Proton Pump Inhibitors and Cardiovascular Events: A Systematic Review

Heart Lung Circ. 2018 Apr;27(4):443-450. doi: 10.1016/j.hlc.2017.10.020. Epub 2017 Nov 20.


Background: Proton pump inhibitors (PPIs) are a commonly prescribed medication that recent data has linked to an increased risk of cardiovascular morbidity and all cause morbidity. The current study sought to perform a systematic review to investigate the link between PPIs and morbidity and mortality METHODS: A systematic review was carried out as per the PRISMA guidelines, with information databases including Pubmed, Medline, and the Cochrane Review Database. English-language studies of all types published from January 1990 to October 2016 were considered. Dichotomous analysis generating odds ratios was performed using RevMan Version 5.3.

Results: Thirty-seven studies were considered, of which five directly compared the effect of PPI use on mortality and/or cardiovascular morbidity (including 22,427 patients in mortality datasets, and 354,446 patients in morbidity datasets). For patients taking PPIs, all cause mortality (OR 1.68 [95% CI 1.53-1.84], p<0.001) and rate of major cardiovascular events (OR 1.54 [95% CI 1.11-2.13], p=0.01) were significantly higher.

Conclusions: The current systematic review demonstrates that, in patients using PPIs, there was a significant increase in morbidity due to cardiovascular disease. Careful consideration should be given to the prescription of PPIs while clinical equipoise remains. Further research in the area is required.

Keywords: ADMA; Cardiovascular disease; Mortality; Myocardial infarct; Nitric oxide; Proton pump inhibitor.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Cardiovascular Diseases* / chemically induced
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / metabolism
  • Cause of Death / trends
  • Gastroesophageal Reflux / drug therapy*
  • Gastroesophageal Reflux / metabolism
  • Global Health
  • Humans
  • Morbidity / trends
  • Nitric Oxide / metabolism
  • Proton Pump Inhibitors / adverse effects*
  • Survival Rate / trends


  • Proton Pump Inhibitors
  • Nitric Oxide