The Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) study demonstrated a significant increase in myocardial infarction events with dabigatran compared with warfarin, provoking renewed interest in whether vitamin K antagonists are useful drugs for the prevention of myocardial infarction in high-risk patients with atrial fibrillation. Present analyses examined whether there was an increased risk of myocardial infarction associated with non-warfarin anticoagulants (Stroke Prevention with the ORal direct Thrombin Inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial Fibrillation III and IV, RE-LY, Amadeus) or "anticoagulant equivalents" (Atrial fibrillation Clopidogrel Trial with Irbesartan for the prevention of Vascular Events) in patients with atrial fibrillation who are prescribed anticoagulation for stroke thromboprophylaxis. The overall annual event rate for those receiving warfarin was 0.98% compared with 1.32% for those receiving comparators. Warfarin was associated with a significant reduction in myocardial infarction (relative risk 0.77; 95% confidence interval (CI), 0.63-0.95), an effect largely driven by the RE-LY trial. Sensitivity analyses, excluding RE-LY, revealed a nonsignificant reduction in myocardial infarctions (relative risk 0.83; 95% CI, 0.62-1.10); an analogous analysis excluding the Atrial fibrillation Clopidogrel Trial with Irbesartan for the prevention of Vascular Events demonstrated a significant reduction in myocardial infarctions (relative risk 0.80; 95% CI, 0.64-1.00). Warfarin might provide a protective effect against myocardial infarction compared with non-warfarin anticoagulants or "anticoagulation equivalents" in patients with atrial fibrillation who are prescribed anticoagulation for stroke thromboprophylaxis.
"The risk of stroke is markedly increased in AF patients, and anticoagulants are preferred to antiplatelets due to their superiority in stroke prevention . However, anticoagulants are also effective in preventing myocardial infarctions , although their effect on mortality has not been adequately addressed . As regards vascular and all-cause mortality, antiplatelets are just as effective as anticoagulants according to a Cochrane review . "
[Show abstract][Hide abstract] ABSTRACT: To study mortality rates among patients with diabetes and concomitant atrial fibrillation (AF), prescribed different cardiovascular drugs in primary health care.
Study population consisted of men (n = 1319) and women (n = 1094) aged >=45 years from a database including 75 primary care centres in Sweden. Cox regression analysis, with hazard ratios (HRs), 95% confidence interval (95% CIs) and mortality (years to death) as outcome, and Laplace regression, with difference in time to first 10% mortality (with 95% CI), were performed. Independent variables were prescribed cardiovascular drugs. Regression models were adjusted for a propensity score calculated separately for each prescribed drug class (comprising age, cardiovascular co-morbidities, education, marital status and pharmacotherapy).
Overall mortality was lower in the whole sample for anticoagulants vs no treatment (HR 0.45; 95% CI 0.26-0.77); and among patients < 80 years for anticoagulants vs. antiplatelets (HR 0.44; 95% CI 0.25-0.78); while among individuals aged >=80 years, antiplatelets (HR 0.47; 95% CI 0.26-0.87) and anticoagulants (HR 0.49; 95% CI 0.24-1.00) vs. no treatment were equally effective. Statins were associated with lower mortality among those <80 years (HR 0.45; 95% CI 0.29-0.71). Laplace regression models in the whole sample, with years to first 10% of total mortality as outcome, were significant for: among patients < 80 years anticoagulants vs. no treatment 2.70 years (95% CI 0.04-5.37), anticoagulants vs. antiplatelets 2.31 years (95% CI 0.84-3.79), and those >=80 1.78 years (95% CI 1.04-2.52).
Our findings suggest that antiplatelets could exert a beneficial effect among those above 80 years.
[Show abstract][Hide abstract] ABSTRACT: A substantial portion of patients with atrial fibrillation (AF) also have coronary artery disease (CAD) and are at risk for coronary events. Warfarin is known to reduce these events, but increase the risk of bleeding. We assessed the effects of apixaban compared with warfarin in AF patients with and without prior CAD.
In ARISTOTLE, 18,201 patients with AF were randomized to apixaban or warfarin. History of CAD was defined as documented CAD, prior myocardial infarction, and/or history of coronary revascularization. We analyzed baseline characteristics and clinical outcomes of patients with and without prior CAD and compared outcomes by randomized treatment using Cox models. A total of 6639 (36.5%) patients had prior CAD. These patients were more often male, more likely to have prior stroke, diabetes, and hypertension, and more often received aspirin at baseline (42.2% vs. 24.5%). The effects of apixaban were similar among patients with and without prior CAD on reducing stroke or systemic embolism and death from any cause (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.71-1.27, P for interaction=0.12; HR 0.96, 95% CI 0.81-1.13, P for interaction=0.28). Rates of myocardial infarction were numerically lower with apixaban than warfarin among patients with and without prior CAD. The effect of apixaban on reducing major bleeding and intracranial hemorrhage was consistent in patients with and without CAD.
In patients with AF, apixaban more often prevented stroke or systemic embolism and death and caused less bleeding than warfarin, regardless of the presence of prior CAD. Given the common occurrence of AF and CAD and the higher rates of cardiovascular events and death, our results indicate that apixaban may be a better treatment option than warfarin for these high-risk patients.
International journal of cardiology 10/2013; 170(2). DOI:10.1016/j.ijcard.2013.10.062 · 4.04 Impact Factor
"If the trend for a higher rate of myocardial infarction in dabigatran-treated (0.91 and 0.88%) versus 0.72% in warfarin-treated patients in the RE-LY trial may be related to the platelet-activating activity of dabigatran is unexplained . A further explanation for the lower rate of myocardial infarction in VKA-treated patients might be that VKA are protective against myocardial infarction . Concerns about cardiovascular side effects of dabigatran are further substantiated by a recently published meta-analysis comprising seven trials including 30,514 patients that reported acute coronary events as secondary outcomes. "
[Show abstract][Hide abstract] ABSTRACT: Dabigatran is an oral thrombin inhibitor which has been approved in several countries as an alternative to vitamin-K-antagonists for the prevention of stroke or embolism in atrial fibrillation patients. Dabigatran is introduced into clinical practice, although many issues regarding this drug are still unclear, like laboratory monitoring, use in elderly patients, drug- and food-interactions and use in patients with renal insufficiency. Additionally, there is no antidote for dabigatran. Thus, aim of the present review is to give an overview of concerns and unresolved issues concerning dabigatran.
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