P5732Prasugrel or clopidogrel in non-ST-elevation acute coronary syndrome with CYP2C19 genetic variants undergoing percutaneous coronary intervention

Abstract

Background: CYP2C19 genetic variant (CYP2C19∗2 or ∗3 loss‐of‐function allele) is linked with high‐on‐treatment platelet reactivity (HPR) during clopidogrel therapy. There is insufficient data offered any significant influence of LOF alleles on the platelet response to half‐dose prasugrel in patients with non‐ST‐elevation acute coronary syndromes (NSTE‐ACS). Methods: In the PRAISE‐GENE trial, 70 eligible patients with carriage of LOF alleles were screened by the Spartan RX CYP2C19 system (Spartan Bioscience Inc, Ottawa, Canada), randomized to receive either prasugrel (n=35, 30‐mg load followed by 5 mg maintenance daily) or clopidogrel (n=35, 600‐mg load followed by 75 mg maintenance daily). The pharmacokinetic response was assessed at post‐loading status, post‐24 hours and 30 days with VerifyNow method. Results: In comparison to clopidogrel, prasugrel achieved significantly lower P2Y12 reaction units [119 (56‐175) vs. 245 (189‐299)], [34 (8‐58) vs. 196 (122‐244)], and [134 (98‐189) vs. 203 (144‐248)] at each time‐point measurement, respectively. For the primary endpoint, the HPR rate in prasugrel was lower than thatin clopidogrel (2.9% vs. 25.7%, p=0.013) at post‐loading 24 hours, (20.0% vs. 45.7%, p=0.041) at chronic post‐30‐day status as well. More than 60% of study population suffered from periprocedural myonecrosis based any post‐procedure cTn elevation within 48 hours (65.7% for clopidogrel vs. 60.0% for prasugrel, p=0.805; relative risk: 0.91, 95% CI: 0.64‐1.31, p=0.494). In regression analy‐sis, neither VN‐HPR at post‐loading status before PCI nor prasugrel treatment was not associated with myonecrosis, interestingly, current smoking had a 44% reduction in thisevent (relative risk 0.56, 95% CI: 0.34‐0.93, p=0.026). For safety endpoint, only 3 patients (4.3%) experienced minor bleedings (BARC: type 1), especially in prasurel group (8.6%), without occurrence of ischemic event during 30‐day period. [Figure Presented] Conclusions: Half‐dose prasugrel (30/5mg) still maintained potent platelet in‐hibition in NSTE‐ACS patients with carriage of CYP2C19∗2 or ∗3 allele, with moderate increase in minor bleedings, not significantly. The PRAISE‐GENE trial (NCT01641510) exhibited that periprocedural myonecrosis was commonly oc‐curred by troponin assessment, however, without any influence on the adverse events in the short‐term observation. Funding Acknowledgements: The Ministry of Health & Welfare (No. HI14C1731) and National Research Foundation of Korea (NRF) (No. 2015R1D1A1A09057025).