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1.
Stroke ; 50(8): 2093-2100, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31221054

RESUMO

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

2.
Int J Stroke ; 14(5): 548-554, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30943878

RESUMO

RATIONALE AND HYPOTHESIS: Surgical removal of spontaneous intracerebral hemorrhage may reduce secondary destruction of brain tissue. However, large surgical trials of craniotomy have not demonstrated definitive improvement in clinical outcomes. Minimally invasive surgery may limit surgical tissue injury, and recent evidence supports testing these approaches in large clinical trials. METHODS AND DESIGN: MISTIE III is an investigator-initiated multicenter, randomized, open-label phase 3 study investigating whether minimally invasive clot evacuation with thrombolysis improves functional outcomes at 365 days compared to conservative management. Patients with supratentorial intracerebral hemorrhage clot volume ≥ 30 mL, confirmed by imaging within 24 h ofknown symptom onset,and intact brainstem reflexes were screened with a stability computed tomography scan at least 6 h after diagnostic scan. Patients who met clinical and imaging criteria (no ongoing coagulopathy; no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly; and stable hematoma size on consecutive scans) were randomized to either minimally invasive surgery plus thrombolysis or medical therapy. The sample size of 500 was based on findings of a phase 2 study. STUDY OUTCOMES: The primary outcome measure is dichotomized modified Rankin Scale 0-3 vs. 4-6 at 365 days adjusting for severity variables. Clinical secondary outcomes include dichotomized extended Glasgow Outcome Scale and all-cause mortality at 365 days; rate and extent of parenchymal blood clot removal; patient disposition at 365 days; efficacy at 180 days; type and intensity of ICU management; and quality of life measures. Safety was assessed at 30 days and throughout the study.

3.
Trials ; 20(1): 107, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736833

RESUMO

BACKGROUND: Inter-observer variability in stroke aetiological classification may have an effect on trial power and estimation of treatment effect. We modelled the effect of misclassification on required sample size in a hypothetical cardioembolic (CE) stroke trial. METHODS: We performed a systematic review to quantify the reliability (inter-observer variability) of various stroke aetiological classification systems. We then modelled the effect of this misclassification in a hypothetical trial of anticoagulant in CE stroke contaminated by patients with non-cardioembolic (non-CE) stroke aetiology. Rates of misclassification were based on the summary reliability estimates from our systematic review. We randomly sampled data from previous acute trials in CE and non-CE participants, using the Virtual International Stroke Trials Archive. We used bootstrapping to model the effect of varying misclassification rates on sample size required to detect a between-group treatment effect across 5000 permutations. We described outcomes in terms of survival and stroke recurrence censored at 90 days. RESULTS: From 4655 titles, we found 14 articles describing three stroke classification systems. The inter-observer reliability of the classification systems varied from 'fair' to 'very good' and suggested misclassification rates of 5% and 20% for our modelling. The hypothetical trial, with 80% power and alpha 0.05, was able to show a difference in survival between anticoagulant and antiplatelet in CE with a sample size of 198 in both trial arms. Contamination of both arms with 5% misclassified participants inflated the required sample size to 237 and with 20% misclassification inflated the required sample size to 352, for equivalent trial power. For an outcome of stroke recurrence using the same data, base-case estimated sample size for 80% power and alpha 0.05 was n = 502 in each arm, increasing to 605 at 5% contamination and 973 at 20% contamination. CONCLUSIONS: Stroke aetiological classification systems suffer from inter-observer variability, and the resulting misclassification may limit trial power. TRIAL REGISTRATION: Protocol available at reviewregistry540 .


Assuntos
Ensaios Clínicos como Assunto/métodos , Embolia/complicações , Cardiopatias/complicações , Modelos Estatísticos , Tamanho da Amostra , Acidente Vascular Cerebral/etiologia , Terminologia como Assunto , Anticoagulantes/uso terapêutico , Ensaios Clínicos como Assunto/estatística & dados numéricos , Interpretação Estatística de Dados , Embolia/diagnóstico , Embolia/tratamento farmacológico , Cardiopatias/diagnóstico , Cardiopatias/tratamento farmacológico , Humanos , Variações Dependentes do Observador , Inibidores da Agregação de Plaquetas/uso terapêutico , Fatores de Risco , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento
4.
Lancet ; 393(10175): 1021-1032, 2019 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-30739747

RESUMO

BACKGROUND: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. METHODS: MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. FINDINGS: Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). INTERPRETATION: For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. FUNDING: National Institute of Neurological Disorders and Stroke and Genentech.


Assuntos
Hemorragia Cerebral/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Idoso , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
5.
Dysphagia ; 34(5): 698-707, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30612234

RESUMO

Oropharyngeal dysphagia is prevalent in several at-risk populations, including post-stroke patients, patients in intensive care and the elderly. Dysphagia contributes to longer hospital stays and poor outcomes, including pneumonia. Early identification of dysphagia is recommended as part of the evaluation of at-risk patients, but available bedside screening tools perform inconsistently. In this study, we developed algorithms to detect swallowing impairment using a novel accelerometer-based dysphagia detection system (DDS). A sample of 344 individuals was enrolled across seven sites in the United States. Dual-axis accelerometry signals were collected prospectively with simultaneous videofluoroscopy (VFSS) during swallows of liquid barium stimuli in thin, mildly, moderately and extremely thick consistencies. Signal processing classifiers were trained using linear discriminant analysis and 10,000 random training-test data splits. The primary objective was to develop an algorithm to detect impaired swallowing safety with thin liquids with an area under receiver operating characteristic curve (AUC) > 80% compared to the VFSS reference standard. Impaired swallowing safety was identified in 7.2% of the thin liquid boluses collected. At least one unsafe thin liquid bolus was found in 19.7% of participants, but participants did not exhibit impaired safety consistently. The DDS classifier algorithms identified participants with impaired thin liquid swallowing safety with a mean AUC of 81.5%, (sensitivity 90.4%, specificity 60.0%). Thicker consistencies were effective for reducing the frequency of penetration-aspiration. This DDS reached targeted performance goals in detecting impaired swallowing safety with thin liquids. Simultaneous measures by DDS and VFSS, as performed here, will be used for future validation studies.

6.
J Am Heart Assoc ; 7(22): e010133, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30571487

RESUMO

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT ; 53.1% of patients with  HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

7.
PLoS One ; 13(11): e0208142, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30475912

RESUMO

BACKGROUND AND PURPOSE: Central adjudication of serious adverse events (SAEs) can be undertaken in clinical trials, especially for open-label studies where outcome assessment may be at risk of bias. This study explored the effect of central adjudication of SAEs on the safety results of the Efficacy of Nitric Oxide in Stroke (ENOS) Trial. METHODS: ENOS assigned patients with acute stroke at random to receive either transdermal glyceryl trinitrate (GTN) or no GTN and to Stop or Continue previous antihypertensive treatment. SAEs were reported by local investigators who were not blinded to treatment allocation. Central adjudicators, blinded to treatment allocation, reviewed the investigators reports and used evidence available to confirm or re-categorise the classification of event, likely causality, diagnosis and expectedness of event. RESULTS: Of 4011 patients enrolled in ENOS, 1473 SAEs were reported by local investigators; this was reduced to 1444 after the review by adjudicators, with 29 re-classified as not an SAE. There was fair agreement between investigators and adjudicators regarding likely causality, with 808 agreements and 644 disagreements (56% crude agreement, weighted kappa, κ = 0.31). Agreement increased upon dichotomisation of the causality categories, with 1432 agreements and 20 disagreements (99% crude agreement, kappa = 0.54). Repeating the main trial safety analysis with investigator reported events showed that adjudication had no effect on the main trial safety conclusions. CONCLUSIONS: In a large trial, with many SAEs reported, central adjudication of these events did not affect trial conclusions. This suggests that adjudication of SAEs in a clinical trial where the intervention already has a well-established safety profile may not be necessary. Potential efficiency savings (financial, logistical) can be made through not adjudicating SAEs.

8.
Eur Stroke J ; 3(3): 291-298, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30246150

RESUMO

Background: Elderly patients are at high risk of complications after stroke, such as infections and fever. The occurrence of these complications has been associated with an increased risk of death or dependency.Hypothesis: Prevention of aspiration, infections, or fever with metoclopramide, ceftriaxone, paracetamol, or any combination of these in the first four days after stroke onset will improve functional outcome at 90 days in elderly patients with acute stroke. Design: International, 3 × 2-factorial, randomised-controlled, open-label clinical trial with blinded outcome assessment (PROBE) in 3800 patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and an NIHSS score ≥ 6. Patients will be randomly allocated to any combination of oral, rectal, or intravenous metoclopramide (10 mg thrice daily); intravenous ceftriaxone (2000 mg once daily); oral, rectal, or intravenous paracetamol (1000 mg four times daily); or usual care, started within 24 h after symptom onset and continued for four days or until complete recovery or discharge from hospital, if earlier.Outcome: The primary outcome measure is the score on the modified Rankin Scale at 90 days (± 14 days), as analysed with multiple regression.Summary: This trial will provide evidence for a simple, safe and generally available treatment strategy that may reduce the burden of death or disability in patients with stroke at very low costs.Planning: First patient included in May 2016; final follow-up of the last patient by April 2020.Registration: ISRCTN, ISRCTN82217627, https://doi.org/10.1186/ISRCTN82217627.

9.
Int J Stroke ; 13(7): 759-765, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29720045

RESUMO

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains particularly for ischemic stroke. The "Blood pressure in Acute Stroke Collaboration" commenced in the mid-1990s focussing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, Blood pressure in Acute Stroke Collaboration planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, including both intracerebral hemorrhage and ischemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on hemodynamic variables. Methods and design Individual patient data from randomized controlled trials of blood pressure management in participants with ischemic stroke and/or intracerebral hemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 h), acute (<48 h), and sub-acute (<168 h) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in pre-specified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, hemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration.

10.
Eur J Heart Fail ; 20(7): 1139-1145, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29493058

RESUMO

AIMS: To evaluate the effects of digoxin in patients with the newly described phenotype of heart failure (HF) and mid-range ejection fraction (HFmrEF), attributed to mild left ventricular systolic dysfunction. METHODS AND RESULTS: We carried out a retrospective analysis of the Digitalis Investigation Group (DIG) trial which had 7788 patients available for analysis with a left ventricular ejection fraction (LVEF) ranging between 3% and 85%. We compared the effect of digoxin to placebo in three mutually exclusive groups of patients defined by LVEF category: <40% (HF with reduced LVEF, HFrEF, n = 5874), 40-49% (HFmrEF, n = 1195) and ≥50% (HF with preserved LVEF, HFpEF, n = 719). The primary outcome was the composite of cardiovascular death or HF hospitalisation. Patients with HFmrEF resembled patients with HFrEF, more than those with HFpEF, with respect to age, sex and aetiology but were more like HFpEF patients with respect to blood pressure and the prevalence of hypertension. Event rates in patients with HFmrEF were similar to those in HFpEF and much lower than in HFrEF. Digoxin reduced the primary endpoint in patients with HFrEF, mainly due to reduced HF hospitalisation: the digoxin/placebo hazard ratio (HR) for HF hospitalisation was 0.71 [95% confidence interval (CI) 0.65-0.77]. The digoxin/placebo HR for HF hospitalisation in patients with HFmrEF was 0.80 (95% CI 0.63-1.03) and 0.85 (95% CI 0.62-1.17) in those with HFpEF. The digoxin/placebo HR for the composite of HF death or HF hospitalisation was 0.74 (95% CI 0.68-0.81) in HFrEF, 0.83 (95% CI 0.66-1.05) in HFmrEF and 0.88 (95% CI 0.65-1.19) in HFpEF. CONCLUSIONS: In this study, event rates in patients with HFmrEF were closer to those in HFpEF than HFrEF. Digoxin had most effect on HF hospitalisation in patients with HFrEF, an intermediate effect in HFmrEF, and the smallest effect in HFpEF.

12.
Int J Stroke ; 13(2): 175-189, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29171359

RESUMO

Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0-1) at 3-6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0-1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21-1.68 and 1.43, 1.23-1.65, respectively), but not in those outside the age-revised label (1.06, 0.90-1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76-1.25 and 1.01, 0.86-1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99-1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19-2.01 and 1.37, 1.17-1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97-1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77-1.26 and 1.02, 0.87-1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98-1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.

13.
Int J Stroke ; 13(1): 47-56, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-27543501

RESUMO

Background Previous studies suggested that enlarged perivascular spaces are neuroimaging markers of cerebral small vessel disease. However, it is not clear whether enlarged perivascular spaces are associated with cognitive impairment. We aimed to determine the cross-sectional relationship between enlarged perivascular spaces and small vessel disease, and to investigate the relationship between enlarged perivascular spaces and subsequent cognitive impairment in patients with recent cerebral ischemic event. Methods Anonymized data were accessed from the virtual international stroke trial archive. We rated number of lacunes, white matter hyperintensities, brain atrophy, and enlarged perivascular spaces with validated scales on magnetic resonance brain images after the index stroke. We defined cognitive impairment as a mini mental state examination score of ≤26, recorded at one year post stroke. We examined the associations between enlarged perivascular spaces and clinical and imaging markers of small vessel disease at presentation and clinical evidence of cognitive impairment at one year using linear and logistic regression models. Results We analyzed data on 430 patients with mean (±SD) age 64.7 (±12.7) years, 276 (64%) males. In linear regression analysis, age (ß = 0.24; p < 0.001), hypertension (ß = 0.09; p = 0.025), and deep white matter hyperintensities (ß = 0.31; p < 0.001) were associated with enlarged perivascular spaces. In logistic regression analysis, basal ganglia enlarged perivascular spaces were independently associated with cognitive impairment at one year after adjusting for clinical confounders (OR = 1.72, 95% CI = 1.22-2.42) and for clinical and imaging confounders (OR = 1.54; 95% CI = 1.03-2.31). Conclusions Our data show that in patients with ischemic cerebral events, enlarged perivascular spaces are cross-sectionally associated with age, hypertension, and white matter hyperintensities and suggest that enlarged perivascular spaces in the basal ganglia are associated with cognitive impairment after one year.


Assuntos
Gânglios da Base/diagnóstico por imagem , Disfunção Cognitiva/patologia , Espaço Extracelular/diagnóstico por imagem , Ataque Isquêmico Transitório/patologia , Acidente Vascular Cerebral/patologia , Idoso , Gânglios da Base/patologia , Disfunção Cognitiva/complicações , Estudos Transversais , Feminino , Humanos , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem
14.
J Am Heart Assoc ; 6(12)2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-29220330

RESUMO

BACKGROUND: The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. METHODS AND RESULTS: Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA2DS2-VASc score >4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke. CONCLUSIONS: In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Isquemia Encefálica/prevenção & controle , Hemorragia/epidemiologia , Vitamina K/antagonistas & inibidores , Doença Aguda , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Recidiva , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento
15.
Neurology ; 89(21): 2143-2150, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29070665

RESUMO

OBJECTIVE: In patients with acute ischemic stroke, we aimed to investigate the relation between preexisting small vessel disease (SVD) and the amount of blood-brain barrier (BBB) leakage in ischemic and nonischemic area before IV thrombolysis. METHODS: We retrospectively accessed anonymous patient-level data from the Stroke Imaging Repository and the Virtual International Stroke Trials Archive resources and included patients treated with IV thrombolysis with pretreatment MRI. We rated SVD features using validated qualitative magnetic resonance (MR) scales. Leakage of BBB was assessed with postprocessing of perfusion-weighted images. We evaluated associations between SVD features (individually and summed in a global SVD score) and BBB leakage using linear regression analysis, adjusting for major clinical confounders. RESULTS: A total of 212 patients, mean age (±SD) 69.5 years (±16.1), 102 (48%) male, had available MR before IV thrombolysis. Evidence of BBB leakage was present in 175 (80%) and 205 (94%) patients in the ischemic and nonischemic area, respectively. Lacunar infarcts (ß = 0.17, p = 0.042) were associated with BBB leakage in the ischemic area, and brain atrophy was associated with BBB leakage in both ischemic (ß = 0.20, p = 0.026) and nonischemic (ß = 0.27, p = 0.001) areas. Increasing SVD grade was independently associated with BBB leakage in both ischemic (ß = 0.26, p = 0.007) and nonischemic (ß = 0.27, p = 0.003) area. CONCLUSIONS: Global SVD burden is associated with increased BBB leakage in both acutely ischemic and nonischemic area. Our results support that SVD score has construct validity, and confirm a relation between SVD and BBB disruption also in patients with acute stroke.


Assuntos
Barreira Hematoencefálica/fisiopatologia , Doenças de Pequenos Vasos Cerebrais/etiologia , Doenças de Pequenos Vasos Cerebrais/patologia , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Isquemia Encefálica/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Tomografia Computadorizada por Raios X
16.
Neurology ; 89(15): 1561-1568, 2017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-28887377

RESUMO

OBJECTIVE: To determine outcomes and risks of IV thrombolysis (IVT) in patients with acute ischemic stroke (AIS) >80 years of age within 3 hours compared to >3 to 4.5 hours recorded in the Safe Implementation of Treatment in Stroke (SITS) International Stroke Thrombolysis Registry. METHODS: A total of 14,240 (year 2003-2015) patients >80 years of age with AIS were treated with IVT ≤4.5 hours of stroke onset (3,558 in >3-4.5 hours). Of these, 8,658 (2,157 in >3-4.5 hours) were treated otherwise according to the European Summary of Product Characteristics (EU SmPC) criteria for alteplase. Outcomes were 3-month functional independence (modified Rankin Scale score 0-2), mortality, and symptomatic intracerebral hemorrhage (SICH)/SITS. Results were compared between the groups treated in >3 to 4.5 and ≤3 hours. RESULTS: Median age was 84 years; 61% were female in both groups. Median NIH Stroke Scale score was 12 vs 14 in the >3- to 4.5- and ≤3-hour group, respectively. Three-month functional independence was 34% vs 35% (adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.69-0.89, p < 0.001); mortality was 31% vs 32% (aOR 1.10, 95% CI 0.97-1.25, p = 0.13); and SICH/SITS was 2.7% vs 1.6% (aOR 1.72, 95% CI 1.25-2.35, p = 0.001). In EU SmPC-compliant patients, 3-month functional independence was 36 vs 37% (aOR 0.79, 95% CI 0.68-0.92, p = 0.002), mortality was 29% vs 29.6% (aOR 1.10, 95% CI 0.95-1.28, p = 0.20), and SICH/SITS was 2.7% vs 1.6% (aOR 1.62, 95% CI 1.12-2.34, p = 0.01). CONCLUSIONS: In this observational study, unselected patients >80 years of age treated with IVT after 3 hours vs earlier had a slightly higher rate of SICH and similar unadjusted functional outcome but poorer adjusted outcome. The absolute difference between the treatment groups is small, and elderly patients should not be denied IVT in the later time window solely because of age without other contraindications.


Assuntos
Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento , Idoso de 80 Anos ou mais , Hemorragia Cerebral/etiologia , Europa (Continente) , Feminino , Humanos , Masculino , Avaliação de Resultados (Cuidados de Saúde) , Curva ROC , Sistema de Registros , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Fatores de Tempo
17.
Neurology ; 89(10): 997-1002, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28794250

RESUMO

OBJECTIVE: To compare the prognostic accuracy of various acute stroke prognostic scales using a large, independent, clinical trials dataset. METHODS: We directly compared 8 stroke prognostic scales, chosen based on focused literature review (Acute Stroke Registry and Analysis of Lausanne [ASTRAL]; iSCORE; iSCORE-revised; preadmission comorbidities, level of consciousness, age, and neurologic deficit [PLAN]; stroke subtype, Oxfordshire Community Stroke Project, age, and prestroke modified Rankin Scale [mRS] [SOAR]; modified SOAR; Stroke Prognosis Instrument 2 [SPI2]; and Totaled Health Risks in Vascular Events [THRIVE]) using individual patient-level data from a clinical trials archive (Virtual International Stroke Trials Archive [VISTA]). We calculated area under receiver operating characteristic curves (AUROC) for each scale against 90-day outcomes of mRS (dichotomized at mRS >2), Barthel Index (>85), and mortality. We performed 2 complementary analyses: the first limited to patients with complete data for all components of all scales (simultaneous) and the second using as many patients as possible for each individual scale (separate). We compared AUROCs and performed sensitivity analyses substituting extreme outcome values for missing data. RESULTS: In total, 10,777 patients contributed to the analyses. Our simultaneous analyses suggested that ASTRAL had greatest prognostic accuracy for mRS, AUROC 0.78 (95% confidence interval [CI] 0.75-0.82), and SPI2 had poorest AUROC, 0.61 (95% CI 0.57-0.66). Our separate analyses confirmed these results: ASTRAL AUROC 0.79 (95% CI 0.78-0.80 and SPI2 AUROC 0.60 (95% CI 0.59-0.61). On formal comparative testing, there was a significant difference in modified Rankin Scale AUROC between ASTRAL and all other scales. Sensitivity analysis identified no evidence of systematic bias from missing data. CONCLUSIONS: Our comparative analyses confirm differences in the prognostic accuracy of stroke scales. However, even the best performing scale had prognostic accuracy that may not be sufficient as a basis for clinical decision-making.


Assuntos
Acidente Vascular Cerebral/diagnóstico , Idoso , Área Sob a Curva , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Ensaios Clínicos como Assunto , Conjuntos de Dados como Assunto , Avaliação da Deficiência , Feminino , Humanos , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/mortalidade , Masculino , Prognóstico , Curva ROC , Acidente Vascular Cerebral/mortalidade
18.
Int J Stroke ; 12(6): 606-614, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28534706

RESUMO

Limited data exist on clot composition and detailed characteristics of arterial thrombi associated with large vessel occlusion in acute ischemic stroke. Advances in endovascular thrombectomy and related imaging modalities have created a unique opportunity to analyze thrombi removed from cerebral arteries. Insights into thrombus composition, etiology, physical properties and neurovascular interactions may lead to future advancements in acute ischemic stroke treatment and improved clinical outcomes. Advances in imaging techniques may enhance clot characterization and inform therapeutic decision-making prior to treatment and reveal stroke etiology to guide secondary prevention. Current imaging techniques can provide some information about thrombi, but there remains much to evaluate about relationships that may exist among thrombus composition, occlusion characteristics and treatment outcomes. Improved pathophysiological characterization of clot types, their properties and how these properties change over time, together with clinical correlates from ongoing studies, may facilitate revascularization with thrombolysis and thrombectomy. Interdisciplinary approaches covering clinical, engineering and scientific aspects of thrombus research will be key to advancing the understanding of thrombi and improving acute ischemic stroke therapy. This consensus statement integrates recent research on clots and thrombi retrieved from cerebral arteries and provides a rationale for further analyses, including current opportunities and limitations.


Assuntos
Isquemia Encefálica/patologia , Consenso , Acidente Vascular Cerebral/patologia , Terapia Trombolítica , Trombose/patologia , Isquemia Encefálica/complicações , Humanos , Acidente Vascular Cerebral/terapia , Terapia Trombolítica/métodos , Trombose/complicações , Resultado do Tratamento
19.
Cardiovasc Drugs Ther ; 31(3): 295-301, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28516318

RESUMO

PURPOSE: Vitamin K antagonists (VKAs) are the standard of care for stroke prevention in patients with atrial fibrillation (AF); therefore, there is not equipoise when comparing newer oral anticoagulants with placebo in this setting. METHODS: To explore the effect of apixaban on mortality in patients with AF, we performed a meta-analysis of apixaban versus placebo using a putative placebo analysis based on randomized controlled clinical trials that compared warfarin, aspirin, and no antithrombotic control. We used data from two prospective randomized controlled trials for our comparison of apixaban versus warfarin (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) and apixaban versus aspirin (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment). Using meta-analysis approaches, we indirectly compared apixaban with an imputed placebo with respect to the risk of death in patients with AF. We used results from meta-analyses of randomized trials as our reference for the comparison between warfarin and placebo/no treatment, and aspirin and placebo/no treatment. RESULTS: In these meta-analyses, a lower rate of death was seen both with warfarin (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.57-0.97) and aspirin (OR 0.86, 95% CI 0.69-1.07) versus placebo/no treatment. Using data from ARISTOTLE and AVERROES, apixaban reduced the risk of death by 34% (95% CI 12-50%; p = 0.004) and 33% (95% CI 6-52%; p = 0.02), respectively, when compared with an imputed placebo. The pooled reduction in all-cause death with apixaban compared with an imputed placebo was 34% (95% CI 18-47%; p = 0.0002). CONCLUSIONS: In patients with AF, indirect comparisons suggest that apixaban reduces all-cause death by approximately one third compared with an imputed placebo.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Idoso , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Causas de Morte , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Efeito Placebo , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Varfarina/uso terapêutico
20.
Stroke ; 48(7): 1827-1834, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28546325

RESUMO

BACKGROUND AND PURPOSE: Significance and management of blood pressure (BP) changes in acute stroke care are unclear. Here, we aimed to investigate the impact of 24-hour BP variability (BPV) on outcome in patients with acute ischemic stroke treated with intravenous thrombolysis. METHODS: From the Safe Implementation of Treatment in Stroke International Stroke Thrombolysis registry, 28 976 patients with documented pre-treatment systolic BP at 2 and 24 hours were analyzed. The primary measure of BP variability was successive variability. Data were preprocessed using coarsened exact matching. We assessed early neurological improvement, symptomatic intracerebral hemorrhage (SICH), and long-term functional outcome (modified Rankin Scale [mRS] at 90 days) by binary and ordinal regression analyses. RESULTS: Attempts to explain successive variation for analysis of BPV with patients characteristics at admission found systolic BP (5.5% variance) to be most influential, yet 92% of BPV variance remained unexplained. Independently from systolic BP, successive variation for analysis of BPV was associated with poor functional outcome mRS score of 0 to 2 (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.90-0.98), disadvantage across the shift of mRS (OR, 1.04; 95% CI, 1.01-1.08), mortality (OR, 1.10; 95% CI, 1.01-1.08), SICHSITS (OR, 1.14; 95% CI, 1.06-1.23), and SICHECASS (OR, 1.24; 95% CI, 1.10-1.40; ECASS [European Cooperative Acute Stroke Study 2]). Analyzing successive variation for analysis of BPV as a function of pre-treatment, systolic BP significantly improved the prediction of functional outcome (mRS score of 0-1, mRS score of 0-2, neurological improvement, mRS-shift: all Pinteraction<0.01). Excluding patients with atrial fibrillation in a sensitivity analysis gave consistent results overall. CONCLUSIONS: This study suggests the need for a more individual BP management accounting for pre-treatment BP and the acute BP course (ie, BPV) to achieve best possible outcome for the patient.


Assuntos
Pressão Sanguínea/fisiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Terapia Trombolítica/tendências , Idoso , Pressão Sanguínea/efeitos dos fármacos , Estudos de Coortes , Feminino , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento
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