Letter to the Editor: Methodology vs reality - deciphering cardiovascular safety of proton pump inhibitors in dual antiplatelet therapy

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.