Female Stroke: Sex Differences in Acute Treatment and Early Outcomes of Acute Ischemic Stroke

Anna K. Bonkhoff, MD; André Karch, MD; Ralph Weber, MD; Jürgen Wellmann, PhD; Klaus Berger, MD

Disclosures

Stroke. 2021;52(2):406-415. 

In This Article

Abstract and Introduction

Abstract

Background and Purpose: Men and women are differently affected by acute ischemic stroke (AIS) in many aspects. Prior studies on sex disparities were limited by moderate sample sizes, varying years of data acquisition, and inconsistent inclusions of covariates leading to controversial findings. We aimed to analyze sex differences in AIS severity, treatments, and early outcome and to systematically evaluate the effect of important covariates in a large German stroke registry.

Methods: Analyses were based on the Stroke Registry of Northwestern Germany from 2000 to 2018. We focused on admission-stroke severity and disability, acute recanalization treatment, and early stroke outcomes. Potential sex divergences were investigated via odds ratio (OR) using logistic regression models. Covariates were introduced in 3 steps: (1) base models (age and admission year), (2) partially adjusted models (additionally corrected for acute stroke severity and recanalization treatment), (3) fully adjusted models (additionally adjusted for onset-to-admission time interval, prestroke functional status, comorbidities, and stroke cause). Models were separately fitted for the periods 2000 to 2009 and 2010 to 2018.

Results: Data from 761 106 patients with AIS were included. In fully adjusted models, there were no sex differences with respect to treatment with intravenous thrombolysis (2000–2009: OR, 0.99 [95% CI, 0.94–1.03]; 2010–2018: OR, 1.0 [0.98–1.02]), but women were more likely to receive intraarterial therapy (2010–2018: OR, 1.12 [1.08–1.15]). Despite higher disability on admission (2000–2009: OR, 1.10 [1.07–1.13]; 2010–2018: OR, 1.09 [1.07–1.10]), female patients were more likely to be discharged with a favorable functional outcome (2003–2009: OR, 1.05 [1.02–1.09]; 2010–2018: OR, 1.05 [1.04–1.07]) and experienced lower in-hospital mortality (2000–2009: OR, 0.92 [0.86–0.97]; 2010–2018: OR, 0.91 [0.88–0.93]).

Conclusions: Female patients with AIS have a higher chance of receiving intraarterial treatment that cannot be explained by clinical characteristics, such as age, premorbid disability, stroke severity, or cause. Women have a more favorable in-hospital recovery than men because their higher disability upon admission was followed by a lower in-hospital mortality and a higher likelihood of favorable functional outcome at discharge after adjustment for covariates.

Introduction

Stroke incidence, prevalence, and mortality have declined in all age groups, but the world-wide absolute burden of stroke is projected to increase as the relation between stroke and age remains constant during the demographic change with aging populations.[1] Women are expected to share a disproportionately higher fraction of this burden, indicating the need to optimize acute ischemic stroke (AIS) treatments and address sex-specific characteristics in these efforts.[2] A thorough understanding of sex-related differences in stroke severity at initial presentation, AIS recanalization treatments, and early outcomes after stroke, as well as how these differences are influenced by further sociodemographic and clinical factors is an important prerequisite to efficiently draft a catalog of such sex-stratified clinical measures. Prior reports have shown that stroke affects men and women differently in many ways.[3,4] With respect to stroke severity at presentation, many studies found an increased symptom load in women.[5–7] A meta-analysis on the uptake of intravenous thrombolysis (IVT) showed a less frequent administration in women compared with men.[8] In contrast, a recent study, that captured Germany-wide numbers of thrombolyzed patients between 2013 and 2017, could not substantiate any differences in IVT uptake between male and female patients.[9] The same study, however, reported widely diverging numbers of mechanical thrombectomy between the sexes: women were more likely than men to undergo this acute treatment across the entire age range.

These previous findings often originated from smaller studies, were obtained in narrow time windows, or did not include potential confounders. Thus, the direction, magnitude and clinical relevance of sex differences remain controversial and their interaction with other important characteristics requires further elucidation. The aim of this study was thus to analyze sex differences in symptom severity and disability upon admission, the administration of AIS treatments, in-hospital mortality, and functional outcome at discharge in a large German stroke registry, comprising 19 years of data. In particular, we systematically increased the number of key covariates to evaluate their influence on the estimation of sex differences in depth.

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