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Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Acute Pancreatitis: A Population-Based Cohort Study

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Abstract

Introduction

There are conflicting reports on the effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) on acute pancreatitis incidence.

Objective

The aim was to determine whether use of ACE inhibitors and ARBs is associated with the incidence of acute pancreatitis, compared with use of dihydropyridine calcium channel blockers (dCCBs).

Methods

We assembled two population-based, new-user, active comparator cohorts using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository and Office for National Statistics from 1998 to 2018, with follow-up until 2019. The first cohort included 304,083 ACE inhibitor initiators and 194,431 dCCB initiators. The second cohort included 29,160 ARB initiators and 203,610 dCCB initiators. Cox proportional hazards models were fit to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of acute pancreatitis, comparing ACE inhibitors and ARBs, separately, with dCCBs. Models were weighted using standardized mortality ratio weights generated from calendar time-specific propensity scores.

Results

ACE inhibitors were associated with an increased risk of acute pancreatitis, compared with dCCBs (64.3 vs 45.2 per 100,000 person-years, respectively; HR 1.45, 95% CI 1.15–1.83). The number needed to harm after 2 and 5 years of use was 2438 and 1019, respectively. In contrast, ARBs were not associated with an increased risk of acute pancreatitis, compared with dCCBs (40.1 vs 47.6 per 100,000 person-years, respectively; HR 0.88, 95% CI 0.60–1.31).

Conclusions

ACE inhibitors were associated with a modest increased risk of acute pancreatitis compared with dCCBs. This association should be balanced with the known clinical benefits of ACE inhibitors in hypertension management. In contrast, no association was observed with ARBs.

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Authors and Affiliations

  1. Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montreal, QC, H3T 1E2, Canada

    Julie Rouette, Hui Yin & Laurent Azoulay

  2. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada

    Julie Rouette & Laurent Azoulay

  3. Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montreal, Canada

    Emily G. McDonald

  4. Division of Experimental Medicine, McGill University, Montreal, Canada

    Emily G. McDonald

  5. Division of Gastroenterology, McGill University Health Centre, Montreal, QC, Canada

    Alan Barkun

  6. Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada

    Laurent Azoulay

Authors
  1. Julie Rouette
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  2. Hui Yin
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  3. Emily G. McDonald
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  4. Alan Barkun
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  5. Laurent Azoulay
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Corresponding author

Correspondence to Laurent Azoulay.

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Funding

This work was supported by a Foundation Scheme grant from the Canadian Institutes of Health Research (FDN-143328). JR is the recipient of a Doctoral Award from the Canadian Institutes of Health Research (FRN-152254) and a Doctoral Award from the Fonds de Recherche du Québec- Santé. EGM holds a Chercheur-Clinicien Junior 1 award from the Fonds de Recherche du Québec- Santé. LA holds a Chercheur-Boursier Senior Award from the Fonds de Recherche du Québec - Santé and is the recipient of a William Dawson Scholar award from McGill University. The funding sources had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Conflict of interest

JR received consulting fees for work unrelated to this study from Biogen. LA received consulting fees from Janssen and Pfizer for work unrelated to this study. HY, EGM, and AB have no conflicts to disclose.

Ethical approval

The study complied with the Declaration of Helsinki. The study protocol was approved by the Independent Scientific Advisory Committee of the CPRD (protocol number 20_000225R) and the Research Ethics Board of the Jewish General Hospital, Montreal, Canada (number 2021-2748).

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Author contribution

All authors conceived and designed the study, interpreted the data, critically revised the manuscript for important intellectual content, and approved the final version of the manuscript. LA acquired the data. JR, HY, and LA conducted the analyses. JR drafted the manuscript. LA attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. LA is accountable for all aspects of the work.

Data and code availability

The data cannot be shared publicly due to the privacy policy of the Clinical Practice Research Datalink.

Supplementary Information

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Rouette, J., Yin, H., McDonald, E.G. et al. Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Acute Pancreatitis: A Population-Based Cohort Study. Drug Saf 45, 65–74 (2022). https://doi.org/10.1007/s40264-021-01128-1

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  • DOI: https://doi.org/10.1007/s40264-021-01128-1

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