Evaluation of response to loading doses of clopidogrel therapy in patients undergoing percutaneous coronary intervention (PCI)

Abstract

Kheria Saade, Manal El-Hamamsy, Mona Hamdy, Ahmed Magdy Mohamed

Clopidogrel resistance plays a key role in ischemic recurrence after Percutaneous coronary intervention (PCI). The cytochrome P450 (CYP)–dependent conversion of Clopidogrel to its active metabolite may contribute to the variability in antiplatelet effect of Clopidogrel. To evaluate the response to 600 mg Clopidogrel loading dose versus 300 mg loading dose in patients undergo PCI. A total of 51 patients categorized to two groups: Group I consisted of 11 males (64.7%) and 6 females (35.3%) received 300 mg loading does, while Group II consisted of 28 males (82.4%) and 6 females (17.6%) received 600 mg Clopidogrel loading does. Detection of Clopidogrel response was assessed by measuring of the platelet aggregation percentage and CYP2C19 *2 assay in both groups. Clopidogrel resistance was defined by an arbitrary cut off value of ˂10% with respect definition as compared to control value. The percentage of Clopidogrel response among the studied patients was 29.2% for 300 mg Clopidogrel and 70.8% for 6oo mg Clopidogrel loading dose. In non or poor response to Clopidogrel group 10 patients (37%), were resistance to 300mg dose and 17 patients (63%) were resistance to 600mg Clopidogrel dose. Clopidogrel resistance groups were more likely have CYP2C19 genotype (CYP2C19*1.CYP2C19*2) (GA). There were highly significant association between good response group, non and poor response groups as regarding to genotype CYP2C19*1, CYP2C19*1 (GG) carriers and CYP2C19*1,CYP2C19*2 (GA) carriers. Platelet aggregation after 600mg Clopidogrel in both CYP2C19*1, CYP2C19*1 (GG) carriers and CYP2C19*1, CYP2C19*2(GA) carriers is statistically non significant with basal aggregation, before PCI and after PCI, while significant with day after PCI and highly significant with inhibition percentage before PCI. Platelet aggregation after 300mg Clopidogrel in both CYP2C19*1, CYP2C19*1 (GG) carriers and CYP2C19*1, CYP2C19*2(GA) carries is a statistically non significant with basal aggregation, before PCI, day after PCI, and after PCI, while significant with inhibition percentage before PCI. There was no variable individual response to the anti platelet effect of the standard dose (300mg) and higher loading dose (600mg) Clopidogrel therapy, but a variable individual response to Clopidogrel between patients carries CYP2C19*1.CYP2C19*2 (GA) genotype and carries CYP2C19*1.CYP2C19*1 (GG) genotype.

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