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Background: We explored the influence of low-dose intravenous alteplase and intensive blood pressure lowering on outcomes of acute ischemic stroke according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: ENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended blood pressure lowering in acute ischemic stroke patients. In those who had baseline computed tomography or magnetic resonance imaging angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration, and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models. Results: There were 940 participants: 607 in alteplase arm only, 243 in blood pressure arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56–2.90]) but comparable in MVO (1.34 [0.96–1.88]) groups. There were no differences in associations of alteplase dose or blood pressure lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54–1.30]/0.48 [0.25–0.91]/0.99 [0.75–2.09], Pinteraction = 0.28; intensive versus standard blood pressure lowering 1.32 [0.74–2.38]/0.78 [0.31–1.94]/1.24 [0.64–2.41], Pinteraction = 0.41), except for a borderline significant difference for intensive blood pressure lowering and increased early neurologic deterioration (0.63 [0.14–2.72]/0.17 [0.02–1.47]/2.69 [0.90–8.04], Pinteraction = 0.05). Conclusions: Functional outcome by dose of alteplase or intensity of blood pressure lowering is not modified by vascular obstruction status/site according to analyses from ENCHANTED, although these results are compromised by low statistical power. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifiers: NCT01422616 [ABSTRACT FROM AUTHOR]

Background and purpose: This was an investigation of the differential effects of early intensive versus guideline‐recommended blood pressure (BP) lowering between lacunar and non‐lacunar acute ischaemic stroke (AIS) in the BP arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: In 1,632 participants classified as having definite or probable lacunar (n = 454 [27.8%]) or non‐lacunar AIS according to pre‐specified definitions based upon clinical and adjudicated imaging findings, mean BP changes over days 0–7 were plotted, and systolic BP differences by treatment between subgroups were estimated in generalized linear models. Logistic regression models were used to estimate the BP treatment effects on 90‐day outcomes (primary, an ordinal shift of modified Rankin scale scores) across lacunar and non‐lacunar AIS after adjustment for baseline covariables. Results: Most baseline characteristics, acute BP and other management differed between lacunar and non‐lacunar AIS, but mean systolic BP differences by treatment were comparable at each time point (all pinteraction > 0.12) and over 24 h post‐randomization (−5.5, 95% CI −6.5, −4.4 mmHg in lacunar AIS vs. −5.6, 95% CI −6.3, −4.8 mmHg in non‐lacunar AIS, pinteraction = 0.93). The neutral effect of intensive BP lowering on functional outcome and the beneficial effect on intracranial haemorrhage were similar for the two subgroups (all pinteraction > 0.19). Conclusions: There were no differences in the treatment effect of early intensive versus guideline‐recommended BP lowering across lacunar and non‐lacunar AIS. [ABSTRACT FROM AUTHOR]

Background and Purpose: The influence of specific brain lesions on health-related quality of life (HRQoL) after acute ischemic stroke (AIS) is uncertain. We aimed to identify imaging predictors of poor HRQoL in alteplase-treated participants of the alteplase dose arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: ENCHANTED was an international trial of low- versus standard-dose intravenous alteplase in AIS patients, with functional outcome (modified Rankin scale [mRS]) and HRQoL on the 5-dimension European Quality of Life Scale (EQ-5D) assessed at 90 days post-randomization. Brain images were analyzed centrally by trained assessors. Multivariable logistic regression was undertaken in the study population randomly divided (2:1) into training (development) and validation (performance) groups, with age (per 10-year increase), ethnicity, baseline National Institutes of Health Stroke Scale (NIHSS) score, diabetes mellitus, premorbid function (mRS score 0 or 1), and proxy respondent, forced into all models. Data are presented with odds ratios (ORs) and 95% confidence intervals (CIs). Results: Eight prediction models were developed and validated in 2,526 AIS patients (median age 67.5 years; 38.4% female; 61.7% Asian) with complete brain imaging and 90-day EQ-5D utility score data. The best performance model included acute ischemic changes in the right (OR 1.69, 95% CI: 1.24–2.29) and deep (OR 1.50, 95% CI: 1.03–2.19) middle cerebral artery (MCA) regions. Several background features of brain frailty – atrophy, white matter change, and old infarcts – were significantly associated with adverse physical but not emotional HRQoL domains. Conclusions: In thrombolysed AIS patients, right-sided and deep ischemia within the MCA territory predict poor overall HRQoL, whilst features of old cerebral ischemia are associated with reduced physical HRQoL. [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]