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OBJECTIVE: To investigate whether an earlier time to achieving and maintaining systolic blood pressure (SBP) at 120 to 140 mmâ Hg is associated with favorable outcomes in a cohort of patients with acute intracerebral hemorrhage. METHODS: We pooled individual patient data from randomized controlled trials registered in the Blood Pressure in Acute Stroke Collaboration. Time was defined as time form symptom onset plus the time (hour) to first achieve and subsequently maintain SBP at 120 to 140 mmâ Hg over 24 hours. The primary outcome was functional status measured by the modified Rankin Scale at 90 to 180 days. A generalized linear mixed models was used, with adjustment for covariables and trial as a random effect. RESULTS: A total of 5761 patients (mean age, 64.0 [SD, 13.0], 2120 [36.8%] females) were included in analyses. Earlier SBP control was associated with better functional outcomes (modified Rankin Scale score, 3-6; odds ratio, 0.98 [95% CI, 0.97-0.99]) and a significant lower risk of hematoma expansion (0.98, 0.96-1.00). This association was stronger in patients with bigger baseline hematoma volume (>10 mL) compared with those with baseline hematoma volume ≤10 mL (0.006 for interaction). Earlier SBP control was not associated with cardiac or renal adverse events. CONCLUSIONS: Our study confirms a clear time relation between early versus later SBP control (120-140 mmâ Hg) and outcomes in the one-third of patients with intracerebral hemorrhage who attained sustained SBP levels within this range. These data provide further support for the value of early recognition, rapid transport, and prompt initiation of treatment of patients with intracerebral hemorrhage.
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Anti-Hipertensivos , Acidente Vascular Cerebral , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Pressão Sanguínea/fisiologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Resultado do Tratamento , Hemorragia Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Hematoma/tratamento farmacológicoRESUMO
INTRODUCTION: We know little about the evolution of perihaematomal oedema (PHO) >24 h after ICH onset. We aimed to determine the trajectory of PHO after ICH onset and its association with outcome. METHODS: We did a prospective cohort study using a pre-specified scanning protocol in adults with first-ever spontaneous ICH and measured absolute PHO volumes on CT head scans at ICH diagnosis and 3 ± 2, 7 ± 2, and 14 ± 2 days after ICH onset. We used the largest ICH if ICHs were multiple. The primary outcomes were (a) the trajectory of PHO after ICH onset and (b) the association between PHO (absolute volume at the time when most repeat CT head scans were obtained, and change in PHO volume at this time compared with the first CT head scan) and poor functional outcome (modified Rankin scale 3-6 at 90 days). We pre-specified multivariable logistic regression models of this association adjusting analyses for potential confounders: age, GCS, infratentorial ICH location, and intraventricular extension. RESULTS: In 106 participants of whom 49 (46%) were female, with a median ICH volume 7 mL (interquartile range [IQR] 2-22 mL), the trajectory of median PHO volume increased from 14 mL (IQR: 7-26 mL) at diagnosis to 18 mL (IQR: 8-40 mL) at 3 ± 2 days (n = 87), 20 mL (IQR: 8-48 mL) at 7 ± 2 days (n = 93) and 21 mL (IQR: 10-54 mL) at 14 ± 2 days (n = 78) (p = <0.001). PHO volume at each time point was collinear with ICH volume at diagnosis (ârâ >0.7), but the change in PHO volume between diagnosis and each time point was not. Given collinearity, we used total lesion (i.e., ICH + PHO) volume instead of PHO volume in a logistic regression model of its association at each time point with outcome. Increasing total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome (adjusted OR per mL 1.02, 95% CI: 1.00-1.03; p = 0.036), but the increase in PHO volume between diagnosis and day 7 ± 2 was not associated with poor functional outcome (adjusted OR per mL 1.03, 95% CI: 0.99-1.07; p = 0.132). CONCLUSION: PHO volume increases throughout the first 2 weeks after onset of mild to moderate ICH. Total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome, but the change in PHO volume between diagnosis and day 7 ± 2 was not. Prospective cohort studies with larger sample sizes are needed to investigate these associations and their modifiers.
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Blood pressure (BP) elevations often complicate the management of intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage, the most serious forms of acute stroke. Despite consensus on potential benefits of BP lowering in the acute phase of intracerebral hemorrhage, controversies persist over the timing, mechanisms, and approaches to treatment. BP control is even more complex for subarachnoid hemorrhage, where there are rationales for both BP lowering and elevation in reducing the risks of rebleeding and delayed cerebral ischemia, respectively. Efforts to disentangle the evidence has involved detailed exploration of individual patient data from clinical trials through meta-analysis to determine strength and direction of BP change in relation to key outcomes in intracerebral hemorrhage, and which likely also apply to subarachnoid hemorrhage. A wealth of hemodynamic data provides insights into pathophysiological interrelationships of BP and cerebral blood flow. This focused update provides an overview of current evidence, knowledge gaps, and emerging concepts on systemic hemodynamics, cerebral autoregulation and perfusion, to facilitate clinical practice recommendations and future research.
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Isquemia Encefálica , Hemorragia Subaracnóidea , Pressão Sanguínea , Isquemia Encefálica/etiologia , Hemorragia Cerebral/complicações , Circulação Cerebrovascular/fisiologia , Humanos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/terapiaRESUMO
BACKGROUND AND PURPOSE: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. METHODS: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150-180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130-140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1-24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. RESULTS: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71-0.82]; P<0.001 and 0.86 [95% CI, 0.76-0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93-1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06-1.31]; P=0.002 and 1.34 [1.11-1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98-1.14]; P=0.184). CONCLUSIONS: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01422616.
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Pressão Sanguínea , Hipertensão , AVC Isquêmico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertensão/terapia , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/prevenção & controle , AVC Isquêmico/etiologia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/terapia , Pessoa de Meia-Idade , Estudos Prospectivos , Ativador de Plasminogênio Tecidual/efeitos adversosRESUMO
OBJECTIVE: A study was undertaken to assess whether cerebral small vessel disease (SVD) computed tomographic (CT) biomarkers are associated with long-term outcome after intracerebral hemorrhage. METHODS: We performed a prospective, community-based cohort study of adults diagnosed with spontaneous intracerebral hemorrhage between June 1, 2010 and May 31, 2013. A neuroradiologist rated the diagnostic brain CT for acute intracerebral hemorrhage features and SVD biomarkers. We used severity of white matter lucencies and cerebral atrophy, and the number of lacunes to calculate the CT SVD score. We assessed the association between CT SVD biomarkers and either death, or death or dependence (modified Rankin Scale scores = 4-6) 1 year after first-ever intracerebral hemorrhage using logistic regression, adjusting for known predictors of outcome. RESULTS: Within 1 year of intracerebral hemorrhage, 224 (56%) of 402 patients died. In separate models, 1-year death was associated with severe atrophy (adjusted odds ratio [aOR] = 2.54, 95% confidence interval [CI] = 1.44-4.49, p = 0.001) but not lacunes or severe white matter lucencies, and CT SVD sum score ≥ 1 (aOR = 2.50, 95% CI = 1.40-4.45, p = 0.002). Two hundred seventy-seven (73%) of 378 patients with modified Rankin Scale data were dead or dependent at 1 year. In separate models, 1-year death or dependence was associated with severe atrophy (aOR = 3.67, 95% CI = 1.71-7.89, p = 0.001) and severe white matter lucencies (aOR = 2.18, 95% CI = 1.06-4.51, p = 0.035) but not lacunes, and CT SVD sum score ≥ 1 (aOR = 2.81, 95% CI = 1.45-5.46, p = 0.002). INTERPRETATION: SVD biomarkers on the diagnostic brain CT are associated with 1-year death and dependence after intracerebral hemorrhage, independent of known predictors of outcome. ANN NEUROL 2021;89:266-279.
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Encéfalo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Acidente Vascular Cerebral Hemorrágico/diagnóstico por imagem , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Atrofia , Encéfalo/patologia , Estudos de Coortes , Feminino , Acidente Vascular Cerebral Hemorrágico/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Razão de Chances , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH). METHODS: A prespecified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE databases from inception to 23 June 2020 to identify randomised controlled trials that compared active BP-lowering agents versus placebo or intensive versus guideline BP-lowering targets for adults <7 days after ICH onset. The primary outcome was function (distribution of scores on the modified Rankin scale) 90 days after randomisation. Radiological outcomes were absolute (>6 mL) and proportional (>33%) haematoma growth at 24 hours. Meta-analysis used a one-stage approach, adjusted using generalised linear mixed models with prespecified covariables and trial as a random effect. RESULTS: Of 7094 studies identified, 50 trials involving 11 494 patients were eligible and 16 (32.0%) shared patient-level data from 6221 (54.1%) patients (mean age 64.2 [SD 12.9], 2266 [36.4%] females) with a median time from symptom onset to randomisation of 3.8 hours (IQR 2.6-5.3). Active/intensive BP-lowering interventions had no effect on the primary outcome compared with placebo/guideline treatment (adjusted OR for unfavourable shift in modified Rankin scale scores: 0.97, 95% CI 0.88 to 1.06; p=0.50), but there was significant heterogeneity by strategy (pinteraction=0.031) and agent (pinteraction<0.0001). Active/intensive BP-lowering interventions clearly reduced absolute (>6 ml, adjusted OR 0.75, 95%CI 0.60 to 0.92; p=0.0077) and relative (≥33%, adjusted OR 0.82, 95%CI 0.68 to 0.99; p=0.034) haematoma growth. INTERPRETATION: Overall, a broad range of interventions to lower BP within 7 days of ICH onset had no overall benefit on functional recovery, despite reducing bleeding. The treatment effect appeared to vary according to strategy and agent. PROSPERO REGISTRATION NUMBER: CRD42019141136.
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Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hemorragia Cerebral/tratamento farmacológico , Hipertensão/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Patients with premorbid functional impairment are generally excluded from acute stroke trials. We aimed to determine the impact of including such patients in the Head Positioning in acute Stroke Trial (HeadPoST) and early additional impairment on outcomes. METHODS: Post hoc analyses of HeadPoST, an international, cluster-randomized crossover trial of lying-flat versus sitting-up head positioning in acute stroke. Associations of early additional impairment, defined as change in modified Rankin scale (mRS) scores from premorbid levels (estimated at baseline) to Day 7 ("early ΔmRS"), and poor outcome (mRS score 3-6) at Day 90 were determined with generalized linear mixed model. Heterogeneity of the trial treatment effect was tested according to premorbid mRS scores 0-1 versus 2-5. RESULTS: Of 8,285 patients (38.9% female, mean age 68 ± 13 years) with complete data, there were 1,984 (23.9%) with premorbid functional impairment (mRS 2-5). A significant linear association was evident for early ∆mRS and poor outcome (per 1-point increase in ΔmRS, adjusted odds ratio 1.20, 95% confidence interval 1.14-1.27; p < 0.0001). Patients with greater premorbid functional impairment were less likely to develop additional impairment, but their risk of poor 90-day outcome significantly increased with increasing (worse) premorbid mRS scores (linear trend p < 0.0001). There was no heterogeneity of the trial treatment effect by level of premorbid function. CONCLUSIONS: Early poststroke functional impairment that exceeded premorbid levels was associated with worse 90-day outcome, and this association increased with greater premorbid functional impairment. Yet, including premorbid impaired patients in the HeadPoST did not materially affect the subsequent treatment effect. CLINICAL TRIAL REGISTRATION: HeadPoST is registered at http://www.ClinicalTrials.gov (NCT02162017).
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Pessoas com Deficiência , Estudos Multicêntricos como Assunto , Posicionamento do Paciente , Seleção de Pacientes , Postura , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Feminino , Estado Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Decúbito Dorsal , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Patient-centered care prioritizes patient beliefs and values towards wellbeing. We aimed to map functional status (modified Rankin Scale [mRS] scores) and health-related quality of life on the European Quality of Life 5-dimensional questionnaire (EQ-5D) to derive utility-weighted (UW) stroke outcome measures and test their statistical properties and construct validity. METHODS: UW-mRS scores were derived using linear regression, with mRS as a discrete ordinal explanatory response variable in 8 large international acute stroke trials. Linear regression models were used to validate UW-mRS scores by assessing differences in mean UW-mRS scores between the treatment groups of each trial. To explore the variability in EQ-5D between individual mRS categories, we generated receiver operator characteristic curves for EQ-5D to differentiate between sequential mRS categories and misclassification matrix to classify individual patients into a matched mRS category based on the closest UW-mRS value to their observed individual EQ-5D value. RESULTS: Among 22 946 acute stroke patients, derived UW-mRS across mRS scores 0 to 6 were 0.96, 0.83, 0.72, 0.54, 0.22, -0.18, and 0, respectively. Both UW-mRS and ordinal mRS scores captured divergent treatment effects across all 8 acute stroke trials. The sample sizes required to detect the treatment effects using UW-mRS scores as a continuous variable were almost half that required in trials for a binary cut point on the mRS. Area under receiver operator characteristic curves based on EQ-5D utility values varied from 0.66 to 0.81. Misclassification matrix showed moderate agreement between actual and matched mRS scores (kappa, 0.68 [95% CI, 0.67-0.68]). CONCLUSIONS: Medical strategies that target avoiding dependency may provide maximum benefit in terms of poststroke health-related quality of life. Despite variable differences with mRS scores, the UW-mRS provides efficiency gains as a smaller sample size is required to detect a treatment effect in acute stroke trials through use of continuous scores. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00226096, NCT00716079, NCT01422616, NCT02162017, NCT00120003, NCT02123875. URL: http://ctri.nic.in; Unique identifier: CTRI/2013/04/003557. URL: https://www.isrctn.com; Unique identifier: ISRCTN89712435.
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Isquemia Encefálica/diagnóstico , Isquemia Encefálica/psicologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/psicologia , Inquéritos e Questionários/normas , Humanos , Modelos Lineares , Estudos Multicêntricos como Assunto/métodos , Estudos Multicêntricos como Assunto/normas , Qualidade de Vida/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Resultado do TratamentoRESUMO
BACKGROUND: Early systolic blood pressure (SBP) reduction is believed to improve outcome after spontaneous intracerebral hemorrhage (ICH), but there has been a limited assessment of SBP trajectories in individual patients. We aimed to determine the prognostic significance of SBP trajectories in ICH. METHODS: We collected routine data on spontaneous ICH patients from two healthcare systems over 10 years. Unsupervised functional principal components analysis (FPCA) was used to characterize SBP trajectories over first 24 h and their relationship to the primary outcome of unfavorable shift on modified Rankin scale (mRS) at hospital discharge, categorized as an ordinal trichotomous variable (mRS 0-2, 3-4, and 5-6 defined as good, poor, and severe, respectively). Ordinal logistic regression models adjusted for baseline SBP and ICH volume were used to determine the prognostic significance of SBP trajectories. RESULTS: The 757 patients included in the study were 65 ± 23 years old, 56% were men, with a median (IQR) Glasgow come scale of 14 (8). FPCA revealed that mean SBP over 24 h and SBP reduction within the first 6 h accounted for 76.8% of the variation in SBP trajectories. An increase in SBP reduction (per 10 mmHg) was significantly associated with unfavorable outcomes defined as mRS > 2 (adjusted-OR = 1.134; 95% CI 1.044-1.233, P = 0.003). Compared with SBP reduction < 20 mmHg, worse outcomes were observed for SBP reduction = 40-60 mmHg (adjusted-OR = 1.940, 95% CI 1.129-3.353, P = 0.017) and > 60 mmHg, (adjusted-OR = 1.965, 95% CI 1.011, 3.846, P = 0.047). Furthermore, the association of SBP reduction and outcome varied according to initial hematoma volume. Smaller SBP reduction was associated with good outcome (mRS 0-2) in small (< 7.42 mL) and medium-size (≥ 7.42 and < 30.47 mL) hematomas. Furthermore, while the likelihood of good outcome was low in those with large hematomas (≥ 30.47 mL), smaller SBP reduction was associated with decreasing probability of severe outcome (mRS 5-6). CONCLUSION: Our analyses suggest that in the first 6 h SBP reduction is significantly associated with the in-hospital outcome that varies with initial hematoma volume, and early SBP reduction > 40 mmHg may be harmful in ICH patients. For early SBP reduction to have an effective therapeutic effect, both target levels and optimum SBP reduction goals vis-à-vis hematoma volume should be considered.
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Anti-Hipertensivos , Hipotensão , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Hemorragia Cerebral/tratamento farmacológico , Hospitais , Humanos , Hipotensão/tratamento farmacológico , Masculino , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the extent to which the effects of intensive blood pressure (BP) lowering are modified by doses of alteplase in thrombolysis-eligible acute ischemic stroke (AIS) patients. METHODS: Prespecified analyses of the Enhanced Control of Hypertension and Thrombolysis Stroke Study for patients enrolled in both arms: (i) low-dose (0.6 mg/kg body weight) or standard-dose (0.9 mg/kg) alteplase and (ii) intensive (target systolic BP [SBP] 130-140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) BP management. The primary outcome was functional recovery, measured by a shift in scores on modified Rankin scale at 90 days. The safety outcome was any intracranial hemorrhage (ICH). RESULTS: There were 925 participants (mean age 67 years, 39% female, 77% Asian) randomized to both arms: 242 randomly assigned to guideline/standard-dose (GS); 234 to guideline/low-dose (GL); 227 to intensive/standard-dose (IS); and 222 to intensive/low-dose (IL). Overall, average SBP levels within 24 h were lower in the low-dose compared to standard-dose alteplase group (146 and 144 vs. 151 and 150 mm Hg, for GS and GL vs. IS and IL, respectively, p < 0.0001). There was no heterogeneity of the effects of BP lowering (intensive vs. guideline) on functional recovery between standard-dose (OR 0.81, 95% CI 0.59-1.12) and low-dose alteplase (1.06, 0.77-1.47; p = 0.25 for interaction). Similar results were observed for ICH (p = 0.50 for interaction). CONCLUSIONS: In thrombolysis-treated patients with predominantly mild-to-moderate severity AIS, intensive BP lowering neither improve functional recovery, either with low- or standard-dose intravenous alteplase, nor beneficially interact with low-dose alteplase in reducing ICH. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT01422616).
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Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Hipertensão/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/efeitos adversos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hemorragias Intracranianas/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Intraventricular extension of intracerebral haemorrhage (ICH) predicts poor outcome, but the significance of delayed intraventricular haemorrhage (dIVH) is less well defined. We determined the prognostic significance of dIVH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2). METHODS: Pooled analyses of the INTERACT CT substudies-international, multicentre, prospective, open, blinded end point, randomised controlled trials of patients with acute spontaneous ICH and elevated systolic blood pressure (SBP)-randomly assigned to intensive (<140â mmâ Hg) or guideline-based (<180â mmâ Hg) SBP management. Participants had blinded central analyses of baseline and 24â h CTs, with dIVH defined as new intraventricular haemorrhage (IVH) on the latter scan. Outcomes of death and major disability were defined by modified Rankin Scale scores at 90â days. RESULTS: There were 349 (27%) of 1310 patients with baseline IVH, and 107 (11%) of 961 initially IVH-free patients who developed dIVH. Significant associations of dIVH were prior warfarin anticoagulation, high (≥15) baseline National Institutes of Health Stroke Scale score, larger (≥15â mL) ICH volume, greater ICH growth and higher achieved SBP over 24â h. Compared with those who were IVH-free, dIVH had greater odds of 90-day death or major disability versus initial IVH (adjusted ORs 2.84 (95% CI 1.52 to 5.28) and 1.87 (1.36 to 2.56), respectively (p trend <0.0001)). CONCLUSIONS: Although linked to factors determining greater ICH growth including poor SBP control, dIVH is independently associated with poor outcome in acute small to moderate-size ICH. TRIAL REGISTRATION NUMBERS: NCT00226096 and NCT00716079.
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Hemorragia Cerebral/diagnóstico , Ventrículos Cerebrais/irrigação sanguínea , Hemorragia/diagnóstico , Idoso , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/mortalidade , Ventrículos Cerebrais/diagnóstico por imagem , Avaliação da Deficiência , Feminino , Hemorragia/complicações , Hemorragia/diagnóstico por imagem , Hemorragia/mortalidade , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: Intraventricular hemorrhage (IVH) with spontaneous intracerebral hemorrhage indicates a poor prognosis but uncertainty exists over the pattern of association. We aimed to elucidate risk associations of IVH and outcome in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) data set. METHODS: INTERACT2 was an international prospective, open-blinded end point, randomized controlled trial in 2839 patients with intracerebral hemorrhage (<6 hours) with elevated systolic blood pressure randomly assigned to intensive (target systolic blood pressure <140 mm Hg) or guideline-based (systolic blood pressure <180 mm Hg) blood pressure management. Associations of baseline IVH in 740 of 2613 (28%) patients and poor outcomes (death and major disability defined on the modified Rankin Scale) at 90 days were determined in linear and logistic regression models. RESULTS: Patients with IVH were significantly older and with greater neurological impairment, history of ischemic stroke, and larger hematomas more often deep hemisphere located at presentation, after adjustment for other baseline variables. Death or major disability occurred in 66% with IVH versus 49% in intracerebral hemorrhage-alone patients (adjusted odds ratio, 1.68; 95% confidence interval, 1.38-2.06; P<0.01). Associations of IVH volume and clinical outcomes were strong and near continuous. Adjusted analyses by thirds of IVH volume indicate thresholds of ≈5 and 10 mL for significantly increased odds of death and death or major disability, respectively. CONCLUSIONS: A strong association exists between the amount of IVH and poor outcome in intracerebral hemorrhage. An IVH volume of 5 to 10 mL emerges as a significant threshold for decision making on prognosis in these patients. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079.
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Neoplasias Encefálicas/patologia , Hemorragia Cerebral/patologia , Doença Aguda , Idoso , Pressão Sanguínea , Bases de Dados Factuais , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Análise de Regressão , Sístole , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to better define the shape of association between the degree ("magnitude") of early (< 1 h) reduction in systolic blood pressure (SBP) and outcomes in patients with acute intracerebral hemorrhage (ICH) through pooled analysis of the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) and second Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) datasets. METHODS: Association of the continuous magnitude of SBP reduction described using cubic splines and an ordinal measure of the functional outcome on the modified Rankin scale (mRS) scores at 90 days were analyzed in generalized linear mixed models. Models were adjusted for achieved (mean) and variability (standard deviation, SD) of SBP between 1 and 24 h, various baseline covariates, and trial as a random effect. RESULTS: Among 3796 patients (mean age 63.1 (SD = 13.0) years; female 37.4%), with a mean magnitude (< 1 h) of SBP reduction of 28.5 (22.8) mmHg, those with larger magnitude were more often non-Asian and female, had higher baseline SBP, received multiple blood pressure (BP) lowering agents, and achieved lower SBP levels in 1-24 h. Compared to those patients with no SBP reduction within 1 h (reference), the adjusted odds of unfavorable functional outcome, according to a shift in mRS scores, were lower for SBP reductions up to 60 mmHg with an inflection point between 32 and 46 mmHg, but significantly higher for SBP reductions > 70 mmHg. Similar J-shape associations were evident across various time epochs across 24 h and consistent according to baseline hematoma volume and SBP and history of hypertension. INTERPRETATION: A moderate degree of rapid SBP lowering is associated with improved functional outcome after ICH, but large SBP reductions over 1 h (e.g. from > 200 to target < 140 mmHg) were associated with reduction, or reversal, of any such benefit.
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Hipertensão , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Pressão Sanguínea , Hemorragia Cerebral/complicações , Hemorragia Cerebral/terapia , Hematoma , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Resultado do TratamentoRESUMO
INTRODUCTION: Blood pressure (BP) lowering reduces the risk of recurrent stroke after intracerebral haemorrhage (ICH). However, implementation of BP lowering in clinical practice in the UK is unknown. PATIENTS AND METHODS: We identified adults with first-ever incident ICH to quantify the proportion who survived >14 days after hospital discharge and were prescribed BP-lowering medication in a prospective, population-based, inception cohort study in the Lothian region of Scotland during June 2010-May 2012 and January-December 2019. After the first cohort, we analysed reasons for avoiding BP-lowering medication in a sample from the Lothian region of the Scottish Stroke Care Audit during January 2017-November 2017, which informed a quality improvement intervention that was implemented in the second cohort. RESULTS: After efforts to improve monitoring and lowering of BP amongst ICH survivors, there was an increase in the proportion of patients prescribed BP-lowering medication at hospital discharge between the first and second population-based cohorts (81/130 [62%] vs. 68/89 [76%]; P = 0.028). Compared with patients not prescribed BP-lowering medication at hospital discharge, patients prescribed BP-lowering medication presented with higher systolic BP (177 vs. 156 mm Hg, P = 0.002 and 180 vs. 149 mm Hg, P < 0.001, in the first and second population-based cohorts, respectively), and were more likely to have pre-morbid hypertension (85% vs. 33%, P < 0.001 and 72% vs. 29%, P < 0.001) and atrial fibrillation (35% vs. 4%, P < 0.001 and 26% vs. 5%, P < 0.034). CONCLUSION: In this population-based study, the proportion of patients with ICH who were prescribed BP-lowering medication at hospital discharge increased after a quality improvement intervention.
RESUMO
BACKGROUND: Patients with stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) are at risk of recurrent ICH, ischaemic stroke, and other serious vascular events. We aimed to analyse these risks in population-based studies and compare them with the risks in RESTART, which assessed antiplatelet therapy after ICH. METHODS: We pooled individual patient data from two prospective, population-based inception cohort studies of all patients with an incident firs-in-a-lifetime ICH in Oxfordshire, England (Oxford Vascular Study; April 1, 2002, to Sept 28, 2018) and Lothian, Scotland, UK (Lothian Audit of the Treatment of Cerebral Haemorrhage; June 1, 2010, to May 31, 2013). We quantified the absolute and relative risks of recurrent ICH, ischaemic stroke, or any serious vascular event (non-fatal stroke, non-fatal myocardial infarction, or vascular death), stratified by ICH location (lobar vs non-lobar) and comorbid atrial fibrillation (AF). We compared pooled event rates with those after allocation to avoid antiplatelet therapy in RESTART. FINDINGS: Among 674 patients (mean age 74·7 years [SD 12·6], 320 [47%] men) with 1553 person-years of follow-up, 46 recurrent ICHs (event rate 3·2 per 100 patient-years, 95% CI 2·0-5·1) and 25 ischaemic strokes (1·7 per 100 patient-years, 0·8-3·3) were reported. Patients with lobar ICH (n=317) had higher risk of recurrent ICH (5·1 per 100 patient-years, 95% CI 3·6-7·2) than patients with non-lobar ICH (n=355; 1·8 per 100 patient-years, 1·0-3·3; hazard ratio [HR] 3·2, 95% CI 1·6-6·3; p=0·0010), but there was no evidence of a difference in the risk of ischaemic stroke (1·8 per 100 patient-years, 1·0-3·2, vs 1·6 per 100 patient-years, 0·6-4·4; HR 1·1, 95% CI 0·5-2·8). Conversely, there was no evidence of a difference in recurrent ICH rate in patients with AF (n=147; 3·3 per 100 patient-years, 95% CI 1·0-10·7) compared with those without (n=526; 3·2 per 100 patient-years, 2·2-4·7; HR 0·9, 95% CI 0·4-2·1), but the risk of ischaemic stroke was higher with AF (6·3 per 100 patient-years, 3·7-10·9, vs 0·7 per 100 patient-years, 0·1-5·6; HR 8·2, 3·3-20·3; p<0·0001), resulting in patients with AF having a higher risk of all serious vascular events than patients without AF (15·5 per 100 patient-years, 10·0-24·1, vs 6·8 per 100 patient-years, 3·6-12·5; HR 1·78, 95% CI 1·16-2·74; p=0·0090). Only for patients with lobar ICH without comorbid AF was the risk of recurrent ICH greater than the risk of ischaemic stroke (5·2 per 100 patient-years, 95% CI 3·6-7·5, vs 0·9 per 100 patient-years, 0·2-4·8; p=0·00034). Comparing data from the pooled population-based studies with that from patients allocated to not receive antiplatelet therapy in RESTART, there was no evidence of a difference in the rate of recurrent ICH (3·5 per 100 patient-years, 95% CI 1·9-6·0, vs 4·4 per 100 patient-years, 2·6-6·1) or ischaemic stroke (3·4 per 100 patient-years, 1·9-5·9, vs 5·3 per 100 patient-years, 3·3-7·2). INTERPRETATION: The risks of recurrent ICH, ischaemic stroke, and all serious vascular events after ICH differ by ICH location and comorbid AF. These data enable risk stratification of patients in clinical practice and ongoing randomised trials. FUNDING: UK Medical Research Council, Stroke Association, British Heart Foundation, Wellcome Trust, and the National Institute for Health Research Oxford Biomedical Research Centre.
Assuntos
Hemorragia Cerebral/complicações , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/fisiopatologia , Hemorragia Cerebral/fisiopatologia , Infarto Cerebral/fisiopatologia , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Fatores de Risco , Escócia/epidemiologiaRESUMO
Intracerebral hemorrhage (ICH) represents a major, global, unmet health need with few treatments. A significant minority of ICH patients present taking an anticoagulant; both vitamin-K antagonists and increasingly direct oral anticoagulants. Anticoagulants are associated with an increased risk of hematoma expansion, and rapid reversal reduces this risk and may improve outcome. Vitamin-K antagonists are reversed with prothrombin complex concentrate, dabigatran with idarucizumab, and anti-Xa agents with PCC or andexanet alfa, where available. Blood pressure lowering may reduce hematoma growth and improve clinical outcomes and careful (avoiding reductions ≥60 mm Hg within 1 h), targeted (as low as 120-130 mm Hg), and sustained (minimizing variability) treatment during the first 24 h may be optimal for achieving better functional outcomes in mild-to-moderate severity acute ICH. Surgery for ICH may include hematoma evacuation and external ventricular drainage to treat hydrocephalus. No large, well-conducted phase III trial of surgery in ICH has so far shown overall benefit, but meta-analyses report an increased likelihood of good functional outcome and lower risk of death with surgery, compared to medical treatment only. Expert supportive care on a stroke unit or critical care unit improves outcomes. Early prognostication is difficult, and early do-not-resuscitate orders or withdrawal of active care should be used judiciously in the first 24-48 h of care. Implementation of acute ICH care can be challenging, and using a care bundle approach, with regular monitoring of data and improvement of care processes can ensure consistent and optimal care for all patients.
Assuntos
Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Dabigatrana/uso terapêutico , Hematoma/terapia , Humanos , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
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.
Assuntos
AVC Isquêmico/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Ativador de Plasminogênio Tecidual/uso terapêutico , Fatores Etários , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Modelos Estatísticos , Fatores de Risco , Método Simples-CegoRESUMO
BACKGROUND: There is persistent uncertainty over the benefits of early intensive systolic blood pressure lowering in acute intracerebral hemorrhage. In particular, over the timing, target, and intensity of systolic blood pressure control for optimum balance of potential benefits (i.e. functional recovery) and risks (e.g. cerebral ischemia). AIMS: To determine associations of early systolic blood pressure lowering parameters and outcomes in patients with a hypertensive response in acute intracerebral hemorrhage. Secondary aims are to identify the modifying effects of patient characteristics and an optimal systolic blood pressure lowering profile. METHODS: Individual participant data pooled analyses of two large, multicenter, randomized controlled trials specifically undertaken to assess the effects of early intensive systolic blood pressure reduction on clinical outcomes in acute intracerebral hemorrhage: the Intensive Blood Pressure in Acute Intracerebral Hemorrhage Trial (INTERACT2) and the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) trial. Combined data will include baseline characteristics; systolic blood pressure in the first 24 h; process of care measures; and key efficacy and safety outcomes. OUTCOMES: The primary outcome is functional recovery, defined by an ordinal distribution of scores on the modified Rankin scale at 90 days post-randomization. Secondary outcomes include various standard binary cut-points for disability-free survival on the modified Rankin scale, and health-related quality of life at 90 days. Safety outcomes include symptomatic hypotension requiring corrective therapy and early neurologic deterioration within 24 h, and deaths, any serious adverse event, and cardiac and renal serious adverse events, within 90 days. DISCUSSION: A pre-determined protocol was developed to facilitate successful collaboration and reduce analysis bias arising from prior knowledge of the findings. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifiers for INTERACT2 (NCT00716079) and ATACH-II (NCT01176565).
Assuntos
Anti-Hipertensivos/uso terapêutico , Hemorragia Cerebral/epidemiologia , Hipertensão/epidemiologia , Doença Aguda , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/mortalidade , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/mortalidade , Seleção de Pacientes , Qualidade de Vida , Recuperação de Função Fisiológica , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: An early elevation in blood pressure (BP) is common after spontaneous intracerebral hemorrhage (ICH), has various potential causes, and is predictive of poor outcome. We aimed to determine the predictors of this phenomenon, in pooled analyses of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials [INTERACT1 (nâ=â404) and INTERACT2 (nâ=â2829)]. METHODS: INTERACT trials were international, open, blinded endpoint, randomized controlled trials of patients with spontaneous ICH (<6âh) and elevated SBP (150-220âmmHg) assigned to intensive (target SBPâ<â140âmmHg) or guideline-recommended (SBPâ<â180âmmHg) treatment. Multivariable linear and logistic regression models were used to determine associations between baseline variables and the high admission BP, with continuous and binary SBP measures, respectively. RESULTS: Among 3233 patients (mean age 63 years; 37% female; baseline mean SBP 179âmmHg), both analytic approaches showed significant positive associations of high admission BP with history of hypertension, admission hyperglycemia at least 6.5âmmol/l, elevated heart rate, and greater neurological severity (National Institutes of Health Stroke Scale scores); and significant negative associations with prior use of antithrombotic agents and longer time from onset to randomization. CONCLUSION: The high admission BP of mild-to-moderate acute ICH is related to autonomic nervous system activated 'stress' rather than hematoma location and mass effect. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.