不同维持剂量氯吡格雷对氯吡格雷抵抗急性冠状动脉综合征患者的有效性及安全性研究

A comparative study on the efficacy and safety of different maintenance doses of clopidogrel treatment in ACS patients with low response to clopidogrel

目的探讨对于冠状动脉介入治疗的氯吡格雷低反应的急性冠状动脉综合征(ACS)患者,能否通过增加氯吡格雷维持剂量来降低血小板聚集率,改善临床预后,从而为氯吡格雷低反应的ACS患者围手术期药物选择提供依据。方法选择诊断为ACS并行经皮冠状动脉介入治疗(PCI)的氯吡格雷低反应患者208例。随机分为2组,A组(常规剂量组)PCI术前给予600mg氯吡格雷负荷量,术后给予75mg氯吡格雷维持剂量至少1年;B组(双倍剂量组)PCI术前给予600mg氯吡格雷负荷量,术后给予150mg氯吡格雷维持剂量30d,以后继续给予75mg氯吡格雷维持剂量至少1年。1血小板聚集率测定:测定各组患者入院时的基础血小板聚集率及氯吡格雷600mg负荷量用药4h、维持量氯吡格雷用药后7、14、30、90、180d的血小板聚集率。2临床随访:所有患者均在180d内进行随访,观察不同维持剂量组主要心脏不良事件(MACE)事件和出血事件的发生率。结果 12组患者维持量氯吡格雷用药后7d的血小板聚集率差异无统计学意义;14、30、90、180d的血小板聚集率双倍剂量组较常规剂量组显著降低,差异有统计学意义。2随访180d结果显示双倍剂量组较常规剂量组MACE事件发生率有所减少,但是差异无统计学意义;2组出血事件发生率差异也无统计学意义。结论 PCI术后应用150mg氯吡格雷维持剂量与常规氯吡格雷维持剂量相比,可进一步降低氯吡格雷低反应患者的血小板聚集率,但是MACE事件发生率无明显降低,且不增加出血事件的发生率。

Objective To investigate whether a higher clopidogrel maintenance dosage is associated with a signifi- cant reduced rate of platelet aggregation after percutaneous coronary intervention （PCI） in ACS patients with low response to clopidogrel and to evaluate its efficacy and safety in a short-term in this study. Methods Two hundred and eight ACS patients with low response to clopidogrel were enrolled from October 2011 to May 2013. They were randomly divided into two groups： group A（regular dose group） were given 600 mg clopidogrel loading dose before PCI and 75 rag clopidogrel maintenance dose at least 1 year after PCI; group B（double dose group） were given 600 mg clopidogrel loading dose be- fore PCI and 150 mg clopidogrel maintenance dose for 30 days after PCI, after this continued to give 75 nag clopidogrel maintenance dose for 1 year. ①Determination of platelet aggregation rate： the basic platelet aggregation rate was measured on admission, then the platelet aggregation of 4 hours after taking 600 mg clopidogrel was measured, 7, 14, 30, 90 and 180 days after taking different clopidogrel maintenance dose were measured as wall. ②Clinical follow-up., all the patients were followed up within 180 days, and were observed the incidence of MACE and bleeding events in the different mainte- nance dose group. Results ①The platelet aggregation of 7 days after taking different clopidogrel maintenance dose were of no significant difference; there was significant difference between two groups on the 14, 30, 90 and the 180 days after taking different clopidogrel maintenance dose. ②Double dose group did not reduce the incidence of MACE events obviously compared with the conventional dose group, and the incidence of bleeding events were of no significant difference in the two groups. Conclusion Compared with the conventional maintenance dose clopidogrel, double maintenance dose clopi- dogrel reduced the platelet aggregation obviously in the ACS patients with low response to clopidogrel, and did not in- crease the incidence of bleeding events, but did not reduce the incidence of MACE events obviously.