不同负荷剂量氯吡格雷对急性冠脉综合征患者PCI术后近期预后的影响

Effects of high loading dose of clopidogrel on short-term outcomes in patients with acute coronary syndromes undergoing percutaneous coronary intervention

目的:前瞻性评价不同负荷剂量氯吡格雷治疗急性冠脉综合征的临床疗效和安全性。方法:入选219例接受冠状动脉介入治疗(PCI)的非ST段抬高型急性冠脉综合征患者,随机分为术前顿服氯吡格雷300mg(300mg组,n=108)或600mg(600mg组,n=111)。比较两组抗血小板聚集作用、术前/术后生化指标、术后30d主要心脏不良事件(MACE)及出血并发症。结果:两组基础临床和蛋白C(PC)情况以及术前肌酸激酶-同工酶/肌钙蛋白(CK-MB/TNI)均无统计学差异。利用二磷酸腺苷(ADP)诱导血小板聚集率法,与300mg组相比,600mg组抗血小板作用显著增强[ADP～2h:(47.3±20.8)%对(55.7±17.8)%,P<0.01;ADP～4h:(41.1±21.1)%对(49.5±18.8)%,P<0.01;ADP～6h:(34.8±16.4)%对(43.5±14.7)%,P<0.01],术后即刻CK-MB[(4.4±4.7)ng/ml对(6.7±5.6)ng/ml,P<0.01]、TNI[(0.4±1.6)ng/ml对(0.9±2.1)ng/ml,P<0.05]和TIMI0～1级血流发生率(1.8%对6.5%,P>0.05)均明显降低。Kaplan-Meier生存分析显示,600mg组术后30d无事件生存率显著高于300mg组(97.3%对90.7%,P<0.05)。多因素Logistic回归分析显示,600mg氯吡格雷治疗是降低术后30dMACE发生率的独立决定因素(OR=0.18,P<0.01)。300mg组与600mg组的出血并发症总发生率(1.9%对3.6%)、严重出血(0.9%对0%)、轻度出血(0.9%对2.7%)、输血(0%对0.9%)、血小板减少症(0)均无统计学差异(P>0.05)。结论:600mg氯吡格雷治疗急性冠脉综合征能显著改善临床预后且不增加出血风险。

Objective：This prospective study aimed to investigate the safety and efficacy of high loading dose of clopidogrel on clinical outcomes in patients with acute coronary syndromes （ACS） undergoing percutaneous coronary intervention （PCI）. Methods： Two hundred and nineteen consecutive patients with non-ST-elevation ACS were randomly allocated to either 300 mg clopidogrel （300mg group, n = 108） or 600mg clopidogrel （600mg group, n = 111） loading dose before PCI. Baseline characteristics, PCI features, myocardial biomarkers during hospitalization were compared between the two groups, as well as major adverse cardiac events （MACE, including death, acute myocardial infarction, and target vessel revascularization at 30 days after discharge. Results： Clinical characteristics, PCI features and pre-procedure CK MB/TNI were comparable between the two groups. Compared with 300mg group, the anti-platelet effect of clopidogrel was significantly enhanced （ADP- 2h： 47. 3 ± 20. 8 % vs 55. 7 ± 17.8% ,P〈0.01;ADP-4h：41.1 ± 21.1 % vs49.5 ± 18.8 % ,P〈0.01;ADP-6h：34.8 ± 16.4 vs 43.5 ± 14.7% ,P〈0.01）in 600mg group, and the post-procedure CK-MB/TNI and rate of TIMI 0-1 flow were significantly lower in 600mg group than in 300rag group （CK-MB： 4.4 ± 4.7ng/ml vs 6.7 ± 5.6ng/mI, P〈0.01; TNI： 0.4 ± 1.6ng/mlvs0.9 ± 2.1ng/ml, P〈0.05; TIMI 0-1 flow： 1.8%0 vs6.5%,P〉0.05））, as well as MACE rate at 30 days after discharge （2.70/oo vs 9. 3%,P^0. 05）. Multivariate logistic regression analysis revealed that 600mg clopidogrel loading dose （OR = 0. 18, P〈 0.01） was an independent predictor for 30 day-MACE rate at follow up. There was no significant difference in hemorrhagic complications between 300rag group and 600mg group （1.9 % vs 3.6%, P〉 0.05）. Conclusion： High loadingdose of clopidogrel （600mg） is safe and significantly improves short-term clinical outcomes for patients with ACS undergoing PCI.