CYP2C19 intermediate and poor metabolizer variants were associated with a 2.664-fold increased risk of major adverse cardiovascular events at 1 year compared to extensive metabolizers in patients undergoing percutaneous coronary intervention.
Cohort (n=519)
No
Does CYP2C19 intermediate or poor metabolizer status increase the risk of MACE in coronary heart disease patients undergoing PCI treated with clopidogrel?
CYP2C19 intermediate and poor metabolizer genotypes significantly reduce the antiplatelet efficacy of clopidogrel and increase the risk of MACE at 1 year in patients undergoing PCI.
Odds Ratio: 2.664 (95% CI 1.397–5.193)
Tasa de eventos absoluta: 16.3% vs 7.8%
valor p: p=0.004
The impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary intervention (PCI) was investigated. To this end, we assessed the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 h of PCI in 559 patients treated with clopidogrel and followed up for one year for evidence of MACE. CYP2C19 *2 and *3 variants were identified using a clopidogrel-sensitive gene detection kit. Our results showed higher RPA and MAR as well as increased sE-selectin, sCD40L, sP-selectin, MMP-9 and sVCAM-1 levels in CYP2C19 intermediate metabolizer (IM, CYP2C19*1/*2 or *1/*3), poor metabolizer (PM, CYP2C19*2/*2, *2/*3 or *3/*3) and combined IM+PM groups, relative to those in extensive metabolizers (EM, CYP2C19*1/*1). In total, 519 patients completed one year of follow-up, among which 69 (13.3%) experienced MACE. The risk of MACE in CYP2C19 IM+PM patients was 2.664 times higher than that in CYP2C19 EM patients (OR=2.664(1.397–5.193), P=0.004). The data suggest that CYP2C19*2 and *3 variants modulate the drug efficacy of clopidogrel in coronary heart patients undergoing PCI and further enhance the risk of MACE. Accordingly, CYP2C19 pharmacogenetic profiling may be beneficial for coronary heart patients undergoing PCI to predict the efficacy of treatment with clopidogrel. We propose that IM and PM patients should benefit from treatment with higher clopidogrel doses to improve efficacy and reduce the incidence of MACE.
Sun et al. (Thu,) conducted a cohort in Coronary heart disease undergoing percutaneous coronary intervention (n=519). CYP2C19 intermediate and poor metabolizer variants (IM+PM) vs. CYP2C19 extensive metabolizers (EM) was evaluated on Major adverse cardiovascular events (MACE) (OR 2.664, 95% CI 1.397-5.193, p=0.004). CYP2C19 intermediate and poor metabolizer variants were associated with a 2.664-fold increased risk of major adverse cardiovascular events at 1 year compared to extensive metabolizers in patients undergoing percutaneous coronary intervention.