Sex-based differences in the effect of intra-arterial treatment of stroke: analysis of the PROACT-2 study.
OBJECTIVE
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 <or=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.
Hill
Michael D
MD
Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. Michael.hill@calgaryhealthregion.ca
Kent
David M
DM
Hinchey
Judith
J
Rowley
Howard
H
Buchan
Alastair M
AM
Wechsler
Lawrence R
LR
Higashida
Randall T
RT
Fischbein
Nancy J
NJ
Dillon
William P
WP
Gent
Michael
M
Firszt
Carolyn M
CM
Schulz
Gregory A
GA
Furlan
Anthony J
AJ
D000368:Aged; D002545:Brain Ischemia / Q000150:complications; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012727:Sex Characteristics; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D014568:Urokinase-Type Plasminogen Activator; C067551:saruplase