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

•Platelet reactivity cutoffs may predict major adverse cardiovascular events (MACE).•We assessed P2Y12 reaction unit (PRU) cutoff values in PRASFIT-ACS.•MACE occurred in 5.2% and 10.8% in patients with PRU ≤ 262 or > 262, respectively.•The risk of MACE was lower in patients with PRU ≤ 262 at 3 days after PCI.•More prasugrel-treated patients than clopidogrel-treated patients had PRU ≤ 262.

BackgroundFew 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 3 days after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS).MethodsWe 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: 20 mg/3.75 mg) with those of clopidogrel (300 mg/75 mg) on MACE and bleeding events for 24-48 weeks after PCI in ACS patients. PRU was serially measured using the VerifyNow® P2Y12 assay and we assessed the relationship between PRU and MACE.ResultsReceiver operating characteristic curve analysis showed that PRU ≤ 262 at 5-12 h after ADP receptor antagonist loading was the optimal cutoff value for preventing MACE at up to 3 days 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.ConclusionsThe 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.