Efficacy and Safety of the Novel Oral Anticoagulants in Atrial Fibrillation: A Systematic Review and Meta-Analysis of the Literature
Background—Novel oral anticoagulants (NOACs) have been proposed as alternatives to vitamin K antagonists (VKAs) for prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). Individually, NOACs were at least non-inferior to VKAs, but a clear superiority in overall and vascular mortality was not consistently proven.
Methods and Results—We performed a meta-analysis of phase-II and phase-III randomized controlled trials comparing NOACs with VKAs in patients with AF. MEDLINE and EMBASE databases, supplemented with conferences abstract books and www.clinicaltrial.gov, were searched up to July 2012 week 1, without any language restriction. Two reviewers performed independent article review and study quality assessment. Data regarding overall and cardiovascular mortality, stroke or SE, ischemic stroke, major and intracranial bleeding, and myocardial infarction was collected. NOACs were pooled to perform a comparison with VKAs, calculating pooled relative risks (RR) and associated 95%CIs. We retrieved 12 studies (3 administering dabigatran, 4 rivaroxaban, 2 apixaban and 3 edoxaban), enrolling a total of 54875 patients. NOACs significantly reduced total mortality (5.61% vs 6.02%; RR 0.89; 95%CI, 0.83-0.96), cardiovascular mortality (3.45% vs 3.65%; RR 0.89; 95%CI, 0.82-0.98) and stroke/SE (2.40% vs 3.13%; RR 0.77; 95%CI, 0.70-0.86). There was a trend towards reduced major bleeding (RR 0.86; 95%CI, 0.72-1.02), with a significant reduction of intracranial hemorrhage (RR 0.46; 95%CI, 0.39-0.56). No difference in myocardial infarction was observed.
Conclusions—NOACs are associated with an overall clinical benefit compared with VKAs. Additional research is required to confirm these findings outside the context of randomized trials.
- Received April 30, 2012.
- Accepted September 14, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited