尿激酶原和瑞替普酶治疗急性STEMI的疗效和安全性比较

Efficacy and safety comparison between pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction

目的:对比尿激酶原和瑞替普酶治疗急性ST段抬高型心肌梗死(STEMI)的临床疗效和安全性。方法:选择2016年9月至2018年8月河南STEMI注册登记研究在河南省66家医院总共入选的5 479例STEMI患者中接受静脉溶栓治疗的患者,根据患者接受溶栓药物情况,分为尿激酶原组( n=638)和瑞替普酶组( n=702)。收集患者的人口统计学资料、危险因素、既往病史、入院时信息、院内治疗情况等。比较两组临床再通率、住院病死率、住院死亡或放弃治疗、住院期间主要不良心脑血管事件(MACCE,包括死亡或放弃治疗、再发心肌梗死、心力衰竭或缺血性卒中)和溶栓后出血情况。出血采用欧美出血学术研究会(BARC)制定的出血分级。 结果:尿激酶原和瑞替普酶两组STEMI患者的年龄分别为61.8(53.2,69.0)和62.6(52.1,69.8)岁,女性分别占23%(147/638)和25.1%(176/702),差异均无统计学意义( P均>0.05)。尿激酶原和瑞替普酶两组患者的临床再通率相似[82.1%(524/638)比84.9%(596/702), P=0.172],两组发病至开始溶栓的时间分别为194.5(135.0,290.0)min和190.0(126.0,292.0)min,溶通的时间分别为95.0(67.5,120.0)min和95.0(71.0,119.0)min。两组以上时间指标的差异均无统计学意义( P均>0.05)。尿激酶原组和瑞替普酶组的住院病死率[5.5%(35/638)比5.1%(36/702), P=0.770],住院死亡或放弃治疗的比例[8.9%(57/638)比7.7%(54/702), P=0.410],住院MACCE的发生率[13.0%(83/638)比10.4%(73/702), P=0.137]相比差异均无统计学意义。然而,瑞替普酶组溶栓后出血的发生率明显高于尿激酶原组[7.8%(55/702)比3.8%(24/638), P=0.002]。进一步分析发现,瑞替普酶组口腔出血和BARC 1~2级出血的比例较尿激酶原组高,差异均有统计学意义( P均<0.001),而两组脑出血的发生率相似[0.6%(4/638)比0.4%(3/702), P=0.715]。采用广义线性混合模型调整基线资料后,两组疗效和安全性指标的比较结果与调整前一致。对于住院病死率、住院死亡或放弃治疗和住院MACCE,在调整基线资料的基础上加溶栓后出血事件,两组差异仍无统计学意义。 结论:尿激酶原和瑞替普酶两种溶栓药物治疗STEMI的临床疗效相似。安全性方面,脑出血的发生率相似。虽然,瑞替普酶BARC 1~2级出血和口腔出血的发生率高于尿激酶原,但不影响住院结局。

Objective To compare the efficacy and safety of pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction(STEMI).Methods STEMI patients,who received intravenous thrombolytic therapy in Henan STEMI registry between September 2016 and August 2018,were eligible for this study.A total of 5479 patients from 66 hospitals were screened and patients were divided into pro-urokinase group(n=638)and reteplase group(n=702)according to thrombolytic drugs.Data including patient demographics,risk factors,medical histories,patient information at admission,in-hospital treatment,time delays,and clinical events were collected.The clinical recanalization rate,in-hospital mortality,in-hospital death or treatment withdrawal,in-hospital main adverse cardiovascular and cerebrovascular events(MACCE,death or treatment withdrawal,congestive heart failure,reinfarction and ischemic stroke)and post-thrombolysis bleeding were compared between the two groups.Bleeding events were evaluated with Bleeding Academic Research Consortium(BARC)criteria.Results The median age[61.8(53.2,69.0)vs.62.6(52.1,69.8),P=0.833]or the proportion of women[23.0%(147/638)vs.25.1%(176/702),P=0.385]were similar between the pro-urokinase and reteplase groups.Clinical recanalization rates were similar between the pro-urokinase and reteplase groups[82.1%(524/638)vs.84.9%(596/702),P=0.172],and there was no difference in the median time from onset to thrombolysis[194.5(135.0,290.0)min vs.190(126.0,292.0)min,P=0.431]and the median recanalization time[95(67.5,120.0)min vs.95(71.0,119.0)min,P=0.561]between the two groups.There was no significant difference in in-hospital mortality[5.5%(35/638)vs.5.1%(36/702),P=0.770],in-hospital all-cause mortality,treatment withdrawal[8.9%(57/638)vs.7.7%(54/702),P=0.410],and in-hospital MACCE[13.0%(83/638)vs.10.4%(73/702),P=0.137]between pro-urokinase and reteplase groups.However,the incidence of post-thrombolysis bleeding was significantly higher in reteplase group than in pro-urokinase group[7.8%(55/702)vs.3.8%(24/638),P=0.002].Further analysis found that the incidence of oral bleeding and the BARC grades 1-2 bleeding were significantly higher in reteplase group than in pro-urokinase group,whereas the incidence of cerebral hemorrhage was similar between the two groups[0.6%(4/638)vs.0.4%(3/702),P=0.715].The comparison of efficacy and safety outcomes between the two groups after adjusting for baseline characteristics using general linear mixed models was consistent with those before the adjustment.There was no significant difference in in-hospital mortality,in-hospital death or treatment withdrawal,in-hospital MACCE after adjusting for baseline characteristics and post-thrombolysis bleeding between the two groups.Conclusions Pro-urokinase and reteplase have similar clinical efficacy in the treatment of STEMI.In terms of safety,the incidence of cerebral hemorrhage is similar,while the incidence of BARC grades 1-2 bleeding and oral bleeding is higher in reteplase group than in pro-urokinase group,which has no impact on in-hospital outcomes.