Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care

Objective: To investigate the associations between direct oral anticoagulants (DOACs) and risks of bleeding, ischaemic stroke, venous thromboembolism, and all cause mortality compared with warfarin. Design: Prospective open cohort study. Setting: UK general practices contributing to QResearch...

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Main Authors: Vinogradova, Yana, Coupland, Carol, Hill, Trevor, Hippisley-Cox, Julia
Format: Article
Published: BMJ Publishing Group 2018
Subjects:
Online Access:https://eprints.nottingham.ac.uk/52928/
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author Vinogradova, Yana
Coupland, Carol
Hill, Trevor
Hippisley-Cox, Julia
author_facet Vinogradova, Yana
Coupland, Carol
Hill, Trevor
Hippisley-Cox, Julia
author_sort Vinogradova, Yana
building Nottingham Research Data Repository
collection Online Access
description Objective: To investigate the associations between direct oral anticoagulants (DOACs) and risks of bleeding, ischaemic stroke, venous thromboembolism, and all cause mortality compared with warfarin. Design: Prospective open cohort study. Setting: UK general practices contributing to QResearch or Clinical Practice Research Datalink. Participants: 132 231 warfarin, 7744 dabigatran, 37 863 rivaroxaban, and 18 223 apixaban users without anticoagulant prescriptions for 12 months before study entry, subgrouped into 103 270 patients with atrial fibrillation and 92 791 without atrial fibrillation between 2011 and 2016. Main outcome measures: Major bleeding leading to hospital admission or death. Specific sites of bleeding and all cause mortality were also studied. Results: In patients with atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (adjusted hazard ratio 0.66, 95% confidence interval 0.54 to 0.79) and intracranial bleeding (0.40, 0.25 to 0.64); dabigatran was associated with a decreased risk of intracranial bleeding (0.45, 0.26 to 0.77). An increased risk of all cause mortality was observed in patients taking rivaroxaban (1.19, 1.09 to 1.29) or on lower doses of apixaban (1.27, 1.12 to 1.45). In patients without atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (0.60, 0.46 to 0.79), any gastrointestinal bleeding (0.55, 0.37 to 0.83), and upper gastrointestinal bleeding (0.55, 0.36 to 0.83); rivaroxaban was associated with a decreased risk of intracranial bleeding (0.54, 0.35 to 0.82). Increased risk of all cause mortality was observed in patients taking rivaroxaban (1.51, 1.38 to 1.66) and those on lower doses of apixaban (1.34, 1.13 to 1.58). Conclusions: Overall, apixaban was found to be the safest drug, with reduced risks of major, intracranial, and gastrointestinal bleeding compared with warfarin. Rivaroxaban and low dose apixaban were, however, associated with increased risks of all cause mortality compared with warfarin.
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spelling nottingham-529282020-05-04T19:45:17Z https://eprints.nottingham.ac.uk/52928/ Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care Vinogradova, Yana Coupland, Carol Hill, Trevor Hippisley-Cox, Julia Objective: To investigate the associations between direct oral anticoagulants (DOACs) and risks of bleeding, ischaemic stroke, venous thromboembolism, and all cause mortality compared with warfarin. Design: Prospective open cohort study. Setting: UK general practices contributing to QResearch or Clinical Practice Research Datalink. Participants: 132 231 warfarin, 7744 dabigatran, 37 863 rivaroxaban, and 18 223 apixaban users without anticoagulant prescriptions for 12 months before study entry, subgrouped into 103 270 patients with atrial fibrillation and 92 791 without atrial fibrillation between 2011 and 2016. Main outcome measures: Major bleeding leading to hospital admission or death. Specific sites of bleeding and all cause mortality were also studied. Results: In patients with atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (adjusted hazard ratio 0.66, 95% confidence interval 0.54 to 0.79) and intracranial bleeding (0.40, 0.25 to 0.64); dabigatran was associated with a decreased risk of intracranial bleeding (0.45, 0.26 to 0.77). An increased risk of all cause mortality was observed in patients taking rivaroxaban (1.19, 1.09 to 1.29) or on lower doses of apixaban (1.27, 1.12 to 1.45). In patients without atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (0.60, 0.46 to 0.79), any gastrointestinal bleeding (0.55, 0.37 to 0.83), and upper gastrointestinal bleeding (0.55, 0.36 to 0.83); rivaroxaban was associated with a decreased risk of intracranial bleeding (0.54, 0.35 to 0.82). Increased risk of all cause mortality was observed in patients taking rivaroxaban (1.51, 1.38 to 1.66) and those on lower doses of apixaban (1.34, 1.13 to 1.58). Conclusions: Overall, apixaban was found to be the safest drug, with reduced risks of major, intracranial, and gastrointestinal bleeding compared with warfarin. Rivaroxaban and low dose apixaban were, however, associated with increased risks of all cause mortality compared with warfarin. BMJ Publishing Group 2018-07-04 Article PeerReviewed Vinogradova, Yana, Coupland, Carol, Hill, Trevor and Hippisley-Cox, Julia (2018) Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care. BMJ, 362 . k2505/1-k2505/16. ISSN 1756-1833 Direct oral anticoagulants; DOACS; Warfarin; Primary Care; Bleeding; risks of bleeding; Ischaemic stroke; Venous thromboembolism; All cause mortality https://www.bmj.com/content/362/bmj.k2505 doi:10.1136/bmj.k2505 doi:10.1136/bmj.k2505
spellingShingle Direct oral anticoagulants; DOACS; Warfarin; Primary Care; Bleeding; risks of bleeding; Ischaemic stroke; Venous thromboembolism; All cause mortality
Vinogradova, Yana
Coupland, Carol
Hill, Trevor
Hippisley-Cox, Julia
Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care
title Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care
title_full Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care
title_fullStr Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care
title_full_unstemmed Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care
title_short Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care
title_sort risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care
topic Direct oral anticoagulants; DOACS; Warfarin; Primary Care; Bleeding; risks of bleeding; Ischaemic stroke; Venous thromboembolism; All cause mortality
url https://eprints.nottingham.ac.uk/52928/
https://eprints.nottingham.ac.uk/52928/
https://eprints.nottingham.ac.uk/52928/