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Background: Early diagnosis through symptom recognition is vital in the management of acute stroke. However, women who experience stroke are more likely than men to be initially given a nonstroke diagnosis and it is unclear if potential sex differences in presenting symptoms increase the risk of delayed or missed stroke diagnosis. Aims: To quantify sex differences in the symptom presentation of stroke and assess whether these differences are associated with a delayed or missed diagnosis. Methods: PubMed, EMBASE, and the Cochrane Library were systematically searched up to January 2021. Studies were included if they reported presenting symptoms of adult women and men with diagnosed stroke (ischemic or hemorrhagic) or transient ischemic attack (TIA) and were published in English. Mean percentages with 95% confidence intervals (CIs) of each symptom were calculated for women and men. The crude relative risks (RRs) with 95% CI of symptoms being present in women, relative to men, were also calculated and pooled. Any data on the delayed or missed diagnosis of stroke for women compared to men based on symptom presentation were also extracted. Results: Pooled results from 21 eligible articles showed that women and men presented with a similar mean percentage of motor deficit (56% in women vs 56% in men) and speech deficit (41% in women vs 40% in men). Despite this, women more commonly presented with nonfocal symptoms than men: generalized nonspecific weakness (49% vs 36%), mental status change (31% vs 21%), and confusion (37% vs 28%), whereas men more commonly presented with ataxia (44% vs 30%) and dysarthria (32% vs 27%). Women also had a higher risk of presenting with some nonfocal symptoms: generalized weakness (RR 1.49, 95% CI 1.09–2.03), mental status change (RR 1.44, 95% CI 1.22–1.71), fatigue (RR 1.42, 95% CI 1.05–1.92), and loss of consciousness (RR 1.30, 95% CI 1.12–1.51). In contrast, women had a lower risk of presenting with dysarthria (RR 0.89, 95% CI 0.82–0.95), dizziness (RR 0.87, 95% CI 0.80–0.95), gait disturbance (RR 0.79, 95% CI 0.65–0.97), and imbalance (RR 0.68, 95% CI 0.57–0.81). Only one study linking symptoms to definite stroke/TIA diagnosis found that pain and unilateral sensory loss are associated with lower odds of a definite diagnosis in women compared to men. Conclusion: Although women showed a higher prevalence of some nonfocal symptoms, the prevalence of focal neurological symptoms, such as motor weakness and speech deficit, was similar for both sexes. Awareness of sex differences in symptoms in acute stroke evaluation, careful consideration of the full constellation of presenting symptoms, and further studies linking symptoms to diagnostic outcomes can be helpful in improving early diagnosis and management in both sexes. [ABSTRACT FROM AUTHOR]

Background: Stroke and transient ischemic attack confer greater risk of cognitive decline and dementia. Aims: We used data from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a blood pressure-lowering randomized controlled trial in stroke/transient ischemic attack. We evaluated overall and sex-specific differences in treatment effects for cognitive decline/dementia, as well as associations with vascular and stroke-specific predictors,considering death as a competing risk. Methods: Multinomial logistic regression was used to estimate overall and sex-specific odds ratios (OR) (95% confidence intervals (CI)) for treatment effects and predictors associated with the risk of cognitive decline/dementia, and the women-to-men ratio of odds ratio (RORs). Results: Over a median four years, 763 cognitive decline/dementia (30.9% women) were recorded in 5888 participants. Women had lower odds of cognitive decline/dementia than men (OR 0.78, 95%CI 0.63–0.95). Active treatment was associated with lower odds of cognitive decline/dementia (0.84, 0.72–0.98), with no evidence of sex difference. Higher education (0.96,0.94–0.98 (per year)) and baseline Mini-Mental State Examination (MMSE)) were associated with lower odds of cognitive decline/dementia (0.84,0.82–0.86 (per point higher)). Higher diastolic blood pressure (1.11,1.02–1.20 (per 10 mmHg)), low estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (1.27,1.03–1.58), and peripheral arterial disease (1.78,1.26–2.52) were associated with higher odds of cognitive decline/dementia. APOE ɛ4 was not associated with cognitive decline/dementia (1.05 (0.85–1.30)). Low eGFR was more strongly associated with cognitive decline/dementia in women than men (RORs, 1.60 (1.03–2.48)). Diabetes was more strongly associated with men than women. Conclusions: Several risk factors were associated with cognitive decline/dementia in people with prior stroke/transient ischemic attack, with notable sex differences. Long-term cognitive sequelae of stroke should be considered to strengthen joint prevention strategies for stroke, cognitive decline, and dementia. Trial Registration: This trial was not registered because enrolment began before 1 July 2005. [ABSTRACT FROM AUTHOR]

Background and purpose: To examine sex differences in disease profiles and short-term outcomes after acute ischemic stroke treated with recombinant tissue plasminogen activator. Methods: Eight national and regional stroke registries contributed individual participant data from mainland China, Japan, Philippines, Singapore, South Korea and Taiwan in 2005–2018. The primary outcome was ordinal-modified Rankin scale at 90 days. Key safety outcome was symptomatic intracerebral hemorrhage (sICH). Results: Of 4453 patients included in the analyses, 1692 (36.3%) were women who were older, more likely to have a more severe neurological deficit, history of hypertension and atrial fibrillation, and a cardioembolic stroke compared to men. Women were more likely than men to have unfavorable shift of modified Rankin scale (fully adjusted odds ratio) (women vs. men) 1.14, 95% confidence interval 1.02–1.28). There was no significant sex difference for death 1.05 (0.84–1.31) or sICH (1.17, 0.89–1.54). Women were more likely to have unfavorable functional outcome with increasing age (P = 0.022 for interaction). In the age groups 70–80 and ≥80 years, women had a worse functional outcome compared to men (1.22, 1.02–1.47 and 1.43, and 1.06–1.92, respectively). Conclusion: In this pooled data from Asian acute stroke registries, women had poorer prognosis than men after receiving recombinant tissue plasminogen activator for acute ischemic stroke, which worsened with age. Women older than 70 appear to have a worse outcome than men which could be explained by greater stroke severity, more AF, and cardioembolic stroke. [ABSTRACT FROM AUTHOR]

Objectives: Controversy persists over the benefits of low-dose versus standard-dose intravenous alteplase for the treatment of acute ischemic stroke. We sought to determine individual patient factors that contribute to the risk–benefit balance of low-dose alteplase treatment. Methods: Observational study using data from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded-endpoint trial that assessed low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase in acute ischemic stroke patients. Logistic regression models were used to estimate the benefit of good functional outcome (scores 0 or 1 on the modified Rankin scale at 90 days) and risk (symptomatic intracerebral hemorrhage), under both regimens for individual patients. The net advantage for low-dose, relative to standard-dose, alteplase was calculated by dividing excess benefit by excess risk according to a combination of patient characteristics. The algorithms were externally validated in a nationwide acute stroke registry database in South Korea. Results: Patients with an estimated net advantage from low-dose alteplase, compared with without, were younger (mean age of 66 vs. 75 years), had lower systolic blood pressure (148 vs. 160 mm Hg), lower National Institute of Health Stroke Scale score (median of 8 vs. 16), and no atrial fibrillation (10.3% vs. 97.4%), diabetes mellitus (19.2% vs. 22.4%), or premorbid symptoms (defined by modified Rankin scale = 1) (16.3% vs. 37.8%). Conclusion: Use of low-dose alteplase may be preferable in acute ischemic stroke patients with a combination of favorable characteristics, including younger age, lower systolic blood pressure, mild neurological impairment, and no atrial fibrillation, diabetes mellitus, or premorbid symptoms. [ABSTRACT FROM AUTHOR]

Background: The ENhanced Control of Hypertension And Thrombolysis strokE study (ENCHANTED) trial was initiated as a 2 × 2 partial-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial to evaluate in thrombolysis-eligible acute ischemic stroke (AIS) patients whether: (1) Arm A – low-dose (0.6 mg/kg body weight) intravenous (iv) alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage (sICH) compared with standard-dose (0.9 mg/kg body weight) iv alteplase; and (2) Arm B – early intensive blood pressure (BP) lowering (systolic target 130–140 mmHg) has superior efficacy and lower risk of ICH compared with guideline-recommended BP control (systolic target <180 mmHg). Arm A was completed in 2016; Arm B is now concluding. Objective: To outline in detail and make public the predetermined statistical analysis plan (SAP) for the 'BP control' arm of this study. Methods: All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be outlined, and for each item, statistically relevant descriptive elements will be described. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described. Results: A SAP was developed for the results of the BP control arm of this study that is transparent, available to the public, verifiable, and predetermined before completion of data collection. Conclusions: We have developed a predetermined SAP for the ENCHANTED BP control arm to be followed to avoid analysis bias arising from prior knowledge of the study findings. Clinical trial registration: ClinicalTrials.gov (NCT01422616); ISRCTN Register (ISRCTN82387104); Australian New Zealand Clinical Trial Registry (ACTRN12611000236998); EU Clinical Trials Register (2011-005545-12); and Clinical Trials Registry – India (REF/2017/05/014334). [ABSTRACT FROM AUTHOR]