Review
Meta-Analysis of Efficacy and Safety of New Oral Anticoagulants (Dabigatran, Rivaroxaban, Apixaban) Versus Warfarin in Patients With Atrial Fibrillation

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New oral anticoagulants, including apixaban, dabigatran, and rivaroxaban, have been developed as alternatives to warfarin, the standard oral anticoagulation therapy for patients with atrial fibrillation (AF). A systematic review and meta-analysis of randomized controlled trials was performed to compare the efficacy and safety of new oral anticoagulants to those of warfarin in patients with AF. The published research was systematically searched for randomized controlled trials of >1 year in duration that compared new oral anticoagulants to warfarin in patients with AF. Random-effects models were used to pool efficacy and safety data across randomized controlled trials. Three studies, including 44,563 patients, were identified. Patients randomized to new oral anticoagulants had a decreased risk for all-cause stroke and systemic embolism (relative risk [RR] 0.78, 95% confidence interval [CI] 0.67 to 0.92), ischemic and unidentified stroke (RR 0.87, 95% CI 0.77 to 0.99), hemorrhagic stroke (RR 0.45, 95% CI 0.31 to 0.68), all-cause mortality (RR 0.88, 95% CI 0.82 to 0.95), and vascular mortality (RR 0.87, 95% CI 0.77 to 0.98). Randomization to a new oral anticoagulant was associated with a lower risk for intracranial bleeding (RR 0.49, 95% CI 0.36 to 0.66). Data regarding the risks for major bleeding (RR 0.88, 95% CI 0.71 to 1.09) and gastrointestinal bleeding (RR 1.25, 95% CI 0.91 to 1.72) were inconclusive. In conclusion, the new oral anticoagulants are more efficacious than warfarin for the prevention of stroke and systemic embolism in patients with AF. With a decreased risk for intracranial bleeding, they appear to have a favorable safety profile, making them promising alternatives to warfarin.

Section snippets

Methods

We systematically searched the published medical research for RCTs comparing new oral anticoagulants to warfarin in patients with AF. The Cochrane Library, Embase, MEDLINE, Science Citation Index Expanded, and ProQuest's Dissertations and Theses databases were searched from inception through July 2011 without language restriction. The following were used as Medical Subject Heading terms and/or keywords: “new oral anticoagulants,” “oral thrombin inhibitors,” “oral factor Xa inhibitors,”

Results

Our electronic search identified a total of 3,167 reports (Figure 1). After removing duplicates, we screened titles and abstracts, and the full text of 44 publications was retrieved and evaluated for eligibility. Three trials that met our inclusion criteria were identified and included in the present study. One trial was published as an original report3 with a follow-up report providing additional data.9 The other 2 trials were presented as ClinicalTrials.gov entries and were subsequently

Discussion

Our study was designed to compare the efficacy and safety of new oral anticoagulants to that of warfarin in patients with AF. Our systematic search identified 3 trials, evaluating the new oral anticoagulants apixaban,2 dabigatran,3 and rivaroxaban.4 In our meta-analysis, we found that the new oral anticoagulants reduced the risk for a composite end point of stroke and systemic embolism compared to warfarin. New oral anticoagulants were also found to be associated with a lower risk for key

Acknowledgment

We would like to thank Tara Dourian (Jewish General Hospital/McGill University) for her help with data extraction.

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    Mr. Miller is supported by the Ivan Racheff and Clarke McLeod Scholarships funded through the McGill University Research Bursary Program. Dr. Shimony is supported by the Azrieli Fellowship Fund for research at the Jewish General Hospital, Montreal, Quebec, Canada. Dr. Eisenberg is a Chercheur-National of the Fonds de la Recherche en Santé du Quebec.

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