Whiteley William N, Thompson Douglas, Murray Gordon, Cohen Geoff, Lindley Richard I, Wardlaw Joanna, Sandercock Peter
From the Centre for Clinical Brain Sciences (W.N.W., G.C., J.W., P.S.) and Centre for Population Health Sciences (D.T., G.M.), University of Edinburgh, United Kingdom; Neurological & Mental Health Division, George Institute for Global Health, University of Sydney, Australia (R.I.L.); and Neuroimaging Sciences, Edinburgh, United Kingdom (J.W.).
Stroke. 2014 Dec;45(12):3612-7. doi: 10.1161/STROKEAHA.114.006890. Epub 2014 Nov 4.
Prompt thrombolytic therapy with intravenous alteplase reduces disability after acute ischemic stroke. In an exploratory analysis, we examined whether long-term survival varied by baseline characteristics after alteplase.
In this open-treatment, international, randomized, controlled trial, ischemic stroke patients were randomly allocated <6 hours of onset to intravenous alteplase (0.9 mg/kg) plus standard care (n=1515) or standard care alone (n=1520). We followed patients to death, censoring when last known to be alive. We grouped patients by delay to randomization, and good or poor predicted prognosis (calculated from baseline National Institutes of Health Stroke Scale [NIHSS] score and age). We present absolute mortality differences between treated and control groups at 7 days, 6 months, and 18 months poststroke.
Alteplase was not associated with a significant increase in mortality within 18 months (0.6% [95% confidence interval (CI), -2.9% to +4.2] P=0.72] in all patients with complete vital status (99.9%, 3034/3035). In patients randomized <3 hours of stroke, 18-month mortality was lower in the alteplase-treated group than the control group (40.6% [95% CI, 42.6-52.7] versus 47.8% [95% CI, 35.5-45.3]; P=0.0434]. The difference in 18-month mortality between alteplase-treated and control patients was greater in patients who were randomized early (<3 hours) compared with late (3-6 hours; +9% [95% CI, 1-17]; P=0.0317). Alteplase led to a greater improvement in 18-month survival in patients with a poor prognosis than in patients with a good prognosis (+8% [95% CI, 2-14]; P=0.0091).
These exploratory analyses of the third International Stroke Trial (IST-3) trial support improving acute stroke patients' access to earlier alteplase treatment, treatment of patients with poor prognosis, and further randomized controlled trials in minor stroke to replicate these findings.
http://www.controlled-trials.com. Unique identifier: ISRCTN25765518.
急性缺血性卒中后立即静脉注射阿替普酶进行溶栓治疗可减少残疾。在一项探索性分析中，我们研究了阿替普酶治疗后长期生存率是否因基线特征而异。
在这项开放治疗、国际、随机、对照试验中，缺血性卒中患者在发病<6小时内被随机分配接受静脉注射阿替普酶（0.9mg/kg）加标准治疗（n = 1515）或仅接受标准治疗（n = 1520）。我们对患者进行随访直至死亡，在最后一次已知存活时进行截尾。我们根据随机分组延迟时间以及预测预后良好或不良（根据基线美国国立卫生研究院卒中量表[NIHSS]评分和年龄计算）对患者进行分组。我们呈现了卒中后7天、6个月和18个月时治疗组与对照组之间的绝对死亡率差异。
在所有生命状态完整的患者（99.9%，3034/3035）中，阿替普酶在18个月内未导致死亡率显著增加（0.6%[95%置信区间（CI），-2.9%至+4.2]，P = 0.72）。在卒中<3小时随机分组的患者中，阿替普酶治疗组的18个月死亡率低于对照组（40.6%[95%CI，42.6 - 52.7]对47.8%[95%CI，35.5 - 45.3]；P = 0.0434）。与晚期（3 - 6小时）随机分组的患者相比，早期（<3小时）随机分组的患者中，阿替普酶治疗组与对照组患者的18个月死亡率差异更大（+9%[95%CI，1 - 17]；P = 0.0317）。与预后良好的患者相比，阿替普酶使预后不良的患者18个月生存率有更大改善（+8%[95%CI，2 - 14]；P = 0.0091）。
这些对第三次国际卒中试验（IST - 3）的探索性分析支持改善急性卒中患者更早接受阿替普酶治疗的机会、对预后不良患者的治疗，以及在轻度卒中中进行进一步的随机对照试验以重复这些发现。
