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

Proton Pump Inhibitors and Cardiovascular Events: A Systematic Review.

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Department of Vascular Surgery, St George Hospital, Kogarah, NSW, Australia. Electronic address:
Department of Vascular Surgery, St George Hospital, Kogarah, NSW, Australia.



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.


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.


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.


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

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