Clinical question: Is there a difference in efficacy and safety among new oral anticoagulants compared to warfarin in subgroups of patients with atrial fibrillation (Afib)?
Background: Studies of new oral anticoagulants have demonstrated that these agents are at least as safe and effective as warfarin for prevention of stroke and systemic embolism in Afib. This study was designed to look at available phase 3 randomized trials, with the goal of subgroup analysis for both efficacy and bleeding risks.
Study design: Meta-analysis.
Setting: Phase 3 randomized controlled trials of patients with Afib.
Synopsis: The analysis included four trials of Afib patients randomized to receive warfarin or a novel oral anticoagulant (NOAC), including dabigatran, rivaroxaban, apixaban, and edoxaban. In total, 42,411 patients received an NOAC and 29,272 patients received warfarin. Separate analyses were performed for high-dose and low-dose NOACs.
The high-dose NOAC demonstrated a 19% reduction in stroke and systemic embolic events as compared to warfarin, largely due to the reduction of hemorrhagic strokes by the NOAC. The low-dose NOAC showed similar efficacy to warfarin for reduction of stroke and systemic embolic events, with an increase noted in the subset of ischemic stroke in low-dose NOAC. Both doses of NOAC demonstrated a significant reduction in all-cause mortality. NOAC showed a non-significant reduction in bleeding compared to warfarin; however, subset analysis demonstrated an increase in gastrointestinal bleeding with high-dose NOAC and a significant reduction in intracranial hemorrhage with low-dose NOAC.
A notable limitation of the study is that it only included clinical trials in the analysis.
Bottom line: In relation to stroke, systemic embolic events, and all-cause mortality, new oral anticoagulants showed a favorable efficacy and safety profile as compared to warfarin in Afib patients.
Citation: Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962.