Exploring the relationship of platelet aggregation function with efficacy and safety outcomes following the administration of prasugrel and clopidogrel in patients with thrombotic stroke: a post hoc analysis of PRASTRO pooled studies

The P2Y12 receptor inhibitor prasugrel was approved for thrombotic stroke in Japan following the phase 3 clinical trials PRASTRO-I, -II, and -III. However, correlations between elevated platelet reaction unit (PRU) and ischemic event risk remain unclear. This post hoc integrated analysis of PRASTRO-I, -II, and -III assessed the relationships of PRU with efficacy and safety outcomes, and risk factors for high PRU (HPR). Patients from PRASTRO-I, -II, and -III receiving prasugrel or clopidogrel and with PRU values at 4 and 24 weeks after treatment initiation were included. The primary endpoint was PRU at 4 weeks; secondary endpoints included cumulative incidence of ischemic and bleeding events from study drug initiation to 48 weeks. Exploratory univariate and multivariate analyses were conducted to identify HPR risk factors. Of 2688 patients analyzed, 2595 and 2434 had PRU values available at 4 and 24 weeks, respectively. Mean PRU was numerically lower with prasugrel than clopidogrel at 4 weeks (151.3 vs. 195.4) and 24 weeks (143.8 vs. 188.0). CYP2C19 polymorphisms affected PRU at 4 and 24 weeks with clopidogrel but not with prasugrel. PRU at 4 weeks did not predict ischemic and bleeding event incidence up to 48 weeks. The CYP2C19 poor metabolizer phenotype was the strongest HPR risk factor. PRU values at 4 and 24 weeks were numerically lower with prasugrel and unaffected by CYP2C19 genetic polymorphisms. Further research is needed to clarify the relationship of PRU with ischemic and bleeding events.