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Do proton pump inhibitors increase mortality? A systematic review and in-depth analysis of the evidence
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  • Mohamed Ben-Eltriki,
  • Carolyn Green,
  • Malcolm Maclure,
  • Vijaya Musini,
  • Ken Bassett,
  • James M Wright
Mohamed Ben-Eltriki
The University of British Columbia Faculty of Medicine
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Carolyn Green
The University of British Columbia Faculty of Medicine
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Malcolm Maclure
The University of British Columbia Faculty of Medicine
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Vijaya Musini
The University of British Columbia Faculty of Medicine
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Ken Bassett
The University of British Columbia Faculty of Medicine
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James M Wright
University of British Columbia
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Abstract

Aims: Proton pump inhibitors (PPIs) were primarily approved for short term use (2 to 8 weeks). However, PPI use continues to expand. Widely believed to be safe, we reviewed emerging evidence on increased mortality with PPI long-term use. Methods: We searched MEDLINE, Embase and Cochrane Central for evidence from systematic reviews (SR) and primary studies reporting all-cause mortality in adults treated with a PPI for any indication (duration > 12 weeks) compared to patients without PPI treatment (no use, placebo or H2RA use). Data was synthesized, analysed, critically examined and interpreted herein. Results: From 1304 articles, one systematic review (SR) was identified that reported on all-cause mortality. The SR pooled 3 observational studies with data to 1 year: odds ratio, 95% confidence interval (CI) 1.53-1.84. A randomized controlled trial (RCT), the COMPASS (Cardiovascular Outcomes for People Using Anticoagulant Strategies) RCT with data to 3 years: hazard ratio (HR) 1.03, 95% CI 0.92-1.15. The US Veterans Affairs cohort study using a large national dataset with data to 10 years; HR 1.17, 95% CI (1.10-1.24), (NNH) 22. The most common causes of death were from cardiovascular and chronic kidney diseases, with an excess death of 15 and 4 per 1000 patients, respectively over 10-year period. Conclusions: Harms arising from real world medication use are best evaluated using a pharmacovigilance ‘convergence of proof’ approach using data from a variety of sources and varied study designs. Careful appraisal of the totality of available evidence leads to the conclusion that long-term PPI utilization increases mortality