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(Stroke. 2006;37:2322.)
© 2006 American Heart Association, Inc.

Original Contributions

Sex-Based Differences in the Effect of Intra-Arterial Treatment of Stroke

Analysis of the PROACT-2 Study

Michael D. Hill, MD, MSc; David M. Kent, MD, MS; Judith Hinchey, MD; Howard Rowley, MD; Alastair M. Buchan, MB, FRCP (UK); Lawrence R. Wechsler, MD; Randall T. Higashida, MD; Nancy J. Fischbein, MD; William P. Dillon, MD; Michael Gent; Carolyn M. Firszt, MSc; Gregory A. Schulz, MSc; Anthony J. Furlan, MD on behalf of the PROACT-2 Investigators

From the Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.

Correspondence to Michael D. Hill, Associate Professor, Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Foothills Hospital, Rm 1162, 1403 29th St, NW, Calgary, Alberta, T2N 2T9, Canada. E-mail Michael.hill{at}calgaryhealthregion.ca

Background and Purpose— Sex influences outcome after intravenous thrombolysis. In a combined analysis of the tissue plasminogen activator clinical trials, a sex-by-treatment interaction was observed. We sought to confirm that observation in an independent data set.

Methods— Data were from the Pro-Urokinase for Acute Cerebral Thromboembolism-2 (PROACT-2) trial. Baseline factors were compared by sex. The primary outcome was an assessment of a sex-by-treatment interaction term within a logistic regression model, using a modified Rankin Scale score 2 at 90 days as the binary outcome. We also assessed whether there were differences in CT-scan appearance and recanalization at 2 hours post-treatment.

Results— In the PROACT-2 study of intra-arterial stroke thrombolysis, in both women and men, prourokinase resulted in better outcomes than control. A sex by prourokinase treatment interaction was observed, with women showing a larger treatment effect (20% absolute benefit) compared with men (10% absolute benefit). The reason for this interaction is that thrombolytic treatment nullifies the worse outcome for untreated women compared with men. The reasons for effect modification do not include improved recanalization at 2 hours among women.

Conclusions— Women with middle cerebral artery ischemic stroke benefit more from intra-arterial therapy. Further study of how sex affects stroke outcome is needed.

Key Words: gender • stroke • thrombolysis

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