The impact of residual platelet activity and CYP2C19 polymorphism on the prognosis of acute coronary syndrome patients

Abstract

Objective To evaluate the correlation between RPA or the polymorphism of CYP2C19 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 CYP2C19 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 CYP2C19*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) Ω vs (5.2±3.7) Ω, P=0.013; (8.6±6.8) Ω vs (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 risk of 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 with CYP2C19*2 or *3 (HR=0.89, χ2=0.12, P=0.73) did not. Conclusion Clopidogrel low responsiveness is associated with the occurrence of clinical ischemic events; however, patients with CYP2C19 function reduced genetypes do not show higher risk of ischemic episodes though it presented slighly higher RPA. (Chin J Lab Med, 2016, 39: 911-916) Key words: Acute coronary syndrome; Platelet activation; Platelet function tests