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1.
Stroke ; 50(11): 3141-3146, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31570085

RESUMO

Background and Purpose- It is unknown whether the benefit of thrombectomy in late presenting acute stroke patients with imaging evidence of clinical-infarct mismatch is different in patients presenting with wake-up stroke compared with those presenting with witnessed onset or unwitnessed onset. Methods- Prespecified secondary analysis was performed from DAWN (Diffusion Weighted Imaging [DWI] or Computerized Tomography Perfusion [CTP] Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention), a multicenter, prospective, randomized clinical trial with blinded end point assessment comparing thrombectomy with the Trevo device against standard medical therapy in patients with acute stroke and clinical-infarct mismatch presenting 6 to 24 hour after the time last seen well. For the purposes of this study, the primary outcome was the proportion of modified Rankin Scale score 0 to 2 at 90 days. Univariable analysis and multivariable logistic regression was used to assess the relationship between outcome and mode of onset. Results- All 206 enrolled patients were included in the study. Mode of onset was: wake-up stroke (55.3%, n=114), witnessed onset (12.1%, n=25), and unwitnessed onset (32.5%, n=67) with median time last seen well to randomization (13.4±3.7, 10.0±3.7, 14.1±4.9 hours) respectively. Rates of 90-day modified Rankin Scale score of 0 to 2 and symptomatic intracerebral hemorrhage in the thrombectomy arm were not statistically different across patient onset subtypes (P=0.79 and P=0.40, respectively). The benefit of thrombectomy compared with best medical therapy was maintained across all 3 onset modes (rates of 90-day modified Rankin Scale score of 0 to 2 in patients allocated to thrombectomy versus control: wake-up stroke-49.3% versus 10.6%, witnessed onset-63.6% versus 21.4%, UW-41.4% versus 13.2%; P×interaction=0.79). In univariable and multivariable analyses, mode of onset was not identified as a significant predictor of modified Rankin Scale score 0 to 2 at 90 days. Conclusions- In patients with acute ischemic stroke presenting between 6 and 24 hours from time last seen well and harboring clinical-infarct mismatch, the benefit of thrombectomy was similar regardless of the wake-up, unwitnessed, or witnessed mode of onset.

2.
Stroke ; : STROKEAHA119026717, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31619155

RESUMO

Background and Purpose- Novel endovascular thrombectomy (EVT) devices for acute ischemic stroke are often cleared by regulatory agencies on the basis of noninferiority trials. The relation between the noninferiority margins used in trials and the minimal clinically important differences (MCIDs) determined by experts have not been systematically investigated. Methods- Systematic searches were performed to identify (1) all noninferiority design or noninferiority-presented stroke-EVT trials for acute ischemic stroke, (2) all studies determining the MCIDs for the same outcomes, and (3) all noninferiority coronary revascularization trials. Stroke-EVT trial results were reanalyzed using the broad noninferiority margins originally used and narrower noninferiority margins derived from formal MCID studies. Results- We identified 7 noninferiority-designed or noninferiority-interpreted stroke-EVT controlled trials, enrolling 1766 patients, variously comparing coil retrievers, first- and second-generation stent retrievers, and aspiration devices. In 6 trials, the primary outcome was achievement of reperfusion, using noninferiority margins of 15% (3 trials), 10% (2 trials), and 8% (1 trial). In contrast, a stroke expert survey identified the MCID for reperfusion as 3.1% to 5%, and cardiac trials used noninferiority margins of 3.5% to 4.4%. In one stroke-EVT trial, the primary outcome was functional independence, using a noninferiority margin of 15%. However, 2 stroke expert survey studies identified MCIDs for functional independence as having lower values, 5% and 1% to 1.5%. For both reperfusion and functional independence outcomes, all 7 trials demonstrated noninferiority with the broadest noninferiority margin, but only 4 and 3 trials demonstrated noninferiority with actual expert-derived margins for reperfusion and functional independence, respectively. Conclusions- Noninferiority margins used in EVT device trials have regularly exceeded the MCIDs determined by stroke experts, as well as margins used for cardiac devices. New approaches, such as the use of reasonably adequate performance margins, rather than noninferiority margins, are needed to optimize stroke-EVT trial design integrity and trial performance feasibility.

3.
Stroke ; 50(11): 3064-3071, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587658

RESUMO

Background and Purpose- Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods- We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results- Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45-110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98-3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01-0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions- Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN26986053.

4.
Stroke ; 50(11): 3269-3273, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31480968

RESUMO

Background and Purpose- Computed tomographic perfusion (CTP) thresholds associated with follow-up brain infarction may differ by time from symptom onset to imaging and reperfusion. We confirm CTP thresholds over time to imaging and reperfusion in patients with acute ischemic stroke from the HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) data. Methods- Patients with occlusion on CT angiography were acutely imaged with CTP. Noncontrast CT and magnetic resonance-diffusion weighted imaging at 24 to 48 hours defined follow-up infarction. Reperfusion was assessed on conventional angiogram. Tmax, cerebral blood flow (CBF), and cerebral blood volume maps were derived from delay-insensitive CTP postprocessing. These parameters were analyzed using receiver operator characteristics to derive optimal thresholds based on time from stroke onset-to-CTP or to reperfusion. ANOVA and linear regression were used to test whether the derived CTP thresholds were different by time. Results- One hundred thirty-seven patients were included. Tmax thresholds of >15.7 s and >15.8 s and absolute CBF thresholds of <8.9 and <7.5 mL·min-1·100 g-1 for gray matter and white matter respectively were associated with infarct if reperfusion was achieved <90 minutes from CTP with stroke onset-to-CTP <180 minutes. The discriminative ability of cerebral blood volume was modest. There were no statistically significant relationships between stroke onset-to-CTP time and Tmax, CBF, and cerebral blood volume thresholds (all P>0.05). A statistically significant relationship was observed between CTP-to-reperfusion time and the optimal thresholds for Tmax (P<0.001) and CBF (P<0.001). Similar but more modest relationship was noted for onset-to-reperfusion time and optimal thresholds for CBF (P≤0.01). Conclusions- CTP thresholds based on stroke onset and imaging time and taking into account time needed for reperfusion may improve infarct prediction in patients with acute ischemic stroke.

5.
Stroke ; 50(10): 2892-2901, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31480966

RESUMO

Background and Purpose- Brain electrical stimulation, widely studied to facilitate recovery from stroke, has also been reported to confer direct neuroprotection in preclinical models of acute cerebral ischemia. Systematic review of controlled preclinical acute cerebral ischemia studies would aid in planning for initial human clinical trials. Methods- A systematic Medline search identified controlled, preclinical studies of central nervous system electrical stimulation in acute cerebral ischemia. Studies were categorized among 6 stimulation strategies. Three strategies applied different stimulation types to tissues within the ischemic zone (cathodal hemispheric stimulation [CHS], anodal hemispheric stimulation, and pulsed hemispheric stimulation), and 3 strategies applied deep brain stimulation to different neuronal targets remote from the ischemic zone (fastigial nucleus stimulation, subthalamic vasodilator area stimulation, and dorsal periaqueductal gray stimulation). Random-effects meta-analysis assessed electrical stimulation modification of final infarct volume. Study-level risk of bias and intervention-level readiness-for-translation were assessed using formal rating scales. Results- Systematic search identified 28 experiments in 21 studies, including a total of 350 animals, of electrical stimulation in preclinical acute cerebral ischemia. Overall, in animals undergoing electrical stimulation, final infarct volumes were reduced by 37% (95% CI, 34%-40%; P<0.001), compared with control. There was evidence of heterogeneity of efficacy among stimulation strategies (I2=93.1%, Pheterogeneity<0.001). Among the within-ischemic zone stimulation strategies, only CHS significantly reduced the infarct volume (27 %; 95% CI, 22%-33%; P<0.001); among the remote-from ischemic zone approaches, all (fastigial nucleus stimulation, subthalamic vasodilator area stimulation, and dorsal periaqueductal gray stimulation) reduced infarct volumes by approximately half. On formal rating scales, CHS studies had the lowest risk of bias, and CHS had the highest overall quality of intervention-level evidence supporting readiness to proceed to clinical testing. Conclusions- Electrical stimulation reduces final infarct volume across preclinical studies. CHS shows the most robust evidence and is potentially appropriate for progression to early-stage human clinical trial testing as a promising neuroprotective intervention.

6.
Stroke ; 50(9): 2413-2419, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31412753

RESUMO

Background and Purpose- Previous studies have reported less favorable outcome and less effect of endovascular treatment (EVT) after ischemic stroke in women than in men. Our aim was to study the influence of sex on outcome and on the effect of EVT for ischemic stroke in recent randomized trials on EVT. Methods- We used data from 7 randomized controlled trials on EVT within the HERMES collaboration. The primary outcome was 90-day functional outcome (modified Rankin Scale). We compared baseline characteristics and outcomes between men and women. With ordinal logistic regression, we evaluated the association between EVT and 90-day functional outcome for men and women separately, adjusted for potential confounders. We tested for interaction between sex and EVT. Results- We included 1762 patients in the analyses, of whom 833 (47%) were women. Women were older (median, 70 versus 66 years; P<0.001), were smoking less often (30% versus 44%; P<0.001), and had higher collateral grades (grade 3: 46% versus 35%; P<0.001) than men. Functional independence (modified Rankin Scale score, 0-2) at 90 days was reached by 318 women (39%) and 364 men (39%). The effect of EVT on the ordinal modified Rankin Scale was similar in women (adjusted common odds ratio [acOR], 2.13; 95% CI, 1.47-3.07) and men (acOR, 2.16; 95% CI, 1.59-2.96), with a P for interaction of 0.926. Conclusions- Sex does not influence clinical outcome after EVT and does not modify treatment effect of EVT. Therefore, sex should not be a consideration in the selection of patients for EVT.

7.
Stroke ; 50(9): 2420-2427, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31412752

RESUMO

Background and Purpose- We determined the effect of sex on outcome after endovascular stroke thrombectomy in acute ischemic stroke, including lifelong disability outcomes. Methods- We analyzed patients treated with the Solitaire stent retriever in the combined SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) cohorts. Ordinal and logistic regression were used to examine known factors influencing outcome after endovascular stroke thrombectomy and study the effect of sex on the association between these factors and outcomes, including age and time to reperfusion. Years of optimal life after thrombectomy were defined as disability-adjusted life years and calculated by projecting disability through adjusted poststroke life expectancy by sex. Results- Among 389 patients treated with endovascular stroke thrombectomy, 55% were females, and median National Institutes of Health Stroke Scale was 17 (interquartile range, 8-28). There were no differences between females versus males in presenting deficit severity (National Institutes of Health Stroke Scale score, 17 versus 17, P=0.21), occlusion location (69% versus 64% M1, P=0.62), presenting infarct extent (Alberta Stroke Program Early CT Score 8 versus 8, P=0.24), rate of substantial reperfusion (Thrombolysis in Cerebral Infarction 2b/3, 87% versus 83%, P=0.37), onset to reperfusion time (294 versus 302 minutes, P=0.46). Despite older ages (69 versus 64, P<0.001) and higher rate of atrial fibrillation (45% versus 30%, P=0.002) for females compared with males, adjusted rates of functional independence at 90 days were similar (odds ratio, 1.0; 95% CI, 0.6-1.6). After adjusting for age at presentation and stroke severity, females had more years of optimal life (disability-adjusted life year) after endovascular stroke thrombectomy, 10.6 versus 8.5 years (P<0.001). Conclusions- Despite greater age and higher rate of atrial fibrillation, females experienced comparable functional outcomes and greater years of optimal life after intervention compared with males.

8.
Hypertens Res ; 42(11): 1794-1800, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31300722

RESUMO

The purpose of the study was to clarify whether short-acting antihypertensives are associated with the occurrence of ischemic stroke and intracerebral hemorrhage (ICH). This was a retrospective case-crossover study using the Taiwan National Health Insurance Research Database. We identified all adult patients hospitalized with a primary diagnosis of ischemic stroke or ICH between January 2005 and December 2013. For each case, short-term and long-term exposure to short-acting antihypertensives, including nifedipine, labetalol and captopril, during the case vs. control periods were compared, and odd ratios (ORs) and 95% confidence intervals (CIs) for ischemic stroke or ICH were calculated with adjustment for confounders. Among 272785 ischemic stroke and 77798 ICH patients, the mean age was 77.8 ± 14.3 years and 70.8 ± 16.6 years, respectively. The short-term use of the three short-acting antihypertensives were all associated with an increase in the incidence of ischemic stroke (nifedipine: OR 4.51, 95% CIs 3.99-5.11; labetalol: OR 2.07; 95% CIs 1.71-2.51; captopril: OR 1.98, 95% CIs 1.72-2.29) and ICH (nifedipine: OR 2.98, 95% CIs 2.30-3.84; labetalol: OR 2.37; 95% CIs 1.66-3.39; captopril: OR 2.48; 95% CIs 1.69-3.63). The long-term use of short-acting nifedipine for 30 days was associated with a modest increase in the risk for ischemic stroke (OR 1.86; 95% CIs 1.42-2.45). Overall, the short-term use of short-acting antihypertensives is associated with a modest increase in the incidence of stroke, and short-acting nifedipine is linked to a substantial rise in the incidence of ischemic stroke. The long-term use of short-acting nifedipine was also related to an increased incidence of ischemic stroke. Physicians should be cautious of prescribing these short-acting antihypertensives.

9.
J Stroke Cerebrovasc Dis ; 28(10): 104258, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31296476

RESUMO

BACKGROUND: Telestroke is an efficient, cost-effective way to standardize care and improve access to immediate neurologic expertise for rural hospitals and other underserved areas. Hands-free wearable technology potentially allows for faster evaluations that fit easily within prehospital workflows and could improve prehospital triage of stroke patients to appropriate receiving stroke centers. The goal of this study is to assess the feasibility and inter-rater reliability of wearable eyeglass video technology in assessing stroke-related neurologic deficits in patients with suspected acute stroke. METHODS: Consecutive patients with suspected stroke were evaluated concurrently by an on-site neurologist using wearable eyeglass video technology and a remotely located neurologist viewing the patient through an online platform. Inter-rater reliability in assigning National Institutes of Health Stroke Scale (NIHSS) scores was evaluated using inter-rater correlation coefficient (ICC) and weighted kappa scores. RESULTS: Among 17 enrolled patients, mean age was 58 (SD ± 20) and 29% were female. There was a high degree of correlation in total NIHSS score (ICC .99 and weighted kappa .88) and across all NIHSS subitems (ICC .81-1 and weighted kappa .68-1) between the examiner evaluating remotely via wearable eyeglass video technology with access to the patient and the in-person examiner. The maximum difference between the 2 NIHSS scores was 3. CONCLUSIONS: The use of wearable eyeglass video technology in telestroke is feasible and reliable. Use of this technology in the prehospital setting has the potential to improve early assessment of patients with acute stroke symptoms and to facilitate transfer to appropriate stroke centers in the regional systems of care.

10.
JAMA ; 322(3): 252-263, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31310296

RESUMO

Importance: Randomized clinical trials suggest benefit of endovascular-reperfusion therapy for large vessel occlusion in acute ischemic stroke (AIS) is time dependent, but the extent to which it influences outcome and generalizability to routine clinical practice remains uncertain. Objective: To characterize the association of speed of treatment with outcome among patients with AIS undergoing endovascular-reperfusion therapy. Design, Setting, and Participants: Retrospective cohort study using data prospectively collected from January 2015 to December 2016 in the Get With The Guidelines-Stroke nationwide US quality registry, with final follow-up through April 15, 2017. Participants were 6756 patients with anterior circulation large vessel occlusion AIS treated with endovascular-reperfusion therapy with onset-to-puncture time of 8 hours or less. Exposures: Onset (last-known well time) to arterial puncture, and hospital arrival to arterial puncture (door-to-puncture time). Main Outcomes and Measures: Substantial reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), ambulatory status, global disability (modified Rankin Scale [mRS]) and destination at discharge, symptomatic intracranial hemorrhage (sICH), and in-hospital mortality/hospice discharge. Results: Among 6756 patients, the mean (SD) age was 69.5 (14.8) years, 51.2% (3460/6756) were women, and median pretreatment score on the National Institutes of Health Stroke Scale was 17 (IQR, 12-22). Median onset-to-puncture time was 230 minutes (IQR, 170-305) and median door-to-puncture time was 87 minutes (IQR, 62-116), with substantial reperfusion in 85.9% (5433/6324) of patients. Adverse events were sICH in 6.7% (449/6693) of patients and in-hospital mortality/hospice discharge in 19.6% (1326/6756) of patients. At discharge, 36.9% (2132/5783) ambulated independently and 23.0% (1225/5334) had functional independence (mRS 0-2). In onset-to-puncture adjusted analysis, time-outcome relationships were nonlinear with steeper slopes between 30 to 270 minutes than 271 to 480 minutes. In the 30- to 270-minute time frame, faster onset to puncture in 15-minute increments was associated with higher likelihood of achieving independent ambulation at discharge (absolute increase, 1.14% [95% CI, 0.75%-1.53%]), lower in-hospital mortality/hospice discharge (absolute decrease, -0.77% [95% CI, -1.07% to -0.47%]), and lower risk of sICH (absolute decrease, -0.22% [95% CI, -0.40% to -0.03%]). Faster door-to-puncture times were similarly associated with improved outcomes, including in the 30- to 120-minute window, higher likelihood of achieving discharge to home (absolute increase, 2.13% [95% CI, 0.81%-3.44%]) and lower in-hospital mortality/hospice discharge (absolute decrease, -1.48% [95% CI, -2.60% to -0.36%]) for each 15-minute increment. Conclusions and Relevance: Among patients with AIS due to large vessel occlusion treated in routine clinical practice, shorter time to endovascular-reperfusion therapy was significantly associated with better outcomes. These findings support efforts to reduce time to hospital and endovascular treatment in patients with stroke.


Assuntos
Procedimentos Endovasculares , Trombólise Mecânica , Acidente Vascular Cerebral/terapia , Tempo para o Tratamento , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Trombólise Mecânica/efeitos adversos , Trombólise Mecânica/métodos , Pessoa de Meia-Idade , Sistema de Registros , Reperfusão/métodos , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos
11.
Stroke ; 50(9): 2433-2440, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31311465

RESUMO

Background and Purpose- Quantifying the benefit magnitude of combined endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) versus nonreperfusion care in patients with acute ischemic stroke caused by large vessel occlusion would aid organization of regional stroke care systems. Methods- NINDS rt-PA Study (National Institute for Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator) and SWIFT PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment) patients were matched for prognosis (based on age and National Institutes of Health Stroke Scale) and definite/likely anterior circulation large vessel occlusion (based on National Institutes of Health Stroke Scale total score and item pattern), using optimal inverse variance matching, to determine comparative outcomes with nonreperfusion care alone, IVT alone, and IVT+EVT. Results- Matching yielded 240 patients, including 80 each treated with nonreperfusion care, IVT alone, and IVT+EVT, with, respectively, mean age 67.1, 67.1, and 66.9 and presenting deficit severity (National Institutes of Health Stroke Scale) mean 15.8, 15.9, and 15.9. Outcomes at 3 months for IVT+EVT versus nonreperfusion care included freedom from disability (modified Rankin Scale score, 0-1) 48.1% versus 21.3%, P=0.0004; functional independence (modified Rankin Scale score, 0-2) 62.9% versus 32.6, P=0.0001; and reduced disability over all 7 modified Rankin Scale levels, common odds ratio 3.34, P<0.0001. Outcomes for IVT alone versus nonreperfusion care included: freedom from disability 30.0% versus 21.3%, P=0.28 and reduced disability over all 7 modified Rankin Scale levels, common odds ratio 1.14, P=0.65. Compared with nonreperfusion care, the number needed to treat with EVT+IVT for 1 more patient to have reduced disability was 1.8. Conclusions- Matched patient analysis across randomized trials provides evidence that the strategy of combined IVT and mechanical thrombectomy is a highly beneficial treatment strategy for acute ischemic stroke caused by large vessel occlusion patients. A reasonable effect magnitude estimate is that, among every 100 patients treated, combined IVT+EVT reperfusion therapy, compared with no reperfusion therapy, reduces long-term disability in 57, including conferring functional independence upon 30.

12.
Stroke ; 50(9): 2404-2412, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31345135

RESUMO

Background and Purpose- It is unknown whether noncontrast computed tomography (NCCT) can identify patients who will benefit from intra-arterial treatment (IAT) in the extended time window. We sought to characterize baseline Alberta Stroke Program Early CT Score (ASPECTS) in DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and to assess whether ASPECTS modified IAT effect. Methods- Core lab adjudicated ASPECTS scores were analyzed. The trial cohort was divided into 2 groups by qualifying imaging (computed tomography versus magnetic resonance imaging). ASPECTS-by-treatment interaction was tested for the trial coprimary end points (90-day utility-weighted modified Rankin Scale (mRS) score and mRS, 0-2), mRS 0 to 3, and ordinal mRS. ASPECTS was evaluated separately as an ordinal and a dichotomized (0-6 versus 7-10) variable. Results- Of 205 DAWN subjects, 123 (60%) had NCCT ASPECTS, and 82 (40%) had diffusion weighted imaging ASPECTS. There was a significant ordinal NCCT ASPECTS-by-treatment interaction for 90-day utility-weighted mRS (interaction P=0.04) and mRS 0 to 2 (interaction P=0.02). For both end points, IAT effect was more pronounced at higher NCCT ASPECTS. The dichotomized NCCT ASPECTS-by-treatment interaction was significant only for mRS 0 to 2 (interaction P=0.04), where greater treatment benefit was seen in the ASPECTS 7 to 10 group (odds ratio, 7.50 [2.71-20.77] versus odds ratio, 0.48 [0.04-5.40]). A bidirectional treatment effect was observed in the NCCT ASPECTS 0 to 6 group, with treatment associated with not only more mRS 0 to 3 outcomes (50% versus 25%) but also more mRS 5 to 6 outcomes (40% versus 25%). There was no significant modification of IAT effect by diffusion weighted imaging ASPECTS. Conclusions- Baseline NCCT ASPECTS appears to modify IAT effect in DAWN. Higher NCCT ASPECTS was associated with greater benefit from IAT. No treatment interaction was observed for diffusion weighted imaging ASPECTS.

13.
J Neurointerv Surg ; 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266857

RESUMO

BACKGROUND: The time-benefit relationship of endovascular thrombectomy (EVT) according to the size of the core infarct has been incompletely explored in prior studies. We investigated whether established infarct core size on baseline imaging modifies the relationship between onset-to-reperfusion time (OTR) and functional outcomes in patients with acute ischemic stroke treated with EVT. METHODS: We analyzed a database containing individual patient data pooled from three prospective Solitaire stent retriever studies. The inclusion criteria were treatment with a Solitaire device and achievement of substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3). Main analyses were performed in patients with baseline Alberta Stroke Program Early CT Scores (ASPECTSs) of 7-10. RESULTS: Among the 305 patients (mean age 67±13 years, 58% women), the proportions of patients in different categories of pretreatment infarct extent were: small (ASPECTS 9-10) 52.0%, moderate (ASPECTS 7-8) 37.1%, and large (ASPECTS 0-6) 7.6%. The mean OTR was 297±95 min. At 3 months, 60.1% of the patients achieved a good outcome. For OTRs of 2-8 hours, the rates of good outcomes at all time points were higher with higher baseline ASPECTS but declined with similar steepness. Both baseline ASPECTS (OR 1.23 (95% CI 1.04 to 1.45)) and OTR (every 30 min delay, OR 0.80 (95% CI 0.73 to 0.88)) were independently associated with a good 3-month outcome. No interaction between OTR and baseline ASPECTS was observed. CONCLUSIONS: Although patients with higher baseline ASPECTS are more likely to have good clinical outcomes at all OTR intervals after 2 hours, this benefit consistently declines with time, even in patients with a small infarct core, reinforcing the need to treat all patients as quickly as possible.

14.
Stroke ; 50(8): 2156-2162, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31318627

RESUMO

Background and Purpose- TNK (tenecteplase), a newer fibrinolytic agent, has practical delivery advantages over ALT (alteplase) that would make it a useful agent if noninferior in acute ischemic stroke treatment outcome. Accordingly, the most recent US American Heart Association/American Stroke Association acute ischemic stroke guideline recognized TNK as an alternative to ALT, but only based on informal consideration, rather than formal meta-analysis, of completed randomized control trials. Methods- Systematic literature search and formal meta-analysis were conducted per PRISMA guidelines (Preferred Reporting Items for Systemic Reviews and Meta-Analyses), adapted to noninferiority analysis. The primary outcome of freedom from disability (modified Rankin Scale score, 0-1) outcome at 3 m, and additional efficacy and safety outcomes, were analyzed. Results- Systematic search identified 5 trials enrolling 1585 patients (828 TNK, 757 ALT). Across all trials, mean age was 70.8, 58.5% male, baseline National Institutes of Health Stroke Scale mean 7.0, and time from last known well to treatment start mean 148 minutes. All ALT patients received standard 0.9 mg/kg dosing, while TNK dosing was 0.1 mg/kg in 6.8%, 0.25 mg/kg in 24.6%, and 0.4 mg/kg in 68.6%. For the primary end point, crude cumulative rates of disability-free (modified Rankin Scale score, 0-1) 3 m outcome were TNK 57.9% versus ALT 55.4%. Informal, random-effects meta-analysis, the risk difference was 4% (95% CI, -1% to 8%). The lower 95% CI bound fell well within the prespecified noninferiority margin. Similar results were seen for the additional efficacy end points: functional independence (modified Rankin Scale score, 0-2): crude TNK 71.9% versus ALT 70.5%, risk difference 2% (95% CI, -3% to 6%); and modified Rankin Scale shift analysis, common odds ratio 1.21 (95% CI, 0.93-1.57). For safety end points, lower event rates reduced power, but point estimates were also consistent with noninferiority Conclusions- Accumulated clinical trial data provides strong evidence that TNK is noninferior to ALT in the treatment of acute ischemic stroke. These findings provide formal support for the recent guideline recommendation to consider TNK an alternative to ALT.

15.
Cerebrovasc Dis Extra ; 9(2): 72-76, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31344699

RESUMO

BACKGROUND AND PURPOSE: Subject retention into clinical trials is vital, and prehospital enrollment may be associated with higher rates of subject withdrawal than more traditional methods of enrollment. We describe rates of subject retention in a prehospital trial of acute stroke therapy. METHODS: All subjects were enrolled into the NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 clinical trial. Paramedics screened eligible subjects and contacted the physician-investigator using a dedicated in-ambulance cellular phone. Physician-investigators obtained explicit informed consent from the subject or on-scene legally authorized representative (LAR) who reviewed and signed a consent form. Exception from informed consent (EFIC) was utilized in later stages of the study. RESULTS: There were 1,700 subjects enrolled; 1,017 provided consent (60%), 662 were enrolled via LAR (39%), and 21 were enrolled via EFIC (1%). Of the 1,700 patients, 1,413 (83%) completed the 90-day visit, 265 (16%) died prior to the 90-day visit, and 22 (1.3%) withdrew from the study before completion. There were no differences in rates of withdrawal by method of study enrolment, i.e., self-consent (n = 14), 1.4%; LAR (n = 8), 1.2%; EFIC (n = 0) 0%. CONCLUSION: There was a high rate of retention when subjects were enrolled into prehospital stroke research using a phone-based method to obtain explicit consent.

16.
Stroke ; 50(8): 2023-2029, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31216966

RESUMO

Background and Purpose- There is increasing evidence that higher systolic blood pressure variability (SBPV) may be associated with poor outcome in patients with intracerebral hemorrhage (ICH). We explored the association between SBPV and in-hospital ICH outcome. Methods- We collected 10-years of consecutive data of spontaneous ICH patients at 2 healthcare systems. Demographics, medical history, laboratory tests, computed tomography scan data, in-hospital treatments, and neurological and functional assessments were recorded. Blood pressure recordings were extracted up to 24 hours postadmission. SBPV was measured using SD, coefficient of variation, successive variation (SV), range and 1 novel index termed functional SV. The effects of SBPV on the functional outcome at discharge were evaluated by multivariate logistic and ordinal regression analyses for dichotomous and trichotomous modified Rankin Scale categorizations, respectively. In secondary analyses, associations between SBPV, history of hypertension, and hematoma expansion were explored. Results- The analysis included 762 subjects. All 5 SBPV indices were significantly associated with the probability of unfavorable outcome (modified Rankin Scale score, 4-6) in logistic models. In ordinal models, SD, coefficient of variation, range, and functional SV were found to have a significant effect on the probabilities of poor (modified Rankin Scale score, 3-4) and severe/death (modified Rankin Scale score, 5-6) outcomes. Normotensive patients had significantly lower mean SBPV compared with the untreated-hypertension cohort for all SBPV indices and compared with treated-hypertension patients for 3 out of 5 SBPV indices. Lower mean SBPV of treated-hypertension subjects compared with untreated-hypertension subjects was only detected in the SV and functional SV indices (P=0.045). None of the SBPV indices were significantly associated with the probability of hematoma expansion. Conclusions- Higher SBPV in the first 24 hours of admission was associated with unfavorable in-hospital outcome among ICH patients. Further prospective studies are warranted to understand any cause-effect relationship and whether controlling for SBPV may improve the ICH outcome.

17.
J Neurointerv Surg ; 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31239326

RESUMO

BACKGROUND: Despite the proven benefit of neurothrombectomy, intracranial hemorrhage (ICH) remains the most serious procedural complication. The aim of this analysis was to identify predictors of different hemorrhage subtypes and evaluate their individual impact on clinical outcome. METHODS: Pooled individual patient-level data from three large prospective multicenter studies were analyzed for the incidence of different ICH subtypes, including any ICH, hemorrhagic transformation (HT), parenchymal hematoma (PH), subarachnoid hemorrhage (SAH), and symptomatic intracranial hemorrhage (sICH). All patients (n=389) treated with the Solitaire device were included in the analysis. A multivariate stepwise logistic regression model was used to identify predictors of each hemorrhage subtype. RESULTS: General anesthesia and higher baseline Alberta Stroke Program Early CT score (ASPECTS) were associated with a lower probability of any ICH (OR 0.36, p=0.003), (OR 0.80, p=0.032) and HT (OR 0.54, p=0.023), (OR 0.78, p=0.001), respectively. Longer time from onset to treatment was associated with a higher likelihood of HT (OR 1.08, p=0.001) and PH (OR 1.11, p=0.015). Intravenous tissue plasminogen activator (IV-tPA) was also a strong predictor of PH (OR 7.63, p=0.013). Functional independence at 90 days (modified Rankin Scale (mRS) 0-2) was observed significantly less frequently in all hemorrhage subtypes except SAH. None of the patients who achieved functional independence at 90 days had sICH. CONCLUSIONS: General anesthesia and smaller baseline ischemic core are associated with a lower probability of HT whereas IV-tPA and prolonged time to treatment increase the risk of PH after neurothrombectomy. TRIAL REGISTRATION NUMBERS: SWIFT-NCT01054560; post results, SWIFT PRIME-NCT01657461; post results, STAR-NCT01327989; post results.

18.
Int J Stroke ; 14(8): 835-842, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31122171

RESUMO

BACKGROUND: Stroke is a significant burden in Saudi Arabia and the Saudi Ministry of Health's stroke committee has identified an urgent need to improve care. AIM: The purpose of this study was to undertake a health-economic analysis to quantify the impact of developing stroke care in the country. METHODS: An economic model was developed to assess the costs and clinical outcomes associated with an ischemic stroke care development program compared with current stroke care. Based on Saudi epidemiological data, cohorts of ischemic stroke patients enter the model each year for the first 10 years based on increasing incidence. Four treatment options were modeled including reperfusion and non-reperfusion treatments. The development scenario estimates the impact of gradually increasing uptake of more effective treatments over 10 years. Changes in the stroke care organization are considered along with resources required to increase capacity, allowing more patients to be admitted to stroke hospitals and access effective treatments. RESULTS: The stroke care development program is associated with an increase in functionally independent patients and a decrease in disabling strokes compared with current stroke care. Additionally, the development program is associated with estimated cost savings of $602 million over 15 years ($255 million direct costs, $348 million indirect costs). CONCLUSIONS: The model predicts that the stroke care development program is associated with improved patient outcomes and lower overall costs compared with the current stroke care program.

19.
N Engl J Med ; 380(20): 1906-1917, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31091372

RESUMO

BACKGROUND: Cryptogenic strokes constitute 20 to 30% of ischemic strokes, and most cryptogenic strokes are considered to be embolic and of undetermined source. An earlier randomized trial showed that rivaroxaban is no more effective than aspirin in preventing recurrent stroke after a presumed embolic stroke from an undetermined source. Whether dabigatran would be effective in preventing recurrent strokes after this type of stroke was unclear. METHODS: We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding. RESULTS: A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P = 0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively. CONCLUSIONS: In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group. (Funded by Boehringer Ingelheim; RE-SPECT ESUS ClinicalTrials.gov number, NCT02239120.).


Assuntos
Antitrombinas/administração & dosagem , Dabigatrana/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Idoso , Antitrombinas/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Dabigatrana/efeitos adversos , Método Duplo-Cego , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Embolia Intracraniana/tratamento farmacológico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Recidiva , Prevenção Secundária , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade
20.
Stroke ; : STROKEAHA118024582, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31117920

RESUMO

Background and Purpose- Many patients with acute ischemic stroke are not eligible for thrombolysis or mechanical reperfusion therapies due to contraindications, inaccessible vascular occlusions, late presentation, or large infarct core. Sphenopalatine ganglion (SPG) stimulation to enhance collateral flow and stabilize the blood-brain barrier offers an alternative, potentially more widely deliverable, therapy. Methods- In a randomized, sham-controlled, double-masked trial at 41 centers in 7 countries, patients with anterior circulation ischemic stroke not treated with reperfusion therapies within 24 hours of onset were randomly allocated to active SPG stimulation or sham control. The primary efficacy outcome was improvement beyond expectations on the modified Rankin Scale of global disability at 90 days (sliding dichotomy), assessed in the modified intention-to-treat population. The initial planned sample size was 660 patients, but the trial was stopped early when technical improvements in device placement occurred, so that analysis of accumulated experience could be conducted to inform a successor trial. Results- Among 303 enrolled patients, 253 received at least one active SPG or sham stimulation, constituting the modified intention-to-treat population (153 SPG stimulation and 100 sham control). Age was median 73 years (interquartile range, 64-79), 52.6% were female, deficit severity on the National Institutes of Health Stroke Scale was median 11 (interquartile range, 9-15), and time from last known well median 18.6 hours (interquartile range, 14.5-22.5). For the primary outcome, improved 3-month disability beyond expectations, rates in the SPG versus sham treatment groups were 49.7% versus 40.0%; odds ratio, 1.48 (95% CI, 0.89-2.47); P=0.13. A significant treatment interaction with stroke location (cortical versus noncortical) was noted, P=0.04. In the 87 patients with confirmed cortical involvement, rates of improvement beyond expectations were 50.0% versus 27.0%; odds ratio, 2.70 (95% CI, 1.08-6.73); P=0.03. Similar response patterns were observed for all prespecified secondary efficacy outcomes. No differences in mortality or serious adverse event safety end points were observed. Conclusions- SPG stimulation within 24 hours of onset is safe in acute ischemic stroke. SPG stimulation was not shown to statistically significantly improve 3-month disability above expectations, though favorable outcomes were nominally higher with SPG stimulation. Beneficial effects may distinctively be conferred in patients with confirmed cortical involvement. The results of this study need to be confirmed in a larger pivotal study. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03767192.

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