Kent David M, Selker Harry P, Ruthazer Robin, Bluhmki Erich, Hacke Werner
Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA.
Stroke. 2006 Dec;37(12):2963-9. doi: 10.1161/01.STR.0000249005.37120.9f. Epub 2006 Oct 26.
The Stroke-Thrombolytic Predictive Instrument (Stroke-TPI) uses multivariate equations to predict outcomes with and without thrombolysis. We sought to examine whether such a multivariate predictive instrument might be useful in selecting patients with a favorable risk-benefit treatment profile for therapy after 3 hours.
We explored outcomes in patients from 5 major randomized clinical trials testing intravenous recombinant tissue plasminogen activator (rt-PA) classified by the Stroke-TPI as "treatment-favorable" or "treatment-unfavorable." We used iterative bootstrap re-sampling to estimate how such a model would perform on independent test data.
Among patients treated within the 3- to 6-hour window, 67% of patients were classified by Stroke-TPI predicted outcomes as "treatment-favorable" and 33% were classified as "treatment-unfavorable." Outcomes in the treatment-favorable group demonstrated benefit for thrombolysis (modified Rankin Scale score < or =1: 44.0% with rt-PA versus 34.2 with placebo, P=0.005), whereas harm was demonstrated in the treatment-unfavorable group (modified Rankin Scale score < or =1: 31.3% with rt-PA versus 38.3% with placebo; P=0.004). Bootstrap resampling with complete cross-validation showed that the absolute margin of benefit in the treatment-favorable group diminished on average by 36% between derivation and independent validation sets, but still represented a significant tripling of improvement in benefit compared with conventional inclusion criteria (5.2% [interquartile range, 1.7% to 8.6%] versus 1.8% [interquartile range, -0.5 to 4.1], P<0.0001).
Such multivariable risk-benefit profiling may be useful in the selection of acute stroke patients for rt-PA therapy even more than 3 hours after symptom onset. Prospective testing is indicated.
卒中溶栓预测工具（Stroke-TPI）使用多变量方程来预测溶栓和未溶栓的结果。我们试图研究这样一种多变量预测工具是否有助于筛选出治疗风险效益比良好的患者，以便在发病3小时后进行治疗。
我们探讨了5项主要随机临床试验中患者的结局，这些试验测试静脉注射重组组织型纤溶酶原激活剂（rt-PA），根据Stroke-TPI分为“治疗有利”或“治疗不利”。我们使用迭代自助重采样来估计这样一个模型在独立测试数据上的表现。
在3至6小时时间窗内接受治疗的患者中，Stroke-TPI预测结果将67%的患者分类为“治疗有利”，33%分类为“治疗不利”。治疗有利组的结局显示溶栓有益（改良Rankin量表评分≤1：rt-PA组为44.0%，安慰剂组为34.2%，P = 0.005），而治疗不利组显示有害（改良Rankin量表评分≤1：rt-PA组为31.3%，安慰剂组为38.3%；P = 0.004）。完全交叉验证的自助重采样显示，治疗有利组的绝对获益幅度在推导集和独立验证集之间平均减少了36%，但与传统纳入标准相比，获益改善仍显著增加了两倍（5.2%[四分位间距，1.7%至8.6%]对1.8%[四分位间距，-0.5至4.1]，P<0.0001）。
即使在症状发作超过3小时后，这种多变量风险效益分析对于选择急性卒中患者进行rt-PA治疗可能也有用。需要进行前瞻性测试。
