BACKGROUND: 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.
METHODS: 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.
RESULTS: 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 <0.001), at 24 h (2.9% vs. 28.6%, p=0.006), and 
at 30 days (11.4% vs. 34.3%, p=0.004). Prasugrel had a similar rate of optimal 
platelet reactivity at 30 days (71.4% vs. 60.0%, p=0.450). There was no 
significant difference in the occurrence of periprocedural myonecrosis within 
48 h after PCI with clopidogrel and prasugrel (22.9% vs. 17.1%, p>0.960).
CONCLUSIONS: 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.