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

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 Librar...

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Autores principales: López-López, José A, Sterne, Jonathan A C, Thom, Howard H Z, Higgins, Julian P T, Hingorani, Aroon D, Okoli, George N, Davies, Philippa A, Bodalia, Pritesh N, Bryden, Peter A, Welton, Nicky J, Hollingworth, William, Caldwell, Deborah M, Savović, Jelena, Dias, Sofia, Salisbury, Chris, Eaton, Diane, Stephens-Boal, Annya, Sofat, Reecha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704695/
https://www.ncbi.nlm.nih.gov/pubmed/29183961
http://dx.doi.org/10.1136/bmj.j5058
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author López-López, José A
Sterne, Jonathan A C
Thom, Howard H Z
Higgins, Julian P T
Hingorani, Aroon D
Okoli, George N
Davies, Philippa A
Bodalia, Pritesh N
Bryden, Peter A
Welton, Nicky J
Hollingworth, William
Caldwell, Deborah M
Savović, Jelena
Dias, Sofia
Salisbury, Chris
Eaton, Diane
Stephens-Boal, Annya
Sofat, Reecha
author_facet López-López, José A
Sterne, Jonathan A C
Thom, Howard H Z
Higgins, Julian P T
Hingorani, Aroon D
Okoli, George N
Davies, Philippa A
Bodalia, Pritesh N
Bryden, Peter A
Welton, Nicky J
Hollingworth, William
Caldwell, Deborah M
Savović, Jelena
Dias, Sofia
Salisbury, Chris
Eaton, Diane
Stephens-Boal, Annya
Sofat, Reecha
author_sort López-López, José A
collection PubMed
description 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.
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spelling pubmed-57046952017-12-06 Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis López-López, José A Sterne, Jonathan A C Thom, Howard H Z Higgins, Julian P T Hingorani, Aroon D Okoli, George N Davies, Philippa A Bodalia, Pritesh N Bryden, Peter A Welton, Nicky J Hollingworth, William Caldwell, Deborah M Savović, Jelena Dias, Sofia Salisbury, Chris Eaton, Diane Stephens-Boal, Annya Sofat, Reecha BMJ Research 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. BMJ Publishing Group Ltd. 2017-11-28 /pmc/articles/PMC5704695/ /pubmed/29183961 http://dx.doi.org/10.1136/bmj.j5058 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research
López-López, José A
Sterne, Jonathan A C
Thom, Howard H Z
Higgins, Julian P T
Hingorani, Aroon D
Okoli, George N
Davies, Philippa A
Bodalia, Pritesh N
Bryden, Peter A
Welton, Nicky J
Hollingworth, William
Caldwell, Deborah M
Savović, Jelena
Dias, Sofia
Salisbury, Chris
Eaton, Diane
Stephens-Boal, Annya
Sofat, Reecha
Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
title Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
title_full Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
title_fullStr Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
title_full_unstemmed Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
title_short Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
title_sort oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704695/
https://www.ncbi.nlm.nih.gov/pubmed/29183961
http://dx.doi.org/10.1136/bmj.j5058
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