The data-mining study evaluated data collected from more than 16 million clinical documents for 2.9 million patients 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 (1.8 million patients). The web-based electronic health record system (Practice Fusion Inc.) was the secondary source, with data for 1.1 million patients. STRIDE data covered 1994 to 2011; the web database had data from 2007 to 2012.
The researchers evaluated PPI use after an indication for GERD, followed by incidence of myocardial infarction (MI). The PPIs evaluated included dexlansoprazole (Dexilant), esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (Aciphex). Many of these are available in both over-the-counter and prescription strengths.
The research was published online on June 10 in PLOS One.
The researchers observed a link between PPI use and MI in both data sets
The researchers observed a link between PPI use and MI in both data sets. The STRIDE database included 70,477 adult patients with GERD, 22,411 of whom had MI and 45.9 percent of whom 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 observed link was consistent across age groups, and persisted after exclusion of patients receiving 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, an alternative GERD medication, did not have increased risk for MI (adjusted OR = 0.93; 95% CI, 0.86-1.02), according to Healio.
The second data set, which included 227,438 patients with GERD, yielded similar results to the STRIDE database (adjusted OR = 1.19; 95% CI, 1.09-1.3).
The researchers also evaluated data collected from 1,503 patients enrolled in the GenePAD prospective cohort study and calculated a significantly increased risk for cardiovascular-related mortality among PPI users after adjustment for cardiovascular comorbidities (HR = 2; 95% CI, 1.07-3.78).
The researchers say that if pharmacovigilance algorithms
The researchers say that if pharmacovigilance algorithms such as the one employed in this analysis had been available, the increased CV risk associated with lansoprazole use could have been identified as early as 2000.
The researchers note that the results are subject to confounding: PPI use may simply indicate a sicker patient population. But they concluded that their findings are “hypothesis-generating” and warrant additional investigation, according to Healio.
“Our report raises 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,” said one of the authors, Dr. Nicholas J. Leeper, of the divisions of cardiovascular medicine and vascular surgery at Stanford University.