Wahlgren Nils, Ahmed Niaz, Dávalos Antoni, Ford Gary A, Grond Martin, Hacke Werner, Hennerici Michael G, Kaste Markku, Kuelkens Sonja, Larrue Vincent, Lees Kennedy R, Roine Risto O, Soinne Lauri, Toni Danilo, Vanhooren Geert
Department of Neurology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Lancet. 2007 Jan 27;369(9558):275-82. doi: 10.1016/S0140-6736(07)60149-4.
The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) was to assess the safety and efficacy of intravenous alteplase as thrombolytic therapy within the first 3 h of onset of acute ischaemic stroke. Under European Union regulations, SITS-MOST was required to assess the safety profile of alteplase in clinical practice by comparison with results in randomised controlled trials.
6483 patients were recruited from 285 centres (50% with little previous experience in stroke thrombolysis) in 14 countries between 2002 and 2006 for this prospective, open, monitored, observational study. Primary outcomes were symptomatic (a deterioration in National Institutes of Health stroke scale score of >or=4) intracerebral haemorrhage type 2 within 24 h and mortality at 3 months. We compared mortality, the proportion of patients with symptomatic intracerebral haemorrhage as per the Cochrane definition, and functional outcome at 3 months with relevant pooled results from randomised controlled trials.
Baseline characteristics of patients in SITS-MOST were much the same as those in the pooled randomised controlled trials. At 24 h, the proportion of patients with symptomatic intracerebral haemorrhage (per the SITS-MOST protocol) was 1.7% (107/6444; 95% CI 1.4-2.0); at 7 days, the proportion with the same condition as per the Cochrane definition was 7.3% (468/6438; 6.7-7.9) compared with 8.6% (40/465; 6.3-11.6) in the pooled randomised controlled trials. The mortality rate at 3 months in SITS-MOST was 11.3% (701/6218; 10.5-12.1) compared with 17.3% (83/479; 14.1-21.1) in the pooled randomised controlled trials.
These data confirm that intravenous alteplase is safe and effective in routine clinical use when used within 3 h of stroke onset, even by centres with little previous experience of thrombolytic therapy for acute stroke. The findings should encourage wider use of thrombolytic therapy for suitable patients treated in stroke centres.
“卒中溶栓治疗安全实施监测研究”（SITS-MOST）的目的是评估急性缺血性卒中发病3小时内静脉注射阿替普酶作为溶栓治疗的安全性和有效性。根据欧盟法规，SITS-MOST需要通过与随机对照试验结果进行比较，来评估阿替普酶在临床实践中的安全性。
2002年至2006年间，从14个国家的285个中心招募了6483例患者（50%既往几乎没有卒中溶栓经验）参与这项前瞻性、开放性、监测性观察研究。主要结局为24小时内症状性（美国国立卫生研究院卒中量表评分恶化≥4分）2型脑出血和3个月时的死亡率。我们将死亡率、根据Cochrane定义的症状性脑出血患者比例以及3个月时的功能结局与随机对照试验的相关汇总结果进行了比较。
SITS-MOST中患者的基线特征与汇总的随机对照试验中的患者基本相同。24小时时，症状性脑出血患者比例（根据SITS-MOST方案）为1.7%（107/6444；95%CI 1.4 - 2.0）；7天时，根据Cochrane定义的相同情况患者比例为7.3%（468/6438；6.7 - 7.9），而汇总的随机对照试验中为8.6%（40/465；6.3 - 11.6）。SITS-MOST中3个月时的死亡率为11.3%（701/6218；10.5 - 12.1），而汇总的随机对照试验中为17.3%（83/479；14.1 - 21.1）。
这些数据证实，即使是既往几乎没有急性卒中溶栓治疗经验的中心，在卒中发病3小时内使用静脉注射阿替普酶进行常规临床治疗也是安全有效的。这些发现应鼓励在卒中中心对合适的患者更广泛地使用溶栓治疗。
