急性心肌梗死患者替奈普酶溶栓疗效和安全性评价

An angiographic trial to evaluate the efficacy and safety of tenecteplase in Chinese patients with acute myocardial infarction

目的本研究观察替奈普酶（TNK-tPA）对中国急性ST段抬高心肌梗死（STEMI）患者的疗效和安全性。方法2002年10月至2004年3月，在北京市的宣武医院、同仁医院、人民医院、友谊医院和安贞医院，入组急性STEMI发病6h患者，随机给予TNK—tPA或重组组织型纤溶酶原激活剂（rt-PA），给药后90min行冠状动脉造影。主要疗效指标为溶栓治疗90min时，梗死相关动脉TIMI3级血流的患者百分数。其他指标包括90min梗死相关动脉TIMI2／3级血流率、30d的病死率、中重度出血及脑出血发生率。共110例STEMI患者进行统计分析，其中TNK-tPA组58例，rt-PA组52例。结果两组患者溶栓后90min冠状动脉造影TIMI3级血流率分别为68．4％（39／57）和66．7％（34／51，P=1．00）；TIMI2／3级血流分别为89．5％（51／57）和80．4％（41／51，P=0．278）；30d的病死率分别为13．8％（8／58）和9．6％（5／52，P=0．565）；中重度出血及脑出血的发生率分别为8．6％（5／58）和5．8％（3／52，P=0．72）及3．5％（2／58）和1．9％（1／52，P=1．00）。结论TNK—tPA溶栓治疗90min TIMI3级血流率、TIMI2／3级血流率、30d病死率、中重度出血发生率与rt—PA相似；TNK—tPA30d病死率及脑出血发生率虽与rt—PA无统计学差异，但似乎较高，有关TNK—tPA在中国的临床使用，需进一步研究。

Objective In this randomized, open-label, multicenter, angiographic trial, we compared the efficacy and safety of tenecteplase （TNK-tPA） with alteplase （rt-PA） in Chinese patients with acute myocardial infarction. Method Patients with acute ST-elevation myocardial infarction and pain to hospital time within 6 hours from October 2002, to March 2004 were randomly assigned a body weightadjusted bolus of TNK-tPA （0. 53 mg,/kg over more than 10 s, n = 58 ） or front loaded rt-PA （≤ 100 mg, n = 52）. Coronary angiography was performed-at 90 min after initiating study drugs. All patients received aspirin and heparin （target activated partial thromboplastin time： 50-70 s ）. The primary end point of the trial was the rate of TIMI grade 3 flow at 90 minutes. Other end points included the rate of TIMI grade 2/3 flow at 90 minutes, all cause mortality at 30 days, the moderate/severe hemorrhage without intracranial hemorrhage （ICH） and ICH within 30 days. Results TIMI grade 3 flow at 90 minutes （68.4% vs. 66. 7%, P = 1.00）, TIMI grade 2 or 3 at 90 minutes （89. 5% vs. 80. 4%, P =0. 278）, total mortality at 30 days （13. 8% vs. 9. 6% , P=0. 565） , the rate of moderate/severe hemorrhage （8. 6% vs. 5.8% , P = 0. 72） and incidence of ICH （3.5% vs. 1.9% ,P = 1.00） were all similar in TNK-tPA treated patients compared to rt-PA treated patients. Conclusion The efficacy of single-bolus, weight-adjusted TNK-tPA fibrinolytic regimen is equivalent to front-loaded alteplase in terms of the rates of TIMI grade 3 flow, TIMI 2 or 3 flow. Incidences of moderate/severe hemorrhage, ICH and 30-days mortality were similar in TNK-tPA and rt-PA treated patients.