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Incident peptic ulcers and concomitant treatment of direct oral anticoagulants and oral bisphosphonates—a real-world cohort study

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Abstract

Summary

Oral bisphosphonates and direct oral anticoagulants are related to upper gastrointestinal ulcers. The present study investigated whether concomitant use of these drugs increase the risk of upper gastrointestinal ulcers and report no increased risk of upper gastrointestinal ulcers compared to the use of either drug alone, when individuals with previous upper gastrointestinal ulcers are excluded.

Introduction

This study examines whether concomitant use of oral bisphosphonates (oBP) and direct oral anticoagulants (DOAC) increases the risk of peptic ulcers more than any drug alone.

Methods

A population-based cohort study was performed. We sampled a cohort of oBP and DOAC users from a sample of 2,622,742 individuals, consisting of diabetes patients and age- and gender-matched controls, obtained from the Danish National Patient Register. The exposures were concomitant use of oBP and DOAC and single use of DOAC and single use of oBP. The primary endpoint was the first incident peptic ulcer. Information on exposure and outcome were collected from national registries. The period of observation was from 01.01.2008 until 31.12.2018. Unadjusted and adjusted Cox regressions were performed.

Results

8077 individuals received concomitant treatment with DOAC and oBP; 96,451 individuals used DOAC and no oBP; and 118,675 used oBP and no DOAC. The mean duration of follow-up was 1.9 years for concomitant users, 2.5 years for DOAC users, and 4.5 years for oBP users. A total of 4742 individuals with incident peptic ulcers were collected. We observed an increased risk of incident ulcer in users of DOAC and oBP compared to single DOAC treatment in the adjusted analysis (HR = 1.23, 95% CI: 1.03; 1.48). However, the effects were abolished when excluding individuals with a previous ulcer. We observed an increased risk of incident ulcer in users of DOAC and oBP compared to users of oBP in the adjusted model (HR = 1.34, 95% CI: 1.11; 1.63).

Conclusion

Based on our results, concomitant use of oBP and DOAC is associated with a slight increase in the risk of peptic ulcers compared to either drug alone. The prescribing physician should weigh the slight increased risk of ulcer in concomitant users of oBP and DOAC with beneficial reductions in stroke and fractures.

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Funding

The study was supported by a Steno Collaborative grant, Novo Nordisk Foundation Denmark (grant no. NNF18OC0052064).

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Authors and Affiliations

  1. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, 8200, Aarhus, Denmark

    J. Starup-Linde, B. Langdahl & T. Harsløf

  2. Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

    J. Starup-Linde

  3. Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark

    P. Vestergaard

  4. Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark

    P. Vestergaard

  5. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

    P. Vestergaard

Authors
  1. J. Starup-Linde
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  2. B. Langdahl
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  4. T. Harsløf
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Corresponding author

Correspondence to J. Starup-Linde.

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Conflict of interest

BL received research grants to her institution from Amgen and Novo Nordisk. BL has received honoraria for advisory board and/or lectures from UCB, Amgen, Eli Lilly, Gedeon-Richter, and Gilead. The other authors declare no competing interests.

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Starup-Linde, J., Langdahl, B., Vestergaard, P. et al. Incident peptic ulcers and concomitant treatment of direct oral anticoagulants and oral bisphosphonates—a real-world cohort study. Osteoporos Int 33, 1323–1334 (2022). https://doi.org/10.1007/s00198-022-06315-z

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  • DOI: https://doi.org/10.1007/s00198-022-06315-z

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