A data-mining study published on June 10 in PLOS One shows that people who take proton pump inhibitor drugs for gastroesophageal reflux disease (GERD) are at increased risk for heart attacks.
The study evaluated data for 2.9 million patients collected from more than 16 million clinical documents to assess the possible link between proton pump inhibitor (PPI) use and cardiovascular risk, Healio.com reports.
The primary data source was the STRIDE database at Stanford University, with data on 1.8 million patients. The web-based health record system (Practice Fusion Inc.) was the secondary source, with data for 1.1 million patients. STRIDE covered the years 1994 to 2011; the web database covered 2007 to 2012. The research team evaluated PPI use after an indication for GERD, followed by incidence of myocardial infarction (MI). The PPIs evaluated include dexlansoprazole (Dexilant), esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (Aciphex). Many of these drugs are available both over-the-counter and in prescription strength.
A link between PPI use and MI was observed in both data sets. The STRIDE database included 70,477 adult patients with GERD, 22,411 of whom had a myocardial infarction; 45.9 percent of the patients had used one or more PPI. Among these patients, researchers calculated an adjusted OR for MI of 1.16 (95% CI, 1.09-1.24). This association varied slightly according to the specific PPI used (range, 1.08-1.34). The link the researchers observed w`as consistent across age groups, and persisted after excluding patients taking the blood-thinner clopidogrel (adjusted OR = 1.14; 95% CI, 1.06-1.24). (Clopidogrel is used to prevent heart attacks and strokes and strokes in people with heart disease or peripheral vascular disease, or who have had a recent stroke or heart attack, according to Web MD). The researchers noted that patients treated with H2 blockers, alternative GERD medications such as Tagamet and Zantac, did not have increased risk for MI (adjusted OR = 0.93; 95% CI, 0.86-1.02), according to Healio.
The second data set included 227,438 patients with GERD, and yielded similar results to the STRIDE database (adjusted OR = 1.19; 95% CI, 1.09-1.3). Data from 1,503 patients enrolled in the GenePAD prospective cohort study was also evaluated and a significantly increased risk for cardiovascular-related mortality among PPI users was calculated after adjustment for cardiovascular comorbidities (HR = 2; 95% CI, 1.07-3.78). The researchers say that if a pharmacovigilance algorithm such as the one used in this analysis had been available earlier, the increased CV risk associated with lansoprazole use could have been identified as early as 2000.
The researchers note that their results are subject to confounding. It may be that PPI use simply indicates a sicker patient population. But the authors conclude that their findings warrant additional investigation, according to Healio. Dr. Nicholas J. Leeper, one of the authors, who is with the divisions of cardiovascular medicine and vascular surgery at Stanford University, said the results raise “concerns that these drug—which are available over the counter and are among the most commonly prescribed drugs in the world—may not be as safe as we previously assumed.”