Pharmacodynamic effect of adjunctive cilostazol vs. high-dos clopidogrel in acute coronary syndrome patients according to the CYP2C19 genotype (ACCEL-GENOTYPE) study

초록

Purpose: Cilostazol use in ACS patients has been reduced the risks of ischemic events and restenosis in East Asians. Compared with Caucasians, East Asians have higher frequency of CYP2C19 loss-of-function allele (*2 and *3). We compared the pharmacodynamic effect of adjunctive cilostazol vs. high-dose clopidogrel in PCI-treated East Asians with ACS according to the CYP2C19 genotype.Methods: ACS patients were assigned to either clopidogrel 150 mg/d (DOUBLE group; n=139) or cilostazol 100 mg twice a day + clopidogrel 75 mg/d (TRIPLE group; n=136) on top of aspirin. Platelet aggregation (PA) was measured at baseline and at least 30-day follow-up with light transmittance aggregometery (20 μM ADP and 6 μg/ml collagen). PAs were adjusted with known clinical covariates. CYP2C19*2 or *3 genotype was determined. Primary endpoint was the level of 20 μM ADP-induced PA at follow-up. HPR was defined as 20 μM ADP-induced PA >59%.Results: During standard-dose clopidogrel treatment, platelet measurements did not differ according to individual CYP2C19 genotype between the groups (Fig. 1A). PA levels and HPR risk increased across the CYP2C19 genotype (p≤0.174). At follow-up, the TRIPLE vs. DOUBLE group showed significantly lower level of PAs irrespective of the CYP2C19 genotype (Fig. 1B). In the DOUBLE group, the risk of HPR was observed in 27.3% of patients and increased across the CYP2C19 genotype (adjusted p=0.042), whereas the effect of TRIPLE regimen was not significantly influenced with the CYP2C19 genotype (adjusted p=0.289). Similar trend was observed for collagen-induced PA.Conclusion: In PCI-treated East Asians presented with ACS, adjunctive cilostazol exhibited favorable platelet measurements compared with high-dose clopidogrel irrespective of the CYP2C19 genotype.