Comparison of loading with maintenance dose of clopidogrel on platelet reactivity in Chinese with different CYP2C19 genotypes prior to percutaneous coronary intervention.

Background Whether two clopidogrel pretreatment strategies prior to elective percutaneous coronary intervention (PCI): a 300 mg loading dose (LD) in clopidogrel naive patients and a 75 mg maintenance dose (MD) once daily in patients on chronic clopidogrel therapy play the same role in the platelet inhibition in Chinese with different CYP2C19 genotypes remains unknown. We aim to evaluate the impact on platelet inhibition by clopidogrel pretreatment strategy and its interaction effect with CYP2C19 genotype. Methods Chinese patients undergoing PCI (n=840) were assigned to 2x2 groups in the trial according to different clopidogrel pretreatment strategies (470 patients in LD, 370 patients in MD) and CYP2C19 genotypes (494 carriers of any CYP2C19 *2 or *3 loss-of-function allele, 346 non-carriers). The primary outcome was platelet aggregation (PA) as measured by the 10 mu mol/L adenosine diphosphate induced light transmission aggregation. Results Compared with MD group, LD strategy showed a significantly higher PA-((59.22 +/- 11.67)% vs. (52.83 +/- 12.17)%, P<0.01), similar PA difference was observed in CYP2C19 loss-of-function carriers compared with non-carriers ((59.41 +/- 10.91)% vs. (52.10 +/- 12.90)%, P<0.01). LD patients in either the CYP2C19 loss-of-function allele carrier or non-carrier group showed a significantly higher PA compared with MD group ((61.50 +/- 10.61)% vs. (56.84 +/- 10.74)%, P<0.01; (56.06 +/- 12.34)% vs. (46.88 +/- 11.78)%, P<0.01, respectively). A quantitative interaction effect was observed between clopidogrel pretreatment strategy and CYP2C19 genotype (P=0.001). Conclusion The 300 mg LD strategy results in a decreased effect on platelet inhibition compared with the 75 mg MD in Chinese patients receiving clopidogrel prior to PCI, especially in the CYP2C19 *2 or *3 loss-of-function allele non-carriers.