Adequate P2Y12 inhibition by clopidogrel increases adverse clinical events in patients undergoing transcatheter aortic valve replacement

Background Dual antiplatelet therapy (DAPT) has been proposed to explain the increased occurrence of major bleeding events after transcatheter aortic valve replacement (TAVR) despite no relevant study exploring the extent of platelet inhibition by clopidogrel. Purpose To assess whether P2Y12 inhibition by clopidogrel as evaluated by vasodilator-stimulated phosphoprotein (VASP) flow cytometry test impacts clinical outcomes in patients undergoing TAVR. Methods Patients were enrolled in a prospective registry at Nouvel Hopital Civil, Strasbourg, France between February 2010 and May 2019. VASP flow cytometry test was assessed 24 h after the procedure. Responder to clopidogrel was defined by a platelet reactivity index ≤ 50%. The primary endpoint was 90-day major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, myocardial infarction, stroke, and heart failure hospitalization. The secondary endpoint was 1-year MACCE. Results Of the 828 patients with available VASP monitoring, we enrolled 491 TAVR patients with preprocedural clopidogrel therapy. Responders were identified in 22% (n = 110) and low responders in 78% (n = 381) of patients. By multivariate Cox regression analysis, patients responding to clopidogrel (hazard ratio [HR]: 2.16; 95% confidence interval [CI]: 1.16 to 3.91: P = 0.02) and previous PCI (HR: 2.24; 95% CI: 1.07 to 4.81; P = 0.03) were identified as independent predictors of 90-day MACCE. The cumulative event-free survival rate at 90-day and 1-year was significantly lower in the responder group ( Fig. 1 ). Conclusions Appropriate P2Y12 inhibition by clopidogrel is a major determinant of 90-day and 1-year post-TAVR adverse clinical events. In sum, the present data challenge DAPT as a standard therapy during TAVR.