Sex and Gender Considerations in Endovascular Stroke Treatment

Sex and gender differences are recognised as important considerations in personalised medicine. In stroke, women and men may have different risk factors,¹ symptom presentation² and outcomes. Women are more likely to die, be disabled, discharged to a nursing home and have worse quality of life after stroke compared to men.^{3, 4} The reasons for these differences are multifactorial, and require an intersectional approach to be fully understood. Increasing researchers and clinicians’ awareness of these differences is the first step in bridging the sex and gender gap in stroke. In clinical trials that provide the evidence base for practice guidelines, women are underrepresented in stroke in all parts of the treatment chain, from the hyperacute through to rehabilitation and secondary prevention trials.^{5, 6} Unfortunately, the number of women enrolled in trials have not substantially increased in the past 10 years despite adoption of policies that emphasize the inclusion of women in clinical trials^{7, 8} and an increase focus on equity. The challenges to overcome may range from trial design through our consent processes.

Of interest, the five pivotal trials published in 2015 that established endovascular treatment (EVT) as an evidence-based treatment recruited between 41 to 52% females.^9-13 Because it has only been recently established as standard of care, sex and gender differences reporting in EVT studies are few and far between. The current scientific statement by Ospel and colleagues of the American Heart Association/American Stroke Association (AHA/ASA) provides a concise and fair overview of the known and unknowns of sex and gender differences in EVT.

The authors have defined key areas with knowledge gaps where further work is needed—this spans from understanding the optimal EVT technique to differentiating the influence of sex and gender. Furthermore, it provides detailed suggestions on how to assess sex and gender related differences in EVT. For example, researchers and clinicians would not only need to account for sex differences, but also gender differences. Since EVT decision-making is time-critical, these issues can be difficult to address in the acute setting, moreover, data is needed to understand if sex and gender issues influence clinical decision making and access to care. Also, with emerging evidence that clot composition may influence EVT techniques, combined with evidence that clot composition may differ according to sex, smart trial design considering these differences is needed to account for treatment effects in men and women alike. More evidence is required to understand why women receive shorter course of active treatment and more often receive palliative care within the first 24 hours.

This scientific statement has a well-discussed road map for researchers and clinicians. While we agree that in many stroke cases, gender identity can overlap with sex, it is crucial that collecting both sex and gender data in clinical trials is normalised. This will facilitate intersectional analyses as well as afford more robust gender-related findings. In recent years, the researcher’s role in considering sex and gender have been much emphasized but clinicians play a key role as well. With acknowledgement of sex and gender differences in stroke, clinicians are able to evaluate eligibility of EVT more accurately. We suggest an additional road map for policymakers and funders where guidance on overcoming these differences is underscored. It should be mandated that clinical trial protocols and grant application include information on potential sex differences in treatment, how the research groups plan to overcome the differences and ensuring adequate representation women and men. Where relevant, collecting, analysing, and reporting sex and/or gender data should be mandated in studies.

The AHA/ASA scientific statement Toward a Better Understanding of Sex- and Gender-Related Differences in Endovascular Stroke Treatment is an exciting initiation by the stroke scientific community in acknowledging the impact of sex and gender in EVT. We hope other groups will follow.