September 05, 2018
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Insufficient evidence to link PPIs to cardiovascular risk

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Researchers found no solid evidence of an association between proton pump inhibitor monotherapy and increased cardiovascular risk, according to a meta-analysis published in Alimentary Pharmacology & Therapeutics.

Danny Liew, MBBS, PhD, of the department of epidemiology and preventive medicine at Monash University in Melbourne, Australia, and colleagues wrote that the FDA has warned against using PPIs combined with the antiplatelet therapy clopidogrel because the drugs target the same isoenzyme.

“Inhibition of CYP2C19 by PPIs may reduce the bioavailability of the active metabolites of clopidogrel, and attenuate clopidogrel’s cardiovascular benefits,” they wrote. “It has been suggested that the observed risk of PPI use with antiplatelet therapy may be partly due to an increase in cardiovascular risk conferred by PPIs directly. To help address this theory, a systematic review and metaanalysis was conducted to explore the association between cardiovascular risk and PPIs independent of concomitant clopidogrel therapy.”

Liew and colleagues searched the literature for studies with a primary outcome of association between PPI monotherapy and any adverse cardiovascular event. The secondary outcome was association between PPI monotherapy and acute myocardial infarction. They excluded any study that did not report or adjust for concomitant antiplatelet therapy or included patients younger than 18 years.

Investigators included data from 16 studies (eight randomized controlled trials, seven observational studies and one retrospective analysis of a randomized controlled trial) comprising 447,408 patients in their meta-analysis.

In their review of observational studies, Liew and colleagues found an increased risk for any adverse cardiovascular event with PPI monotherapy (RR = 1.25; 95% CI, 1.11-1.42; I² = 81%). However, their analysis of the eight randomized controlled trials found no increased risk (RR = 0.89; 95% CI, 0.34-2.33; I² = 0%).

“Given the limitations of observational data, these results may offer some reassurance when considering the cardiovascular safety of proton pump inhibitor monotherapy, in the context of emerging concerns about the general appropriateness of their widespread use,” Liew and colleagues wrote. – by Alex Young

Disclosures: Liew reports he has served as a speaker, a consultant and an advisory board member for AbbVie, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Pfizer, Sanofi and Shire, and received research funding from AstraZeneca, Bristol-Myers Squibb, Pfizer, Sanofi and Shire. Please see the study for all other authors’ relevant financial disclosures.