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

López-López, JA; Sterne, JAC; Thom, HHZ; Higgins, JPT; Hingorani, AD; Okoli, GN; Davies, PA; ... Sofat, R; + view all (2017) Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ - British Medical Journal , 359 , Article j5058. 10.1136/bmj.j5058. Green open access

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Abstract

Objective: To compare the efficacy, safety, and cost effectiveness of direct acting oral anticoagulants (DOACs) for patients with atrial fibrillation. // Design: Systematic review, network meta-analysis, and cost effectiveness analysis. // Data sources: Medline, PreMedline, Embase, and The Cochrane Library. // Eligibility criteria for selecting studies: Published randomised trials evaluating the use of a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in patients with atrial fibrillation. // Results: 23 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. // Conclusions: The 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 registration: PROSPERO CRD 42013005324.

Type: Article
Title: Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/bmj.j5058
Publisher version: http://dx.doi.org/10.1136/bmj.j5058
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: https://discovery.ucl.ac.uk/id/eprint/10039500
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