Wahlgren Nils, Ahmed Niaz, Eriksson Niclas, Aichner Franz, Bluhmki Erich, Dávalos Antoni, Erilä Terttu, Ford Gary A, Grond Martin, Hacke Werner, Hennerici Michael G, Kaste Markku, Köhrmann Martin, Larrue Vincent, Lees Kennedy R, Machnig Thomas, Roine Risto O, Toni Danilo, Vanhooren Geert
Department of Neurology, Karolinska University Hospital-Solna, Karolinska Institutet, Stockholm, Sweden.
Stroke. 2008 Dec;39(12):3316-22. doi: 10.1161/STROKEAHA.107.510768. Epub 2008 Oct 16.
The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.
The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P<or=0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P<0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration >or=1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.
The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.
The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.
卒中溶栓安全实施监测研究（SITS - MOST）的未调整结果表明，静脉注射阿替普酶耐受性良好，且在缺血性卒中发病3小时内用于常规临床实践时，其效果与随机对照试验（RCT）中观察到的效果相当。我们旨在确定预后预测因素，并将SITS - MOST的结果调整至RCT的基线特征。
研究人群为SITS - MOST（n = 6483）和汇总的RCT（n = 464）中在卒中发病3小时内接受静脉注射阿替普酶治疗的患者。进行多变量向后逐步回归分析（直至P≤0.10）以确定SITS - MOST的预后预测因素。最终多变量模型中出现的变量或SITS - MOST与RCT之间存在差异（P < 0.10）的变量被纳入用于调整结果的预测模型。主要结局指标为症状性脑出血，定义为美国国立卫生研究院卒中量表在7天内恶化≥1分且伴有任何出血（RCT定义）、死亡率，以及3个月时改良Rankin评分为0至2所定义的独立性。
SITS - MOST调整后的症状性脑出血比例为8.5%（95%CI，7.9至9.0），而汇总的RCT为8.6%（6.3至11.6）；死亡率分别为15.5%（14.7至16.2）和17.3%（14.1至21.1）；独立性分别为50.4%（49.6至51.2）和50.1%（44.5至54.7）。在多变量分析中，年龄较大、血糖高、美国国立卫生研究院卒中量表评分高以及影像学扫描显示有新发梗死与所有参数的不良预后相关。收缩压、心房颤动和体重是症状性脑出血额外的预测因素。当前吸烟者症状性脑出血发生率较低。本次卒中前有残疾（改良Rankin评分2至5分）、舒张压、非阿司匹林类抗血小板药物、充血性心力衰竭、在新中心接受治疗的患者以及男性与3个月时的高死亡率相关。
SITS - MOST调整后的结果与相关RCT的结果几乎相同，并强化了先前未调整分析得出的结论。我们确定了几个重要的预后预测因素，以更好地识别适合溶栓治疗中的患者。
