Journal Article

Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis

Bryden, Peter A, Thom, Howard H Z, Sofat, Reecha, López-López, José A, Sterne, Jonathan A C, Bodalia, Pritesh N, Welton, Nicky J, Hollingworth, William, Stephens-Boal, Annya, Dias, Sofia, Eaton, Diane, Higgins, Julian P T, Hingorani, Aroon D, Caldwell, Deborah M, Savović, Jelena, Salisbury, Chris, Davies, Philippa A, Okoli, George N

2017

Overview

AbstractObjectiveTo compare the efficacy, safety, and cost effectiveness of direct acting oral anticoagulants (DOACs) for patients with atrial fibrillation.DesignSystematic review, network meta-analysis, and cost effectiveness analysis.Data sourcesMedline, PreMedline, Embase, and The Cochrane Library.Eligibility criteria for selecting studiesPublished randomised trials evaluating the use of a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in patients with atrial fibrillation.Results23 randomised trials involving 94 656 patients were analysed: 13 compared a DOAC with warfarin dosed to achieve a target INR of 2.0-3.0. Apixaban 5 mg twice daily (odds ratio 0.79, 95% confidence interval 0.66 to 0.94), dabigatran 150 mg twice daily (0.65, 0.52 to 0.81), edoxaban 60 mg once daily (0.86, 0.74 to 1.01), and rivaroxaban 20 mg once daily (0.88, 0.74 to 1.03) reduced the risk of stroke or systemic embolism compared with warfarin. The risk of stroke or systemic embolism was higher with edoxaban 60 mg once daily (1.33, 1.02 to 1.75) and rivaroxaban 20 mg once daily (1.35, 1.03 to 1.78) than with dabigatran 150 mg twice daily. The risk of all-cause mortality was lower with all DOACs than with warfarin. Apixaban 5 mg twice daily (0.71, 0.61 to 0.81), dabigatran 110 mg twice daily (0.80, 0.69 to 0.93), edoxaban 30 mg once daily (0.46, 0.40 to 0.54), and edoxaban 60 mg once daily (0.78, 0.69 to 0.90) reduced the risk of major bleeding compared with warfarin. The risk of major bleeding was higher with dabigatran 150 mg twice daily than apixaban 5 mg twice daily (1.33, 1.09 to 1.62), rivaroxaban 20 mg twice daily than apixaban 5 mg twice daily (1.45, 1.19 to 1.78), and rivaroxaban 20 mg twice daily than edoxaban 60 mg once daily (1.31, 1.07 to 1.59). The risk of intracranial bleeding was substantially lower for most DOACs compared with warfarin, whereas the risk of gastrointestinal bleeding was higher with some DOACs than warfarin. Apixaban 5 mg twice daily was ranked the highest for most outcomes, and was cost effective compared with warfarin.ConclusionsThe network meta-analysis informs the choice of DOACs for prevention of stroke in patients with atrial fibrillation. Several DOACs are of net benefit compared with warfarin. A trial directly comparing DOACs would overcome the need for indirect comparisons to be made through network meta-analysis.Systematic review registrationPROSPERO CRD 42013005324.

• Publisher: British Medical Journal Publishing Group,BMJ Publishing Group LTD,BMJ Publishing Group Ltd
• Subject: Administration, Oral / Anticoagulants / Anticoagulants - administration & dosage / Anticoagulants - adverse effects / Anticoagulants - economics / Anticoagulants - therapeutic use / Antiplatelet therapy / Atrial Fibrillation - complications / Atrial Fibrillation - drug therapy / Atrial Fibrillation - economics / Bleeding / Cardiac arrhythmia / Clinical trials / Cost-Benefit Analysis / Data processing / Drug Costs - statistics & numerical data / Embolism / Evidence-based medicine / Fibrillation / Hemorrhage - chemically induced / Humans / Meta-analysis / Quality-Adjusted Life Years / Randomized Controlled Trials as Topic / Stroke / Stroke - economics / Stroke - etiology / Stroke - prevention & control / Systematic review / Vitamin K / Warfarin