Use of PPIs Tied to Risk for Fatal Diseases

Use of proton pump inhibitors (PPIs) was tied to an increased risk for death from certain diseases including cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer, according to the results of a study published in BMJ.

Specifically, in a longitudinal study of U.S. veteran data suggested that there were 45.20 attributable deaths per 1,000 PPI users: 38.65% due to circulatory system diseases, 28.63% to neoplasms, 13.83% to genitourinary system diseases, and 9.29% to infectious and parasitic diseases.

“The results show a consistent excess of cause specific mortality even among patients without documented gastrointestinal indications for acid suppression drugs – an alarming finding which might help guide the design and implementation of deprescription programs to reduce the number of unnecessary or un-indicated PPI prescriptions,” wrote Yan Xie, of the department of Veterans Affairs St Louis Health Care System, and colleagues.

The study included more than 200,000 new users of PPIs or H2 blockers taken from department of Veterans Affairs databases between July 2002 and June 2004. Patients were followed up to 10 years to look for associations between new PPI use and causes of death.

The most common causes of death were circulatory system diseases (12.45%), neoplasms (9.72%), and respiratory system diseases (4.8%). More deaths occurred among patients taking PPIs than H2 blockers (37.92% vs. 35.69%).

The researchers found a graded relation between cumulative duration of PPI exposure and risk for all-cause mortality and death due to circulatory system diseases, neoplasms, and genitourinary system disease.

An analysis of subcauses of deaths showed that taking PPIs was linked with excess mortality due to cardiovascular disease (15.48 per 1,000 PPI users) and chronic kidney disease (4.19 per 1,000 PPI users ). Even among those patients without documented indication for acid suppression drugs (n=116,377), PPIs were associated with excess mortality due to cardiovascular disease (22.91 per 1,000 PPI users), chronic kidney disease (4.74 per 1,000 PPI users), and upper gastrointestinal cancer (3.12 per 1,000 PPI users).

The researchers noted that these findings should not preclude the use of PPIs when medically indicated, “nevertheless, the findings emphasize the need to promote awareness of potential adverse events of long term PPI use, for better pharmacovigilance, and the need to limit prescription of PPIs to patients where the benefits outweigh potential risks,” they wrote.

Xie Y, Bowe B, Yan Y, et al. Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study. BMJ. 2019;doi:10.1136/bmj.I1580.