Inappropriate Use of Proton Pump Inhibitors Increases Cardiovascular Events in Patients with Coronary Heart Disease

Abstract

Antiplatelet drugs, as the cornerstone of the treatment of coronary heart disease, control the progression of the disease, but bring a higher risk of gastrointestinal bleeding. Relevant guidelines recommend the use of proton pump inhibitors (PPIs) to minimize the risk of gastrointestinal bleeding in patients receiving dual antiplatelet therapy. But for people at low risk of gastrointestinal bleeding, the harms associated with routine use of PPIs may far outweigh the benefits. PPIs increase the risk of lower gastrointestinal bleeding, inhibit the effect of antiplatelet drugs, impair vascular endothelial function, meanwhile induce hypomagnesemia, iron deficiency, vitamins D and K deficiency, etc. Eventually, PPIs may lead to an increase in cardiovascular events. However, the situation is that PPIs are often overused. This review elucidates the mechanisms by which PPIs increase cardiovascular events, thereby reminding clinicians to rationally prescribe PPIs.

Heartburn’s Hidden Impact: A Narrative Review Exploring Gastroesophageal Reflux Disease (GERD) as a Cardiovascular Disease Risk Factor

“…Two studies have argued that inappropriate use of PPIs has unnecessarily increased the risk of adverse cardiovascular outcomes. Hu et al in 2022 and Ma et al in 2022 both reported an increased ASCVD risk associated with GERD, especially in patients without indications for the medications [35,47,48,57].…”

“…PPIs and H2RAs are frequently prescribed to patients with both GERD and concomitant coronary artery disease or previous myocardial infarctions due to concerns about chronic excess gastric acid secretion with chronic NSAID, antiplatelet, and/or anticoagulant agents and the increased risk for upper gastrointestinal bleeding [48]. However, new data suggests that PPIs may play a role in the incidence, progression, and mortality of cardiovascular disease [49].…”

“…Long-term use of PPIs has been shown to increase the risk of cardiovascular events through multiple pathways, including inhibition of lysosomal acidification, impairment of protein homeostasis, and reduction in telomere length, resulting in endothelial dysfunction and endothelial cell senescence [48]. A study by Taneja et al found that subacute administration of PPIs did not produce any toxicological impact on the endothelial tissue, but subchronic administration of PPIs caused moderate vascular endothelial dysfunction in a dose-dependent manner, suggesting a decrease in NO bioavailability and increased oxidative stress may lead to vascular endothelial dysfunction [51].…”

“…Another study by Hamzeloo-Moghadam et al identified several critical genes associated with cardiovascular disease (CTNNB1, HNRNPA1, SRSF4, TRA2A, SFPQ, and RBM5) that can be deregulated with PPI use [49]. Furthermore, several studies have shown that PPIs elevate plasma asymmetrical dimethylarginine (ADMA) levels, an endogenous inhibitor of NO synthase, through inhibition of dimethylarginine dimethylaminohydrolase, an enzyme that degrades ADMA [48,52].…”

Impact of Concomitant Use of Proton Pump Inhibitors and Clopidogrel on Recurrent Stroke and Myocardial Infarction

“…As PPI use increases worldwide, growing concerns about PPI complications have been raised [ 6 , 7 , 8 ]. Specifically, drug interaction with clopidogrel, which is an antiplatelet agent classified as thienopyridines, has been postulated in many recent studies [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Both PPIs and clopidogrel are metabolized by hepatic cytochrome P450 (CYP) enzymes; in the presence of CYP2C19 inhibition, PPIs could reduce the efficacy of clopidogrel’s protective roles in cardiovascular events [ 22 ].…”