De Maria E. Letter to the Editor: Methodology vs reality - deciphering cardiovascular safety of proton pump inhibitors in dual antiplatelet therapy. World J Cardiol 2026; 18(7): 123807 [DOI: 10.4330/wjc.123807]
Corresponding Author of This Article
Elia De Maria, MD, Arrhythmology Lab, Cardiology Unit, Ramazzini Hospital, Via Molinari 1, Carpi 41012, Modena, Italy. e.demaria@inwind.it
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Cardiac & Cardiovascular Systems
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letter
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De Maria E. Letter to the Editor: Methodology vs reality - deciphering cardiovascular safety of proton pump inhibitors in dual antiplatelet therapy. World J Cardiol 2026; 18(7): 123807 [DOI: 10.4330/wjc.123807]
World J Cardiol. Jul 26, 2026; 18(7): 123807 Published online Jul 26, 2026. doi: 10.4330/wjc.123807
Letter to the Editor: Methodology vs reality - deciphering cardiovascular safety of proton pump inhibitors in dual antiplatelet therapy
Elia De Maria
Elia De Maria, Arrhythmology Lab, Cardiology Unit, Ramazzini Hospital, Carpi 41012, Modena, Italy
Author contributions: De Maria E wrote and revised the manuscript.
AI contribution statement: AI (Google Gemini) was used for English editing.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Elia De Maria, MD, Arrhythmology Lab, Cardiology Unit, Ramazzini Hospital, Via Molinari 1, Carpi 41012, Modena, Italy. e.demaria@inwind.it
Received: June 3, 2026 Revised: June 24, 2026 Accepted: July 9, 2026 Published online: July 26, 2026 Processing time: 50 Days and 11.8 Hours
Abstract
Dual antiplatelet therapy (DAPT) is a cornerstone of secondary ischemic prevention following percutaneous coronary intervention. However, DAPT increases the risk of major gastrointestinal bleeding. To mitigate this complication, guidelines suggest prescription of proton pump inhibitors (PPIs) for patients with high-risk profile. The combination of PPI and DAPT has raised concerns because of the risk of drug-drug interaction potentially reducing clopidogrel efficacy and increasing ischemic risk. Randomized controlled trials (RCTs) and observational studies conducted in past years yielded conflicting results. A recent comprehensive meta-analysis recently published in World Journal of Cardiology by Sohail et al evaluated the cardiovascular safety of PPIs in patients with acute coronary syndromes treated with percutaneous coronary intervention and DAPT, including both RCTs and real-world observational studies. By analyzing RCT data independently from observational retrospective cohorts the authors of this meta-analysis successfully untangled the conflicting outcomes and demonstrated that PPI use did not translate into any significant increase in hard cardiovascular endpoints, including acute coronary syndromes, stent thrombosis, all-cause mortality, or cardiac death.
Core Tip: The combination of proton pump inhibitor and dual antiplatelet therapy, in patients undergoing percutaneous coronary intervention, has raised concerns because of the risk of drug-drug interaction potentially reducing clopidogrel efficacy and increasing ischemic risk. A recent meta-analysis, by methodically isolating randomized data from observational biases, proved that the increased cardiovascular risk seen in prior literature was a product of patient-level confounding rather than true biological harm and provided reassurance regarding the safety of combining proton pump inhibitors with clopidogrel.
