血小板反应性对使用比伐卢定抗凝的择期经皮冠状动脉介入治疗患者临床事件的影响

Effect of platelet reactivity on clinical events in patients using bivalirudin in selective percutaneous coronary intervention

目的探讨血小板反应性及其他临床相关因素对使用比伐卢定抗凝的择期经皮冠状动脉介入治疗(PCI)患者术后1年发生不良临床事件的影响。方法本研究为多中心回顾性观察性研究,纳入2017年1月至2018年8月于阜外医院、北部战区总医院、新乡市中心医院行择期PCI,术者考虑为有高出血风险并使用比伐卢定抗凝,且有血栓弹力图(TEG)检测结果的患者632例。使用TEG检测血小板反应性,记录二磷酸腺苷(ADP)诱导的最大振幅(MA_(ADP))值。根据MA_(ADP)值将入选患者分为3组:血小板低反应性(LTPR)组(MA_(ADP)<31 mm,229例)、血小板正常反应性(NTPR)组(31 mm≤MA_(ADP)≤47 mm,207例)及血小板高反应性(HTPR)组(MA_(ADP)>47 mm,196例)。研究终点包括主要不良心脑血管事件(MACCE)和出血事件,MACCE定义为全因死亡、心肌梗死、支架内血栓、卒中和血运重建的复合终点。出血定义为出血学术研究联合会(BARC)2、3和5型出血。使用多因素Cox回归分析使用比伐卢定抗凝的择期PCI患者术后发生MACCE和出血事件的影响因素。结果本研究共纳入632例患者,年龄为(68.3±10.0)岁,其中男性423例(66.9%)。632例患者均完成了1年随访,随访过程中,发生MACCE 48例(7.6%),出血事件11例(1.7%)。LTPR组、NTPR组和HTPR组间MACCE[8.3%(19/229)比6.3%(13/207)比8.2%(16/196),P=0.68]及出血事件发生率[1.8%(4/229)比2.9%(6/207)比0.5%(1/196),P=0.17]差异均无统计学意义。多因素Cox回归分析结果显示,HTPR不是MACCE的独立影响因素(HR=1.25,95%CI 0.67~2.30,P=0.49),仅提示外周血管病史为MACCE发生的独立危险因素(HR=2.47,95%CI 1.19~5.11,P=0.02)。LTPR不是出血事件的独立影响因素(HR=1.35,95%CI 0.39~4.66,P=0.64),出血事件发生的独立影响因素为外周血管病史(HR=3.95,95%CI 1.03~15.22,P=0.05)和血红蛋白水平(HR=0.96,95%CI 0.93~0.99,P=0.01)。结论对于使用比伐卢定抗凝的择期PCI患者,未见血小板反应性与术后1年MACCE及出血事件相关,而外周血管病史是发生MACCE的独立危险因素,外周血管病史和低血红蛋白水平是发生出血的独立危险因素。

Objective To investigate the effect of platelet reactivity and other clinical factors on the postoperative 1-year adverse clinical events in patients who underwent selective percutaneous coronary intervention(PCI)anticoagulated with bivalirudin.Methods This is a multicenter,retrospective and observational study,enrolling 632 patients at high risk of bleeding adjudicated by operators who underwent selective PCI anticoagulated with bivalirudin and had preoperative thrombelastography(TEG)test results in Fuwai Hospital,Northern Theater General Hospital and Xinxiang Central Hospital between January 2017 and August 2018.Platelet reactivity was tested by TEG and adenosine-induced maximal amplitude(MA_(ADP))was recorded.According to MA_(ADP) patients were divided into three groups:low on-treatment platelet reactivity(LTPR)group(MA_(ADP)<31 mm,n=229),normal on-treatment platelet reactivity(NTPR)group(31 mm≤MA_(ADP)≤47 mm,n=207)and high on-treatment platelet reactivity(HTPR)group(MA_(ADP)>47 mm,n=196).The endpoints consisted of major adverse cardiovascular and cerebrovascular events(MACCE)and bleeding events.The definition of MACCE was the composite of all-cause mortality,myocardial infarction,intrastent thrombosis,stroke and revascularization.Bleeding events were defined by bleeding academic research consortium(BARC)type 2,3 and 5 bleeding.Using multivariate Cox regression to analyze the factors of MACCE and bleeding events in patients underwent selective PCI anticoagulated with bivalirudin.Results A total of 632 patients were finally enrolled in the study with age of(68.3±10.0)years and there were 423(66.9%)males.All of 632 patients finished one-year follow-up,and 48(7.6%)patients occurred MACCE and 11(1.7%)patients occurred bleeding events.There was not statistically significant difference in the incidence of MACCE(8.3%(19/229)vs.6.3%(13/207)vs.8.2%(16/196),P=0.68)and bleeding events(1.8%(4/229)vs.2.9%(6/207)vs.0.5%(1/196),P=0.17)in LTPR,NTPR and HTPR group.Multivariate Cox regression showed that HTPR was not the independent factor of MACCE(HR=1.25,95%CI 0.67-2.30,P=0.49),and the history of peripheral vessel disease was the independent risk factor of MACCE(HR=2.47,95%CI 1.19-5.11,P=0.02).LTPR was not the independent factor of bleeding events(HR=1.35,95%CI 0.39-4.66,P=0.64),and the independent factors of bleeding events were history of peripheral vessel disease(HR=3.95,95%CI 1.03-15.22,P=0.05)and hemoglobin(HR=0.96,95%CI 0.93-0.99,P=0.01).Conclusions In patients undergoing selective PCI anticoagulated with bivalirudin,there is no significant association between platelet reactivity and postoperative 1-year MACCE or bleeding events.History of peripheral vessel disease is an independent risk factor of MACCE,and history of peripheral vessel disease and decreased hemoglobin are independent risk factors of bleeding events.