Concomitant Use of Antiplatelet Therapy with Dabigatran or Warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY®) Trial
Background—RE-LY showed that dabigatran etexilate 150 mg bid (DE150) was superior, and 110 mg bid (DE110) non-inferior to warfarin in preventing stroke and systemic embolism (SSE) in patients with atrial fibrillation (AF). In this subgroup analysis, we assess the efficacy and safety of dabigatran in patients who did and didn't receive concomitant antiplatelets
Methods and Results—All comparisons used a cox proportional hazards model with adjustments made for risk factors for bleeding. A time dependent analysis was performed when comparing patients with concomitant antiplatelets to those without. 6952 of 18,113 patients (38.4%) received concomitant ASA or clopidogrel at some time during the study. DE110 was non-inferior to warfarin in reducing SSE, whether patients received antiplatelets (HR=0.93; 95%CI: 0.70-1.25) or not (HR=0.87; 95%CI: 0.66-1.15; interaction p=0.738). There were less major bleeds than warfarin in both subgroups (HR=0.82; 95%CI: 0.67-1.00 for patients who used antiplatelets; HR=0.79; 95% CI: 0.64-0.96 for patients who didn't; interaction p=0.794). DE 150 reduced the primary outcome of SSE compared to warfarin. This effect seemed attenuated among patients who used antiplatelets (HR=0.80, 95%CI: 0.59-1.08) compared to those who didn't (HR=0.52, 95%CI: 0.38-0.72; p for interaction=0.058). Major bleeding was similar to warfarin regardless of antiplatelet use (HR=0.93, 95%CI: 0.76-1.12 for patients who used antiplatelets; HR=0.94, 95%CI: 0.78-1.15 for patients who didn't; p for interaction=0.875). In the time dependent analysis, concomitant use of a single antiplatelet seemed to increase the risk of major bleeding (HR=1.60; 95% CI: 1.42, 1,.82). Dual antiplatelet seemed to increased this even more (HR=2.31; 95% CI: 1.79, 2.98). The absolute risks were lowest on DE110 compared to DE150 or warfarin.
Conclusions—Concomitant antiplatelet drugs appeared to increase the risk for major bleeding in RE-LY without affecting the advantages of dabigatran over warfarin. Choosing between DE110 and DE150 requires a careful assessment of characteristics that influence the balance between benefit and harm.
Clinical Trial Registration Information—ClinicalTrials.gov. Identifier: NCT00262600.
- Received May 25, 2012.
- Accepted November 30, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited