Aims: The current study sought to evaluate the clinical impact of newly reported genetic variations and their association with clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation.
Methods and results: The study enrolled 1,016 consecutive patients with ACS undergoing DES implantation. A total of 19 tag single nucleotide polymorphisms (SNPs) were selected from CYP3A4/5, CYP2C19, P2Y12 and ABCB1 genes. ADP-induced light transmittance aggregometry (LTA) was performed to test the post-procedure maximum platelet agglutination (MPA). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), stent thrombosis, and ischaemic stroke at one-year follow-up after DES placement. The secondary endpoint was the incidence of bleeding events. The post-procedure MPA was calculated and the cut-off point was determined for the HTPR. Using multivariate logistic regression analysis, the carriage of two CYP2C19 LOF alleles was an independent predictor of the post-procedure HTPR (OR: 2.8, 95% CI: 1.70-7.23, p<0.001). Through multivariate Cox regression analysis, the carriage of two CYP2C19 LOF alleles and the post-procedure HTPR were independent predictors of the primary endpoint (HR: 2.3, 95% CI: 1.40-4.97, p<0.001; HR: 2.9, 95% CI: 1.52-5.57, p<0.001, respectively). However, post-procedure MPA did not predict a bleeding event (HR: 0.9, 95% CI: 0.44-1.59, p=0.532).
Conclusions: In patients with ACS, the CYP2C19 LOF allele was associated with post-procedure HTPR and a subsequently increased risk of adverse clinical events at one-year follow-up following DES implantation and clopidogrel administration.