The steady-state time of platelet inhibition by clopidogrel detected by light transmission aggregation
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摘要: 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(PLADP)。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PLADP水平。结果 入选240例患者，住院期间及出院后检测PLADP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PLADP水平显著高于服用氯吡格雷≥30 d的PLADP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PLADP水平显著高于服用氯吡格雷≥30 d PLADP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PLADP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PLADP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PLADP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PLADP水平可准确体现氯吡格雷的长期抗血小板疗效。Abstract: 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(PLADP) was measured by light transmission aggregation(LTA). PLADP 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'PLADP 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 PLADP 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 PLADP 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 PLADP 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 PLADP levels that meet the above detection window would be accurately reflect the long-term pharmacodynamic effect of clopidogrel.
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Key words:
- coronary artery disease /
- clopidogrel /
- platelet aggregation /
- pharmacodynamics
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图 1 住院期间和服用氯吡格雷≥30 d PLADP的比较
Figure 1. Comparison of PLADP detected during hospitalization and after clopidogrel administration ≥30 days
图 2 非负荷剂量组与负荷剂量组住院期间与服用氯吡格雷≥30 d LADP比较
Figure 2. Comparison of PLADP detected between hospitalization and after clopidogrel administration ≥30 days in non-loading and loading dose groups
图 3 非负荷剂量患者住院期间与服用氯吡格雷≥30 d PLADP比较
Figure 3. Comparison of PLADP detected between hospitalization and after clopidogrel administration ≥30 days in non-loading dose patients
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