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. 2025 Jan 3:23969873241309512.
doi: 10.1177/23969873241309512. Online ahead of print.

Effects of sex on imaging-based intravenous thrombolysis for ischaemic stroke with unknown onset time: a pooled analysis of clinical trials

Mayumi Fukuda-Doi  1 , Masatoshi Koga  1 , Götz Thomalla  2 , Märit Jensen  2 , Manabu Inoue  1 , Sohei Yoshimura  1 , Kaori Miwa  1 , Christian Gerloff  2 , Stephen M Davis  3 , Geoffrey A Donnan  3 , Henry Ma  4 , Werner Hacke  5 , Peter Ringleb  5 , Ona Wu  6 , Lee H Schwamm  7 , Steven Warach  8 , Kazunori Toyoda  1
Affiliations

Effects of sex on imaging-based intravenous thrombolysis for ischaemic stroke with unknown onset time: a pooled analysis of clinical trials

Mayumi Fukuda-Doi et al. Eur Stroke J. .

Abstract

Introduction: The effects of imaging-based intravenous thrombolysis on outcomes based on patient sex remain unclear. We aimed to investigate whether outcomes among patients with stroke with an unknown onset time and treated with imaging-based intravenous thrombolysis are influenced by their sex.

Patients and methods: This study was a pooled analysis of individual patient-level data acquired from the Evaluation of unknown Onset Stroke thrombolysis trials. Patients treated with imaging-based intravenous thrombolysis for stroke with an unknown onset time were included. The primary outcome was a favourable outcome (modified Rankin Scale score 0-1) at 90 days. The sex-based difference in outcomes was studied using mixed-effect logistic or ordinal regression models, considering potential heterogeneity across trials.

Results: Out of 509 patients in total, 204 (40.1%) were women. Compared with men, women were older and more likely to have atrial fibrillation. Baseline National Institutes of Health Stroke Scale score was higher and hours from last-known-well to treatment were longer for women than for men. Favourable outcomes occurred less often among women than among men. However, multivariate adjustment revealed a non-significant association between female sex and favourable outcome (adjusted odds ratio: 1.04 [95% confidence interval: 0.66-1.52], p = 0.98).

Discussion and conclusion: Pooled data from the included clinical trials showed that women with ischaemic stroke with an unknown onset time had worse functional outcomes following imaging-based intravenous thrombolysis than did men. However, this sex-based difference can be explained by the higher age and more severe clinical status at onset among women.

Keywords: Thrombolysis; clinical trial; ischaemic stroke; pooled analysis; sex.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MK reports personal fees from Mitsubishi Tanabe Pharma and Daiichi-Sankyo and research support from Daiichi-Sankyo and Nippon Boehringer Ingelheim, all of which are outside of the submitted work. GT reports grants and personal fees from Bayer, personal fees from Acandis, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Daiichi Sankyo, Portola, and Stryker outside of the submitted work. MI reports personal fees from Daiichi Sankyo, Bayer, Bristol Myers Squibb, and Nippon Boehringer Ingelheim outside of the submitted work. CG reports personal fees from Amgen, Bayer Vital, Bristol Myers Squibb, Boehringer Ingelheim, Sanofi Aventis, Abbott, and Prediction Biosciences outside of the submitted work. SMD reports personal fees from Abbott, Boehringer Ingelheim, Bayer, Tide Pharmaceuticals, and Medtronic and grants from the National Health and Medical Research Council of Australia outside of the submitted work. GAD reports grants from the National Health and Medical Research Council Australia during the conduct of the study and personal fees from Allergan, Amgen, Bayer, Boehringer Ingelheim, Pfizer, and Servier outside of the submitted work. WH reports grants from Boehringer Ingelheim. PR reports grants from Boehringer Ingelheim during the conduct of the study and personal fees from Bayer, Boehringer Ingelheim, Pfizer, and Daiichi Sankyo outside of the submitted work. OW reports grants from the NIH, grants and non-financial support from Genentech during the conduct of the study, and personal fees from Penumbra and Genentech outside of the submitted work. OW has a patent ‘Delay-compensated calculation of tissue blood flow’ (US Patent 7,512,435; March 31, 2009) with royalties paid to General Electric, Siemens, Olea Medical, and Imaging Biometrics. LHS reports grants from the National Institute of Neurological Disorders and Stroke (NINDS) and Genentech during the conduct of the study and personal fees from Genentech, Medtronic, and LifeImage outside of the submitted work and served on data safety monitoring boards for Penumbra and the Charite Hospital B_PROUD trial of mobile stroke units. SW reports grants from the NIH (Grant P50NS051343) during the conduct of the study and personal fees from Genentech outside of the submitted work. KT reports grants from the Japan Agency for Medical Research and Development during the conduct of the study and personal fees from Daiichi-Sankyo, Bayer Yakuhin, Bristol Myers Squibb, Otsuka, and Novartis outside of the submitted work. Others: nothing to report.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Data flow diagram.
Figure 2.
Figure 2.
Modified Ranking Scale (mRS) distribution at 90 days based on sex.
See this image and copyright information in PMC

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