Van de Werf F, Arnold A E
Division of Cardiology, University Hospital, Gasthuisberg, Leuven, Belgium.
BMJ. 1988 Nov 26;297(6660):1374-9. doi: 10.1136/bmj.297.6660.1374.
To assess effect of intravenous recombinant tissue type plasminogen activator on size of infarct, left ventricular function, and survival in acute myocardial infarction.
Double blind, randomised, placebo controlled prospective trial of patients with acute myocardial infarction within five hours after onset of symptoms.
Twenty six referral centres participating in European cooperative study for recombinant tissue type plasminogen activator.
Treatment group of 355 patients with acute myocardial infarction allocated to receive intravenous recombinant plasminogen activator. Controls comprised 366 similar patients allocated to receive placebo.
All patients were given aspirin 250 mg and bolus injection of 5000 IU heparin immediately before start of trial. Patients in treatment group were given 100 mg recombinant tissue plasminogen activator over three hours (10 mg intravenous bolus, 50 mg during one hour, and 40 mg during next two hours) by infusion. Controls were given placebo by same method. Full anticoagulation treatment and aspirin were given to both groups until angiography (10-22 days after admission). beta Blockers were given at discharge.
Left ventricular function at 10-22 days, enzymatic infarct size, clinical course, and survival to three month follow up.
Mortality was reduced by 51% (95% confidence interval -76 to 1) in treated patients at 14 days after start of treatment and by 36% (-63 to 13) at three months. For treatment within three hours after myocardial infarction mortality was reduced by 82% (-95 to -31) at 14 days and by 59% (-83 to -2) at three months. During 14 days in hospital incidence of cardiac complications was lower in treated patients than controls (cardiogenic shock, 2.5% v 6.0%; ventricular fibrillation, 3.4% v 6.3%; and pericarditis, 6.2% v 11.0% respectively), but that of angioplasty or artery bypass, or both was higher (15.8% v 9.6%) during the first three months. Bleeding complications were commoner in treated than untreated patients. Most were minor, but 1.4% of treated patients had intracranial haemorrhage within three days after start of infusion. Enzymatic size of infarct, determined by alpha hydroxybutyrate dehydrogenase concentrations, was less (20%, 2p = 0.0018) in treated patients than in controls. Left ventricular ejection fraction was 2.2% higher (0.3 to 4.0) and end diastolic and end systolic volumes smaller by 6.0 ml (-0.2 to -11.9) and 5.8 ml (-0.9 to -10.6), respectively, in treated patients.
Recombinant tissue type plasminogen activator with heparin and aspirin reduces size of infarct, preserves left ventricular function, and reduces complications and death from cardiac causes but at increased risk of bleeding complications4+
评估静脉注射重组组织型纤溶酶原激活剂对急性心肌梗死患者梗死面积、左心室功能及生存率的影响。
对症状发作后5小时内的急性心肌梗死患者进行双盲、随机、安慰剂对照前瞻性试验。
26个参与重组组织型纤溶酶原激活剂欧洲合作研究的转诊中心。
治疗组355例急性心肌梗死患者，分配接受静脉注射重组纤溶酶原激活剂。对照组包括366例类似患者，分配接受安慰剂。
所有患者在试验开始前立即给予阿司匹林250mg及5000IU肝素静脉推注。治疗组患者在3小时内静脉输注100mg重组组织型纤溶酶原激活剂（静脉推注10mg，1小时内输注50mg，接下来2小时内输注40mg）。对照组采用相同方法给予安慰剂。两组均给予充分抗凝治疗及阿司匹林直至血管造影检查（入院后10 - 22天）。出院时给予β受体阻滞剂。
10 - 22天的左心室功能、酶学梗死面积、临床病程及3个月随访时的生存率。
治疗开始后14天，治疗组患者死亡率降低51%（95%置信区间 - 76至1），3个月时降低36%（ - 63至13）。对于心肌梗死后3小时内接受治疗的患者，14天死亡率降低82%（ - 95至 - 31），3个月时降低59%（ - 83至 - 2）。住院14天期间，治疗组患者心脏并发症发生率低于对照组（心源性休克，2.5%对6.0%；心室颤动，3.4%对6.3%；心包炎，6.2%对11.0%），但在前3个月内接受血管成形术或动脉搭桥术或两者的比例更高（15.8%对9.6%）。治疗组出血并发症比未治疗组更常见。大多数为轻微出血，但1.4%的治疗组患者在输注开始后3天内发生颅内出血。通过α - 羟丁酸脱氢酶浓度测定的酶学梗死面积，治疗组患者比对照组小20%（P = 0.0018）。治疗组患者左心室射血分数高2.2%（0.3至4.0），舒张末期和收缩末期容积分别小6.0ml（ - 0.2至 - 11.9）和5.8ml（ - 0.9至 - 10.6）。
重组组织型纤溶酶原激活剂联合肝素和阿司匹林可减小梗死面积，保护左心室功能，降低心脏并发症及心脏原因导致的死亡，但出血并发症风险增加。
