Pharmacodynamic study of prasugrel or clopidogrel in non-ST-elevation acute coronary syndrome with CYP2C19 genetic variants undergoing percutaneous coronary intervention (PRAISE-GENE trial)

• Published in: International journal of cardiology 2020-04, Vol.305, p.11-17
• Main Authors: Jin, Cai De, Kim, Moo Hyun, Guo, Long Zhe, Jin, Enze, Shin, Eun-Seok, Ann, Soe Hee, Cho, Young-Rak, Park, Jong Sung, Kim, Soo Jin, Lee, Michael S.
• Format: Article
• Language: English
• Subjects: Acute Coronary Syndrome - drug therapy; Acute Coronary Syndrome - genetics; Acute Coronary Syndrome - surgery; Blood Platelets; Clopidogrel; CYP2C19 2/3; Cytochrome P-450 CYP2C19 - genetics; Humans; Non-ST-elevation acute coronary syndrome; Percutaneous Coronary Intervention; Periprocedural myonecrosis; Platelet Aggregation Inhibitors; Prasugrel; Prasugrel Hydrochloride; Ticlopidine; Treatment Outcome
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2020.01.058

The CYP2C19*2 or *3 loss-of-function (LOF) allele is associated with high platelet reactivity (HPR) on clopidogrel treatment. East Asians may benefit from a lower dose of prasugrel due to their more potent platelet inhibitory response. The impact of LOF alleles on the pharmacodynamic response to half-dose prasugrel in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) is unknown. Seventy patients with the LOF alleles were assigned to half-dose prasugrel (n = 35, 30-mg load followed by 5 mg daily) or clopidogrel (n = 35, 600-mg load followed by 75 mg daily). The primary endpoint was the rate of HPR, defined as VerifyNow-P2Y12 reaction unit (PRU) >235, at 24 h post loading. Prasugrel achieved a lower PRU compared to clopidogrel after loading (119 [56–175] vs. 245 [189–299]), at 24 h (34 [8–58] vs. 196 [122–244]), and at 30 days (134 [98–189] vs. 203 [144–248]). Prasugrel had a lower rate of HPR after loading (5.7% vs. 57.1%, p 0.960). Half-dose prasugrel provided potent platelet inhibition in NSTE-ACS patients that were carriers of the CYP2C19*2 or *3 allele, with a lower rate of HPR. Periprocedural myonecrosis was not significantly different in the 2 groups. •The CYP2C19*2 or *3 allele is associated with high-on-clopidogrel platelet reactivity.•Half-dose prasugrel provided potent platelet inhibition in carriers of the CYP2C19*2 or *3 allele.•Periprocedural myonecrosis was not significantly different in the 2 groups.