Prevalence and predictors of high-on treatment platelet reactivity during prasugrel treatment in patients with acute coronary syndrome undergoing stent implantation

BACKGROUND: ADP-antagonists such as prasugrel have reduced but yet not overcome the phenomenon of high-on treatment platelet reactivity (HRPR), that has been shown to increase the rate of major cardiovascular events after an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI). However, the exact prevalence and the principal determinants of suboptimal platelet inhibition in patients treated with dual antiplatelet therapy (DAPT) with prasugrel have not been completely clarified and were therefore the aim of the present study. METHODS: We included patients (<75 years and >60kg) treated with DAPT (aspirin+prasugrel) after PCI, mainly for an ACS. Platelet function test evaluation was performed at 1-3 months from discharge. HRPR was assessed by multiplate impedance aggregometry and defined for results above upper limit of normal after ADP stimulation. RESULTS: We included 190 post-ACS patients. HRPR with prasugrel was observed in 19 patients (10%). The prevalence of HRPR was stable in different high-risk subgroups of patients (female gender, hypercholesterolemic, and chronic kidney disease) whereas it was increased in diabetic patients (p=0.045), with a significant interaction between diabetic status and HRPR (p=0.04). However, at multivariate analysis, an impaired metabolic status, with higher levels of glycosylated hemoglobin and low-density lipoprotein (LDL) cholesterol, but not diabetic status, emerged as independent predictors of HRPR with prasugrel [OR (95% CI)=2.1 (1.32-3.33), p=0.002 and OR (95% CI)=1.03 (1.01-1.05), p=0.003, respectively], with a stronger linear relationship between ADP-mediated platelet aggregation and glycosylated hemoglobin levels (r=0.24, p=0.002), than for LDL-cholesterol (r=0.13, p=0.09). CONCLUSIONS: In post-ACS patients treated with PCI and receiving DAPT with prasugrel, HRPR is observed in about 10% of patients. Impaired metabolic status, and especially elevated glycosylated hemoglobin, emerged as independent predictors of the suboptimal effectiveness of prasugrel.