急性心肌梗死替奈普酶溶栓治疗脑卒中与死亡分析

Assessment of the stroke and mortality with tenecteplase versus alteplase for Chinese patients with acute myocardial infarction

目的通过与重组组织型纤溶酶原激活剂(rt-PA)对比,明确替奈普酶(TNK-tPA)治疗中国急性心肌梗死患者的脑卒中和死亡情况。方法2002年10月至2004年3月于北京五家医院入组急性ST段抬高心肌梗死发病6h患者,随机给予TNK-tPA(0.53mg/kg10s以上静推)或rt-PA(前负荷法,≤100mg),观察溶栓30d后脑卒中、脑出血、死亡率及死因。结果110例患者进入统计分析,TNK-tPA组58例,rt-PA组52例。两组患者脑卒中的发生率分别为5.17%和1.92%(TNK-tPA vs.rt-PA,P=0.62);脑出血的发生率分别为3.45%和1.92%(P=1.00);死亡率为13.8%和9.6%(P=0.565)。死亡原因分析,其中心脏破裂:2/58(3.45%)和2/52(3.85%);室颤:1/58(1.72%)和0/52(0);心脏骤停:3/58(5.17%)和1/52(1.92%);脑出血:1/58(1.72%)和0/52(0);休克:1/58(1.72%)和2/52(3.85%);两组比较均无统计学差异。结论初步结果显示,TNK-tPA溶栓治疗脑出血和30d死亡率较高,其安全性对治疗中国患者未得到证实,故目前不能用于临床。其结果可能由于试验过程中冠状动脉介入治疗率高、肝素用量大而导致。TNK-tPA剂量降低是否可改善安全性,有待于进一步研究。

Objective In this randomized trial, we assessed the stroke and mortality for TNK-tPA fibrinolysis in Chinese patients with acute myocardial infarction compared with alteplase. Methods The patients were enrolled with acute ST-elevation myocardial infarction presenting within 6 hours from October 2002, to March 2004 ,in 5 hospitals in Beijing, patients were randomly assigned a bodyweight-adjusted bolus of tenecteplase（0. 53 mg/kg over more than 10 s） or front loaded alteplase （ 100 mg）, and underwent coronary angiography at 90 min after start of study drug. All patients received aspirin and heparin （ target activated partial thromboplastin time 50 - 70 s）. The all stroke, intracranial hemorrhage （ ICH）, all-cause mortality,were assessed at 30 days. Results One hundred and ten patients were eligible to statistically analyze,58 patients were assigned to receive tenecteplase, 52 patients to alteplase. At 30 days, rates of all stroke were similar for the two groups （5.17% for TNK-tPA and 1.92% for alteplase, P = 0. 62） ; rates of ICH were 3.45% and 1.92% （TNK-tPA versus rt-PA, P = 1.00） respectively;mortality rates were almost identical（ 13.8% for TNK-tPA and 9. 6% for rt-PA,P = 0. 565 ）. The cause of mortality was attributed to following complications ：cardiac rupture was 3.45% （2/58） and 3.85% （2/52） ;ventricular fibrillation was 1.72% （ 1/58 ） and 0 （0/52） ; cardiac arrest was 5.17 % （3/58） and 1.92% （1/52） ; ICH was 1.72% （ 1/ 58） and 0 （0/52） ;eardiogenic shock was 1.72% （1/58）and 3.85% （2/52） in two groups respectively, and statistical differences were not significant in each kind of cause of mortality. Conclusions The results of this trial showed, the rates of ICH and mortality at 30 days were higher for TNK-tPA fibrinolysis, in Chinese patients with acute ST-elevation myocardial infarction, it was not accepted for application in general practice in the term of the ICH and mortality at 30 days, these results may be due to the high rate of PCI, high dose of bolus heparin, maybe lower dose of TNK-tPA improve the safety for Chinese patients, so further studies are needed to confirm the safety for tenecteplase in Chinese patients.