Proton Pump Inhibitors Do Not Increase Risk for Cardiovascular Events

Treatment with proton pump inhibitors has no overall effect on risk for cardiovascular events.

Use of proton pump inhibitors (PPIs) do not increase risk for cardiovascular events or mortality, according to study findings published in the European Journal of Internal Medicine.

Researchers conducted a systematic review and meta-analysis of observational studies in MEDLINE, EMBASE, and Scopus databases up until September 2021. They analyzed the relationship between PPI use and risk for cardiovascular events and mortality.

The investigators included 17 studies in their review, excluding only studies with critical risk of bias following risk of bias assessment.

Outcomes of interest included first myocardial infarction, first ischemic stroke, combined cardiovascular events, and cardiovascular mortality.

Overall, pooled analysis of these studies revealed 24,547 cases of first ischemic stroke, 50,824 cases of first myocardial infarction, and 50,329 cases of cardiovascular deaths.

In combination with results from randomized trials it seems therefore questionable, whether PPI intake constitutes a cardiovascular risk factor independent of any possible interaction with clopidogrel.

When analyzing the effects of PPI intake on these cardiovascular events, the researchers calculated pooled hazard ratios (HR) of 1.05 for first myocardial infarction (95% CI, 0.83-1.32), 1.08 for first ischemic stroke (95% CI, 0.97-1.20), 1.05 for all first cardiovascular events (95% CI, 0.96-1.15), and 1.27 (95% CI, 1.11-1.44) for cardiovascular mortality.

PPIs, especially omeprazole, have been known to attenuate the antiplatelet effects of clopidogrel, a P2Y12 inhibitor. After adjusting for confounders and bias, the researchers calculated a pooled HR of 0.99 (95% CI, 0.93-1.04) for the effects of PPI with clopidogrel.

“This qualitative and quantitative synthesis of all available prospective observational studies suggests that PPI intake as a limited treatment of gastroesophageal diseases does not increase the risk of first cardiovascular events,” the study authors wrote. “Reports of increased cardiovascular mortality can largely be explained by publication bias and observational study design biases, such as indication bias and unmeasured confounding. In combination with results from randomized trials it seems therefore questionable, whether PPI intake constitutes a cardiovascular risk factor independent of any possible interaction with clopidogrel.”

Study limitations include data limitations within the included observational studies, lack of ability to capture use of over-the-counter PPIs and combination products, lack of ability to assess duration of PPI intake, and the possibility of low-dose, short-term PPI users diluting the results obtained from high-dose, long-term PPI users.

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.

This article originally appeared on Gastroenterology Advisor

References:

Nolde M, Ahn N, Dreischulte T, et al. Proton pump inhibitors and the risk of cardiovascular events and cardiovascular mortality: A systematic review and meta-analysis of observational studies. Eur J Intern Med. Published online October 1, 2022. doi:10.1016/j.ejim.2022.09.021