Bleeding of new oral anticoagulants for stroke prevention in atrial fibrillation: a meta-analysis of randomized controlled trials.

ABSTRACT

PURPOSE: Oral direct factor Xa inhibitors and oral direct thrombin inhibitors are new oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). We systematically reviewed their risk of major bleeding and efficacy in thromboembolism reduction in AF. METHODS: Eligible randomized controlled trials evaluating NOACs for stroke prevention in AF patients were identified from a systematic search of MEDLINE, EMBASE and the Cochrane database. Risk ratios (RRs) and 95 % confidence intervals (CIs) were calculated using a Mantel-Haenzel random-effects model. RESULTS: A total of 13 studies (n = 61,406) were included. Oral direct factor Xa inhibitors were more effective in reducing stroke and systemic embolism compared to controls (RR 0.71, 95 % CI 0.54-0.92, P = 0.009) or vitamin K antagonists (VKAs) (RR 0.84, 95 % CI 0.74-0.94, P = 0.002), with no significant difference in major and clinically relevant non-major (CRNM) bleeding (against controls RR 0.94, 95 % CI 0.75-1.18, P = 0.60; against VKAs RR 0.90, 95 % 0.69-1.17, P = 0.44). Oral direct thrombin inhibitors were associated with an improved major and CRNM bleeding profile (both comparisons RR 0.88, 95 % CI 0.78-0.98, P = 0.02) and a significant reduction in stroke and systemic embolism (against controls RR 0.79, 95 % CI 0.66-0.93, P = 0.006; against VKAs RR 0.78, 95 % CI 0.66-0.93, P = 0.006). CONCLUSIONS: Oral direct factor Xa inhibitors and oral direct thrombin inhibitors are more effective in reducing stroke and systemic embolism without increasing the risk of major bleeding compared to traditional oral anticoagulants. This favorable risk-benefit balance should be further confirmed by long-term, large-scale safety studies.