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Circulation. 2012 Nov 13;126(20):2381-91. doi: 10.1161/CIRCULATIONAHA.112.115410. Epub 2012 Oct 15.

Efficacy and safety of the novel oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of the literature.

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Department of Clinical and Experimental Medicine, Insubria University, Varese, Italy.



Novel oral anticoagulants (NOACs) have been proposed as alternatives to vitamin K antagonists for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Individually, NOACs were at least noninferior to vitamin K antagonists, but a clear superiority in overall and vascular mortality was not consistently proven.


We performed a meta-analysis of phase II and phase III randomized, controlled trials comparing NOACs with vitamin K antagonists in patients with atrial fibrillation. The MEDLINE and EMBASE databases, supplemented with conference abstract books and, were searched up to the first week of July 2012 with no language restriction. Two reviewers performed independent article review and study quality assessment. Data on overall and cardiovascular mortality, stroke or systemic embolism, ischemic stroke, major and intracranial bleeding, and myocardial infarction were collected. NOACs were pooled to perform a comparison with vitamin K antagonists, calculating pooled relative risks (RRs) and associated 95% confidence intervals (CIs). We retrieved 12 studies (3 administering dabigatran, 4 administering rivaroxaban, 2 administering apixaban, and 3 administering edoxaban) enrolling a total of 54 875 patients. NOACs significantly reduced total mortality (5.61% versus 6.02%; RR, 0.89; 95% CI, 0.83-0.96), cardiovascular mortality (3.45% versus 3.65%; RR, 0.89; 95% CI, 0.82-0.98), and stroke/systemic embolism (2.40% versus 3.13%; RR, 0.77; 95% CI, 0.70-0.86). There was a trend toward 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.


NOACs are associated with an overall clinical benefit compared with vitamin K antagonists. Additional research is required to confirm these findings outside the context of randomized trials.

[Indexed for MEDLINE]

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