Dabigatran Versus Warfarin for Atrial Fibrillation in Real-World Clinical Practice

Atrial fibrillation (AF) is associated with a 5-fold increase in the risk of stroke. For more than a half century, the vitamin K antagonist warfarin has been used for stroke prevention in patients with nonvalvular AF (NVAF). The safe use of warfarin requires frequent blood testing and dose adjustments to maintain therapeutic anticoagulation and prevent bleeding events, as well as dietary and other lifestyle restrictions. In 2010, the first novel oral anticoagulant (NOAC), dabigatran, a direct thrombin inhibitor, became available for the treatment of NVAF. Dabigatran challenged the mainstay of treatment, as use of this agent is a more convenient treatment option, which does not require frequent blood testing or lifestyle restrictions. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) was a large-scale multicenter randomized clinical trial (RCT), evaluating 2 fixed doses of dabigatran (110 mg or 150 mg, twice daily) versus adjusteddose warfarin for >2 years. The study was conducted in 44 countries and included 18 113 patients with NVAF. The trial showed that dabigatran-150 mg was superior to warfarin in preventing ischemic stroke, and had a lower rate of intracranial bleeding, but a higher rate of gastrointestinal bleeding. Dabigatran-110 mg was noninferior to warfarin in preventing ischemic stroke and had a similar rate of gastrointestinal bleeding, but a lower rate of intracranial bleeding. On the basis of the findings from this trial, dabigatran-110 mg and dabigatran-150 mg both became available for the treatment of NVAF in most countries, except in the United States, where the 150 mg, but not the 110 mg, dose was approved. RCTs provide the strongest evidence for drug safety and efficacy. The synthesis of data from multiple and similarly designed RCTs, for a given drug and particular condition, is an important tool in comparative effectiveness research. Such techniques add to the extant body of knowledge by overcoming some of the limitations of individual trials, namely by increasing sample size and improving the precision of effect estimates. Moreover, these techniques allow for the evaluation Background—Trial data for the benefits and risks of dabigatran versus warfarin in the treatment of nonvalvular atrial fibrillation are lacking. We sought to review real-world observational evidence for the comparative effectiveness and safety of these agents. Methods and Results—A systematic search of multiple databases was conducted from first available date to March 10, 2015 for longitudinal, observational studies comparing dabigatran with warfarin. Two reviewers evaluated studies for eligibility and extracted hazard ratios for ischemic stroke and gastrointestinal and intracranial bleeding. hazard ratios were pooled using random-effects meta-analysis. Metaregression was performed to assess treatment-effect heterogeneity. We identified 232 unique citations. Seven retrospective cohort studies met study eligibility criteria, with 348 750 patients and a mean follow-up of 2.2 years. In pooled analyses, dabigatran-150 mg was not superior to warfarin in preventing stroke (hazard ratio, 0.92; 95% confidence interval, 0.84–1.01; P=0.066), but had a significantly lower hazard of intracranial bleeding (0.44; 0.34–0.59; P<0.001). Dabigatran-150 mg had a significantly greater hazard of gastrointestinal bleeding than warfarin (1.23; 1.01–1.50; P=0.041), which was potentiated in studies of older (elderly) versus younger populations (median/mean age, ≥75 versus <75 years; β=1.53; 95% confidence interval, 1.10–2.14; P=0.020). Conclusions—In real-world clinical practice, dabigatran is comparable with warfarin in preventing ischemic stroke among patients with nonvalvular atrial fibrillation. However, dabigatran is associated with a lower risk for intracranial bleeding relative to warfarin, but—particularly among the elderly—a greater risk for gastrointestinal bleeding. Bleeding outcomes from observational studies are consistent with those from the pivotal Randomized Evaluation of Long-Term Anticoagulation Therapy trial. (Circ Cardiovasc Qual Outcomes. 2016;9:126-134. DOI: 10.1161/CIRCOUTCOMES.115.002369.)