Does the sex of acute stroke patients influence the effectiveness of rt-PA?

Hussain, Raja Rizwan; Hussain, Muhammad Shazam; Molina, Carlos A.; Uchino, Ken; Shuaib, Ashfaq; Demchuk, Andrew M.; Alexandrov, Andrei V.; Saqqur, Maher

doi:10.1186/1471-2377-14-60

Cited by 11 publications

(14 citation statements)

References 21 publications

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“…Similar findings of no difference in stroke outcome between men and women were reported in a small randomized study with intra-arterial pro-urokinase [39]. Other studies [40-45], as well as a clinical registry study and systematic review [46], have confirmed that men and women treated with tPA had equal functional outcomes at 3 months, suggesting a potentially greater benefit in treated women. In contrast, one study found that men were more likely to have a better functional outcome at 3 months but higher mortality [47].…”

Section: Sex Differences In Clinical Strokesupporting

confidence: 71%

“…While higher recanalization rates during the first 72 h were seen in a small cohort of women (n=39) by Savitz et al [50], a recent study of patients from the CLOTBUST trial did not find sex as a predictor of recanalization in an adjusted analysis [40]. Two other studies with larger sample size (n=205 and n=81) on intra-arterial administration of tPA or urokinase did not find sex differences in recanalization rates [51, 52].…”

Section: Sex Differences In Clinical Strokementioning

confidence: 99%

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The Importance of Considering Sex Differences in Translational Stroke Research

Ahnstedt

McCullough

Cipolla

2016

Transl. Stroke Res.

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Stroke is the second leading cause of death worldwide and differences between men and women have been documented in incidence, prevalence and outcome. Here, we reviewed the literature on sex differences in stroke severity, mortality, functional outcome and response to therapies after ischemic stroke. Many of the sex differences in stroke severity and mortality are explained by differences in baseline demographics such as older age in women. However, women account for more stroke deaths, consistently suffer from worse stroke outcomes and are more often institutionalized and permanently disabled than men. These sex differences in functional outcome are equalized after treatment with tissue plasminogen activator (tPA) and women may benefit more from treatment than men. However this may depend on race, as African American women have less of a response to tPA than other groups. Regarding endovascular treatments, the few existing studies that have investigated sex differences in stroke outcome point to equal benefit in both sexes, however, many clinical trials are relatively underpowered to detect sex differences. Further, we considered sex-specific effects in animal models of stroke and present recommendations for the performance of stroke studies in female animals. The male-biased use of research animals is distinguished from the clinical situation where there is a disproportionate and growing female stroke population. Stroke in women is greatly understudied and including both sexes is especially important in both preclinical and clinical studies that evaluate potential stroke therapies.

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Section: Sex Differences In Clinical Strokesupporting

confidence: 71%

Section: Sex Differences In Clinical Strokementioning

confidence: 99%

The Importance of Considering Sex Differences in Translational Stroke Research

Ahnstedt

McCullough

Cipolla

2016

Transl. Stroke Res.

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“…Overall, 1,685 studies were identified and screened for retrieval from the analyzed databases. Careful selection based on the criteria described above identified the following 16 reports involving 60,159 patients as being suitable for inclusion in the meta-analysis: Spaander et al, 31 Buijs et al, 30 Hametner et al, 32 Al-hussain et al, 33 Lasek-Bal et al, 34 Nathanson et al, 35 Lorenzano et al, 23 Martinez-Sanchez et al, 29 Forster et al, 25 Jovanovic et al, 36 Meseguer et al, 26 Kent et al, 22 Gomez-Choco et al, 37 Arnold et al, 27 Elkind et al, 28 Hill et al 24 The flowchart for these studies is shown in Fig. 1 .…”

Section: Resultsmentioning

confidence: 99%

The Influence of Sex in Stroke Thrombolysis: A Systematic Review and Meta-Analysis

Liu

Tang

et al. 2018

J Clin Neurol

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Background and PurposeThere is increasing recognition of the importance of stroke in females to both clinical and public health. The natural course of stroke is worse in females than in males, but the evidence regarding sex disparities in the responses to thrombolysis in stroke patents is still controversial. We compared outcomes after thrombolysis treatment between females and males.MethodsClinical trials reported in the Embase, PubMed, and Cochrane Library electronic databases up to March 13, 2017 were included in this analysis. Two reviewers independently extracted the data and conducted quality assessments. Statistical tests were performed to check for heterogeneity and publication bias. Sensitivity analysis was also performed to evaluate the stability of the conclusions.ResultsSixteen reports involving 60,159 patients were available for analysis. The female patients were a 0.89-fold [95% confidence interval (CI)=0.87–0.90, p<0.001], 0.89-fold (95% CI=0.87–0.91, p<0.001), and 1.24-fold (95% CI=1.11–1.36, p<0.001) more likely to obtain good, excellent, and poor functional outcomes, respectively, with no significant difference in the complications of symptomatic intracranial hemorrhage among the sexes [risk ratios (RR)=0.99, 95% CI=0.92–1.07, p=0.81] after thrombolysis treatment. In addition, the prevalence of a good functional outcome did not differ significantly between females and males in the intra-arterial thrombolysis (IAT) group (RR=1.05, 95% CI=0.85–1.29, p=0.67) in a subgroup analysis.ConclusionsThis study has demonstrated that females often exhibit a worse outcome than males after intravenous thrombolysis (IVT), whereas no relevant sex differences were found in outcome or recanalization after IAT, with safety regarding hemorrhage complications from thrombolysis being the same for the sexes. However, IVT should not be withheld from female stroke patients solely based on their sex before the findings are confirmed in further large-scale research.

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“…Given differences in cerebrovascular physiology and stroke mechanism between women and men, sex‐related differences in response to r‐tPA are plausible and have been demonstrated through an analysis of five clinical trials of acute stroke, although updated meta‐analysis was contradictory, as are other studies reporting sex‐related differences in response to IV rt‐PA . The few studies of sex‐related differences in response to endovascular therapy are also conflicting .…”

Section: Discussionmentioning

confidence: 99%

Neuroimaging evolution of ischemia in men and women: an observational study

Dula

Luby

King

et al. 2019

Ann Clin Transl Neurol

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Objective We present an exploratory study for identification of sex differences in imaging biomarkers that could further refine selection of patients for acute reperfusion therapy and trials based on sex and imaging targets. Methods The Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) study included consecutive acute stroke patients who underwent MRI within 24 h of time from last known well and prior to therapy. Those demonstrating a potential therapeutic target on imaging were identified by presence of: (1) arterial occlusion on angiography, (2) focal ischemic region on perfusion maps, or (3) a mismatch of perfusion versus diffusion imaging lesion size. The prevalence of imaging targets within clinically relevant time intervals was calculated for each patient and examined. The relationship of time from stroke onset to probability of detection of imaging targets was evaluated. Results Of 7007 patients screened, of which 86.7% were scanned with MRI, 1092 patients (477/615 men/women) were included in LESION. The probability of imaging target detection was significantly different between men and women, with women more likely to present with all assessed imaging targets, odds ratios between 1.36 and 1.59, P < 0.02, adjusted for NIHSS, age, and time from last known well to MRI scan. This trend held for the entire 24‐h studied. Interpretation Women present more often with treatable ischemic stroke than men. The greater probability of potentially viable and/or treatable imaging targets in women at all time points suggests that tissue injury is slower to evolve in women.

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Does the sex of acute stroke patients influence the effectiveness of rt-PA?

Cited by 11 publications

References 21 publications

The Importance of Considering Sex Differences in Translational Stroke Research

The Importance of Considering Sex Differences in Translational Stroke Research

The Influence of Sex in Stroke Thrombolysis: A Systematic Review and Meta-Analysis

Neuroimaging evolution of ischemia in men and women: an observational study

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