NOACs show no significant difference in bleeding complications vs warfarin
A 2013 meta-analysis of 5 RCTs including 51,895 patients with nonvalvular atrial fibrillation compared the efficacy and safety of the NOACs dabigatran, rivaroxaban, apixaban, and ximelagatran, with the efficacy and safety of warfarin.2 This review included the 3 studies of dabigatran, rivaroxaban, and apixaban from the previously described review, as well as 2 trials of ximelagatran that were not included in the other review (presumably because ximelagatran was no longer available owing to liver toxicity). This review didn’t include the study of edoxaban that was published after the search dates of the literature review.
All trials were designed to show noninferiority. Selection criteria included a study population of at least 3000 patients and use of intention-to-treat analysis. Only 3 of the trials were double-blinded, and 2 were open-label. Mean follow-up was 16 months; median was 24 months.
NOACs were noninferior to vitamin K antagonists in the rate of stroke or systemic embolism (RR=0.82; 95% CI, 0.69-0.98; NNT=200), the rate of death from any cause (RR=0.91; 95% CI, 0.85-0.96; NNT=145), and the rate of hemorrhagic strokes (RR=0.51; 95% CI, 0.41-0.64). NOACs showed no significant difference in major bleeding compared with warfarin (RR=0.83; 95% CI, 0.69-1.0), and were noninferior for minor bleeding (RR=0.88; 95% CI, 0.80-0.97). There was no difference in ischemic stroke (RR=0.87; 95% CI, 0.75-1.06) and major noncerebral bleeding (RR=0.88; 95% CI, 0.73-1.08).
The ACCP weighs in
The American College of Chest Physicians’ 2012 clinical practice guidelines for antithrombotic therapy for atrial fibrillation recommend dabigatran 150 mg twice daily rather than adjusted-dose warfarin therapy for patients with nonvalvular atrial fibrillation requiring thromboembolism prophylaxis (Grade 2B, weak recommendation based on RCTs with important limitations).3