Variability of prasugrel antiplatelet effect in patients with acute coronary syndrome

Abstract

Background. Many reports have demonstrated excessive variability in response to clopidogrel, the most commonly used P2Y12 receptor antagonist. Clopidogrel resistant patients are at increased risk of cardiovascular (CV) events. Prasugrel is a new P2Y12 inhibitor that provides greater and faster platelet inhibition and reduces CV events more effectively than clopidogrel. The aim of this study was to evaluate the variability and efficacy of prasugrel antiplatelet activity in patients presenting with acute coronary syndrome (ACS).

Materials and methods. The study was designed as a prospective, single-center, non-randomized, observational trial. Platelet reactivity (PR) was assessed with the VeryfyNow assay three times during hospitalization in forty-two patients undergoing percutaneous coronary intervention (PCI) for ACS and treated with standard doses of prasugrel.

Results. Platelet aggregation with prasugrel displayed relatively high variability. The platelet aggregation was lowest on the 3rd day of the treatment at 4 p.m. and was significantly different from the measurements obtained on the 3rd and 4th day in the morning (6.0 v. 8.5 U; p = 0.0005 and 6.0 v. 36.5 U; p < 0.00001, respectively), with the latter two differing significantly from each other (p = 0.002). All participants were successfully treated with prasugrel achieving PR < 208 PRU in each measurement, whereas 42.9–80.9% (depending on sampling point) of patients presented very low platelet activity. The subgroups of stable and persistent low PR included a higher percentage of active smokers (73.3 v. 40.7%; p = 0.04 and 80.0 v. 43.8%; p = 0.04, respectively).

Conclusions. Prasugrel treatment is associated with high variability of PR. Nonetheless, prasugrel is a highly effective antiplatelet drug. Active smoking may predispose to strong and stable on-prasugrel platelet inhibition.