复杂冠状动脉病变的非ST抬高型急性冠状动脉综合征患者依诺肝素联合替格瑞洛在经皮冠状动脉介入术后应用的安全和有效性研究

The safety and efficacy of combined application of enoxaparin and ticagrelor in patients with non-ST-elevation acute coronary syndrome and complex coronary artery lesions after percutaneous coronary intervention

目的:探究对于双联抗血小板治疗(DAPT)中,应用替格瑞洛方案的复杂冠状动脉病变的非ST抬高型急性冠状动脉综合征(NSTE-ACS)患者,经皮冠状动脉介入治疗(PCI)围术期联合应用依诺肝素的安全性和有效性。方法:入选了从2015年1月至2016年10月,在首都医科大学附属北京安贞医院,行PCI治疗的复杂冠状动脉病变的NSTE-ACS患者440例,所有入选患者试验过程中均口服阿司匹林和替格瑞洛治疗。将入选患者在PCI术后随机分为非依诺肝素抗凝组(非抗凝组)、依诺肝素皮下抗凝组(抗凝组)治疗,主要研究终点为住院期间及术后12个月出血事件的发生情况;次要终点为围术期心肌损伤及住院期间、1个月、3个月、12个月主要不良心脑血管事件(MACCE)的发生情况。结果:(1)主要终点:抗凝组较非抗凝组明显增加了患者住院期间总出血事件的发生率(23.1%vs.12.8%,P=0.007),主要为TIMI小出血事件发生率的增加(21.2%vs.12.3%,P=0.018),而未增加要出血风险(1.9%vs.0.5%,P=0.372)。多因素Logistic回归分析表明,术后联用依诺肝素为住院期间出血事件的独立预测危险因素(OR=2.171,95%CI:1.270~3.709,P=0.005)。对于院外12个月内的出血情况,两组患者在总出血、TIMI主要出血、TIMI小出血发生率上,均差异无统计学意义。(2)次要终点:PCI术后非抗凝组与抗凝组患者之间在术后PCI相关心肌损伤及术后1个月、3个月、12个月MACCE事件的发生率上,差异均无统计学意义(P>0.05)。结论:对于复杂冠状动脉病变的NSTE-ACS患者,DAPT应用替格瑞洛联合依诺肝素皮下抗凝在PCI围术期应用并无额外的临床获益,且增加患者的出血风险。因此本研究认为对于口服阿司匹林、替格瑞洛的复杂冠状动脉病变的NSTE-ACS患者,PCI术后应谨慎联合应用抗凝治疗。

Objective： To explore the safety and efficacy of enoxaparin combined with ticagrelor in patients with non-ST elevation acute coronary syndrome（ NSTE-ACS） and complex coronary artery lesions after percutaneous coronary intervention（ PCI） Methods： 440 NSTE-ACS patients with complex coronary artery lesions that had undergone the percutaneous coronary intervention were recruited in Beijing Anzhen Hospital affiliated to Capital University from January 2015 to October 2016. All patients were treated with aspirin and ticagrelor during the trial and randomly assigned to anticoagulation group treated with enoxaparin and non-anticoagulation group. The primary endpoint： bleeding events during hospitalization and at 12 months after PCI; The secondary endpoint： perioperative myocardial injury and major adverse cardiac and cerebrovascular events（ MACCEs） during hospitalization and at 1,3 and 12 months after PCI. Results：（1）The incidences of total bleeding events in the anticoagulation group were significantly higher than those in the non-anticoagulation group（ 23. 1% vs. 12. 8%,P = 0. 007） and the two groups had comparable rates of major bleeding（ 1. 9% vs.0. 5%,P = 0. 372） but minor bleeding rates were higher in the anticoagulation group（ 21. 2% vs. 12. 3%,P =0. 018） The result of multivariate logistic regression analysis showed that the postoperative application of enoxaparin was an independent predictor of bleeding risk during hospitalization（ OR = 2. 171,95% CI： 1. 270-3. 709,P = 0. 005） At 12 months after PCI,there were no significant difference in the total bleeding,major bleeding and minor bleeding events between two groups.（2） There was no significant difference in the incidence of perioperative myocardial injury between two groups; No significant differences in MACCE were observed between the two groups at 1 month,3 months and 12 months post-PCI（ P〈0.05） Conclusion： For NSTE-ACS patients with complex coronary lesions,the combination of ticagrelor and enoxaparin after PCI did not bring the additional benefits and may increase the patients＇ bleeding risk after PCI. Therefore,the result suggest that routine anticoagulation therapy after PCI is not necessary for NSTE-ACS patients treated with ticagrelor who have complex coronary lesions.