Confirmation of tPA treatment effect by baseline severity-adjusted end point reanalysis of the NINDS-tPA stroke trials
Confirmation of tPA treatment effect by baseline severity-adjusted end point reanalysis of the NINDS-tPA stroke trials
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DOI：
10.1161/01.str.0000254580.39297.3c
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发表时间：
2007-02-01
期刊：
影响因子：
8.3
通讯作者：
Yafeh, Banafsheh
中科院分区：
文献类型：
--
作者：
Saver, Jeffrey L.;Yafeh, Banafsheh
背景和目的--基线严重性调整终点分析是急性卒中试验中主要终点评估的一种新兴方法，它提供了一种新的方法来调整试验分析，以适应治疗组中呈现中风严重性的基线失衡，这一因素使关键的国家神经疾病研究所和中风组织纤溶酶原激活剂(NIHDS-tPA)试验的结果的解释和接受变得复杂。方法：采用最近的急性缺血性卒中临床试验中应用的滑动标尺二分终点反应者分析方法对NIHDS-tPA卒中试验1和2进行分析。良好的结果是：如果治疗前NIHSS评分为1~7，3个月Rankin评分=0；如果治疗前NIHSS评分为8~14，3个月Rankin评分=0~1；如果治疗前NIHSS评分为>；14，3个月Rankin评分=0~2。结果：两个NIHDS-tPA卒中试验均显示tPA治疗效果显著。在未经调整的分析中，在试验1中，tPA与安慰剂患者的良好结果分别为39.6%和28.6%(优势比1.64，P=0.049)；在试验2中，良好结果分别为35.7%和24.2%(优势比1.74，P=0.024)。在试验1和试验2的所有624名患者中，37.5%的患者预后良好，而26.3%的患者预后良好(优势比1.68，P=0.0034)。在发病至治疗时间91至180分钟的亚组患者中，基线严重程度失衡特别严重的患者中，良好结果分别为36.1%和24.0%(优势比1.80，P=0.021)。在对另外12个已知可预测急性卒中结果的协变量进行调整后，有利于tPA的优势比一般会进一步增加。结论：对NIHDS卒中tPA试验的基线调整的严重程度终点重新分析证实静脉注射tPA是有益的治疗效果。(笔划。2007；38：414-416。)
Background and Purpose-Baseline severity-adjusted end point analysis, an emerging approach to the evaluation of primary end points in acute stroke trials, offers a novel means of adjusting trial analysis for baseline imbalances in presenting stroke severity among treatment groups, a factor that has complicated interpretation and reception of the results of the pivotal National Institute of Neurological Disorders and Stroke tissue plasminogen activator (NIHDS-tPA) trials. Methods-The sliding scale dichotomy end point responder analysis applied in recent acute ischemic stroke clinical trials was used to analyze NIHDS-tPA stroke trials 1 and 2. Good outcomes were: 3-month Rankin scale=0 if pretreatment NIHSS scores were 1 to 7; 3-month Rankin scale=0 to 1 if pretreatment NIHSS scores were 8 to 14; 3-month Rankin scale=0 to 2 if pretreatment NIHSS scores were > 14. Results-Both of the NIHDS-tPA stroke trials showed a statistically significant beneficial treatment effect of tPA. In unadjusted analyses, in trial 1, good outcomes in tPA versus placebo patients were 39.6% versus 28.6% (odds ratio 1.64, P=0.049); in trial 2, 35.7% versus 24.2% (odds ratio 1.74, P=0.024). Among all 624 patients in trials 1 and 2 combined, good outcomes occurred in 37.5% versus 26.3% patients (odds ratio 1.68, P=0.0034). In the 91- to 180- minute onset to treatment time subgroup of patients among whom baseline severity imbalance was particularly severe, good outcomes were noted in 36.1% versus 24.0% (odds ratio 1.80, P=0.021). Odds ratios favoring tPA generally further increased after adjustment for 12 additional covariates known to predict acute stroke outcome. Conclusion-Baseline-adjusted severity end point reanalysis of the NIHDS Stroke tPA trials confirms a beneficial treatment effect of intravenous tPA. (Stroke. 2007;38:414-416.)