Patient Outcomes Using the European Label for Dabigatran: A Post-Hoc Analysis From the RE-LY Database

Study Questions:

What is the efficacy and safety of dabigatran, when used according to the recommended dose regimen in the European (EU) label, as compared to well-controlled warfarin treatment (international normalized ratio [INR], 2-3; median time in therapeutic range, 67.3%)?


In this post-hoc analysis of the RE-LY data set, the investigators simulated how dabigatran (n = 6,004) would compare to well-controlled warfarin (n = 6,022) used according to the EU label. Cox proportional hazards modeling with the treatment group was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).


“EU label simulated dabigatran treatment” was associated with significant reductions in stroke and systemic embolism (HR, 0.74; 95% CI, 0.60-0.91), hemorrhagic stroke (HR, 0.22; 95% CI, 0.11-0.44), death (HR, 0.86; 95% CI, 0.75-0.98), and vascular death (HR, 0.80; 95% CI, 0.68-0.95) compared to warfarin. Dabigatran was also associated with less major bleeding (HR, 0.85; 95% CI, 0.73-0.98), life-threatening bleeding (HR, 0.72; 95% CI, 0.58-0.91), intracranial hemorrhage (HR, 0.28; 95% CI, 0.17-0.45), and “any bleeds” (HR, 0.86; 95% CI, 0.81-0.92), but not gastrointestinal major bleeding (HR, 1.23; 95% CI, 0.96-1.59). The net clinical benefit was significantly better for dabigatran compared to warfarin.


The authors concluded that “EU label simulated dabigatran treatment” may be associated with superior efficacy and safety compared to warfarin, and are in support of the EU label and the 2012 European Society of Cardiology (ESC) atrial fibrillation guideline recommendations.


This post-hoc analysis of the RE-LY trial shows that EU label simulated dabigatran treatment was associated with significant reductions in stroke and systemic embolism, hemorrhagic stroke, death, and vascular death compared to warfarin for stroke prevention in AF. Dabigatran was also associated with less major bleeding, life-threatening bleeding, intracranial hemorrhage, and ‘any bleeding,’ but not gastrointestinal major bleeding. These results are in support of the EU label and the published 2012 ESC AF guideline recommendations. Thus, adherence to EU label/guideline use may result in a meaningful and clinically relevant benefit for dabigatran over warfarin, for both efficacy and safety.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Novel Agents

Keywords: International Normalized Ratio, Stroke, Intracranial Hemorrhages, beta-Alanine, Benzimidazoles, Warfarin, Atrial Fibrillation, Embolism, Hemorrhage

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