Isabella Canavero, MD

Fukuda-Doi M, Yamamoto H, Koga M, Palesch YY, Durkalski-Mauldin VL, Qureshi AI, Yoshimura S, Okazaki S, Miwa K, Okada Y, et al. Sex Differences in Blood Pressure–Lowering Therapy and Outcomes Following Intracerebral Hemorrhage: Results From ATACH-2. Stroke. 2020;51:2282–2286.

Previous data from large stroke cohorts highlighted a globally poorer functional outcome for women than men, although in terms of the major rough outcome measures (mortality, disability, recurrences), no relevant disparities were observed. In fact, the perceived quality of life and the frequent occurrence of post stroke depression seemed to play a major role in determining women’s disadvantage.

Fukuda-Doi et al. further explored sex differences in affecting post ICH outcome, and the response to BP-lowering therapy, by evaluating data from the Antihypertensive Treatment in Intracerebral Hemorrhage-2 (ATACH-2) trial (comparing standard versus intensive BP-lowering strategies). Demographics pointed out heterogeneity between men and women, whom were older and more frequently on antihypertensive before onset. Of note, women more frequently suffered from lobar ICH, while hematoma expansion and perihematomal edema were less common than in men. At 3 month-follow up, women had higher death and disability rate than men, being sex independently associated after multivariate adjustment. The worse outcome despite the favorably lower rate of hematoma expansion and perihematomal edema suggested, again, the existence of additional underlying mechanisms, pointing to psychological, social, and environmental, rather than pathophysiological, factors.

In this view, sex differences should probably be interpreted as “gender” differences, being the former more related to biological and the latter to behavior, lifestyle, and socio-cultural factors. Indeed, poorer prestroke activity and access to medical resources, higher incidence of frailty and social isolation, and higher prevalence of poststroke depression are plausible explanations for women’s poorer outcomes.

The crucial paradox in evaluating women’s post stroke outcome is probably intrinsic in their well-known longer life expectancy, determining social isolation, prolonging duration of disability, thus determining and exacerbating post stroke depression and negatively impacting on the subjective perception of quality of life.

The authors also found a significant interaction between BP-lowering treatment and sex for death or disability. However, the relative treatment effects were comparable, and 95% CIs overlapped, preventing to state that intensive BP-lowering therapy in acute ICH is more beneficial for women. In addition, sex did not modify the association between treatment and renal adverse events. In conclusion, in this prespecified analysis of ATACH-2, women were independently associated with poorer functional outcomes. Intensive systolic BP–lowering therapy did not reduce the poor outcomes in either women or men.

Besides some limitations affecting generalizability, including potential selection bias determined by exclusion of the most severe ICH, an underrepresentation of women on the whole (38%), and the absence of long-term outcomes, the study is built on a large number of study samples from diverse geographical areas, and featured by high-quality data with a limited number of missing.

This study inspires further investigations about the underlying reasons determining sex (and gender) disparities in post stroke outcome, potentially identifying new targets for intervention to ameliorate women’s quality of life after stroke. As a matter of personalized medicine, the role of gender could be considered to tailor individualized clinical care programs in post stroke patients, especially women, thinking beyond the usual risk factors control protocol.