New Study Links Proton Pump Inhibitors Use to an Increased Risk of Heart Attack

A recent study published June 10 in PLOS One shows that proton pump inhibitor (PPI) drugs may increase the risk of heart attacks in patients who take the medications for gastroesophageal reflux disease (GERD).

For the study, researchers evaluated data for 2.9 million patients collected from more than 16 million clinical documents using primarily the STRIDE database at Stanford University, which contained data on 1.8 million patients. Practice Fusion Inc., a web-based health record system, served as the secondary source, with data on 1.1 million patients. The scientists evaluated PPI use after a diagnosis of GERD and focused specifically on the following drugs, according to Healio.com: dexlansoprazole (Dexilant), esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (Aciphex).

The team found a link between PPI use and heart attack in both data sets. The STRIDE database included 70,477 adult patients with GERD, and 22,411 had experienced a myocardial infarction. 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 even after patients receiving clopidogrel – a drug that WebMD says is used to prevent heart attack and stroke in patients with heart disease or peripheral vascular disease, or who have had a recent heart attack or stroke – had been excluded (adjusted OR = 1.14; 95% CI, 1.06-1.24). The researchers noted that patients treated with H2 blockers such as Tagamet or Zantac, an alternative GERD therapy, did not have increased risk for MI (adjusted OR = 0.93; 95% CI, 0.86-1.02), Healio.com reports.

Analysis of the second set, which included 227,438 patients with GERD, revealed similar results as the STRIDE set, (adjusted OR = 1.19; 95% CI, 1.09-1.3). The team also evaluated data from collected from 1,503 patients enrolled in the GenePAD prospective cohort study and calculated a significantly increased risk for CV-related mortality among PPI users after adjustment for CV comorbidities (HR = 2; 95% CI, 1.07-3.78). Like the STRIDE analysis, H2 blockers were not associated with increased risk in this population (HR = 1; 95% CI, 0.14-7.26), according to Healio.com.

The researchers wrote that if an algorithm similar to the one used in this analysis had been available, the increased CV risk associated with lansoprazole use could have been identified as early as 2000. Additionally, the team wrote, the results of the analysis are open to confounding, as PPI use may indicate a sicker population, Healio.com reports.

“Our report raises concerns that these drugs — 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,” researcher Nicholas J. Leeper, MD, of the divisions of cardiovascular medicine and vascular surgery at Stanford University, said in a press release viewed by Healio.com.

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