In an indirect comparison of patients with AF and CHADS2 score ≥3, dabigatran, apixaban, and rivaroxaban had similar rates of stroke/systemic embolism, but apixaban had fewer major hemorrhages.
Meta-Analysis (n=44,535)
Do new oral anticoagulants (dabigatran, apixaban, rivaroxaban) differ in efficacy and safety for stroke prevention in patients with atrial fibrillation?
Adjusted indirect comparisons suggest apixaban may have a lower risk of major hemorrhage compared to dabigatran and rivaroxaban in AF patients with CHADS2 ≥3, with similar efficacy.
BACKGROUND: Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons. METHODS AND RESULTS: We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy RELY), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation ARISTOTLE), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ROCKET-AF), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score ≥3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban. CONCLUSIONS: An indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score ≥3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.
Schneeweiß et al. (2012) conducted a meta-analysis in Atrial Fibrillation (n=44,535). Dabigatran, apixaban, and rivaroxaban vs. Warfarin (indirectly compared to each other) was evaluated on Stroke or systemic embolism. In an indirect comparison of patients with AF and CHADS2 score ≥3, dabigatran, apixaban, and rivaroxaban had similar rates of stroke/systemic embolism, but apixaban had fewer major hemorrhages.