Platelet Responsiveness to Clopidogrel Treatment After Peripheral Endovascular Procedures: The PRECLOP Study: Clinical Impact and Optimal Cutoff Value of On-Treatment High Platelet Reactivity

Abstract

This study aimed to assess the clinical implications and optimal cutoff value of high platelet reactivity (HPR) in patients receiving clopidogrel for peripheral endovascular procedures. As noted in coronary studies, HPR could be related to increased adverse events. This prospective trial included patients receiving clopidogrel 75 mg daily, before and after infrainguinal angioplasty or stenting. Platelet inhibition was assessed with the VerifyNow P2Y12 point-of-care test. Primary endpoints were 1-year clinical events rate (composite endpoint of death, major stroke, major amputation, target vessel revascularization, and bypass) according to the P2Y12 reaction units (PRU)-based quartile distribution, the estimation of the optimal PRU cutoff value for predicting clinical outcome, and the identification of independent predictors influencing event-free survival. In total, 100 consecutive patients were enrolled. The 1-year cumulative events rate was 4% in the first quartile, 12%in the second, 52% in the third, and 84% in the fourth. Pairwise comparisons demonstrated a significant difference in the composite endpoint between successive quartiles (all p< 0.05 except for the first vs. second quartile). According to receiver-operating characteristic curve analysis, the optimal cutoff value for the composite endpoint was PRU≥234 (area under the curve: 0.883; 95% confidence interval [CI]: 0.811 to 0.954; p< 0.0001; sensitivity: 92.1%; specificity: 84.2%). Cox multivariate regression analysis identified HPR (PRU≥234) as the only independent predictor of an increased number of adverse events (hazard ratio: 16.9; 95% CI: 5 to 55; p< 0.0001). On-treatment HPR is associated with markedly increased adverse clinical events in patients undergoing peripheral endovascular procedures. Point-of-care clopidogrel assessment might be useful in individualizing antiplatelet therapy to attain superior clinical results. (High On-Treatment Platelet Reactivity Following Peripheral Endovascular Procedures [PRECLOP]; NCT01744613).