Proton pump inhibitors linked to fatal cases of CVD, CKD, stomach cancer

People who take popular heartburn drugs like Prevacid, Prilosec and Nexium are vulnerable to death from cardiovascular disease, chronic kidney disease (CKD) and upper gastrointestinal cancer, according to new research published in The BMJ. The drugs’ negative effects were most pronounced in those who were taking them long-term without a clear indication, even at low doses.

Senior author Ziyad Al-Aly, MD, and colleagues studied over-the-counter and prescription solutions for heartburn, acid reflux and ulcers—also known as proton pump inhibitors (PPIs)—because in the past they’ve been linked to health issues like dementia, bone fractures and pneumonia. Since they’re one of the most commonly used drug classes in the U.S., prescribed to upwards of 15 million Americans, adverse side effects could have wide-reaching implications.

“Identification of specific causes of death attributable to taking PPIs will inform the public about the risk of taking PPIs in the long term and could inform risk stratification, risk mitigation strategies and help shape the development of deprescription interventions to reduce unnecessary or un-indicated PPI use,” Al-Aly, an assistant professor at the Washington University School of Medicine in St. Louis, and co-authors wrote.

For their research, Al-Aly et al. sorted through de-identified medical records maintained by the U.S. Department of Veterans Affairs between 2002 and 2004. They pulled information for 157,625 patients who’d been newly prescribed PPIs and 56,842 people who’d been newly prescribed another class of acid-suppressants, H2 blockers (Zantac, Pepcid and Tagamet are a few brand-name examples).

After a decade of follow-up, the researchers identified a 17% increased risk of death in the PPI group compared with the H2 blocker group, with an excess 45 deaths per 1,000 people attributable to long-term PPI use. Death rates as a whole were 387 per 1,000 people for PPIs and 342 per 1,000 people for H2 blockers.

The authors said that among people who took PPIs, 38.7% of deaths were related to circulatory system diseases, 28.6% to neoplasms, 13.8% to genitourinary system diseases and 9.3% to infectious and parasitic diseases. Analyses by subcauses of death revealed new use of PPIs was associated with excess mortality from CVD and CKD.

Patients who took PPIs but did so without a medical need—which was more than half of the PPI population—saw the highest death rate from PPI-related causes. In that subset of patients nearly 23 people per 1,000 died of heart disease, 5 per 1,000 died from CKD and 3 per 1,000 died from stomach cancer. Risk seemed to increase with longer-term use of the drugs, even if they were taken at low doses, as was the case for 80% of users.

“Overuse of proton pump inhibitors is not devoid of harm,” Al-Aly and Yan Xie, a biostatician at the Department of Veterans Affairs St. Louis Health Care System, wrote in a BMJ blog. “The totality of the results suggests the need to avoid proton pump inhibitors when not medically indicated; for those who have a medical indication for PPIs, use should be limited to the lowest effective dose and shortest duration possible.”

Al-Aly et al.’s work has reportedly drawn interest from the U.S. FDA, according to the University of Washington.

“PPIs sold over the-counter should have a clearer warning about potential for significant health risks, as well as a clearer warning about the need to limit length of use, generally not to exceed 14 days,” he said in a release. “People who feel the need to take over-the-counter PPIs longer than this need to see their doctors.”