PPIs in Hospitalized Patients May Cause More Harm Than Good

Many patients who are admitted into hospitals are put on proton pump inhibitors (PPIs) both to prevent gastrointestinal bleeding and as heartburn/gastroesophageal reflux disease relief after discharge. But a new study from researchers at the University of Michigan and the VA Ann Arbor Healthcare System finds that PPIs may actually cause more harm to hospitalized patients than good, by leaving patients more vulnerable to infections like pneumonia and Clostridium difficile (C. diff).

Gastric acid has a powerful bactericidal effect, and depletion can allow foreign bacteria to survive in the body. Thus, the inhibition of protective gastric acid secretion that PPIs cause can open patients in the hospital up to infections—and higher risk of death.

“Many patients who come into the hospital are on [PPIs], and we sometimes start them in the hospital to try to prevent gastrointestinal bleeds,” lead author Matthew Pappas, MD, MPH said. “But other researchers have shown that these drugs seem to increase the risk of [other] potentially life-threatening infections. Our new model allows us to compare that increased risk with the risk of upper GI bleeding.”

The study, based on research-based estimates of the risk/benefit of PPIs, measured overall mortality of computer-simulated general medical inpatients. Results showed that about 90% of the patients who started PPI therapy showed a higher risk of dying during their stay than if they hadn’t started. Of the patients who were already on a PPI upon admission, 79% showed a similar increased risk.

These findings suggest that the benefits of using PPIs in bleeding prophylaxis are not strong enough to outweigh the infection/mortality risks. Besides those with the lowest risk of contracting pneumonia and C. diff or those with active bleeding, hospitalized patients should generally avoid PPIs—even those at relatively high risk of gastrointestinal bleeding.

The unique design of the study also has powerful implications on how future risk-benefit balancing studies can be conducted. Simulations using observational data could reduce the need for large prospective clinical trials. Other medications like PPIs, which display not only strong preventative factors but also dangerous side effects, can be analyzed to determine which side—benefits or risks—outweighs the other.

“Physicians have an instinct to want to prevent very bad, though rare events—but everything we do carries risks,” Dr Pappas said. “We need to be mindful of the things we are doing to prevent rare outcomes, and keep the risks in perspective. Computers can help. Any time there are complex risk/benefit tradeoffs, without the possibility of a high-quality trial, this kind of simulation can help us come up with answers to inform clinical care.”