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(Stroke. 2007;38:414.)
© 2007 American Heart Association, Inc.

Research Reports

Confirmation of tPA Treatment Effect by Baseline Severity-Adjusted End Point Reanalysis of the NINDS-tPA Stroke Trials

From Stroke Center and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Calif.

Correspondence to Jeffrey L. Saver, MD, UCLA Stroke Center, 710 Westwood Plaza, Los Angeles, CA 90095. E-mail jsaver{at}ucla.edu

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 (NINDS-tPA) trials.

Methods— The sliding scale dichotomy end point responder analysis applied in recent acute ischemic stroke clinical trials was used to analyze NINDS-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 NINDS-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 NINDS Stroke tPA trials confirms a beneficial treatment effect of intravenous tPA.

Key Words: acute care • acute Rx • acute stroke • clinical trials • emergency medicine • stroke • stroke care • therapy • thrombolysis • thrombolytic Rx

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