Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis

Neurogastroenterol Motil. 2017 Feb;29(2). doi: 10.1111/nmo.12926. Epub 2016 Aug 30.


Background and purpose: Proton pump inhibitors (PPIs) are commonly used as potent gastric acid secretion antagonists for gastro-esophageal disorders and their overall safety in patients with gastro-esophageal reflux disease (GERD) is considered to be good and they are well-tolerated. However, recent studies have suggested that PPIs may be a potential independent risk factor for cardiovascular adverse events. The aim of our meta-analysis was to examine the association between PPI monotherapy and cardiovascular events in patients with GERD.

Methods: A literature search involved examination of relevant databases up to July 2015 including PubMed, Cochrane Library, EMBASE, and, as well as selected randomized controlled trials (RCTs) reporting cardiovascular events with PPI exposure in GERD patients. In addition, the pooled risk ratio (RR) and heterogeneity were assessed based on a fixed effects model of the meta-analysis and the I2 statistic, respectively.

Key results: Seventeen RCTs covering 7540 patients were selected. The pooled data suggested that the use of PPIs was associated with a 70% increased cardiovascular risk (RR=1.70, 95% CI: [1.13-2.56], P=.01, I2 =0%). Furthermore, higher risks of adverse cardiovascular events in the omeprazole subgroup (RR=3.17, 95% CI: [1.43-7.03], P=.004, I2 =25%) and long-term treatment subgroup (RR=2.33, 95% CI: [1.33-4.08], P=.003, I2 =0%) were found.

Conclusion & inferences: PPI monotherapy can be a risk factor for cardiovascular adverse events. Omeprazole could significantly increase the risk of cardiovascular events and, so, should be used carefully.

Keywords: cardiovascular events; gastro-esophageal reflux disease; meta-analysis; proton pump inhibitors.

Publication types

  • Meta-Analysis

MeSH terms

  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / epidemiology*
  • Gastroesophageal Reflux / drug therapy*
  • Gastroesophageal Reflux / epidemiology*
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / adverse effects
  • Humans
  • Omeprazole / administration & dosage
  • Omeprazole / adverse effects
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects*
  • Randomized Controlled Trials as Topic / methods
  • Risk Factors


  • Gastrointestinal Agents
  • Proton Pump Inhibitors
  • Omeprazole