Regular PPI Use and Risk of All-cause and Cause-specific Mortality

Pavankumar Kamat


August 10, 2021


  • Regular use of proton pump inhibitors (PPIs) was not associated with an increased risk of all-cause and cause-specific mortality.

Why this matters

  • In clinical practice, there is no reason to discontinue PPI use for a valid indication because of concerns about increased mortality.

  • The potential long-term effects other than mortality are yet to be determined.

Study design

  • A prospective population-based cohort study of 440,840 participants (38,065 PPI users; 402,775 PPI non-users) from the UK Biobank.

  • Independent associations between regular PPI use and the risk of all-cause and cause-specific mortality were evaluated.

  • Funding: National Natural Science Foundation of China and others.

Key results

  • Over a median follow-up of 5.9 years, 13,154 deaths were reported.

  • After adjusting for confounders, regular PPI use vs no use was not significantly associated with an increased risk of all-cause mortality (adjusted HR [aHR], 1.05; 95% CI, 0.97-1.13).

  • Regular PPI use vs no use was not significantly associated with a higher risk of mortality from (aHR; 95% CI):

    • neoplasms (1.06; 0.97-1.15);

    • circulatory system diseases (0.96; 0.83-1.10);

    • respiratory system diseases (1.10; 0.90-1.35);

    • digestive system diseases (1.23; 0.90-1.68);

    • external causes (1.12; 0.79-1.59); and

    • other causes (1.14; 0.96-1.36).


  • Potential misclassification of PPI exposure.


He Q, Xia B, Meng W, Fan D, Kuo ZC, Huang J, Qin X, Zou H, He Y, Zhang C, Fang S, Pan Y, Yang M, Yuan J. No Associations Between Regular Use of Proton Pump Inhibitors and Risk of All-Cause and Cause-Specific Mortality: A Population-Based Cohort of 0.44 Million Participants. Am J Gastroenterol. 2021 Jul 27 [Epub ahead of print]. doi: 10.14309/ajg.0000000000001377. doi: 10.1016/j.cgh.2021.01.014. PMID: 34313608.  View full text

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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