Dabigatran is a univalent low-molecular-weight direct thrombin inhibitor that has been developed as an alternative to vitamin K antagonists (VKAs). However, uncertainty remains regarding dabigatran's safety profile with respect to bleeding. Our objective was to compare the risk of bleeding and all-cause mortality of dabigatran with that of VKAs in a systematic review and meta-analysis of randomized controlled trials (RCTs). We systematically searched MEDLINE, Embase, and the Cochrane Library of clinical trials to identify RCTs comparing the bleeding risk of dabigatran (150 mg twice daily) with that of VKAs. Included RCTs had treatment duration ≥90 days and were published in English or French. Data were meta-analyzed using random-effects models. Five RCTs (n = 20,332) were included in our systematic review. Study populations consisted of patients with atrial fibrillation (n = 18,615) and venous thromboembolism (n = 7,998). When data were pooled across the 4 RCTs (n = 17,466) without overlapping populations, dabigatran was not associated with an increased risk of major bleeding compared with VKAs (relative risk [RR] 0.92, 95% confidence interval [CI] 0.81 to 1.05). Dabigatran was associated with a decreased risk of intracranial bleeding (RR 0.40, 95% CI 0.27 to 0.59) but an increased risk of gastrointestinal bleeding (RR 1.51, 95% CI 1.23 to 1.84). Dabigatran was also associated with a trend toward decreased all-cause mortality (RR 0.90, 95% CI 0.80 to 1.01). In conclusion, results suggest that dabigatran has a favorable safety profile with respect to bleeding compared with VKAs.
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