Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6-month or 24-month DAPT duration : insights from the PRODIGY trial

Background: Proton-pump inhibitors (PPIs) are frequently prescribed in combination with clopidogrel, but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention (PCI) and dual antiplatelet therapy with clopidogrel plus aspirin. Methods and Results: In the Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia (PRODIGY) trial, 1970 patients were randomized to 6or 24-month DAPT at 30 days from index procedure. Among them, 738 patients (37.5%) received PPI (mainly lansoprazole; 90.1%) at the time of randomization. PPI users were older, most likely to be woman, had a lower creatinine clearance, presented more frequently with acute coronary syndrome (ACS) and had a higher CRUSADE bleeding score. After adjustment, the primary efficacy endpoint (composite of all-cause death, myocardial infarction and cerebrovascular accident) was similar between no PPI and PPI users (9.2% vs 11.5%; adj. HR: 1.051; 95% confidence interval [CI] 0.7881.400; p=0.736). Bleeding rates did not differ between the two groups (BARC type 2, 3 or 5: adj. HR 0.996; 95% CI 0.672-1.474; p=0.980). Net clinical adverse events (NACE) were also similar in no PPI and PPI patients (12.9% vs 14.9%; adj. HR: 0.99; 95% CI 0.772-1.268; p=0.93). Results remained consistent at sensitivity analysis when focusing on the 548 patients who remained on PPI for the whole study duration. Conclusions: The current findings suggest that the concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcome.