Systematic review of evidence on thrombolytic therapy for acute ischaemic stroke
Systematic review of evidence on thrombolytic therapy for acute ischaemic stroke
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DOI：
10.1016/s0140-6736(97)03022-5
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发表时间：
1997-08-30
期刊：
影响因子：
168.9
通讯作者：
Counsell, C
中科院分区：
文献类型：
--
作者：
Wardlaw, JM;Warlow, CP;Counsell, C
背景最近急性缺血性卒中的溶栓治疗试验给出了明显相互矛盾的结果。只有一项试验，国家神经疾病研究所和中风试验组织纤溶酶原激活剂(TPA)，表明溶栓治疗肯定是有益的，为了理解这些结果，我们对所有可用的急性缺血性中风溶栓治疗的随机试验进行了系统的回顾。方法从所有可用的溶栓治疗与对照的急性缺血性中风的随机试验(具有随机前CT)中，我们检查了大约前两周的死亡，在试验随访期结束时所有原因死亡和功能结果(残疾)的表格数据，以及早期症状性和致死性颅内出血。结果12项试验包括3435名患者，3435名患者其中694人(20%)死亡，2567人中1001人(39%)在随访结束时功能依赖(随访时间因试验而异，但最长为6个月)。在3435例患者中，214例(6%)有早期症状或致死性颅内出血。溶栓治疗与早期死亡(每1000名接受治疗的患者中91例[95%可信区间54-134])和总死亡(37/1000[20-83])显著相关，但死亡或依赖患者的综合结果中的患者数量显著减少(每1000名接受治疗的患者减少65例[28-107])。在每1000名接受治疗的患者中约70例额外有症状的颅内出血(其中51例死亡)中，有大量有症状和致命性的颅内出血溶栓治疗--这在所有最近的试验中都是相似的--在中风后3小时内随机抽取的患者中，死亡或依赖治疗的患者数量显著减少(每1000名接受治疗的患者中死亡或依赖治疗的患者减少141例[75-206]，死亡人数无显著增加(每1000名接受治疗的患者中有9例死亡[-39至70])。在随访结束时的总死亡率试验之间存在显著的异质性，这可能部分是由于在溶栓治疗的前24小时内使用抗血栓药物的不同；中风严重程度的不同包括：溶栓治疗的时间窗口；以及使用溶栓药物的剂量。与使用tPA的试验相比，没有直接比较tPA与链激酶组或尿激酶组的结果：与使用tPA的试验相比，接受链激酶组的患者的不良结局可能是由于纳入了更严重的中风、更多的抗血栓药物的使用、更高的剂量以及更长的治疗时间。解释溶栓需要在大型随机试验中进行进一步的测试，因为风险似乎很大，而且益处尚不确定。有效治疗的时间窗口仍不清楚。没有客观证据表明tPA比链激酶更安全；当考虑到试验设计和基线变量的差异时，明显的危险和益处可能是相似的。
Background Recent trials of thrombolytic therapy in acute ischaemic stroke have given apparently conflicting results. Only one trial, the National Institute of Neurological Disorders and Stroke trial of tissue plasminogen activator (tPA), suggested that thrombolysis was definitely beneficial, To make sense of these results, we have done a systematic review of all available randomised trials of thrombolysis in acute ischaemic stroke.Methods From all available completed randomised trials of thrombolytic therapy compared with control in acute ischaemic stroke (with prerandomisation CT), we checked tabular data on deaths during roughly the first 2 weeks, deaths from all causes and functional outcome (disability) at the end of the trial follow-up period, and early symptomatic and fatal intracranial haemorrhages.Findings 12 trials included 3435 patients, of whom 694 (20%) were dead and 1001 (39%) of 2567 were functionally dependent at the end of follow-up (duration of follow-up varied between trials, but the longest was 6 months). 214 (6%) of the 3435 patients had early symptomatic or fatal intracranial haemorrhages. Thrombolytic therapy was associated with a significant excess of early deaths (91 per 1000 patients treated [95% CI 54-134]), and total deaths (37 per 1000 [20-83]), but there was nevertheless a significant reduction in the number of patients in the combined outcome of dead or dependent (65 fewer per 1000 patients treated [28-107]). There was a substantial and significant excess of symptomatic and fatal intracranial haemorrhages with thrombolysis-which was similar in all recent trials-of about 70 extra symptomatic intracranial haemorrhages per 1000 patients treated (of which 51 per 1000 were fatal), In the cohort of patients randomised within 3 h of stroke, there was a significant reduction in the number of patients who were dead or dependent al the end of follow-up (141 fewer dead or dependent per 1000 patients treated [75-206] and a non-significant increase in the number dead (nine per 1000 treated [-39 to 70]). There was significant heterogeneity between the trials for total deaths at the end of follow-up, which may be partly explained by differences in the use of antithrombotic drugs within the first 24 h of thrombolysis; the variation in severity of strokes included: the time window to thrombolytic treatment; and the dose of thrombolytic drug used. There were no direct comparisons of tPA with streptokinase or urokinase: much of the poor outcome in the streptokinase-treated patients might be explained by the inclusion of more severe strokes, greater use of antithrombotic drugs, higher doses, and the longer time to treatment compared with the trials that used tPA.Interpretation Thrombolysis requires further testing in large randomised trials because the risks seem substantial, and the benefit uncertain. The time window for effective treatment remains unclear. There is no objective evidence to suggest that tPA is safer than streptokinase; the apparent hazards and benefits may be similar when differences in trial design and baseline variables are accounted for.