in the liver, largely because of efficient first-pass uptake; passive diffusion through hepatocyte cell membranes is primarily responsible for hepatic uptake of lipophilic statins, while hydrophilic agents are taken up by active carrier-mediated processes. Pravastatin and rosuvastatin show greater hepatoselectivity than lipophilic agents, as well as a reduced potential for uptake by peripheral cells. The bioavailability of the statins differs greatly, from 5% for lovastatin and simvastatin to 60% or greater for cerivastatin and pitavastatin. Clinical studies have demonstrated rosuvastatin to be the most effective for reducing

  19. Targeting Inflammation and Oxidative Stress in Atrial Fibrillation: Role of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibition with Statins

    PubMed Central

    Pinho-Gomes, Ana Catarina; Reilly, Svetlana; Brandes, Ralf P.

    2014-01-01

    Abstract Significance: Atrial fibrillation (AF) is a burgeoning health-care problem, and the currently available therapeutic armamentarium is barely efficient. Experimental and clinical evidence implicates inflammation and myocardial oxidative stress in the pathogenesis of AF. Recent Advances: Local and systemic inflammation has been found to both precede and follow the new onset of AF, and NOX2-dependent generation of reactive oxygen species in human right atrial samples has been independently associated with the occurrence of AF in the postoperative period in patients undergoing cardiac surgery. Anti-inflammatory and antioxidant agents can prevent atrial electrical remodeling in animal models of atrial tachypacing and the new onset of AF after cardiac surgery, suggesting a causal relationship between inflammation/oxidative stress and the atrial substrate that supports AF. Critical Issues: Statin therapy, by redressing the myocardial nitroso-redox balance and reducing inflammation, has emerged as a potentially effective strategy for the prevention of AF. Evidence indicates that statins prevent AF-induced electrical remodeling in animal models of atrial tachypacing and may reduce the new onset of AF after cardiac surgery. However, whether statins have antiarrhythmic properties in humans has yet to be conclusively demonstrated, as data from randomized controlled trials specifically addressing the relevance of statin therapy for the primary and secondary prevention of AF remain scanty. Future Directions: A better understanding of the mechanisms underpinning the putative antiarrhythmic effects of statins may afford tailoring AF treatment to specific clinical settings and patient's subgroups. Large-scale randomized clinical trials are needed to support the indication of statin therapy solely on the basis of AF prevention. Antioxid. Redox Signal. 20, 1268–1285. PMID:23924190

  20. [Cardiovascular prevention in the sportsman: a role for statins?].

    PubMed

    Rabaeus, M

    2013-07-17

    Official guidelines bring regularly the physician to consider a statin treatment in physically active individuals, including athletes. Several factors speak against such an attitude: the available risk scores are far from precise and do not sufficiently take into account lifestyle; when you correct for the level of physical activity, cholesterol loses its' predictive value; physical activity diminishing cardiovascular risk by at least a factor 2, an athlete is always at low risk. In addition, the secondary effects of statins are liable to interfere significantly with sport activities, paradoxically increasing the risk. Statin prescription should not be envisaged in athletes. PMID:23971324

  1. Impact of Statins on Gene Expression in Human Lung Tissues

    PubMed Central

    Lane, Jérôme; van Eeden, Stephan F.; Obeidat, Ma’en; Sin, Don D.; Tebbutt, Scott J.; Timens, Wim; Postma, Dirkje S.; Laviolette, Michel; Paré, Peter D.; Bossé, Yohan

    2015-01-01

    Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that alter the synthesis of cholesterol. Some studies have shown a significant association of statins with improved respiratory health outcomes of patients with asthma, chronic obstructive pulmonary disease and lung cancer. Here we hypothesize that statins impact gene expression in human lungs and may reveal the pleiotropic effects of statins that are taking place directly in lung tissues. Human lung tissues were obtained from patients who underwent lung resection or transplantation. Gene expression was measured on a custom Affymetrix array in a discovery cohort (n = 408) and two replication sets (n = 341 and 282). Gene expression was evaluated by linear regression between statin users and non-users, adjusting for age, gender, smoking status, and other covariables. The results of each cohort were combined in a meta-analysis and biological pathways were studied using Gene Set Enrichment Analysis. The discovery set included 141 statin users. The lung mRNA expression levels of eighteen and three genes were up-regulated and down-regulated in statin users (FDR < 0.05), respectively. Twelve of the up-regulated genes were replicated in the first replication set, but none in the second (p-value < 0.05). Combining the discovery and replication sets into a meta-analysis improved the significance of the 12 up-regulated genes, which includes genes encoding enzymes and membrane proteins involved in cholesterol biosynthesis. Canonical biological pathways altered by statins in the lung include cholesterol, steroid, and terpenoid backbone biosynthesis. No genes encoding inflammatory, proteases, pro-fibrotic or growth factors were altered by statins, suggesting that the direct effect of statin in the lung do not go beyond its antilipidemic action. Although more studies are needed with specific lung cell types and different classes and doses of statins, the improved health outcomes and survival observed in statin

  2. Combination therapy for the treatment of dyslipidemia.

    PubMed

    Streja, Dan

    2004-03-01

    Statins have been proven to reduce cardiovascular risk, and guidelines for cardiovascular prevention recommend statin therapy in a wide range of patients. However, in spite of the dramatic success in large randomized clinical trials, two thirds of patients administered statins are not protected against cardiovascular events. This has prompted a search for additional targets for therapy. The pandemic of metabolic syndrome and type 2 diabetes has led to a dramatic increase in the prevalence of dyslipidemia. This, in turn, has prompted a resurgence of the search for drugs and algorithms that favorably affect high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) metabolism and function. Fibrates are the best-studied class of agents to be used as an addition to statins since they have also been proven to reduce clinical events as a monotherapy. However, there is a need for large safety trials of statin-fibrate combination therapy. Statin-niacin combination therapy has proven to be safe and effective in altering lipoprotein pattern. Randomized clinical trials and more research on the mechanism of action of niacin are necessary. Inhibitors of cholesterol ester transfer protein and HDL therapy drugs are in early developmental stages, and are the most promising potential additions to the current arsenal. PMID:15083597

  3. What Is Aggressive Violence?

    ERIC Educational Resources Information Center

    Singer, Dorothy G.; Luca, Wendy

    1985-01-01

    Responses to a questionnaire dealing with what constitutes aggressive violence on television indicate that health care providers tend to rate items describing acts on television as more aggressive than television writers, producers, and executives do. (MBR)

  4. Neurobiological Patterns of Aggression.

    ERIC Educational Resources Information Center

    Hunt, Robert D.

    1993-01-01

    Describes chemical model for patterns of aggressive behavior. Addresses cultural, neurobiological, and cognitive factors that affect violent children. Identifies five patterns of aggression (overaroused, impulsive, affective, predatory, and instrumental) and examines these dimensions of aggression for each pattern: baseline, precipitators,…

  5. Concomitant Statin Use Has a Favorable Effect on Gemcitabine-Erlotinib Combination Chemotherapy for Advanced Pancreatic Cancer

    PubMed Central

    Moon, Do Chang; Lee, Hee Seung; Lee, Yong Il; Chung, Moon Jae; Park, Jeong Youp; Park, Seung Woo; Song, Si Young; Chung, Jae Bock

    2016-01-01

    Purpose Erlotinib-gemcitabine combined chemotherapy is considered as the standard treatment for unresectable pancreatic cancer. This study aimed to determine the clinical factors associated with response to this treatment. Materials and Methods This retrospective study included 180 patients with unresectable pancreatic cancer who received ≥2 cycles of gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy between 2006 and 2014. "Long-term response" was defined as tumor stabilization after >6 chemotherapy cycles. Results The median progression-free survival (PFS) and overall survival (OS) were 3.9 and 8.1 months, respectively. On univariate analysis, liver metastasis (p=0.023) was negatively correlated with long-term response. Locally advanced stage (p=0.017), a history of statin treatment (p=0.01), and carcinoembryonic antigen levels <4.5 (p=0.029) had a favorable effect on long-term response. On multivariate analysis, a history of statin treatment was the only independent favorable factor for long-term response (p=0.017). Prognostic factors for OS and PFS were significantly correlated with liver metastasis (p=0.031 and 0.013, respectively). A history of statin treatment was also significantly associated with OS after adjusting for all potential confounders (hazard ratio, 0.48; 95% confidence interval, 0.26–0.92; p=0.026). Conclusion These results suggest that statins have a favorable effect on "long-term response" to gemcitabine-erlotinib chemotherapy in unresectable pancreatic cancer patients. Statins may have a chemoadjuvant role in stabilizing long-term tumor growth. PMID:27401642

  6. Association of Common Variants in the Human Eyes Shut Ortholog, EYS, with Statin-Induced Myopathy: Evidence for Additional Functions of EYS

    PubMed Central

    Isackson, Paul J.; Ochs-Balcom, Heather M.; Ma, Changxing; Harley, John B.; Peltier, Wendy; Tarnopolsky, Mark; Sripathi, Naganand; Wortmann, Robert L.; Simmons, Zachary; Wilson, Jon D.; Smith, Stephen A.; Barboi, Alexandru; Fine, Edward; Baer, Alan; Baker, Steven; Kaufman, Kenneth; Cobb, Beth; Kilpatrick, Jeffrey R.; Vladutiu, Georgirene D.

    2011-01-01

    Introduction Of nearly 38 million people in the U.S. receiving statin therapy, 0.1–0.5% experience severe or life-threatening myopathic side effects. Methods We performed a genome-wide association study (GWAS) in patients with severe statin myopathy versus a statin-tolerant group to identify genetic susceptibility loci. Results Replication studies in independent groups of severe statin myopathy (n=190) and statintolerant controls (n=130) resulted in the identification of three SNPs, rs9342288, rs1337512 and rs3857532, in the eyes shut homolog (EYS) on chromosome 6 suggestive of an association with risk for severe statin myopathy (p=0.0003–0.0008). Analysis of EYS cDNA demonstrated that EYS gene products are complex and expressed with relative abundance in the spinal cord as well as in the retina. Discussion Structural similarities of these EYS gene products to members of the Notch signaling pathway and to agrin suggest a possible functional role in the maintenance and regeneration of the structural integrity of skeletal muscle. PMID:21826682

  7. Statin treatment is associated with reduction in serum levels of receptor activator of NF-κB ligand and neutrophil activation in patients with severe carotid stenosis.

    PubMed

    Lenglet, Sébastien; Quercioli, Alessandra; Fabre, Mathias; Galan, Katia; Pelli, Graziano; Nencioni, Alessio; Bauer, Inga; Pende, Aldo; Python, Magaly; Bertolotto, Maria; Spinella, Giovanni; Pane, Bianca; Palombo, Domenico; Dallegri, Franco; Mach, François; Vuilleumier, Nicolas; Montecucco, Fabrizio

    2014-01-01

    Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN), RANKL/osteoprotegerin (OPG) ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content) as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques. PMID:24648660

  8. Statins and Risk of New-Onset Diabetes Mellitus

    MedlinePlus

    ... Association Cardiology Patient Page Statins and Risk of New-Onset Diabetes Mellitus Ravi V. Shah and Allison ... most common adverse effects, and recent concerns about new-onset diabetes mellitus to help patients and providers ...

  9. Relative safety profiles of high dose statin regimens

    PubMed Central

    Escobar, Carlos; Echarri, Rocio; Barrios, Vivencio

    2008-01-01

    Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses. PMID:18827903

  10. Relationship between Statin Utilization and Socioeconomic Deprivation in Hungary

    PubMed Central

    Boruzs, Klára; Juhász, Attila; Nagy, Csilla; Ádány, Róza; Bíró, Klára

    2016-01-01

    The risk of premature mortality caused by cardiovascular diseases (CVDs) is approximately three times higher in the Central Eastern European region than in high income European countries, which suggests a lack and/or ineffectiveness of preventive interventions against CVDs. The aim of the present study was to provide data on the relationship between premature CVD mortality, statin utilization as a preventive medication and socioeconomic deprivation at the district level in Hungary. As a conceptually new approach, the prescription of statins, the prescription redemption and the ratio between redemption and prescription rates were also investigated. The number of prescriptions for statins and the number of redeemed statin prescriptions were obtained from the National Health Insurance Fund Administration of Hungary for each primary healthcare practice for the entire year of 2012. The data were aggregated at the district level. To define the frequency of prescription and of redemption, the denominator was the number of the 40+-year-old population adjusted by the rates of 60+-year-old population of the district. The standardized mortality rates, frequency of statin prescriptions, redeemed statin prescriptions, and ratios for compliance in relation to the national average were mapped using the “disease mapping” option, and their association with deprivation (tertile of deprivation index as a district-based categorical covariate) was defined using the risk analysis capabilities within the Rapid Inquiry Facility. The risk analysis showed a significant positive association between deprivation and the relative risk of premature cardiovascular mortality, and a reverse J-shaped association between the relative frequency of statin prescriptions and deprivation. Districts with the highest deprivation showed a low relative frequency of statin prescriptions; however, significantly higher primary compliance (redemption) was observed in districts with the highest deprivation

  11. Long Complete Remission Achieved with the Combination Therapy of Cisplatin and Gemcitabine in a Patient with Aggressive Natural Killer Cell Leukemia

    PubMed Central

    Koepke, John

    2015-01-01

    Aggressive natural killer cell leukemia (ANKL) is a rare and often lethal lymphoproliferative disorder. Patients may present with constitutional symptoms, jaundice, skin infiltration, lymphadenopathy, and hepatosplenomegaly. ANKL can progress quickly to multiorgan failure and survival is usually measured in weeks. Although a rapid and accurate diagnosis is critical, unfortunately there is no hallmark diagnostic marker of ANKL. We report a case of a 48-year-old male who was able to obtain a complete remission following cisplatin-based chemotherapy. We describe the details of the chemotherapy regimens used and a literature review of the treatment of ANKL. PMID:25694835

  12. Increasing Parent Satisfaction of Children's Therapy through an Audio-Visual Investigation of Reactions to Children's Aggressive, Assertive or Passive Anger Responses.

    ERIC Educational Resources Information Center

    Anderson, Fay B.

    This document presents a practicum designed to address the problems encountered when a child in nondirective play therapy becomes able to express emotions and parents, unable to accept their child's new expressions of anger, withdraw the child from therapy at a time when he or she is most vulnerable. The development and implementation of a program…

  13. [Mechanisms of action of statins and their pleiotropic effects].

    PubMed

    Davignon, J; Mabile, L

    2001-02-01

    This brief review and update considers a few aspects of the mechanisms of action of statins, especially those related to some of the pleiotropic effects that have clinical relevance. The beneficial effect on endothelial dysfunction is a class effect that is related not only to the lowering of plasma LDL-cholesterol but also to a direct effect on nitric oxide (NO) production. It is an early and sustained effect, linked to oxidative processes, that deserves particular attention since endothelial dysfunction is intimately linked to atherogenesis. Awareness of the anti-inflammatory effect came about following the observation that statin administration in humans reduces markers of inflammation in the circulation. The importance of these observations is ascribable to the fact that atherosclerosis is an inflammatory disease, that the inflammatory process in a coronary artery is now measurable in vivo in humans, that it contributes to the progression and the destabilization of the plaque, and also, because statins exert a number of effects that tend to stabilize it. Statins, and particularly lipophilic statins, in general inhibit cell proliferation, seemingly by multifaceted mechanisms. These include inhibition of cell cycle progression, induction of apoptosis, reduction of cyclooxygenase-2 activity and an enhancement of angiogenesis. At the center of these mechanisms stands the ability to inhibit G protein prenylation through a reduction of farnesylation and geranylgeranylation. This effect has been used to show that statins are anticarcinogenic in vitro and in animals. The clinical relevance of such a property remains to be proven but is supported by promising observations in animals and in humans which are detailed in this review. Finally, the ability of lipophilic statins to increase the production of bone morphogenetic protein-2 (BMP-2), and to enhance osteogenesis in animals combined with the results of several clinical studies should stimulate physicians to

  14. Use of lipid-lowering agents (statins) during pregnancy.

    PubMed Central

    Hosokawa, Akiko; Bar-Oz, Benjamin; Ito, Shinya

    2003-01-01

    QUESTION: A 34-year-old patient of mine is taking a 'statin' for hyperlipidemia. She is planning pregnancy and is worried about the safety of the drug. How should I advise her? ANSWER: Limited evidence from animal and human studies indicates that statins should not be taken during pregnancy. If a patient is inadvertently exposed during pregnancy, however, termination does not appear to be medically indicated. PMID:12836860

  15. [Statins available from chemist shops will not positively affect health].

    PubMed

    Stalenhoef, A F H

    2007-06-23

    Statins should not become available as over- or behind-the-counter drugs at chemist shops. The efficacy of these drugs when given in low dosages has not been proved although the negative aspect of possible side effects remains a realistic possibility. The use of statins as compensation for an unhealthy lifestyle is not desirable and there is a danger that patients with high vascular risk would receive treatment without being adequately supervised. PMID:17668606

  16. Statins Reduce Melanoma Development and Metastasis through MICA Overexpression.

    PubMed

    Pich, Christine; Teiti, Iotefa; Rochaix, Philippe; Mariamé, Bernard; Couderc, Bettina; Favre, Gilles; Tilkin-Mariamé, Anne-Françoise

    2013-01-01

    Survival of melanoma patients after metastases detection remains short. Several clinical trials have shown moderate efficiency in improving patient survival, and the search for pharmacological agents to enhance the immune response and reduce melanoma metastases is still necessary. Statins block the mevalonate pathway, which leads to decreases in GTPase isoprenylation and activity, particularly those of the Ras superfamily. They are widely used as hypocholesterolemic agents in cardiovascular diseases and several studies have shown that they also have protective effects against cancers. Furthermore, we have previously demonstrated that treatment of melanoma cells with inhibitors of the mevalonate pathway, such as statins, favor the development of specific adaptive immune responses against these tumors. In the present study, we tested statin impact on the innate immune response against human metastatic melanoma cells. Our data shows that treatment of two human melanoma cell lines with statins induced a weak but significant increase of MHC class I Chain-related protein A (MICA) membrane expression. Peroxisome Proliferator-Activated Receptor gamma is involved in this statin-induced MICA overexpression, which is independent of Ras and Rho GTPase signaling pathways. Interestingly, this MICA overexpression makes melanoma cells more sensitive to in vitro lysis by NK cells. The impact of statin treatment on in vivo development of melanoma tumors and metastases was investigated in nude mice, because murine NK cells, which express NKG2D receptors, are able to recognize and kill human tumor cells expressing MICA. The results demonstrated that both local tumor growth and pulmonary metastases were strongly inhibited in nude mice injected with statin-treated melanoma cells. These results suggest that statins could be effective in melanoma immunotherapy treatments. PMID:23493799

  17. Statins: The Good, the Bad, and the Unexpected.

    PubMed

    Mager, Diana R

    2016-01-01

    More than 13 million Americans are taking statin drugs in order to lower cholesterol levels and thereby avoid potential cardiovascular disease. Home healthcare clinicians are well suited to educate patients about this sometimes-controversial medication class. The purpose of this article is to describe the link between cholesterol and statins, and to provide an overview for healthcare providers including drug actions, indications, and possible adverse effects. PMID:27348033

  18. Clinical review: Statins and trauma--a systematic review.

    PubMed

    Jansen, Jan O; Lord, Janet M; Thickett, David R; Midwinter, Mark J; McAuley, Daniel F; Gao, Fang

    2013-01-01

    Statins, in addition to their lipid-lowering properties, have anti-inflammatory actions. The aim of this review is to evaluate the effect of pre-injury statin use, and statin treatment following injury. MEDLINE, EMBASE, and CENTRAL databases were searched to January 2012 for randomised and observational studies of statins in trauma patients in general, and in patients who have suffered traumatic brain injury, burns, and fractures. Of 985 identified citations, 7 (4 observational studies and 3 randomised controlled trials (RCTs)) met the inclusion criteria. Two studies (both observational) were concerned with trauma patients in general, two with patients who had suffered traumatic brain injury (one observational, one RCT), two with burns patients (one observational, one RCT), and one with fracture healing (RCT). Two of the RCTs relied on surrogate outcome measures. The observational studies were deemed to be at high risk of confounding, and the RCTs at high risk of bias. Three of the observational studies suggested improvements in a number of clinical outcomes in patients taking statins prior to injury (mortality, infection, and septic shock in burns patients; mortality in trauma patients in general; mortality in brain injured patients) whereas one, also of trauma patients in general, showed no difference in mortality or infection, and an increased risk of multi-organ failure. Two of three RCTs on statin treatment in burns patients and brain injured patients showed improvements in E-selectin levels and cognitive function. The third, of patients with radial fractures, showed no acceleration in fracture union. In conclusion, there is some evidence that pre-injury statin use and post-injury statin treatment may have a beneficial effect in patients who have suffered general trauma, traumatic brain injury, and burns. However, these studies are at high risk of confounding and bias, and should be regarded as 'hypothesisgenerating'. A well-designed RCT is required to

  19. Mechanism of Drug-Drug Interactions Between Warfarin and Statins.

    PubMed

    Shaik, Abdul Naveed; Bohnert, Tonika; Williams, David A; Gan, Lawrence L; LeDuc, Barbara W

    2016-06-01

    The anticoagulant drug warfarin and the lipid-lowering statin drugs are commonly co-administered to patients with cardiovascular diseases. Clinically significant drug-drug interactions (DDIs) between these drugs have been recognized through case studies for many years, but the biochemical mechanisms causing these interactions have not been explained fully. Previous theories include kinetic alterations in cytochrome P-450-mediated drug metabolism or disturbances of drug-protein binding, leading to anticoagulant activity of warfarin; however, neither the enantioselective effects on warfarin metabolism nor the potential disruption of drug transporter function have been well investigated. This study investigated the etiology of the DDIs between warfarin and statins. Liquid chromatography-mass spectrometry methods were developed and validated to quantify racemic warfarin, 6 of its hydroxylated metabolites, and pure enantiomers of warfarin; these methods were applied to study the role of different absorption, distribution, metabolism, and excretion properties, leading to DDIs. Plasma protein binding displacement of warfarin was performed in the presence of statins using equilibrium dialysis method. Substrate kinetics of warfarin and pure enantiomers were performed with human liver microsomes to determine the kinetic parameters (Km and Vmax) for the formation of all 6 hydroxywarfarin metabolites, inhibition of warfarin metabolism in the presence of statins, was determined. Uptake transport studies of warfarin were performed using overexpressing HEK cell lines and efflux transport using human adenocarcinoma colonic cell line cells. Fluvastatin significantly displaced plasma protein binding of warfarin and pure enantiomers; no other statin resulted in significant displacement of warfarin. All the statins that inhibited the formation of 10-hydroxywarfarin, atorvastatin, pitavastatin, and simvastatin were highly potent compared to other statins; in contrast, only fluvastatin

  20. Toxicity of statins on rat skeletal muscle mitochondria.

    PubMed

    Kaufmann, P; Török, M; Zahno, A; Waldhauser, K M; Brecht, K; Krähenbühl, S

    2006-10-01

    We investigated mitochondrial toxicity of four lipophilic stains (cerivastatin, fluvastatin, atorvastatin, simvastatin) and one hydrophilic statin (pravastatin). In L6 cells (rat skeletal muscle cell line), the four lipophilic statins (100 micromol/l) induced death in 27-49% of the cells. Pravastatin was not toxic up to 1 mmol/l. Cerivastatin, fluvastatin and atorvastatin (100 micromol/l) decreased the mitochondrial membrane potential by 49-65%, whereas simvastatin and pravastatin were less toxic. In isolated rat skeletal muscle mitochondria, all statins, except pravastatin, decreased glutamate-driven state 3 respiration and respiratory control ratio. Beta-oxidation was decreased by 88-96% in the presence of 100 micromol/l of the lipophilic statins, but only at higher concentrations by pravastatin. Mitochondrial swelling, cytochrome c release and DNA fragmentation was induced in L6 cells by the four lipophilic statins, but not by pravastatin. Lipophilic statins impair the function of skeletal muscle mitochondria, whereas the hydrophilic pravastatin is significantly less toxic. PMID:17013560

  1. Effects of Statins on the Risk of Hepatocellular Carcinoma

    PubMed Central

    Mansourian, Pejman G.; Yoneda, Masato; Krishna Rao, M.; Martinez, Fernando J.; Schiff, Eugene R.

    2014-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer morbidity and mortality worldwide and is one of the few cancers that is increasing in incidence. This cancer often arises in the setting of hepatic cirrhosis; however, it can also occur in patients with chronic hepatitis B virus infection without cirrhosis. Statins have been used for many years for the prevention and treatment of cardiovascular disease. Based on recent meta-analy-ses, these lipid-lowering agents are now being investigated for a class effect observed in the prevention of carcinogenesis. There are robust data suggesting that statins can alter biochemical pathways involved in tumorigenesis and cell survival and, thus, have a protective effect by reducing the risk of development of several types of cancer. In recent years, several studies have demonstrated that statins also can specifically decrease the risk of HCC development. Because statins are underutilized in patients with preexisting liver disease, understanding the role of statins in the prevention of HCC is important, and changes in practice guidelines supporting the use of statins as chemoprotective agents may be warranted. PMID:25904829

  2. Statin-Induced Rhabdomyolysis: A Comprehensive Review of Case Reports

    PubMed Central

    Mendes, Polyana; Robles, Priscila Games

    2014-01-01

    ABSTRACT Purpose: To identify case reports of statin-induced rhabdomyolysis and summarize common predisposing factors, symptoms, diagnostic findings, functional outcomes, characteristics, treatment, and rehabilitation. Method: MEDLINE, CINAHL, SCOPUS, and PEDro databases were searched (1990–2013) for relevant case reports using the search terms “Statins,” “Rhabdomyolysis,” “Myalgia,” “Muscle damage,” “Muscle injury,” and “Myopathy.” Relevance (based on title and abstract) was assessed by one investigator; two investigators independently reviewed the relevant articles to determine inclusion in the review. Results: A total of 112 cases met the inclusion criteria. The majority were in men (70%) and people over 45 years of age (mean 64 [SD 14] years). Simvastatin was the most commonly reported statin (n=55); the majority of cases reported the use of concomitant medications such as fibrates (n=25). Weakness (n=65) and muscle pain (n=64) were the most common symptoms. In 19 cases, the patient was referred to rehabilitation, but the case reports do not include descriptions of the treatment. Conclusion: Statin-induced rhabdomyolysis was more commonly reported when statins were used in conjunction with other drugs, which potentiated its effect. Research is needed to identify the role of exercise and rehabilitation following statin-induced rhabdomyoloysis since muscle damage may be severe and may have long-term effects on muscle function. PMID:24799748

  3. Statins are Associated With a Reduced Risk of Brain Cancer

    PubMed Central

    Chen, Brian K.; Chiu, Hui-Fen; Yang, Chun-Yuh

    2016-01-01

    Abstract The aim of this study was to investigate whether statin utilization is associated with brain cancer risk. A population-based case–control study was conducted using nationally representative claims data from the National Health Insurance Bureau in Taiwan. Cases included all patients 50 years and older who received an index diagnosis of brain cancer between 2004 and 2011. Our controls were matched by age, sex, and index date. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using multiple logistic regression. We examined 213 brain cancer cases and 852 controls. The unadjusted ORs for any statin prescription was 0.77 (95% CI = 0.50–1.18) and the adjusted OR was 0.59 (95% CI = 0.37–0.96). Compared with no use of statins, the adjusted ORs were 0.68 (95% CI = 0.38–1.24) for the group having been prescribed with statins with cumulative defined daily dose (DDD) below 144.67 DDDs and 0.50 (95% CI = 0.28–0.97) for the group with the cumulative statin use of 144.67 DDDs or more. The results of this study suggest that statins may reduce the risk of brain cancer. PMID:27124024

  4. Dietary modulators of statin efficacy in cardiovascular disease and cognition.

    PubMed

    Wang, Huifen; Blumberg, Jeffrey B; Chen, C-Y Oliver; Choi, Sang-Woon; Corcoran, Michael P; Harris, Susan S; Jacques, Paul F; Kristo, Aleksandra S; Lai, Chao-Qiang; Lamon-Fava, Stefania; Matthan, Nirupa R; McKay, Diane L; Meydani, Mohsen; Parnell, Laurence D; Prokopy, Max P; Scott, Tammy M; Lichtenstein, Alice H

    2014-08-01

    Cardiovascular disease remains the leading cause of morbidity and mortality in the United States and other developed countries, and is fast growing in developing countries, particularly as life expectancy in all parts of the world increases. Current recommendations for the prevention of cardiovascular disease issued jointly from the American Academy of Cardiology and American Heart Association emphasize that lifestyle modification should be incorporated into any treatment plan, including those on statin drugs. However, there is a dearth of data on the interaction between diet and statins with respect to additive, complementary or antagonistic effects. This review collates the available data on the interaction of statins and dietary patterns, cognition, genetics and individual nutrients, including vitamin D, niacin, omega-3 fatty acids, fiber, phytochemicals (polyphenols and stanols) and alcohol. Of note, although the available data is summarized, the scope is limited, conflicting and disparate. In some cases it is likely there is unrecognized synergism. Virtually no data are available describing the interactions of statins with dietary components or dietary pattern in subgroups of the population, particularly those who may benefit most were positive effects identified. Hence, it is virtually impossible to draw any firm conclusions at this time. Nevertheless, this area is important because were the effects of statins and diet additive or synergistic harnessing the effect could potentially lead to the use of a lower intensity statin or dose. PMID:24813475

  5. Statin safety: an appraisal from the adverse event reporting system.

    PubMed

    Davidson, Michael H; Clark, John A; Glass, Lucas M; Kanumalla, Anju

    2006-04-17

    The adverse event (AE) profiles of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) agents are of great interest, in particular the most recently approved statin, rosuvastatin. The forwarding of reports of AEs has been shown to be influenced by several reporting biases, including secular trend, the new drug reporting effect, product withdrawals, and publicity. Comparative assessments that use AE reporting rates are difficult to interpret under these circumstances, because such effects can themselves lead to marked increases in AE reporting. Consequently, many comparative reporting rate analyses are best carried out in conjunction with other metrics that put reporting burden into context, such as report proportion. All-AE reporting rates showed a temporal profile that resembled those of other statins when marketing cycle and secular trend were taken into account. A before-and-after cerivastatin withdrawal comparison showed a substantial increase in the reporting of AEs of interest for the statin class overall. Report proportion analyses indicated that the burden of rosuvastatin-associated AEs was similar to that for other statin agents. Analyses of monthly reporting rates showed that the reporting of rosuvastatin-associated rhabdomyolysis and renal failure have increased following AE-specific mass media publicity. Postrosuvastatin AE reporting patterns were comparable to those seen with other statins and did not resemble cerivastatin. PMID:16581327

  6. Relational aggression in marriage.

    PubMed

    Carroll, Jason S; Nelson, David A; Yorgason, Jeremy B; Harper, James M; Ashton, Ruth Hagmann; Jensen, Alexander C

    2010-01-01

    Drawing from developmental theories of relational aggression, this article reports on a study designed to identify if spouses use relationally aggressive tactics when dealing with conflict in their marriage and the association of these behaviors with marital outcomes. Using a sample of 336 married couples (672 spouses), results revealed that the majority of couples reported that relationally aggressive behaviors, such as social sabotage and love withdrawal, were a part of their marital dynamics, at least to some degree. Gender comparisons of partner reports of their spouse's behavior revealed that wives were significantly more likely to be relationally aggressive than husbands. Structural equation modeling demonstrated that relational aggression is associated with lower levels of marital quality and greater marital instability for both husbands and wives. Implications are drawn for the use of relational aggression theory in the future study of couple conflict and marital aggression. PMID:20698028

  7. Bias in Observational Studies of Prevalent Users: Lessons for Comparative Effectiveness Research From a Meta-Analysis of Statins

    PubMed Central

    Danaei, Goodarz; Tavakkoli, Mohammad; Hernán, Miguel A.

    2012-01-01

    Randomized clinical trials (RCTs) are usually the preferred strategy with which to generate evidence of comparative effectiveness, but conducting an RCT is not always feasible. Though observational studies and RCTs often provide comparable estimates, the questioning of observational analyses has recently intensified because of randomized-observational discrepancies regarding the effect of postmenopausal hormone replacement therapy on coronary heart disease. Reanalyses of observational data that excluded prevalent users of hormone replacement therapy led to attenuated discrepancies, which begs the question of whether exclusion of prevalent users should be generally recommended. In the current study, the authors evaluated the effect of excluding prevalent users of statins in a meta-analysis of observational studies of persons with cardiovascular disease. The pooled, multivariate-adjusted mortality hazard ratio for statin use was 0.77 (95% confidence interval (CI): 0.65, 0.91) in 4 studies that compared incident users with nonusers, 0.70 (95% CI: 0.64, 0.78) in 13 studies that compared a combination of prevalent and incident users with nonusers, and 0.54 (95% CI: 0.45, 0.66) in 13 studies that compared prevalent users with nonusers. The corresponding hazard ratio from 18 RCTs was 0.84 (95% CI: 0.77, 0.91). It appears that the greater the proportion of prevalent statin users in observational studies, the larger the discrepancy between observational and randomized estimates. PMID:22223710

  8. [Recognizing and assessing aggressive behaviour in dogs].

    PubMed

    Schalke, E; Hackbarth, H

    2006-03-01

    Within the population the sensitivity to aggressive behaviour in dogs has increased. The authorities are confronted with a problem: if any incident occurs it is their task to decide whether the dogs involved constitute a threat to other people or whether the charge is only the result of a quarrel between neighbours. For this reason, an examination of the dogs with regard to their aggressive behaviour is necessary. Seen from the biological point of view, aggressive behaviour is one of four possibilities a dog can chose from to solve a conflict. The dog's intention in showing aggressive behaviour is to eliminate disturbances and to maintain a distance in space and time. Aggressive behaviour might also be necessary to acquire or defend resources essential to the dog's life. This is to secure its survival and its success in reproduction. One can see from this that aggressive behaviour is a very important and biologically necessary adjustment factor. However, when living together with man aggressive behaviour might become a problem. For the assessment and the therapy of the problem it is necessary to exa-mine the behaviour shown by the dog with regard to its cause. To be able to do this an exact anamnesis, a medical check, and an examination of the dog on the basis of its display in special situations are necessary. For this reason, exclusively veterinarians with a special further education in the field of behaviour should carry out the examination of dogs. PMID:16669189

  9. Time-related trends in variability of cIMT changes in statin trials

    PubMed Central

    Davidson, Michael H.; Tomassini, Joanne E.; Jensen, Erin; Neff, David; Polis, Adam B.; Tershakovec, Andrew M.

    2015-01-01

    This brief article provides complementary data supporting the results reported in “Changing Characteristics of Statin-related cIMT Trials from 1988 to 2006” [1]. That article described time-related trends in baseline factors and study characteristics that may have influenced the variability of carotid intima media thickness (cIMT) endpoints (mean of mean and maximum common carotid artery [CCA]/cIMT) in published statin trials. In this brief report, additional details for the studies included in the analysis, and further supporting data, including mean of the maximum CCA/cIMT changes and subgroup data (mean and maximum CCA/cIMT) are provided. For the analysis, study-level data was extracted from 17 statin cIMT trials conducted during 1988–2006, selected on the basis of having at least one statin monotherapy arm in the absence of mixed therapy, and baseline- and study-end values for mean mean and mean maximum CCA/cIMT endpoints. The baseline mean CCA/cIMT, maximum mean CCA/cIMT and LDL-C levels, and annualized cIMT changes were estimated for the overall studies, those conducted before/after 2000, and in risk-based subgroups. Interestingly, all 8 studies conducted before 2000 were significant for cIMT change in which patients did not receive prior LLT; whereas after 2000, the results were more variable and in 4 of 6 trials that did not show a significant cIMT change, patients had received prior treatment. Baseline mean maximum cIMT and LDL-C levels, and annualized changes in studies conducted before 2000 were higher than those conducted after 2000, similar to the results reported in the original article for the mean mean cIMT endpoint. These findings were consistent across study populations of patients with CHD risk versus those without, and in studies with greater LDL-C reductions and with thickened baseline cIMT at study entry for both mean and maximum cIMT changes. Taken together, these results are consistent with trends in recent years toward greater use of

  10. Authoritarianism and sexual aggression.

    PubMed

    Walker, W D; Rowe, R C; Quinsey, V L

    1993-11-01

    In Study 1, 198 men completed the Right Wing Authoritarianism, Sex Role Ideology, Hostility Towards Women, Acceptance of Interpersonal Violence, Adversarial Sexual Beliefs, and Rape Myth Acceptance scales, as well as measures of past sexually aggressive behavior and likelihood of future sexual aggression. As predicted, authoritarianism and sex role ideology were as closely related to self-reported past and potential future sexually aggressive behavior as were the specifically sexual and aggression-related predictors. Among 134 men in Study 2, authoritarianism and sex guilt positively correlated with each other and with self-reported past sexual aggression. In both studies, the relationship of authoritarianism and sexual aggression was larger in community than in university samples. PMID:8246111

  11. Statin Use Mitigate the Benefit of Omega-3 Fatty Acids Supplementation-A Meta-Regression of Randomized Trials.

    PubMed

    Sethi, Ankur; Bajaj, Anurag; Khosla, Sandeep; Arora, Rohit R

    2016-01-01

    During last 2 decades, multiple studies have evaluated omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation for cardiovascular prevention. The benefit found in previous studies was not demonstrated in more contemporary trials. We aimed to investigate effect of study characteristics, particularly concomitant statin therapy on results of randomized controlled trials. We systematically searched electronic databases for randomized controlled trials evaluating ω-3 PUFA supplementation and reporting clinical outcomes. A meta-analysis was performed using a random effect model, followed by a meta-regression of dose, docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio, and duration of treatment and use of lipid-lowering/statin therapy in control group. Twenty-three studies with 77,776 patients (38,910 PUFA; 38,866 controls) were included. PUFA had no effect on total mortality [risk ratio (RR) = 0.96; 95% confidence interval (CI), 0.92-1.01] and myocardial infarction (RR = 0.87; 95% CI, 0.73-1.02), but marginally reduced cardiovascular mortality (RR = 0.93; 95% CI, 0.87-0.98). Lower control group statin use (b = 0.222, P = 0.027) and higher DHA/EPA (b = -0.105, P = 0.033) ratio was associated with higher reduction in total mortality. Duration and dose had no effect. None of the variables except duration had significant effect on reduction in cardiovascular mortality by PUFA supplementation. There was evidence of publication bias. Statin use may mitigate, and higher DHA/EPA ratio is associated with the beneficial effect of PUFA supplementation. PMID:25036814

  12. Balanced pan-PPAR activator bezafibrate in combination with statin: comprehensive lipids control and diabetes prevention?

    PubMed

    Tenenbaum, Alexander; Fisman, Enrique Z

    2012-01-01

    atherosclerotic plaque regression in thoracic and abdominal aorta and improved endothelial function. In addition, bezafibrate has important fibrinogen-related properties and anti-inflammatory effects. In clinical trials bezafibrate was highly effective for cardiovascular risk reduction in patients with metabolic syndrome and atherogenic dyslipidemia. The principal differences between bezafibrate and other fibrates are related to effects on glucose level and insulin resistance. Bezafibrate decreases blood glucose level, HbA1C, insulin resistance and reduces the incidence of T2DM compared to placebo or other fibrates. Currently statins are the cornerstone of the treatment and prevention of cardiovascular diseases related to atherosclerosis. However, despite the increasing use of statins as monotherapy for low density lipoprotein- cholesterol (LDL-C) reduction, a significant residual cardiovascular risk is still presented in patients with atherogenic dyslipidemia and insulin resistance, which is typical for T2DM and metabolic syndrome. Recently, concerns were raised regarding the development of diabetes in statin-treated patients. Combined bezafibrate/statin therapy is more effective in achieving a comprehensive lipid control and residual cardiovascular risk reduction. Based on the beneficial effects of pan-PPAR agonist bezafibrate on glucose metabolism and prevention of new-onset diabetes, one could expect a neutralization of the adverse pro-diabetic effect of statins using the strategy of a combined statin/fibrate therapy. PMID:23150952

  13. Observational data for comparative effectiveness research: an emulation of randomised trials to estimate the effect of statins on primary prevention of coronary heart disease

    PubMed Central

    Danaei, Goodarz; García Rodríguez, Luis A.; Cantero, Oscar Fernández; Logan, Roger; Hernán, Miguel A.

    2013-01-01

    This article reviews methods to estimate treatment effectiveness research using observational data. The basic idea is using an observational study to emulate a hypothetical randomised trial by comparing initiators vs. non-initiators of treatment. After adjustment for baseline confounders, one can estimate the analogue of the intention-to-treat effect. We also explain two approaches to adjust for imperfect adherence using the per-protocol and as-treated analyses after adjusting for measured time-varying confounding and selection bias using inverse probability weighting of marginal structural models. As an example, we implemented these methods to estimate the effect of statins for primary prevention of coronary heart disease (CHD) using data from electronic medical records in the United Kingdom. Despite strong confounding by indication, our approach detected a potential benefit of statin therapy. The analogue of the intention-to-treat hazard ratio of CHD was 0.89 (0.73, 1.09) for statin initiators vs. noninitiators. The hazard ratio of CHD was 0.84 (0.54, 1.30) in the per-protocol analysis and 0.79 (0.41, 1.41) in the as-treated analysis for 2-years of use vs. no use. In contrast, a conventional comparison of current users vs. never users of statin therapy resulted in a hazard ratio of 1.31 (1.04, 1.66). We provide a flexible and annotated SAS program to implement the proposed analyses. PMID:22016461

  14. Is the peripheral arterial disease in low risk type 2 diabetic patients influenced by body mass index, lipidemic control, and statins?

    PubMed Central

    Solanki, Jayesh Dalpatbhai; Makwana, Amit H.; Mehta, Hemant B.; Gokhale, Pradnya A.; Shah, Chinmay J.

    2016-01-01

    Objective: To correlate BMI, lipidemic control, and statin therapy with PAD measured by ABI in low risk type 2 diabetics. Materials and Methods: A sample of 101 nonsmoking, asymptomatic type 2 diabetics (50 males, 51 females) with known glycemic (fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin) and lipidemic (total cholesterol, lipoproteins, and triglycerides [TGAs]) control was taken. Vascular Doppler was used to derive ABI and PAD was defined as ABI <0.9. ABI values were compared amongst groups and P < 0.05 was considered statistically significant. Results: We found fairly good lipid but poor glycemic control and prevalence of PAD 30%. There was insignificantly low ABI profile in patient having BMI ≥25, hyperlipidemia and absent statin therapy with odds ratio being highest for TGAs ≥150 (3.23) followed by BMI ≥25 (2.61), high-density lipoprotein ≤50 (1.61), low-density lipoprotein ≥100 (1.20), and disuse of statin (1.14) with significance only for BMI. Conclusion: We observed small, insignificant PAD risk by dyslipidemia or non-use of statins in low-risk ambulatory T2DM patients, not so by BMI. This suggests importance of good glycemic control, maintenance of optimum weight, and lifestyle modifications as primary prevention rather than opting for costly and inefficient secondary prevention. PMID:27440953

  15. Comparative Effectiveness of Generic and Brand-Name Statins on Patient Outcomes

    MedlinePlus

    ... Summaries for Patients Comparative Effectiveness of Generic and Brand-Name Statins on Patient Outcomes The full report is titled “Comparative Effectiveness of Generic and Brand-Name Statins on Patient Outcomes. A Cohort Study.” ...

  16. Statins and Male Sexual Health: A Retrospective Cohort Analysis

    PubMed Central

    Richard, Davis; Reveles, Kelly R.; Ali, Sayed K.; Mortensen, Eric M.; Frei, Christopher R.; Mansi, Ishak

    2014-01-01

    Introduction Conflicting reports exist regarding the role of statins in male gonadal and sexual function. Some studies report a beneficial effect, particularly for erectile dysfunction (ED), through statins’ anti-inflammatory and cardiovascular protective properties. Others suggest that statins might be associated with sexual dysfunction through negative effects on hormone levels. Aim To compare the risk of gonadal or sexual dysfunction in statin-users versus non-users in a single payer healthcare system. Methods A retrospective cohort study of all male patients (30-85 years) enrolled in Tricare San Antonio market. Using 79 baseline characteristics, we created a propensity score-matched cohort of statin-users and non-users. The study duration was divided into a baseline period (October 1, 2003 to September 30, 2005), to describe patient baseline characteristics, and a follow-up period (October 1, 2005 to March 1, 2012) to determine patient outcomes. Statin-users were defined as those prescribed a statin for ≥3 months between October 1, 2004 and September 30, 2005. Main Outcome Measures Outcomes were identified as the occurrence of benign prostatic hypertrophy (BPH), ED, infertility, testicular dysfunction, or psychosexual dysfunction during the follow-up period as identified by inpatient or outpatient International Classification of Diseases, 9th Revision, Clinical Modification codes. Logistic regression was used to determine the association of statin use with patient outcomes. Results Of 20,731 patients who met study criteria, we propensity score-matched 3,302 statinusers with 3,302 non-users. Statin use in men was not significantly associated with an increased or decreased risk of BPH (OR 1.08; 95% CI 0.97-1.19), ED (OR 1.01; 95% CI 0.90-1.13), infertility (OR 1.22; 95% CI 0.66-2.29), testicular dysfunction (OR 0.91; 95% CI 0.73-1.14), or psychosexual dysfunction (OR 1.03; 95% CI 0.94-1.14). Conclusions Statin use was not associated with increased risk of

  17. Mechanisms and assessment of statin-related muscular adverse effects

    PubMed Central

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-01-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

  18. Case-control study of statin prevention of mould infections.

    PubMed

    Thompson, Jessica N; Huycke, Mark M; Greenfield, Ronald A; Kurdgelashvili, George; Gentry, Chris A

    2011-09-01

    Invasive mould infections (IMI) are associated with significant morbidity and mortality. In vitro studies have demonstrated that hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have activity against several pathogenic moulds including Zygomycetes and Aspergillus spp. The aim of our study was to determine if statin use is a preventive factor for the development of IMI. This was a retrospective case-control study of 10 United States Veterans Affairs Medical Centers that comprise the Veterans Integrated Service Network (VISN) 16. Cases with IMI and controls were identified from 2001 to 2008. Controls were matched by age, facility, history of transplantation, presence of chronic steroid use and presence of human immunodeficiency virus infection (HIV). Two hundred and thirty-eight patients were included. Independent variables associated with the development of IMI were history of solid malignant tumours (OR 2.63, 1.41-4.87) and hypertension (OR 2.29, 1.13-4.68). Statin use within 3 months of index date was not an independent variable for prevention or development of IMI. No level of exposure to a statin drug appeared to influence the development of infection. This retrospective case-control study suggests that despite evidence of in vitro activity, statins may not decrease risk of IMI. Prospective, controlled trials may be necessary to investigate any potential clinical benefit. PMID:21554419

  19. The nocebo effect in the context of statin intolerance.

    PubMed

    Tobert, Jonathan A; Newman, Connie B

    2016-01-01

    The nocebo effect, the inverse of the placebo effect, is a well-established phenomenon that is under-appreciated in cardiovascular medicine. It refers to adverse events, usually purely subjective, that result from expectations of harm from a drug, placebo, other therapeutic intervention or a nonmedical situation. These expectations can be driven by many factors including the informed consent form in a clinical trial, warnings about adverse effects communicated by clinicians when prescribing a drug, and information in the media about the dangers of certain treatments. The nocebo effect is the best explanation for the high rate of muscle and other symptoms attributed to statins in observational studies and clinical practice, but not in randomized controlled trials, where muscle symptoms, and rates of discontinuation due to any adverse event, are generally similar in the statin and placebo groups. Statin-intolerant patients usually tolerate statins under double-blind conditions, indicating that the intolerance has little if any pharmacological basis. Known techniques for minimizing the nocebo effect can be applied to the prevention and management of statin intolerance. PMID:27578103

  20. Statins and oxidative stress in chronic heart failure.

    PubMed

    Costa, Sónia; Reina-Couto, Marta; Albino-Teixeira, António; Sousa, Teresa

    2016-01-01

    Statins are the most commonly prescribed drugs for the treatment of dyslipidemia. They are also recommended in primary and secondary prevention of cardiovascular disease. In addition to decreasing cholesterol synthesis, statins interfere with the synthesis of isoprenoid intermediates, which may explain many of their pleiotropic properties, including their antioxidant effects. Oxidative stress is defined as an imbalance between the synthesis of reactive oxygen species and their elimination by antioxidant defense systems, with a prevailing pro-oxidant status that results in macromolecular damage and disruption of cellular redox signaling. Reactive oxygen species interfere with various processes that affect cardiac structure and function, contributing to the contractile dysfunction, myocardial hypertrophy and fibrosis observed in the pathophysiology of heart failure. By regulating several molecular pathways that control nicotinamide adenine dinucleotide phosphate oxidase and endothelial nitric oxide synthase activity, statins help restore redox homeostasis. These drugs also contribute to the control of inflammation and appear to have a protective role in various diseases. The results of observational studies and clinical trials with statins in heart failure have not been consensual. This review aims to analyze the role of oxidative stress in heart failure and the molecular mechanisms underlying statins' antioxidant properties. It also examines current scientific evidence on the use of these drugs as a specific treatment for heart failure. PMID:26763895

  1. Recent findings on the health effects of omega-3 fatty acids and statins, and their interactions: do statins inhibit omega-3?

    PubMed Central

    2013-01-01

    Early randomized controlled trials (RCTs) demonstrated the health benefits of omega-3 fatty acids (n-3), whereas recent RCTs were negative. We now address the issue, focusing on the temporal changes having occurred: most patients in recent RCTs are no longer n-3 deficient and the vast majority are now treated with statins. Recent RCTs testing n-3 against arrhythmias suggest that n-3 reduce the risk only in patients not taking a statin. Other recent RCTs in secondary prevention were negative although, in a post-hoc analysis separating statin users and non-users, non-significant protection of n-3 was observed among statin non-users whereas statin users had no effect. Recent RCTs testing statins - after the implementation of the New Clinical Trial Regulation in 2007 - are negative (or flawed) suggesting that the lack of effect of n-3 cannot be attributed to a parallel protection by statins. Finally, statins favor the metabolism of omega-6 fatty acids (n-6), which in turn inhibits n-3 and, contrary to n-3, they increase insulin resistance and the risk of diabetes. Thus, n-3 and statins are counteractive at several levels and statins appear to inhibit n-3. PMID:23289647

  2. Angry and Aggressive Students

    ERIC Educational Resources Information Center

    Larson, Jim

    2008-01-01

    Students who engage in physical aggression in school present a serious challenge to maintaining a safe and supportive learning environment. Unlike other forms of student aggression, fighting is explicit, is violent, and demands attention. A fight between students in a classroom, hallway, or the lunchroom brings every other activity to a halt and…

  3. Girls' Aggressive Behavior

    ERIC Educational Resources Information Center

    Owens, Larry; Shute, Rosalyn; Slee, Phillip

    2004-01-01

    In contrast to boys' bullying behavior which is often overt and easily visible, girls' aggression is usually indirect and covert. Less research has been conducted on the types of bullying that girls usually engage in. Using focus groups composed of teenaged girls, Dr. Owens and colleagues examine the nature of teenage girls' indirect aggression.

  4. Testosterone and Aggression.

    ERIC Educational Resources Information Center

    Archer, John

    1994-01-01

    Studies comparing aggressive and nonaggressive prisoners show higher testosterone levels among the former. While there is limited evidence for a strong association between aggressiveness and testosterone during adolescence, other studies indicate that testosterone levels are responsive to influences from the social environment, particularly those…

  5. Aggression: Psychopharmacologic Management

    PubMed Central

    Conlon, Patrick; Frommhold, Kristine

    1989-01-01

    Aggression may be part of a variety of psychiatric diagnoses. The appropriate treatment requires that the physician recognize the underlying cause. Pharmacologic agents may form part of the overall treatment of the patient. The number of possible drugs for treating aggression has expanded rapidly, and it is important that the physician be familiar with the various options avilable. PMID:21248947

  6. Social Aggression among Girls.

    ERIC Educational Resources Information Center

    Underwood, Marion K.

    Noting recent interest in girls' social or "relational" aggression, this volume offers a balanced, scholarly analysis of scientific knowledge in this area. The book integrates current research on emotion regulation, gender, and peer relations, to examine how girls are socialized to experience and express anger and aggression from infancy through…

  7. Third Person Instigated Aggression.

    ERIC Educational Resources Information Center

    Gaebelein, Jacquelyn

    Since many acts of aggression in society are more than simply an aggressor-victim encounter, the role played by third person instigated aggression also needs examination. The purpose of this study was to develop a laboratory procedure to systematically investigate instigation. In a competitive reaction time task, high and low Machiavellian Males…

  8. Neuropsychiatry of Aggression

    PubMed Central

    Lane, Scott D.; Kjome, Kimberly L.; Moeller, F. Gerard

    2010-01-01

    Synopsis Aggression is a serious medical problem that can place both the patient and the health care provider at risk. Aggression can result from medical, neurologic and or psychiatric disorders. A comprehensive patient evaluation is needed. Treatment options include pharmacotherapy as well as non-pharmacologic interventions, both need to be individualized to the patient. PMID:21172570

  9. CHOP versus CHOP plus ESHAP and high-dose therapy with autologous peripheral blood progenitor cell transplantation for high-intermediate-risk and high-risk aggressive non-Hodgkin's lymphoma.

    PubMed

    Intragumtornchai, T; Prayoonwiwat, W; Numbenjapon, T; Assawametha, N; O'Charoen, R; Swasdikul, D

    2000-12-01

    The purpose of the study was to compare conventional cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy with CHOP (3 courses) plus etoposide/methylprednisolone/high-dose cytarabine/cisplatin (ESHAP), high-dose therapy (HDT), and autologous peripheral blood progenitor cell transplantation (PBPCT) as front-line treatment for poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). Between May 1, 1995, and April 30, 1998, 58 patients, aged 15-55 years, newly diagnosed with poor-prognosis aggressive NHL (category F-H by the Working Formulation) were enrolled. According to the age-adjusted international prognostic index, 65% of the patients were high-risk cases and 35% made up the high-intermediate group. After 3 courses of CHOP, 25 of 48 patients were randomized to continue with CHOP, and 23 were randomized to receive 2-4 cycles of ESHAP followed by HDT and PBPCT. There was no significant difference in the rate of complete remission between the two groups (36%, 95% confidence interval [CI]: 18%-57% in CHOP vs. 43%, 95% CI: 23%-65% in ESHAP/HDT) (P = 0.77). With a median follow-up duration of 39 months, the 4-year failure-free survival (FFS) was superior in the ESHAP/HDT group (38%, 95% CI: 18%-58% vs. 15%, 95% CI: 4%-32%) (P = 0.04). The disease-free survival was marginally different in favor of the ESHAP/HDT arm (90%, 95% CI: 47%-98% vs. 37%, 95% CI: 7%-69%) (P = 0.06). The 4-year overall survival between the two treatment arms was comparable (51%, 95% CI: 28%-70% for ESHAP/HDT vs. 30%, 95% CI: 13%-48% for CHOP) (P = 0.25). Treatment-related mortalities were not significantly different between both groups (17%, 95% CI: 5%-39% for ESHAP/HDT vs. 8%, 95% CI: 1%-26% for CHOP) (P = 0.41). However, only 61% of the patients assigned to the ESHAP/HDT arm underwent HDT and PBPCT. As compared with CHOP, the corporate regimen of CHOP/ESHAP/HDT seems to improve the FFS in patients with newly diagnosed, poor-prognosis aggressive NHL. PMID:11707834

  10. Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors.

    PubMed

    Manuel, Edwin R; Chen, Jeremy; D'Apuzzo, Massimo; Lampa, Melanie G; Kaltcheva, Teodora I; Thompson, Curtis B; Ludwi