THE ASSOCIATION BETWEEN CONCOMITANT PROTON-PUMP INHIBITOR USE AND CLINICAL OUTCOMES IN PATIENTS WITH ACUTE CORONARY SYNDROMES TREATED WITH PRASUGREL VERSUS CLOPIDOGREL AND MANAGED WITHOUT REVASCULARIZATION: INSIGHTS FROM THE TRILOGY ACS STUDY

Abstract

Background: There is conflicting evidence regarding the interaction among proton-pump inhibitors (PPIs), platelet P2Y12 inhibitors, and clinical outcomes in ACS patients. Methods: We evaluated 7243 ACS patients aged <75 y with UA/NSTEMI managed without revascularization enrolled in TRILOGY ACS, and analyzed the association between baseline PPI use and study treatment effect of prasugrel vs clopidogrel over 30 months. Adjusted hazard ratio (HR) estimates were derived using Cox proportional models weighted for inverse propensity of PPI use. Results: 1666 patients (23%) were taking a PPI at randomization. Those on PPIs at baseline were older, more likely to have NSTEMI and undergo angiography before randomization, and less likely to have prior heart failure (Table). Among those on PPI at baseline vs those not on PPI, there was no difference in adjusted risk of the primary efficacy endpoint of CV death, MI, or stroke with prasugrel (adjusted HR=1.11; 95% CI: 0.86–1.43), but there was a higher risk with PPI use with clopidogrel (adjusted HR=1.50; 95% CI: 1.19–1.89); interaction p=0.09. Conclusions: Patients with ACS managed medically and taking a PPI at baseline had a higher risk profile than those not on a PPI. Long-term risk of ischemic outcomes associated with PPI use was higher in those treated with clopidogrel vs those treated with prasugrel. Future analyses will evaluate this association with respect to the overall TRILOGY efficacy and safety results, including dedicated platelet function analyses.