Fueling the fire of debate on PPI safety, a new observational study in BMJ Open found the use of proton pump inhibitors for at least a year was associated with a 51% higher risk of early death, compared with 31% among those treated for six months to a year and 17% for three- to six-month use.

The findings, based on medical records from about 350,000 users of acid suppressants from the Department of Veterans Affairs, showed a 25 percent increased risk of death in the patients who took a PPI compared with the people who took H2 blockers — about one extra death for every 500 people taking PPIs for a year.

However, as with several other studies, the researchers did not look at patients’ cause of death. This is a fundamental aspect of scientific research: the difference between a correlation (as in this study) and a cause-and-effect. Correlation studies are one of the weakest forms of science, and are open to multiple interpretations. As an example of a potential explanation, if a patient with chest pain presented to the doctor there is a good chance that they would be started on a PPI. And a lot of those patients would not have reflux but actually cardiac disease–disease they might die of within the next year. And this type of analysis explains the correlation without any specific cause-and-effect.

It’s also why we continually focus on the heart first when evaluating chest pain, or if we do undertake reflux therapy we often did it in parallel with a cardiac workup.

-Manoj K. Mehta, MD

See the article on MSN here.