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Arrhythmias and sudden death
Original research
Non-vitamin K antagonist oral anticoagulants, proton pump inhibitors and gastrointestinal bleeds
  1. Joris Komen1,2,
  2. Anton Pottegård3,
  3. Paul Hjemdahl4,
  4. Aukje K Mantel-Teeuwisse1,
  5. Björn Wettermark5,
  6. Maja Hellfritzsch3,
  7. J Hallas3,
  8. Ron Herings6,
  9. Lisa Smits6,
  10. Thomas Forslund4,
  11. Olaf Klungel1
  1. 1 Clinical Pharmacology and Pharmacoepidemiology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
  2. 2 Department of Healthcare Development, Stockholm Region Public Healthcare Services Committee, Stockholm, Sweden
  3. 3 Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark
  4. 4 Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden
  5. 5 Department of Pharmacy, Pharmacoepidemiology and Social Pharmacy, Uppsala University, Uppsala, Sweden
  6. 6 PHARMO Institute, Utrecht, The Netherlands
  1. Correspondence to Joris Komen, Utrecht University, Utrecht 3508 TC, The Netherlands; j.j.komen{at}uu.nl

Abstract

Objective To evaluate if proton pump inhibitor (PPI) treatment reduces the risk of upper gastrointestinal bleeding (UGIB) in patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs).

Design We used a common protocol, common data model approach to conduct a cohort study including patients with AF initiated on a NOAC in Stockholm, Denmark and the Netherlands from April 2011 until July 2018. The outcome of interest was a UGIB diagnosed in a secondary care inpatient setting. We used an inverse probability weighted (IPW) Poisson regression to calculate incidence rate ratios (IRRs), contrasting PPI use to no PPI use periods.

Results In 164 290 NOAC users with AF, providing 272 570 years of follow-up and 39 938 years of PPI exposure, 806 patients suffered a UGIB. After IPW, PPI use was associated with lower UGIB rates (IRR: 0.75; 95% CI: 0.59 to 0.95). On an absolute scale, the protective effect was modest, and was found to be largest in high-risk patients, classified as age 75–84 years (number needed to treat for 1 year (NNTY): 787), age ≥85 years (NNTY: 667), HAS-BLED score ≥3 (NNTY: 378) or on concomitant antiplatelet therapy (NNTY: 373).

Conclusion Concomitant treatment with a PPI in NOAC-treated patients with AF is associated with a reduced risk of severe UGIB. This indicates that PPI cotreatment can be considered, in particular among the elderly patients, patients with a HAS-BLED score ≥3, and/or in patients on concomitant antiplatelet therapy.

  • atrial fibrillation
  • oral anticoagulants

Data availability statement

Data may be obtained from a third party and are not publicly available. Ethical and privacy reasons prohibit sharing of data from all three databases.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/heartjnl-2021-319332

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    Data availability statement

    Data may be obtained from a third party and are not publicly available. Ethical and privacy reasons prohibit sharing of data from all three databases.

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    Footnotes

    • Contributors JK, AP, PH, MH, JH, TF and OK were involved in designing the study. JK, AP and RH were involved in analysing the data. All authors were involved in drafting and critically revising the manuscript. All authors approved the final version of the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests JK reports personal fees from Boehringer Ingelheim, outside the submitted work. AP reports grants from Alcon, grants from Almirall, grants from Astellas, grants from AstraZeneca, grants from Boehringer Ingelheim, grants from Novo Nordisk, grants from Servier, grants from LEO Pharma, outside the submitted work. JH reports grants from AstraZeneca, outside the submitted work. RH and LS report other fees from University of Utrecht, during the conduct of the study.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.