Risk of mortality between warfarin and direct oral anticoagulants: population-based cohort studies

Zixuan Wang; Julian Matthewman; John Tazare; Qiuyan Yu; Ka Shing Cheung; Celine S. L. Chui; Esther W. Y. Chan; Krishnan Bhaskaran; Liam Smeeth; Ian C. K. Wong; Ian J. Douglas; Angel Y. S. Wong

doi:10.1186/s12916-024-03808-y

Risk of mortality between warfarin and direct oral anticoagulants: population-based cohort studies

Zixuan Wang^*, Julian Matthewman, John Tazare, Qiuyan Yu, Ka Shing Cheung, Celine S. L. Chui, Esther W. Y. Chan, Krishnan Bhaskaran, Liam Smeeth, Ian C. K. Wong, Ian J. Douglas, Angel Y. S. Wong

^*Corresponding author for this work

Aston Pharmacy School

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Direct oral anticoagulants (DOACs) have been reported to be associated with a higher risk of mortality compared with an older alternative, warfarin using primary care data in the United Kingdom (UK). However, other studies observed contradictory findings. We therefore aimed to investigate the association between mortality and warfarin, compared with DOACs. Methods: We conducted cohort studies using UK Clinical Practice Research Datalink (CPRD) Aurum and Hong Kong Clinical Data Analysis and Reporting System (CDARS) to identify the association between warfarin and hazard of mortality, compared to DOACs. Individuals with non-valvular atrial fibrillation aged ≥ 18 years who had first anticoagulant therapy (warfarin or DOAC) during 1/1/2011–31/12/2019 were included. Results: Compared with DOAC use, a lower hazard of all-cause mortality was found in warfarin users (hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.77–0.86) in CPRD; while a higher hazard was observed in warfarin users (HR = 1.31, 95% CI = 1.24–1.39) in CDARS, versus DOAC users. In our exploratory analysis, consistent results were seen in both databases when stratified warfarin users by time in therapeutic range (TTR) using post-baseline measurements: a lower hazard of all-cause mortality in warfarin users with TTR ≥ 65% (CPRD: HR = 0.68, 95% CI = 0.65–0.72; CDARS: HR = 0.86, 95% CI = 0.77–0.96) and increased hazard in warfarin users with TTR < 65% (CPRD: HR = 1.14, 95% CI = 1.05–1.23; CDARS: HR = 1.59, 95% CI = 1.50–1.69), versus DOAC users. Conclusions: The differences in hazard of all-cause mortality associated with warfarin compared with DOAC, in part may depend on anticoagulation control in warfarin users. Notably, this study is unable to establish a causal relationship between warfarin and mortality stratified by TTR, versus DOACs, requiring future studies for further investigation.

Original language	English
Article number	597
Number of pages	12
Journal	BMC Medicine
Volume	22
Issue number	1
Early online date	23 Dec 2024
DOIs	https://doi.org/10.1186/s12916-024-03808-y
Publication status	Published - Dec 2024

Bibliographical note

Copyright © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/

Keywords

Direct anticoagulant
Warfarin
Mortality

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Copyright © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/
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Cite this

@article{5086ee68da7b4fb3b2eaaea333cb32be,

title = "Risk of mortality between warfarin and direct oral anticoagulants: population-based cohort studies",

abstract = "Background: Direct oral anticoagulants (DOACs) have been reported to be associated with a higher risk of mortality compared with an older alternative, warfarin using primary care data in the United Kingdom (UK). However, other studies observed contradictory findings. We therefore aimed to investigate the association between mortality and warfarin, compared with DOACs. Methods: We conducted cohort studies using UK Clinical Practice Research Datalink (CPRD) Aurum and Hong Kong Clinical Data Analysis and Reporting System (CDARS) to identify the association between warfarin and hazard of mortality, compared to DOACs. Individuals with non-valvular atrial fibrillation aged ≥ 18 years who had first anticoagulant therapy (warfarin or DOAC) during 1/1/2011–31/12/2019 were included. Results: Compared with DOAC use, a lower hazard of all-cause mortality was found in warfarin users (hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.77–0.86) in CPRD; while a higher hazard was observed in warfarin users (HR = 1.31, 95% CI = 1.24–1.39) in CDARS, versus DOAC users. In our exploratory analysis, consistent results were seen in both databases when stratified warfarin users by time in therapeutic range (TTR) using post-baseline measurements: a lower hazard of all-cause mortality in warfarin users with TTR ≥ 65% (CPRD: HR = 0.68, 95% CI = 0.65–0.72; CDARS: HR = 0.86, 95% CI = 0.77–0.96) and increased hazard in warfarin users with TTR < 65% (CPRD: HR = 1.14, 95% CI = 1.05–1.23; CDARS: HR = 1.59, 95% CI = 1.50–1.69), versus DOAC users. Conclusions: The differences in hazard of all-cause mortality associated with warfarin compared with DOAC, in part may depend on anticoagulation control in warfarin users. Notably, this study is unable to establish a causal relationship between warfarin and mortality stratified by TTR, versus DOACs, requiring future studies for further investigation.",

keywords = "Direct anticoagulant, Warfarin, Mortality",

author = "Zixuan Wang and Julian Matthewman and John Tazare and Qiuyan Yu and Cheung, {Ka Shing} and Chui, {Celine S. L.} and Chan, {Esther W. Y.} and Krishnan Bhaskaran and Liam Smeeth and Wong, {Ian C. K.} and Douglas, {Ian J.} and Wong, {Angel Y. S.}",

note = "Copyright {\textcopyright} The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article{\textquoteright}s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/",

year = "2024",

month = dec,

doi = "10.1186/s12916-024-03808-y",

language = "English",

volume = "22",

journal = "BMC Medicine",

issn = "1741-7015",

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TY - JOUR

T1 - Risk of mortality between warfarin and direct oral anticoagulants: population-based cohort studies

AU - Wang, Zixuan

AU - Matthewman, Julian

AU - Tazare, John

AU - Yu, Qiuyan

AU - Cheung, Ka Shing

AU - Chui, Celine S. L.

AU - Chan, Esther W. Y.

AU - Bhaskaran, Krishnan

AU - Smeeth, Liam

AU - Wong, Ian C. K.

AU - Douglas, Ian J.

AU - Wong, Angel Y. S.

N1 - Copyright © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/

PY - 2024/12

Y1 - 2024/12

N2 - Background: Direct oral anticoagulants (DOACs) have been reported to be associated with a higher risk of mortality compared with an older alternative, warfarin using primary care data in the United Kingdom (UK). However, other studies observed contradictory findings. We therefore aimed to investigate the association between mortality and warfarin, compared with DOACs. Methods: We conducted cohort studies using UK Clinical Practice Research Datalink (CPRD) Aurum and Hong Kong Clinical Data Analysis and Reporting System (CDARS) to identify the association between warfarin and hazard of mortality, compared to DOACs. Individuals with non-valvular atrial fibrillation aged ≥ 18 years who had first anticoagulant therapy (warfarin or DOAC) during 1/1/2011–31/12/2019 were included. Results: Compared with DOAC use, a lower hazard of all-cause mortality was found in warfarin users (hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.77–0.86) in CPRD; while a higher hazard was observed in warfarin users (HR = 1.31, 95% CI = 1.24–1.39) in CDARS, versus DOAC users. In our exploratory analysis, consistent results were seen in both databases when stratified warfarin users by time in therapeutic range (TTR) using post-baseline measurements: a lower hazard of all-cause mortality in warfarin users with TTR ≥ 65% (CPRD: HR = 0.68, 95% CI = 0.65–0.72; CDARS: HR = 0.86, 95% CI = 0.77–0.96) and increased hazard in warfarin users with TTR < 65% (CPRD: HR = 1.14, 95% CI = 1.05–1.23; CDARS: HR = 1.59, 95% CI = 1.50–1.69), versus DOAC users. Conclusions: The differences in hazard of all-cause mortality associated with warfarin compared with DOAC, in part may depend on anticoagulation control in warfarin users. Notably, this study is unable to establish a causal relationship between warfarin and mortality stratified by TTR, versus DOACs, requiring future studies for further investigation.

AB - Background: Direct oral anticoagulants (DOACs) have been reported to be associated with a higher risk of mortality compared with an older alternative, warfarin using primary care data in the United Kingdom (UK). However, other studies observed contradictory findings. We therefore aimed to investigate the association between mortality and warfarin, compared with DOACs. Methods: We conducted cohort studies using UK Clinical Practice Research Datalink (CPRD) Aurum and Hong Kong Clinical Data Analysis and Reporting System (CDARS) to identify the association between warfarin and hazard of mortality, compared to DOACs. Individuals with non-valvular atrial fibrillation aged ≥ 18 years who had first anticoagulant therapy (warfarin or DOAC) during 1/1/2011–31/12/2019 were included. Results: Compared with DOAC use, a lower hazard of all-cause mortality was found in warfarin users (hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.77–0.86) in CPRD; while a higher hazard was observed in warfarin users (HR = 1.31, 95% CI = 1.24–1.39) in CDARS, versus DOAC users. In our exploratory analysis, consistent results were seen in both databases when stratified warfarin users by time in therapeutic range (TTR) using post-baseline measurements: a lower hazard of all-cause mortality in warfarin users with TTR ≥ 65% (CPRD: HR = 0.68, 95% CI = 0.65–0.72; CDARS: HR = 0.86, 95% CI = 0.77–0.96) and increased hazard in warfarin users with TTR < 65% (CPRD: HR = 1.14, 95% CI = 1.05–1.23; CDARS: HR = 1.59, 95% CI = 1.50–1.69), versus DOAC users. Conclusions: The differences in hazard of all-cause mortality associated with warfarin compared with DOAC, in part may depend on anticoagulation control in warfarin users. Notably, this study is unable to establish a causal relationship between warfarin and mortality stratified by TTR, versus DOACs, requiring future studies for further investigation.

KW - Direct anticoagulant

KW - Warfarin

KW - Mortality

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DO - 10.1186/s12916-024-03808-y

M3 - Article

SN - 1741-7015

VL - 22

JO - BMC Medicine

JF - BMC Medicine

IS - 1

M1 - 597

ER -

Risk of mortality between warfarin and direct oral anticoagulants: population-based cohort studies

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Keywords

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