NEW ORLEANS – Use of proton pump inhibitors (PPIs) is associated with an increased risk of first stroke, according to data presented at the 2016 American Heart Association Scientific Sessions in New Orleans.1

“PPIs have been associated with unhealthy vascular function, including heart attacks, kidney disease, and dementia,” Thomas Sehested, MD, study author and a researcher at the Danish Heart Foundation in Copenhagen, Denmark, said in a statement.2 “We wanted to see if PPIs also posed a risk for ischemic stroke, especially given their increasing use in the general population.”

In order to better understand the effects of PPIs on stroke risk, Dr Sehested and colleagues performed a retrospective cohort study using nationwide Danish registries to identify patients older than 30 years of age who had had an elective endoscopy between 1997 and 2012. Patients with cardiovascular disease at baseline were excluded.

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Ultimately, 244,679 people were included in the study (mean age: 57 years), of which 44% filled a prescription for a PPI. Notably, PPI users were older and had more comorbidities, including atrial fibrillation, than their non-user counterparts.

Over the course of follow-up, 9489 first-time stroke events occurred. After adjusting for age, sex, atrial fibrillation, hypertension, diabetes, heart failure, peptic ulcer, cancer, chronic kidney disease, and NSAID use, the researchers found that there was a time-dependent association between PPI use and stroke (incidence rate ratio [IRR]: 1.21; 95% confidence interval [CI], 1.16-1.27; P <.001). A dose-response relationship was also observed between PPI use and risk of ischemic stroke, with risk increases as much as 94% for patients taking pantoprazole. Notably, Histamine H2 receptor antagonists had no association with stroke risk (IRR: 0.99; 95% CI, 0.83-1.21; P =.99).

“At one time, PPIs were thought to be safe, without major side effects,” Dr Sehested said.2 “This study further questions the cardiovascular safety of these drugs.”

While there was no observed risk for H2 blockers, the authors could not determine if this class of drugs is safer in this population, noting that a randomized controlled trial focused on the cardiovascular safety of these drugs is warranted.2

Disclosures: Dr Torp-Pedersen reports serving as consultant or advisory board member for Cardiome, Merck, Sanofi, and Daiichi, and receiving grant support from Bristol-Myers Squibb. Dr Gislason reports grant support from Bristol-Myers Squibb, Boehringer-Ingelheim, Bayer, Pfizer, and AstraZeneca.


  1. Sehested TSG, Fosbol EL, Hansen PW, Charlot MG, Torp-Pedersen C, Gislason GH. Abstract 765. Proton pump inhibitor use increases the associated risk of first-time ischemic stroke. A nationwide cohort study. Presented at: the 2016 American Heart Association Scientific Sessions. November 12-16, 2016; New Orleans, LA.
  2. Popular heartburn medication may increase ischemic stroke risk [press release]. Dallas, TX: American Heart Association/American Stroke Association Newsroom;  November 15, 2016.

This article originally appeared on The Cardiology Advisor