Dabigatran Versus Warfarin

Abstract

Background and Purpose— Intracranial hemorrhage rates are higher in Asians than non-Asians, especially in patients receiving warfarin. This randomized evaluation of long-term anticoagulation therapy subgroup analysis assessed dabigatran etexilate (DE) and warfarin effects on stroke and bleeding rates in patients from Asian and non-Asian countries. Methods— There were 2782 patients (15%) from 10 Asian countries and 15 331 patients from 34 non-Asian countries. A Cox regression model, with terms for treatment, region, and their interaction was used. Results— Rates of stroke or systemic embolism in Asians were 3.06% per year on warfarin, 2.50% per year on DE 110 mg BID (DE 110), and 1.39% per year on DE 150 mg BID (DE 150); in non-Asians, the rates were 1.48%, 1.37%, and 1.06% per year with no significant treatment-by-region interactions. Hemorrhagic stroke on warfarin occurred more often in Asians than non-Asians (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3–4.7; P =0.007), with significant reductions for DE compared with warfarin in both Asian (DE 110 versus warfarin HR, 0.15; 95% CI, 0.03–0.66 and DE 150 versus warfarin HR, 0.22; 95% CI, 0.06–0.77) and non-Asian (DE 110 versus warfarin HR, 0.37; 95% CI, 0.19–0.72 and DE 150 versus warfarin HR, 0.28; 95% CI, 0.13–0.58) patients. Major bleeding rates in Asians were significantly lower on DE (both doses) than warfarin (warfarin 3.82% per year, DE 110 2.22% per year, and DE 150 2.17% per year). Conclusions— Hemorrhagic stroke rates were higher on warfarin in Asians versus non-Asians, despite similar blood pressure, younger age, and lower international normalized ratio values. Hemorrhagic strokes were significantly reduced by DE in both Asians and non-Asians. DE benefits were consistent across Asian and non-Asian subgroups. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00262600.

Efficacy and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Asians With Nonvalvular Atrial Fibrillation

“…Dabigatran with 110 mg twice daily was the only low‐dose NOAC that was independently compared with warfarin among the 3 pivotal NOAC studies 2. The Asian subgroup analysis from the RE‐LY trial (Randomized Evaluation of Long‐Term Anticoagulation Therapy) indicated that low‐dose dabigatran caused a similar risk of thromboembolic events (HR, 0.82; 95% CI, 0.55–1.24) and a significantly lower risk of major bleeding (HR, 0.57; 95% CI, 0.38–0.86) compared with warfarin 29. Our findings in ≈88% of patients taking low‐dose dabigatran in Taiwan are in line with the findings from the RE‐LY trial, with lower risks of thromboembolic events (HR, 0.82; 95% CI, 0.68–0.98) and major bleeding (HR, 0.65; 95% CI, 0.53–0.80) for dabigatran versus warfarin.…”

Secondary prophylactic treatment and long‐term prognosis after TIA and different subtypes of stroke. A 25‐year follow‐up hospital‐based observational study

“…Another explanation could be that it was the selection of few patients with high risk among the AC‐treated men (Kim et al., 2011). The observation period of the patients with CE cerebral infarction in this trial could not be compared with NOAC trials in which the mean and median observation times were only between 1 and 2 years (Alberts et al., 2012; Diener et al., 2012; Hankey, 2014; Hori et al., 2013; Lopes et al., 2012). …”

“…Due to the verified beneficial effects of NOACs in patients with AF compared with warfarin (Alberts et al., 2012; Diener et al., 2012; Hankey, 2014; Hori et al., 2013; Lopes et al., 2012) and the observation in the present trial of a higher annual risk of death during treatment with APT versus AC in men compared with women, this trial supported studies evaluating NOACs, especially in male patients with arterial thromboembolism or myocardial infarction.…”

“…In primary or secondary prophylactic treatment of patients with AF, AC and APT have each been shown to be a better alternative than a placebo, with warfarin better than APT but with an increased risk of bleeding (Alberts, Eikelboom, & Hankey, 2012; Blackshear et al., 1996; Connolly et al., 2008; Fuster et al., 2006; Hart, Pearce, & Aguilar, 2007; Hylek et al., 2003; Laupacis et al., 1994). Novel oral anticoagulants (NOACs) have been reported to have the same effects or to perform even better than warfarin with an equal or lower risk of major bleeding (Alberts et al., 2012; Hankey, 2014; Hori et al., 2013; Lopes et al., 2012), and NOACs have shown large differences in their favor regarding the risk of stroke or systemic embolism, compared with ASA (Alberts et al., 2012; Diener et al., 2012). …”

Safety, pharmacokinetics and pharmacodynamics of idarucizumab, a specific dabigatran reversal agent in healthy Japanese volunteers: a randomized study

“…A sub‐analysis in Japanese patients from the Randomized Evaluation of Long‐term anticoagulant therapY (RE‐LY) trial indicated similar safety and efficacy for DE vs warfarin and higher bleeding rates for warfarin in Asians vs non‐Asians6, 7; this was attributed to postulated genetic differences in blood coagulation between Asian and non‐Asian subjects. The reductions in hemorrhagic stroke and major bleeding rates were comparable between Asians vs non‐Asian patients treated with DE 8…”