A study has linked long-term use of drugs known as proton pump inhibitors (PPIs), usually used to treat heartburn, ulcers and acid reflux, to fatal cases of cardiovascular disease, chronic kidney disease and upper gastrointestinal cancer.
The study, conducted by researchers at Washington University School of Medicine in St. Louis and Veterans Affairs St. Louis Health Care System, also found that such risks increase with the duration of PPI use even when taken at low doses.
For the study, researchers sifted through de-identified medical records in a database maintained by the U.S. Department of Veterans Affairs. Examining medical data acquired from July 2002 to June 2004, the researchers identified 157,625 people, mostly Caucasian men aged 65 and older, who had been newly prescribed PPIs, and 56,842 people who had been newly prescribed another class of acid-suppression drugs known as H2 blockers. They followed the patients, 214,467 in total, for up to 10 years.
The researchers found a 17 percent increased risk of death in the PPI group compared with the H2 blocker group. They calculated 45 excess deaths attributable to long-term PPI use per 1,000 people. Death rates for PPIs were 387 per 1,000 people, and death rates for H2 blockers were 342 per 1,000.
Specifically, 15 per 1,000 of the PPI users died from heart disease; four per 1,000 from chronic kidney disease, and two per 1,000 from stomach cancer. Death rates due to cardiovascular disease were 88 among the PPI group, as against 73 among the H2 blockers group; that due to stomach cancer, 6 in the PPI group, as against 4 in the H2 blockers group; and due to chronic kidney disease, 8 in the PPI group, as against 4 in the H2 blocker group.
Additionally, the study found that more than half of the people taking PPIs did so without a medical need. Among this group, PPIs-related deaths were more common, with almost 23 people per 1,000 dying from heart disease, almost 5 per 1,000 from chronic kidney disease, and 3 from stomach cancer.
The study also found that more than 80 percent of PPI users were on low doses of the prescription drug, or those equivalent to doses offered in over-the-counter versions. “This suggests the risk may not be limited to prescription PPIs, but it also may occur at over-the-counter doses,” said senior author Ziyad Al-Aly, an assistant professor of medicine at the Washington University School of Medicine.
“Taking PPIs over many months or years is not safe, and now we have a clearer picture of the health conditions associated with long-term PPI use,” said Al-Aly.
In the next step, the researchers will continue to study adverse health effects related to PPIs, in particular regarding those at the highest risk.
More than 15 million Americans have prescriptions for PPIs. Further, many millions more purchase the drugs over the counter and take them without being under a doctor’s care and often indefinitely.
The study was published online Thursday in the journal The BMJ.