Are Proton Pump Inhibitors Truly Dangerous?

Are Proton Pump Inhibitors Truly Dangerous?

Vanessa M. Shami, MD, FASGE, reviewing Lo CH, et al. Gastroenterology 2022 Jun 30.

The use of proton pump inhibitors (PPIs) has continually increased over the past 20 to 30 years. As a result, interest has grown in the possible association of PPIs with adverse events and even mortality. This prospective cohort study used data from the Nurses’ Health Study (2004-2018) and the Health Professionals Follow-up Study (2004-2018). It used a modified lag-time approach to study the association between PPI use and mortality. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality according to PPI use.  

For the study, 50,156 women and 21,731 men were followed for 832,026 person-years and a median of 13.8 years. There were 22,125 deaths: 4592 from cancer, 5404 from cardiovascular diseases, and 12,129 from other causes. PPI users had significantly higher risks of all-cause mortality and mortality due to cancer, cardiovascular diseases, respiratory diseases, and digestive diseases than nonusers of PPIs. 

After applying lag-times of up to 6 years, the associations were no longer statistically significant (all-cause: HR, 1.04; 95% CI, 0.97-1.11; cancer: HR, 1.07; 95% CI, 0.89-1.28; cardiovascular diseases: HR, 0.94; 95% CI, 0.81-1.10; respiratory diseases: HR, 1.20; 95% CI, 0.95-1.50; and digestive diseases: HR, 1.38; 95% CI, 0.88-2.18). There was increased mortality due to renal disease (HR, 2.45; 95% CI, 1.59-3.78). However, there was a lack of information on potential cofounders. Therefore, long-term PPI use was not associated with higher risks of all-cause and cause-specific mortality.

Vanessa M. Shami, MD, FASGE


These data should reassure health care providers and patients alike that using PPIs does not increase the risk of all-cause mortality. Still, it is essential to limit its use to patients in whom the drug is clinically indicated.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.


Lo CH, Ni P, Yan Y, et al. Association of proton pump inhibitor use with all-cause and cause-specific mortality. Gastroenterology 2022 Jun 30. (Epub ahead of print) (

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