Comparison of Associations of Reduced Estimated Glomerular Filtration Rate With Stroke Outcomes Between Hypertension and No Hypertension.
ABSTRACT: We compared the association of low estimated glomerular filtration rate (eGFR) with stroke outcomes among patients with hypertension and without hypertension.We used the China stroke registry to identify patients on discharge with the diagnosis of stroke in 2012 and 2013. Low eGFR was defined as <60 mL/min/1.73 m2. Multivariable analysis was used to evaluate the association of low eGFR with 1-year all-cause mortality, recurrent stroke, poor functional outcome defined as 3 to 6 in modified Rankin Scale (mRS), and ordinal mRS, where the interaction of eGFR category and hypertension status was investigated.Of 5082 patients without hypertension, 221 patients (4.4%) had low eGFR, as compared with 1378 patients (8.6%) previously diagnosed with hypertension. In patients without hypertension, the adjusted odds ratios with 95% confidence interval of low eGFR was 1.88 (1.23-2.88) for all-cause mortality, 1.36 (0.66-2.83) for recurrent stroke, 2.14 (1.45-3.16) for poor functional outcome, and 2.07 (1.58-2.70) for ordinal mRS. In patients with hypertension, low eGFR was associated with all stroke outcomes: 1.80 (1.50-2.16) for all-cause mortality, 1.52 (1.20-1.91) for recurrent stroke, 1.30 (1.11-1.52) for poor functional outcome, and 1.31 (1.18-1.46) for ordinal mRS. The significant interaction between eGFR categories and hypertension was only found for poor functional outcome (P=0.046) and ordinal mRS (P=0.002).Effect of low eGFR on all-cause mortality and recurrent stroke in patients without hypertension was not significantly different from that in patients with hypertension, but low-eGFR patients without hypertension had a higher risk of stroke-related disability than those with hypertension.
Project description:To investigate the association of low estimated glomerular filtration rate (eGFR) <60 mL/min with recurrent stroke risk and to evaluate whether add-on renin-angiotensin system modulator therapy is associated with lower recurrent stroke risk in patients with low eGFR.We analyzed the database of a multicenter trial involving 18,666 patients with recent ischemic stroke followed for 2.5 years. Primary outcome was time to first recurrent stroke. Independent associations of low eGFR with outcome in the entire cohort and add-on telmisartan treatment with outcome among those with low eGFR were evaluated.Low eGFR was observed in 3630 (20.1%) patients. Patients with low eGFR were older, more likely women, with a known history of hypertension. In unadjusted analyses, patients with low eGFR were more likely to experience a recurrent stroke (hazard ratio, 1.34; 95% confidence interval, 1.20-1.49). After adjusting for confounders, low eGFR was still associated with recurrent stroke but to a lesser extent (hazard ratio, 1.16; 95% confidence interval, 1.04-1.31). Telmisartan treatment among patients with low eGFR was not independently associated with recurrent stroke (hazard ratio, 1.08; 95% confidence interval, 0.89-1.31).Low eGFR is independently associated with a higher risk of recurrent stroke, but short-term add-on telmisartan therapy does not seem to mitigate this risk.http://www.clinicaltrials.gov. Unique identifier: NCT00153062.
Project description:In the Interventional Management of Stroke (IMS) III trial, we sought to demonstrate evidence of a differential treatment effect of endovascular treatment of acute ischemic stroke compared with intravenous tissue-type plasminogen activator, according to baseline collateral status measured using computed tomographic angiography.Of 656 patients enrolled in Interventional Management of Stroke III trial, 306 had baseline computed tomographic angiography. Of these, 185 patients had M1 middle cerebral artery ± intracranial internal carotid artery occlusion, where baseline collateral status could be measured. Collateral status was assessed by consensus using 3 different ordinal scales and categorized as good, intermediate, and poor. Multivariable modeling was used to assess the effect of collateral status and treatment type on clinical outcome by modified Rankin Scale (mRS 0-2, mRS 0-1, and the ordinal mRS).Of 185 patients, 126 randomized to endovascular therapy (87.6% recanalized, 41.3% 90-day mRS 0-2) and 59 to intravenous tissue-type plasminogen activator only (60.5% recanalized, 30.5% 90-day mRS 0-2). In multivariable modeling, collateral status was a significant predictor of all clinical outcomes (P<0.05). Maximal benefit with endovascular treatment across all clinical outcomes was seen in patients with intermediate collaterals, some benefit in patients with good collaterals, and none in patients with poor collaterals, although small sample size limited the power of the analysis to show a statistically significant interaction between collateral status and treatment type (P>0.05).Using data from a large randomized controlled trial (IMS III), we show that baseline computed tomographic angiography collaterals are a robust determinant of final clinical outcome and could be used to select patients for endovascular therapy.URL: http://www.clinicaltrials.gov/ct2/show/. Unique identifier: 0020NCT00359424.
Project description:Although increasing evidence suggests that hyperglycemia following acute stroke adversely affects clinical outcome, whether the association between glycaemia and functional outcome varies between stroke patients with\without pre-diagnosed diabetes remains controversial. We aimed to investigate the relationship between the fasting blood glucose (FBG) and the 6-month functional outcome in a subgroup of SMART cohort and further to assess whether this association varied based on the status of pre-diagnosed diabetes.Data of 2862 patients with acute ischemic stroke (629 with pre-diagnosed diabetics) enrolled from SMART cohort were analyzed. Functional outcome at 6-month post-stroke was measured by modified Rankin Scale (mRS) and categorized as favorable (mRS:0-2) or poor (mRS:3-5). Binary logistic regression model, adjusting for age, gender, educational level, history of hypertension and stroke, baseline NIHSS and treatment group, was used in the whole cohort to evaluate the association between admission FBG and functional outcome. Stratified logistic regression analyses were further performed based on the presence/absence of pre-diabetes history.In the whole cohort, multivariable logistical regression showed that poor functional outcome was associated with elevated FBG (OR1.21 (95%CI 1.07-1.37), p = 0.002), older age (OR1.64 (95% CI1.38-1.94), p<0.001), higher NIHSS (OR2.90 (95%CI 2.52-3.33), p<0.001) and hypertension (OR1.42 (95%CI 1.13-1.98), p = 0.04). Stratified logistical regression analysis showed that the association between FBG and functional outcome remained significant only in patients without pre-diagnosed diabetes (OR1.26 (95%CI 1.03-1.55), p = 0.023), but not in those with premorbid diagnosis of diabetes (p = 0.885).The present results demonstrate a significant association between elevated FBG after stroke and poor functional outcome in patients without pre-diagnosed diabetes, but not in diabetics. This finding confirms the importance of glycemic control during acute phase of ischemic stroke especially in patients without pre-diagnosed diabetes. Further investigation for developing optimal strategies to control blood glucose level in hyperglycemic setting is therefore of great importance.ClinicalTrials.gov NCT00664846.
Project description:Background:Seizures after ischemic stroke have not been well-studied. We aim to determine the frequency, determinants, and significance of early seizures after thrombolysis for acute ischemic stroke. Methods:Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, multicenter, randomized controlled trial where patients with acute ischemic stroke were randomized to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) IV alteplase. The protocol prespecified prospective data collection on in-hospital seizures over 7 days postrandomization. Logistic regression models were used to determine variables associated with seizures and their significance on poor outcomes of death or disability (modified Rankin scale scores 3-6), symptomatic intracerebral hemorrhage (sICH), and European Quality of Life 5-Dimensions questionnaire [EQ-5D] over 90 days. Results:Data were available for 3,139 acute ischemic stroke participants, of whom 42 (1.3%) had seizures at a median 22.7 hours after the onset of symptoms. Baseline variables associated with seizures were male sex (odds ratio [OR] 2.19, 95% confidence interval [CI] 1.07-4.50), severe neurologic impairment (NIH Stroke Scale score ?10; OR 2.16, 95% CI 1.06-4.40), and fever (OR 4.55, 95% CI 2.37-8.71). Seizures independently predicted poor recovery: death or major disability (OR 2.88, 95% CI 1.28-6.47), unfavorable ordinal shift of mRS scores (OR 1.94, 95% CI 1.10-3.39), and lower than median EQ-5D health utility index score (OR 3.50, 95% CI 1.37-8.91). There was no association of seizures with sICH in adjusted analysis. Conclusions:In thrombolysis-treated patients with acute ischemic stroke, seizures are uncommon, occur early, and predict poor recovery. Clinicaltrialsgov identifier:NCT01422616.
Project description:Importance:Reduction of subsequent disabling stroke is the main goal of preventive treatment in the acute setting after transient ischemic attack (TIA) or minor ischemic stroke. Objective:To evaluate the superiority of ticagrelor added to aspirin in preventing disabling stroke and to understand the factors associated with recurrent disabling stroke. Design, Setting, and Participants:The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) was a randomized clinical trial conducted between January 22, 2018, and December 13, 2019, with a 30-day follow-up, at 414 hospitals in 28 countries. The trial included 11?016 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk TIA, including 10?803 with modified Rankin Scale score (mRS) recorded at 30 days. Interventions:Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-30) or placebo within 24 hours of symptom onset. All patients received aspirin, 300 to 325 mg on day 1 followed by 75 to 100 mg daily for days 2 to 30. Main Outcomes and Measures:Time to the occurrence of disabling stroke (progression of index event or new stroke) or death within 30 days, as measured by mRS at day 30. Disabling stroke was defined by mRS greater than 1. Results:Among participants with 30-day mRS greater than 1, mean age was 68.1 years, 1098 were female (42.6%), and 2670 had an ischemic stroke (95.8%) as a qualifying event. Among 11?016 patients, a primary end point with mRS greater than 1 at 30 days occurred in 221 of 5511 patients (4.0%) randomized to ticagrelor and in 260 of 5478 patients (4.7%) randomized to placebo (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99, P?=?.04). A primary end point with mRS 0 or 1 at 30 days occurred in 70 of 5511 patients (1.3%) and 87 of 5478 patients (1.6%) (HR, 0.79; 95% CI, 0.57-1.08; P?=?.14). The ordinal analysis of mRS in patients with recurrent stroke showed a shift of the disability burden following a recurrent ischemic stroke in favor of ticagrelor (odds ratio, 0.77; 95% CI, 0.65-0.91; P?=?.002). Factors associated with disability were baseline National Institutes of Health Stroke Scale score 4 to 5, ipsilateral stenosis of at least 30%, Asian race/ethnicity, older age, and higher systolic blood pressure, while treatment with ticagrelor was associated with less disability. Conclusions and Relevance:In patients with TIA and minor ischemic stroke, ticagrelor added to aspirin was superior to aspirin alone in preventing disabling stroke or death at 30 days and reduced the total burden of disability owing to ischemic stroke recurrence. Trial Registration:ClinicalTrials.gov Identifier: NCT03354429.
Project description:Background:Ordinal/shift analyses of ordered measures like the modified Rankin Scale(mRS) are underused as primary trial outcomes for neurological disorders - despite statistical advantages - potentially hindered by poor clinical interpretability versus dichotomies, and by valuing state-transitions equally (linear scale). Weighted ordinal analyses incorporating step-changes at key transitions might have greater statistical validity and clinical applicability. Methods:In a prospective population-based cohort of ischaemic stroke (Oxford Vascular Study, recruited 2002-2014), we stratified 5-year outcomes of death, dementia, and/or institutionalization, health/social-care costs, and EuroQol-derived quality-adjusted life-expectancy(QALE) by 3-month mRS. We compared root-mean-square errors(RMSEs) from linear regressions for these outcomes with the mRS coded as a linear scale versus incorporating a spline at transitions 1-2, 2-3, or 3-4. We derived 3-month mRS weights for probability of 5-year death/dementia/institutionalization using age/sex-adjusted logistic regressions, and cost and QALE weights from 1000-bootstraps. We applied these weights to analyse recent trials of thrombectomy for acute ischaemic stroke. Findings:Among 1,607 patients, a non-linear (S-shaped) relationship was observed between 3-month mRS and each 5-year outcome, with RMSEs 18-73% lower using a spline at mRS 2-3 versus a linear representation. Age/sex-adjusted probability weights for 5-year death/dementia/institutionalization were: mRS 0=0.19; 1=0.27; 2=0.41; 3=0.73; 4=0.77; 5=0.94 (mRS 6=1 by definition). Similar trends were seen with costs; estimated 5-year QALEs were: mRS 0=3.88; 1=3.49; 2=3.01; 3=1.87; 4=1.30; 5=0.06; 6=0. Results were similar stratifying by age/sex, and excluding pre-morbidly disabled patients. Using a weighted ordinal approach, estimates of thrombectomy impact were more favourable than estimates with dichotomous approaches, 5-year cost reductions being 29% higher than with 0-2/3-6, and over three-fold higher than with 0-1/2-6 dichotomy. Interpretation:Our findings favour weighting the mRS in ordinal analyses for stroke and other neurological disorders, as state-transitions differ in clinical prognosis, quality-of-life, and costs. These weights could also be used for prognostication and cost-effectiveness analyses. Funding:Wellcome Trust, Wolfson Foundation, NIHR Oxford Biomedical Research Centre, Rhodes Trust.
Project description:OBJECTIVE:To compare how 3 common representations (ordinal vs dichotomized as 0-1/2-6 or 0-2/3-6) of the modified Rankin Scale (mRS)-a commonly used trial outcome measure-relate to long-term outcomes, and quantify trial ineligibility rates based on premorbid mRS. METHODS:In consecutive patients with ischemic stroke in a population-based, prospective, cohort study (Oxford Vascular Study; 2002-2014), we related 3-month mRS to 1-year and 5-year disability and death (logistic regressions), and health/social care costs (generalized linear model), adjusted for age/sex, and compared goodness-of-fit values (C statistic, mean absolute error). We also calculated the proportion of patients in whom premorbid mRS score >1 or >2 would result in exclusion from trials using dichotomous analysis. RESULTS:Among 1,607 patients, the ordinal mRS was more strongly related to 5-year mortality than both the 0-1/2-6 and 0-2/3-6 dichotomies (all p < 0.0001). Results were similar for 5-year disability, and 5-year care costs were also best captured by the ordinal model (change in mean absolute error vs age/sex: -$3,059 for ordinal, -$2,805 for 0-2/3-6, -$1,647 for 0-1/2-6). Two hundred forty-four (17.1%) 3-month survivors had premorbid mRS score >2 and 434 (30.5%) had mRS score >1; both proportions increased with female sex, socioeconomic deprivation, and age (all p < 0.0001). CONCLUSION:The ordinal form of the 3-month mRS relates better to long-term outcomes and costs in survivors of ischemic stroke than either dichotomy. This finding favors using ordinal approaches in trials analyzing the mRS. Exclusion of patients with higher premorbid disability by use of dichotomous primary outcomes will also result in unrepresentative samples.
Project description:Objective To improve the selection of patients with acute ischaemic stroke for intra-arterial treatment using a clinical decision tool to predict individual treatment benefit.Design Multivariable regression modelling with data from two randomised controlled clinical trials.Setting 16 hospitals in the Netherlands (derivation cohort) and 58 hospitals in the United States, Canada, Australia, and Europe (validation cohort).Participants 500 patients from the Multicenter Randomised Clinical Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands trial (derivation cohort) and 260 patients with intracranial occlusion from the Interventional Management of Stroke III trial (validation cohort).Main outcome measures The primary outcome was the modified Rankin Scale (mRS) score at 90 days after stroke. We constructed an ordinal logistic regression model to predict outcome and treatment benefit, defined as the difference between the predicted probability of good functional outcome (mRS score 0-2) with and without intra-arterial treatment.Results 11 baseline clinical and radiological characteristics were included in the model. The externally validated C statistic was 0.69 (95% confidence interval 0.64 to 0.73) for the ordinal model and 0.73 (0.67 to 0.79) for the prediction of good functional outcome, indicating moderate discriminative ability. The mean predicted treatment benefit varied between patients in the combined derivation and validation cohort from -2.3% to 24.3%. There was benefit of intra-arterial treatment predicted for some individual patients from groups in which no treatment effect was found in previous subgroup analyses, such as those with no or poor collaterals.Conclusion The proposed clinical decision tool combines multiple baseline clinical and radiological characteristics and shows large variations in treatment benefit between patients. The tool is clinically useful as it aids in distinguishing between individual patients who may experience benefit from intra-arterial treatment for acute ischaemic stroke and those who will not.Trial registration clinicaltrials.gov NCT00359424 (IMS III) and isrctn.com ISRCTN10888758 (MR CLEAN).
Project description:Background: Post-ischemic inflammatory response might be affected by many factors. We chose leukocyte count as a marker of inflammatory response and investigated whether the effects of leukocyte count on the clinical outcomes in acute ischemic stroke patients are different according to different factors. Methods: We derived data from the China National Stroke Registry II. Patients with ischemic stroke were classified into four groups by leukocyte count quartiles within the first 24 h after admission. Adverse clinical outcomes were defined as recurrent stroke, all-cause death, and poor functional outcomes (3 ? mRS ? 5) at 3-months and 1-year follow-up. The subgroup factors were age, sex, history of hypertension, history of diabetes, history of previous stroke, or transient ischemic attack and smoking status. We assessed the association between leukocyte count and adverse clinical outcomes and evaluated this association in different subgroups. Results: A total of 14,678 patients were included. Patients in higher quartiles were likely to be younger, male, smokers, and drinkers, and to have a shorter time from symptom onset to arrival, a more proportion of history of diabetes, atrial fibrillation, and hypertension, and a higher severity of stroke. Higher quartiles were associated with elevated risk of adverse clinical outcomes at 3-months and 1-year follow-up. Leukocyte count had a moderate accuracy to predict clinical outcomes. There was no difference in the relationship between leukocyte count and adverse clinical outcomes across subgroups such as age, sex, history of hypertension, and smoking. The effect of leukocyte count on all-cause death was pronounced among patients with previous stroke or transient ischemic attack, and the effect of leukocyte count on short-term poor functional outcomes was also pronounced among patients without diabetes. Conclusions: Leukocyte count is associated with short-term and long-term clinical outcomes of acute ischemic stroke and may have predictive value, especially in patients with certain specific characteristics.
Project description:Background:Atrial fibrillation is an important risk factor for ischemic stroke, and is associated with an increased risk of poor outcome after ischemic stroke. Endovascular thrombectomy is safe and effective in acute ischemic stroke patients with large vessel occlusion of the anterior circulation. This meta-analysis aims to investigate whether there is an interaction between atrial fibrillation and treatment effect of endovascular thrombectomy, and secondarily whether atrial fibrillation is associated with worse outcome in patients with ischemic stroke due to large vessel occlusion. Methods:Individual patient data were from six of the recent randomised clinical trials (MR CLEAN, EXTEND-IA, REVASCAT, SWIFT PRIME, ESCAPE, PISTE) in which endovascular thrombectomy plus standard care was compared to standard care alone. Primary outcome measure was the shift on the modified Rankin scale (mRS) at 90?days. Secondary outcomes were functional independence (mRS 0-2) at 90?days, National Institutes of Health Stroke Scale score at 24?h, symptomatic intracranial hemorrhage and mortality at 90?days. The primary effect parameter was the adjusted common odds ratio, estimated with ordinal logistic regression (shift analysis); treatment effect modification of atrial fibrillation was assessed with a multiplicative interaction term. Results:Among 1351 patients, 447 patients had atrial fibrillation, 224 of whom were treated with endovascular thrombectomy. We found no interaction of atrial fibrillation with treatment effect of endovascular thrombectomy for both primary (p-value for interaction: 0.58) and secondary outcomes. Regardless of treatment allocation, we found no difference in primary outcome (mRS at 90?days: aOR 1.11 (95% CI 0.89-1.38) and secondary outcomes between patients with and without atrial fibrillation. Conclusion:We found no interaction of atrial fibrillation on treatment effect of endovascular thrombectomy, and no difference in outcome between large vessel occlusion stroke patients with and without atrial fibrillation.