Proton-pump inhibitor (PPI) use was not associated with higher risks of all-cause mortality and mortality due to major causes, an observational study found.
Researchers conducted a prospective cohort study using data collected from the Nurses' Health Study (2004-2018) and the Health Professionals Follow-up Study (2004-2018) to assess mortality according to PPI use. To avoid protopathic bias, researchers did not consider any increased PPI use during an excluded period, which could stem from comorbid conditions prior to death. Results were published June 22 by Gastroenterology.
The study included 50,156 women and 21,731 men followed for 832,026 person-years and a median of 13.8 years; over 90% were White. There were 22,125 deaths, including 4,592 deaths from cancer, 5,404 deaths from cardiovascular diseases, and 12,129 deaths from other causes. A total of 10,998 women (21.9%) and 2,945 men (13.6%) started PPIs at some point during the study period, and PPI use increased from 6.1% to 10.0% in women and from 2.5% to 7.0% in men over time.
Compared to nonusers of PPIs, PPI users had significantly higher risks of all-cause mortality and mortality due to cancer, cardiovascular diseases, respiratory diseases, and digestive diseases. When lag times of up to six years were applied, the associations were attenuated and no longer statistically significant for most causes (hazard ratios, 1.03 [95% CI, 0.96 to 1.10] for all-cause mortality, 1.06 [95% CI, 0.88 to 1.28] for cancer,0.96 [95% CI, 0.82 to 1.12] for cardiovascular diseases, 1.14 [95% CI, 0.89 to 1.45] for respiratory diseases, and 1.31 [95% CI, 0.80 to 2.14] for digestive diseases), with the exception of death from renal disease (hazard ratio, 2.45; 95% CI, 1.59 to 3.78). Risks for all-cause and cause-specific mortality did not appear to increase with longer PPI use.
“Patients with various medical conditions may use PPIs prior to death which leads to protopathic bias when evaluating mortality risk in PPI users. We utilized a modified lag-time approach and found no association between PPI use and all-cause mortality and mortality due to major causes after accounting for protopathic bias,” the authors concluded. “Despite the lack of association with risk of death, it remains prudent to recommend the use of these agents to patients with appropriate indications and for the minimally effective duration.” They called for additional research in other racial, ethnic, and socioeconomic groups.