The impact of residual platelet activity and CYP2C19 polymorphism on the prognosis of acute coronary syndrome patients / 中华检验医学杂志

ABSTRACT

Objective To evaluate the correlation between RPA or the polymorphism of CYP 2C19 and the incidence of ischemic events and the influence on the clinical prognosis .Methods A case-control study was used.A total of 202 patients [male 66%,(63 ±11) years] with ACS on aspirin and clopidogrel treatment were recruited , whose RPA were measured by whole blood aggregometry ( WBA ) , and their CYP2C19 polymorphism were also tested .Their clinical ischemic events were recorded in the mean follow-up period of 16 months.The RPA cut-off values for antiplatelet low-responsiveness were defined by the receiver operator characteristic curve ( ROC); the relationships of clinical outcomes with RPA and CYP 2C19 were assessed by the Kaplan-Meier survival analysis.Results CYP2C19*2 (681G>A) present in 52.5% of recruited patients and*3 (636G>A) present in12.9%.RPA induced by adenosine diphosphate ( ADP) showed significant difference among CYP 2C19*2 or *3 heterozygotes, CYP2C19*2 or *3 homozygotes and noncarriers (χ2 =9.318, P=0.009);whereas, RPA induced by arachidonic acid (AA) (χ2 =2.441, P=0.295) and the incidence of ischemic events (χ2 =0.513, P=0.774) were not.During follow-up, 18 (9%) patients experienced clinical ischemic episodes , and their RPA were higher than patients without ischemic episodes [(8.6 ±4.8) Ωvs (5.2 ±3.7) Ω, P =0.013; (8.6 ±6.8) Ωvs (1.6 ±3.7) Ω, P <0.001].Moreover, employing 6.5 Ω(induced by ADP) and 2.5 Ω(induced by AA) as cutoff values,RPA showed optimal negative predictive values (97%, 96%) and poor positive predictive values (16%,29%).Survival analysis showed, statistically, patients with clopidogrel low-responsiveness had higher riskof ischemic episodes than patients with clopidogrel responsiveness (HR =2.86, χ2 =11.27,P =0.0008);however, patients with aspirin low responsiveness (HR =1.77, χ2 =1.74, P =0.19) or patients withCYP2C19*2 or *3 (HR =0.89, χ2 =0.12, P =0.73) did not.Conclusion Clopidogrel lowresponsiveness is associated with the occurrence of clinical ischemic events ; however, patients withCYP2C19 function reduced genetypes do not show higher risk of ischemic episodes though it presented slighlyhigher RPA.