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

Study Questions:

Are the new oral anticoagulants more effective or safer than warfarin in patients with atrial fibrillation (AF)?

Methods:

This was a meta-analysis of three randomized clinical trials that compared warfarin to dabigatran (150 mg twice daily), rivaroxaban (20 mg/day), or apixaban (5 mg twice daily) in a total of 44,563 patients (mean age 70-73 years) with nonvalvular AF.

Results:

Dabigatran and apixaban significantly reduced the risk of stroke (including hemorrhagic) and systemic embolism compared to warfarin by 34% and 20%, respectively, whereas rivaroxaban was noninferior to warfarin in regards to this efficacy endpoint. In a pooled analysis, the new anticoagulants reduced the risk of stroke/systemic embolism by 22%. The risk of major bleeding was 30% lower with apixaban than warfarin, whereas dabigatran and rivaroxaban were noninferior to warfarin in regards to this safety endpoint. The risk of intracranial bleeding was reduced by 59%, 34%, and 58% by dabigatran, rivaroxaban, and apixaban, respectively. The risk of gastrointestinal bleeding was increased by 50% and 46% compared to warfarin by dabigatran and rivaroxaban, respectively, whereas the risk of gastrointestinal bleeding did not differ significantly between apixaban and warfarin.

Conclusions:

The authors concluded that dabigatran, rivaroxaban, and apixaban are more effective than warfarin for preventing strokes in patients with nonvalvular AF, and have a favorable safety profile.

Perspective:

Dabigatran, a direct thrombin inhibitor, binds to thrombin and blocks its capacity to convert fibrinogen to fibrin. Rivaroxaban and apixaban are direct factor Xa inhibitors. Based on the available evidence, it appears that among these three new anticoagulants, apixaban has the most favorable risk:benefit ratio compared to warfarin.

Keywords: Stroke


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