Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P
Department of Neurology, University of Heidelberg, Germany.
Lancet. 1998 Oct 17;352(9136):1245-51. doi: 10.1016/s0140-6736(98)08020-9.
Thrombolysis for acute ischaemic stroke has been investigated in several clinical trials, with variable results. We have assessed the safety and efficacy of intravenous thrombolysis with alteplase (0.9 mg/kg bodyweight) within 6 h of stroke onset.
This non-angiographic, randomised, double-blind, trial enrolled 800 patients in Europe, Australia, and New Zealand. Computed tomography was used to exclude patients with signs of major infarction. Alteplase (n=409) and placebo (n=391) were randomly assigned with stratification for time since symptom onset (0-3 h or 3-6 h). The primary endpoint was the modified Rankin scale (mRS) at 90 days, dichotomised for favourable (score 0-1) and unfavourable (score 2-6) outcome. Analyses were by intention to treat.
165 (40.3%) alteplase-group patients and 143 (36.6%) placebo-group patients had favourable mRS outcomes (absolute difference 3.7%, p=0.277). In a posthoc analysis of mRS scores dichotomised for death or dependency, 222 (54.3%) alteplase-group and 180 (46.0%) placebo-group patients had favourable outcomes (score 0-2; absolute difference 8.3%, p=0.024). Treatment differences were similar whether patients were treated within 3 h or 3-6 h. 85 (10.6%) patients died, with no difference between treatment groups at day 90+/-14 days (43 alteplase, 42 placebo). Symptomatic intracranial haemorrhage occurred in 36 (8.8%) alteplase-group patients and 13 (3.4%) placebo-group patients.
The results do not confirm a statistical benefit for alteplase. However, we believe the trend towards efficacy should be interpreted in the light of evidence from previous trials. Despite the increased risk of intracranial haemorrhage, thrombolysis with alteplase at a dose of 0.9 mg/kg in selected patients may lead to a clinically relevant improvement in outcome.
急性缺血性卒中的溶栓治疗已在多项临床试验中进行了研究，结果各异。我们评估了在卒中发作6小时内静脉注射阿替普酶（0.9mg/kg体重）的安全性和有效性。
这项非血管造影、随机、双盲试验在欧洲、澳大利亚和新西兰招募了800名患者。使用计算机断层扫描排除有大面积梗死迹象的患者。阿替普酶组（n = 409）和安慰剂组（n = 391）根据症状发作后的时间（0 - 3小时或3 - 6小时）进行分层随机分配。主要终点是90天时的改良Rankin量表（mRS），分为良好（评分0 - 1）和不良（评分2 - 6）结局。分析采用意向性治疗。
165名（40.3%）阿替普酶组患者和143名（36.6%）安慰剂组患者有良好的mRS结局（绝对差异3.7%，p = 0.277）。在对死亡或依赖进行二分法的mRS评分的事后分析中，222名（54.3%）阿替普酶组和180名（46.0%）安慰剂组患者有良好结局（评分0 - 2；绝对差异8.3%，p = 0.024）。无论患者是在3小时内还是3 - 6小时内接受治疗，治疗差异相似。85名（10.6%）患者死亡，在90±14天时治疗组之间无差异（阿替普酶组43例，安慰剂组42例）。有症状的颅内出血发生在36名（8.8%）阿替普酶组患者和13名（3.4%）安慰剂组患者中。
结果未证实阿替普酶有统计学益处。然而，我们认为应根据先前试验的证据来解读疗效趋势。尽管颅内出血风险增加，但在选定患者中以0.9mg/kg的剂量使用阿替普酶进行溶栓可能会导致结局有临床相关的改善。
