光比浊法检测氯吡格雷血小板抑制作用的稳态时间

The steady-state time of platelet inhibition by clopidogrel detected by light transmission aggregation

目的:探究冠心病患者服用氯吡格雷后血小板抑制作用达到稳态的时间,为氯吡格雷药效学研究提供借鉴。方法:入选接受经皮冠状动脉介入治疗且服用氯吡格雷3 d后的冠心病患者,采用光比浊法检测二磷酸腺苷诱导的血小板聚集率(PL;)。分别比较检测时已服用氯吡格雷不同天数患者住院期间和服用氯吡格雷30 d后的PL;水平。结果:入选240例患者,住院期间及出院后检测PL;距离首次服用氯吡格雷的时间分别为6(5,8)d和39(35,47)d,患者住院期间PL;水平显著高于服用氯吡格雷≥30 d的PL;水平[36(25,46)%vs 29(20,44)%,P<0.01]。入选患者中未服用负荷剂量(仅予维持剂量75 mg/d)氯吡格雷者156例,住院期间PL;水平显著高于服用氯吡格雷≥30 d PL;水平[36(25,46)%vs 28(19,42)%,P<0.01];此类患者中住院期间服用氯吡格雷≥6 d者,住院期间与服用氯吡格雷30 d的PL;水平差异无统计学意义(P>0.05)。入选患者中服用氯吡格雷负荷剂量(150 mg或300 mg)者84例,住院期间与服用氯吡格雷≥30 d的PL;水平差异无统计学意义[(35.99±15.38)%vs(32.61±16.30)%,P>0.05];检测时已服用氯吡格雷不同天数患者住院期间与服用氯吡格雷30 d的PL;水平差异均无统计学意义(P>0.05)。结论:冠心病患者服用维持量氯吡格雷≥6 d或负荷加维持量氯吡格雷≥3 d时残余血小板聚集功能与服用氯吡格雷30 d后相当;在以上时间窗检测的PL;水平可准确体现氯吡格雷的长期抗血小板疗效。

Objective:To explore the steady-state time of platelet inhibition by clopidogrel and provide a reference for the pharmacodynamic study of clopidogrel.Methods:Patients with coronary artery disease undergoing percutaneous coronary intervention(PCI)were recruited after their taking clopidogrel for more than 3 days.Platelet aggregation induced by adenosine diphosphate(PL;)was measured by light transmission aggregation(LTA).PL;levels of patients who had taken clopidogrel for different days at the time of detection were compared during hospitalization and after clopidogrel administration≥30 days.Results:A total of 240 patients were enrolled in the study.The time between detection of platelet aggregation function and initial administration of clopidogrel was 6(5,8)and 39(35,47)days in hospitalization and after discharge,respectively.Patients’PL;levels measured during the hospital were significantly higher than those measured after clopidogrel administration≥30 days[36(25,46)%vs 29(20,44)%,P<0.01].For the 156 patients who were treated without loading-dose(only a maintenance dose of 75 mg/day)clopidogrel,a similar result was found.i.e.the average in-hospital PL;level was significantly higher than that measured after clopidogrel administration≥30 days[36(25,46)%vs 28(19,42)%,P<0.01].However,no significant difference was found for each group of patients in whom the detection time point exceeded 6 days of clopidogrel treatment(P>0.05).In addition,for the 84 patients who were treated with loading-dose clopidogrel of either 150 mg or 300 mg daily,no significant difference in PL;level was found comparing the in-hospital levels and that measured after clopidogrel administration≥30 days[(35.99±15.38)%vs(32.61±16.30)%,P>0.05].There was no significant difference in PL;for patients who had taken clopidogrel for different days during hospitalization and after clopidogrel administration≥30 days(P>0.05).Conclusion:The in-hospital residual platelet aggregation would be equivalent to that measured after clopidogrel administration≥30 days if a patient takes a maintenance-dose clopidogrel for≥6 days or loading-plus maintenance-dose clopidogrel for≥3 days.The PL;levels that meet the above detection window would be accurately reflect the long-term pharmacodynamic effect of clopidogrel.