The association between proton pump inhibitors and the risk of gastrointestinal bleeding in oral anticoagulants users

Zixuan Wang; Qiuyan Yu; Charlotte Warren-Gash; Krishnan Bhaskaran; Clémence Leyrat; Ka Shing Cheung; Celine S. L. Chui; Esther W. Chan; Ian C. K. Wong; Amitava Banerjee; Liam Smeeth; Ian J. Douglas; Angel Y. S. Wong

doi:10.1038/s44325-024-00037-3

The association between proton pump inhibitors and the risk of gastrointestinal bleeding in oral anticoagulants users

Zixuan Wang
, Qiuyan Yu
, Charlotte Warren-Gash
, Krishnan Bhaskaran
, Clémence Leyrat
, Ka Shing Cheung
, Celine S. L. Chui
, Esther W. Chan
, Ian C. K. Wong
, Amitava Banerjee
, Liam Smeeth
, Ian J. Douglas
, Angel Y. S. Wong^*

^*Corresponding author for this work

The University of Hong Kong, Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, Hong Kong SAR, China, ROR: https://ror.org/02zhqgq86, GRID: grid.194645.b, ISNI: 0000 0001 2174 2757
London School of Hygiene and Tropical Medicine, Faculty of Epidemiology and Population Health, London, United Kingdom, ROR: https://ror.org/00a0jsq62, GRID: grid.8991.9, ISNI: 0000 0004 0425 469X
The University of Hong Kong, School of Public Health, Li Ka Shing, Faculty of Medicine, Hong Kong, China, ROR: https://ror.org/02zhqgq86, GRID: grid.194645.b, ISNI: 0000 0001 2174 2757

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

4 Citations (Scopus)

9 Downloads (Pure)

Abstract

Current evidence of whether proton pump inhibitor (PPI) reduces the risk of gastrointestinal bleeding (GIB) associated with oral anticoagulants (OACs) is limited. Propensity score-weighted cohort and case-crossover studies were conducted separately in England and Hong Kong between 2011.01.01 and 2019.12.31. In the cohort design, we compared the hazards of hospitalised GIB in OAC + PPI users with OAC only users in people with atrial fibrillation and found higher hazard of GIB in OAC + PPI users in both settings. In the case-crossover design, elevated odds of exposure to PPI only, OAC only and OAC + PPI associated with GIB between 30-day hazard and referent periods were similarly found in both settings. Overall, the evidence of an elevated risk of OAC + PPI associated with GIB compared with OAC only was modest in the cohort study. Our case-crossover study suggested that residual confounding is likely to explain the association, suggesting that concomitant prescription of PPI with OAC did not modify GIB.

Original language	English
Article number	11
Number of pages	11
Journal	npj Cardiovascular Health
Volume	2
Issue number	1
Early online date	12 Apr 2025
DOIs	https://doi.org/10.1038/s44325-024-00037-3
Publication status	Published - 12 Apr 2025

Bibliographical note

Copyright © The Author(s) 2025. 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/

Data Access Statement

Computing code and study protocol are available from the corresponding author upon request for reproducing the results. However, the study data cannot be made available to other researchers because of the terms specified in Data Use Agreements.

Funding

This work was supported by the British Heart Foundation (FS/19/19/34175) and the Laboratory of Data Discovery for Health (D24H) funded by AIR@InnoHK administered by Innovation and Technology Commission, the Government of the Hong Kong Special Administrative Region, China. L.S. reports grants from Wellcome, MRC, NIHR, UKRI, British Council, GSK, British Heart Foundation, and Diabetes UK outside this work. I.D. holds grants from NIHR, GSK and AIR@InnoHK administered by Innovation and Technology Commission. C.L. is supported by the UK Medical Research Council (Skills Development Fellowship MR/T032448/1). C.W.G. is funded by a Wellcome Career Development Award (225868/Z/22/Z). K.B. is funded by a Wellcome Senior Research Fellowship (220283/Z/20/Z).

Access to Document

10.1038/s44325-024-00037-3Licence: CC BY 4.0

Z Wang et al_association between proton pump inhibitors and the risk of gastrointestinal bleeding in oral anticoagulants users
Copyright © The Author(s) 2025. 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/
Final published version, 818 KBLicence: CC BY 4.0

Cite this

Wang, Z., Yu, Q., Warren-Gash, C., Bhaskaran, K., Leyrat, C., Cheung, K. S., Chui, C. S. L., Chan, E. W., Wong, I. C. K., Banerjee, A., Smeeth, L., Douglas, I. J., & Wong, A. Y. S. (2025). The association between proton pump inhibitors and the risk of gastrointestinal bleeding in oral anticoagulants users. npj Cardiovascular Health, 2(1), Article 11. https://doi.org/10.1038/s44325-024-00037-3

@article{a11ff5ea5bff4f17bf320f368eb632e0,

title = "The association between proton pump inhibitors and the risk of gastrointestinal bleeding in oral anticoagulants users",

abstract = "Current evidence of whether proton pump inhibitor (PPI) reduces the risk of gastrointestinal bleeding (GIB) associated with oral anticoagulants (OACs) is limited. Propensity score-weighted cohort and case-crossover studies were conducted separately in England and Hong Kong between 2011.01.01 and 2019.12.31. In the cohort design, we compared the hazards of hospitalised GIB in OAC + PPI users with OAC only users in people with atrial fibrillation and found higher hazard of GIB in OAC + PPI users in both settings. In the case-crossover design, elevated odds of exposure to PPI only, OAC only and OAC + PPI associated with GIB between 30-day hazard and referent periods were similarly found in both settings. Overall, the evidence of an elevated risk of OAC + PPI associated with GIB compared with OAC only was modest in the cohort study. Our case-crossover study suggested that residual confounding is likely to explain the association, suggesting that concomitant prescription of PPI with OAC did not modify GIB.",

author = "Zixuan Wang and Qiuyan Yu and Charlotte Warren-Gash and Krishnan Bhaskaran and Cl{\'e}mence Leyrat and Cheung, \{Ka Shing\} and Chui, \{Celine S. L.\} and Chan, \{Esther W.\} and Wong, \{Ian C. K.\} and Amitava Banerjee and Liam Smeeth and Douglas, \{Ian J.\} and Wong, \{Angel Y. S.\}",

note = "Copyright {\textcopyright} The Author(s) 2025. 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 = "2025",

month = apr,

day = "12",

doi = "10.1038/s44325-024-00037-3",

language = "English",

volume = "2",

journal = "npj Cardiovascular Health",

issn = "2948-2836",

number = "1",

}

TY - JOUR

T1 - The association between proton pump inhibitors and the risk of gastrointestinal bleeding in oral anticoagulants users

AU - Wang, Zixuan

AU - Yu, Qiuyan

AU - Warren-Gash, Charlotte

AU - Bhaskaran, Krishnan

AU - Leyrat, Clémence

AU - Cheung, Ka Shing

AU - Chui, Celine S. L.

AU - Chan, Esther W.

AU - Wong, Ian C. K.

AU - Banerjee, Amitava

AU - Smeeth, Liam

AU - Douglas, Ian J.

AU - Wong, Angel Y. S.

N1 - Copyright © The Author(s) 2025. 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 - 2025/4/12

Y1 - 2025/4/12

N2 - Current evidence of whether proton pump inhibitor (PPI) reduces the risk of gastrointestinal bleeding (GIB) associated with oral anticoagulants (OACs) is limited. Propensity score-weighted cohort and case-crossover studies were conducted separately in England and Hong Kong between 2011.01.01 and 2019.12.31. In the cohort design, we compared the hazards of hospitalised GIB in OAC + PPI users with OAC only users in people with atrial fibrillation and found higher hazard of GIB in OAC + PPI users in both settings. In the case-crossover design, elevated odds of exposure to PPI only, OAC only and OAC + PPI associated with GIB between 30-day hazard and referent periods were similarly found in both settings. Overall, the evidence of an elevated risk of OAC + PPI associated with GIB compared with OAC only was modest in the cohort study. Our case-crossover study suggested that residual confounding is likely to explain the association, suggesting that concomitant prescription of PPI with OAC did not modify GIB.

AB - Current evidence of whether proton pump inhibitor (PPI) reduces the risk of gastrointestinal bleeding (GIB) associated with oral anticoagulants (OACs) is limited. Propensity score-weighted cohort and case-crossover studies were conducted separately in England and Hong Kong between 2011.01.01 and 2019.12.31. In the cohort design, we compared the hazards of hospitalised GIB in OAC + PPI users with OAC only users in people with atrial fibrillation and found higher hazard of GIB in OAC + PPI users in both settings. In the case-crossover design, elevated odds of exposure to PPI only, OAC only and OAC + PPI associated with GIB between 30-day hazard and referent periods were similarly found in both settings. Overall, the evidence of an elevated risk of OAC + PPI associated with GIB compared with OAC only was modest in the cohort study. Our case-crossover study suggested that residual confounding is likely to explain the association, suggesting that concomitant prescription of PPI with OAC did not modify GIB.

UR - https://www.nature.com/articles/s44325-024-00037-3

U2 - 10.1038/s44325-024-00037-3

DO - 10.1038/s44325-024-00037-3

M3 - Article

SN - 2948-2836

VL - 2

JO - npj Cardiovascular Health

JF - npj Cardiovascular Health

IS - 1

M1 - 11

ER -

The association between proton pump inhibitors and the risk of gastrointestinal bleeding in oral anticoagulants users

Abstract

Bibliographical note

Data Access Statement

Funding

Access to Document

Other files and links

Fingerprint

Cite this