Background: High platelet reactivity (HPR) after clopidogrel treatment is linked to an increased risk of periprocedural myocardial infarction (PMI). The occurrence of PMI that could be associated with CYP2C19 genotype status was our hypothesis.
Methods and results: A total of 233 patients with non-ST elevation acute coronary syndromes (NSTACS) undergoing uneventful elective percutaneous coronary intervention were included. Platelet reactivity was assessed by thrombelastograph at 24 h after 300 mg clopidogrel loading. HPR was defined as ≥70% adenosine diphosphate-induced platelet aggregation. The CYP2C19*2 and *3 loss-of-function (LOF) alleles were determined using DNA microarray method. Patients with PMI had significantly higher on-clopidogrel platelet reactivity compared to those without PMI (60.0±24.4% vs. 43.0±24.0%, P<0.001). HPR was more frequently observed in patients with PMI and was the strongest risk factor of PMI in multivariate analysis (OR(adj)=4.348, 95% CI: 1.846-10.241, P=0.001). Furthermore, the incidence of HPR was significantly associated with the carriage of 2 CYP2C19 LOF alleles. Compared with non-carriers, patients carrying 2 CYP2C19 LOF alleles had a 3.000-fold increased risk (95% CI: 1.071-8.400, P=0.037) for PMI in multivariate analysis. However, inclusion of HPR as a covariate in the regression model changed the significant relationship between the carriage of 2 CYP2C19 LOF alleles and PMI.
Conclusions: Among Chinese patients with NSTACS, carriers with 2 CYP2C19 LOF alleles are more prone to HPR, which is associated with an increased risk for PMI.