Non-vitamin K antagonist oral anticoagulants, proton pump inhibitors and gastrointestinal bleeds

Joris Komen*, Anton Pottegård, Paul Hjemdahl, Aukje K. Mantel-Teeuwisse, Björn Wettermark, Maja Hellfritzsch, J. Hallas, Ron Herings, Lisa Smits, Thomas Forslund, Olaf Klungel

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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.

Original languageEnglish
Article number319332
Issue number8
Pages (from-to)613-618
Publication statusPublished - 25. Mar 2022


  • atrial fibrillation
  • oral anticoagulants
  • Administration, Oral
  • Humans
  • Risk Factors
  • Stroke/etiology
  • Proton Pump Inhibitors/adverse effects
  • Anticoagulants/therapeutic use
  • Platelet Aggregation Inhibitors/adverse effects
  • Aged, 80 and over
  • Gastrointestinal Hemorrhage/chemically induced
  • Aged
  • Atrial Fibrillation/complications
  • Cohort Studies


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