氯吡格雷抵抗的发生率、影响因素及干预策略研究

Prevalence,risk factors and management strategy of clopidogrel resistance in patients with coronary heart disease

目的通过检测冠心病患者二磷酸腺苷(adenosine diphosphate,ADP)诱导的血小板聚集、血浆P选择素(CD62P)浓度及可溶性CD40配体(sCD40L)的浓度,了解氯吡格雷抵抗在冠心病患者的发生率及影响因素,探讨氯吡格雷抵抗的干预策略。方法130例受选对象在服用氯吡格雷75 mg/d前、服药5天后,测定血小板聚集(plateletaggregation)、CD62P浓度及sCD40L的浓度。根据ADP诱导的血小板聚集降低程度分为氯吡格雷抵抗组和非氯吡格雷抵抗组。对氯吡格雷抵抗患者随机分为氯吡格雷剂量加倍(150 mg/d)和维持原有剂量两组,5天后重复测定血小板聚集率、血浆CD62P浓度及sCD40L浓度。结果服用氯吡格雷5天后测得氯吡格雷抵抗的发生率分别为16.2%(ADP 10μmol/L)和14.6%(ADP 20μmol/L)。对氯吡格雷抵抗患者剂量加倍干预5天后测得剂量加倍组的血小板聚集为(8.1±3.1)Ω,较服氯前(10.9±3.6)Ω有所降低(P<0.05);维持剂量组的血小板聚集为(7.4±5.7)Ω,较服氯前(9.9±5.1)Ω有所降低,但差异无统计学意义(P>0.05)。剂量加倍组中氯吡格雷抵抗患者由10例降低为3例(30.0%),维持原剂量组中氯吡格雷抵抗患者由9例降低为5例(55.6%)。结论氯吡格雷的抗血小板作用存在时间和剂量依赖性。

Objective To observe the efficacy of clopidogrel for the prevalence and influential factors of clopidogrel resistance in patients with coronary heart disease, to explore the management strategy of clopidogrel resistance by＇measuring adenosine diphosphate（ADP） （10 and 20 μmol/L） induced platelet aggregation,and to know the expression of sCD40L and CD62P in plasma from coronary heart disease patients. Methods A total of 130 coronary heart disease patients were studied,their platelet aggregation,the expression of sCD40L and CD62P in plasma, before clopidogrel administration （baseline） and at 5 days after clopidogrel administration were measured. According to the value of platelet aggregation prior to and 5 days after clopidogrel administration, patients were divided into clopidogrel resistance group and non-clopidogrel resistance group. Platelet aggregation and the expression of sCD40L and CD62P in plasma of the nonresponders were tested at 5 days after drugs management. Results Among 130 patients, 19（14.6%） patients were found clopidogrel resistance by measuring ADP （20 μmol/L） induced platelet aggregation, 21 （ 16.2 %） nonresponders were found by measuring 10 μmol/L ADP induced platelet aggregation. In high dose group, platelet aggregation of the baseline was （10.9±3.6） Ω, platelet aggregation by management after 5 days was （8.1 ± 3.1 ） Ω, which was significantly lower than the baseline level （ P 〈0.05）. In maintenance dose group, platelet aggregation of the baseline was （9.9 ± 5.1） Ω, platelet aggregation by management after 5 days was （7.4 ± 5.7） Ω, which was not significantly lower than the baseline level （ P〈0.05）. Ten patients in high dose group reduced to 3 nonresponders （the prevalence of clopidogrel resistance was 30.0 %）, and 9 patients in maintenance dose group reduced to 5 nonresponders （the prevalence of clopidogrel resistance was 55.6%）. Conclusion Clopidogrel-induced platelet inhibition is dose-and time-dependent.