Optimal cutoff value of P2Y12 reaction units to prevent major adverse cardiovascular events in the acute periprocedural period: post-hoc analysis of the randomized PRASFIT-ACS study

Abstract

Background: Few studies have examined the effects of on-treatment platelet reactivity on the risk of major adverse cardiovascular events (MACE). We aimed to determine the optimal cutoff value of P2Y12 reaction units (PRUs) to prevent MACE occurring within 3days after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS).

Methods: We performed post-hoc analyses of 1363 patients enrolled in PRASFIT-ACS, which compared the effects of a prasugrel regimen adjusted for Japanese patients (loading dose/maintenance dose: 20mg/3.75mg) with those of clopidogrel (300mg/75mg) on MACE and bleeding events for 24-48weeks after PCI in ACS patients. PRU was serially measured using the VerifyNow® P2Y12 assay and we assessed the relationship between PRU and MACE.

Results: Receiver operating characteristic curve analysis showed that PRU ≤262 at 5-12h after ADP receptor antagonist loading was the optimal cutoff value for preventing MACE at up to 3days after PCI. The incidences of MACE were 5.2% and 10.8% in patients with PRU ≤262 or >262, respectively (odds ratio 0.50, 95% confidence interval 0.25-0.99, p<0.01). Significantly more prasugrel-treated patients had lower on-treatment platelet reactivity (defined as PRU ≤262) compared with clopidogrel-treated patients (79.9% vs. 30.4%, p<0.0001). Similar differences were observed between the prasugrel and clopidogrel groups for patients with normal or reduced-function CYP2C19 alleles.

Conclusions: The optimal PRU cutoff value for preventing MACE was 262 in Japanese ACS patients. Prasugrel rapidly reduced PRU with a large proportion of patients having low on-treatment platelet reactivity.

Keywords: Acute coronary syndrome; CYP2C19; Clopidogrel; Major adverse cardiovascular event; Platelet reactivity; Prasugrel.