注射用重组人TNK组织型纤溶酶原激活剂溶栓治疗急性ST段抬高型心肌梗死的疗效和安全性评价  

Efficacy and safety of recombinant human TNK tissue-typeplasminogen activator in patients with acute myocardial infarction

作　　者：翟玫[1] 陈纪林 乔树宾 华潞[1] 李一石[1] 

机构地区：[1]卫生部心血管药物临床研究重点实验室,中国医学科学院阜外医院,北京协和医学院,北京100037 [2]中国医学科学院阜外医院冠心病诊治中心,北京100037

出　　处：《中国新药杂志》2016年第1期82-86,92,共6页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项-《心血管创新药物临床研究技术平台建设》(2012ZX09303-008-001);2010年国家临床重点专科建设项目-卫生部重点实验室项目;国家“十五”重大科技专项“创新药物和中药现代化”(2002AA2Z3333)

摘　　要：目的：与注射用重组人组织型纤溶酶原激活剂（rt-PA）进行比较,评价注射用重组人TNK组织型纤溶酶原激活剂（rh TNK-t PA）对中国人急性心肌梗死溶栓治疗的疗效和安全性。方法：这项研究在中国13家医院完成,为盲法、随机、对照试验。预试验中各4例患者分别给予rh TNK-t PA 15和20 mg,确定本研究药物剂量为rh TNK-t PA 20 mg一次给药。自2005年7月至2007年5月,研究共入选251例患者。入选患者随机分为rh TNK-t PA组和rt-PA组。rh TNK-t PA组患者5~10 s内静脉推注rh TNK-t PA 20 mg;rt-PA组先匀速静注8 mg,剩余42 mg在90 min内持续静脉泵入,主要疗效评价指标为给药90 min后冠状动脉造影显示的梗死相关血管（IRA）TIMI血流分级;临床评估不能行冠脉造影者以冠脉再通间接指标判断血管再通率做为主要疗效评价指标（具有以下1＋2,或1＋3＋4,或2＋3＋4判定为血管再通）：1心电图ST段抬高最显著的导联在溶栓开始后2 h内回降≥50%。2 CK-MB或CK酶峰提前到距发病后14 h以内。3自溶栓开始后2 h内,胸痛完全缓解或减轻70%以上。4开始溶栓2 h内出现再灌注心律失常。结果：182例患者行90 min冠脉造影（rh TNK-t PA组93例,rt-PA组89例）,结果显示rh TNK-t PA组冠状动脉通畅率（TIMI2级~3级）显著高于rt-PA组（82.80%vs 67.42%）,rh TNK-t PA组达到TIMI3级血流者亦显著高于rt-PA组（65.59%vs 53.93%）。69例（rh TNK-t PA组31例,rt-PA组38例）患者以冠脉再通间接指标判断血管通畅率,rh TNK-t PA组与rt-PA组血管通畅率相近（80.65%vs 81.58%）。两组脑出血发生率相同（每组各1例）。两组小出血事件发生率相近（16.94%vs 17.32%）。结论：rh TNK-t PA 20 mg 90 min冠状动脉造影通畅率明显高于rt-PA组,rh TNK-t PA 20 mg溶栓治疗中国的急性心肌梗死患者安全有效。Objective： To evaluate the safty and efficacy of recombinant human TNK tissue-type plasminogen activator（ rhTNK-t PA） for injection in Chinese patients with acute myocardial infaction by comparison with recombinant human tissue-type plasminogen activator（ rt-PA） for injection. Methods： This blinded,randomized,controlled trial was conducted in 13 hospitals in China. After a pilot study in 4 patients receiving rhTNK-t PA 15 mg or 20 mg,the dose of rhTNK-t PA in this study was determined to be 20 mg given at a time. From July 2005 to May2007,251 patients were enrolled. All the patients were randomized to either rhTNK-t PA or rt-PA treatment. The rhTNK-t PA was administered by an intravenous bolus of 20 mg over 5 ~ 10 s. The rt-PA was administered by an intravenous bolus of 8 mg followed by infusion of 42 mg over 90 min. The primary endpoint was TIMI flow of the infarct-related artery（ IRA） by coronary angiography at 90 min after initiation of treatment. For the patients who couldn＇t receive coronary angiography,IRA flow was evaluated by indirect indicators including decline of elevating ST segment,peak of CK-MB or CK,remission of chest pain and reperfusion arrhythmia. Results： One hundred and eighty-two patients received angiograms for TIMI flow at 90 min after initation of treatment（ n = 93 for rhTNKt PA,n = 89 for rt-PA）. The rhTNK-t PA group had significantly higher patency rate than the rt-PA group（ TIMI 2and 3： 82. 80% vs 67. 42%; TIMI 3： 65. 59% vs 53. 93%）. The 69 patients in the two groups（ n = 31 for rhTNK-t PA,n = 38 for rt-PA） who had IRA flow evaluation by indirect indicators had similar patency rates（ 80. 65%vs 81. 58%）. The cerebral hemorrhage incidence was the same for the two groups（ 1 patient in each group）. Mild bleeding rate was similar for both groups（ 16. 94% vs 17. 32%）. Conclusion： TNK-t PA 20 mg is effective and safe for Chinese patients with acute myocardial infaction. There is statistically significant superiority of rhTNK-t PA over rt-PA in

关 键 词：急性心肌梗死 溶栓治疗 重组人TNK组织型纤溶酶原激活剂 重组人组织型纤溶酶原激活剂 

分 类 号：R969.4[医药卫生—药理学]