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BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).
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Arginina , Eptifibatida , AVC Isquêmico , Peptídeos , Ácidos Pipecólicos , Inibidores da Agregação Plaquetária , Sulfonamidas , Humanos , Ácidos Pipecólicos/administração & dosagem , Ácidos Pipecólicos/uso terapêutico , Ácidos Pipecólicos/efeitos adversos , Arginina/análogos & derivados , Arginina/efeitos adversos , Feminino , Idoso , Eptifibatida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Método Simples-Cego , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/uso terapêutico , AVC Isquêmico/tratamento farmacológico , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Peptídeos/uso terapêutico , Quimioterapia Combinada , Terapia Trombolítica/efeitos adversos , Fibrinolíticos/efeitos adversos , Fibrinolíticos/administração & dosagem , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas/induzido quimicamente , Idoso de 80 Anos ou mais , Infusões IntravenosasRESUMO
A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days.
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Surtos de Doenças , Fusariose , Fusarium , Doença Iatrogênica , Meningite Fúngica , Humanos , Antifúngicos/uso terapêutico , Fusariose/epidemiologia , Fusariose/etiologia , Fusarium/isolamento & purificação , Doença Iatrogênica/epidemiologia , Meningite Fúngica/epidemiologia , Meningite Fúngica/etiologia , México/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Internacionalidade , Imunocompetência , Farmacorresistência Fúngica , Analgesia Epidural/efeitos adversosRESUMO
Importance: The benefit of endovascular stroke therapy (EVT) in large vessel occlusion (LVO) ischemic stroke is highly time dependent. Process improvements to accelerate in-hospital workflows are critical. Objective: To determine whether automated computed tomography (CT) angiogram interpretation coupled with secure group messaging can improve in-hospital EVT workflows. Design, Setting, and Participants: This cluster randomized stepped-wedge clinical trial took place from January 1, 2021, through February 27, 2022, at 4 comprehensive stroke centers (CSCs) in the greater Houston, Texas, area. All 443 participants with LVO stroke who presented through the emergency department were treated with EVT at the 4 CSCs. Exclusion criteria included patients presenting as transfers from an outside hospital (n = 158), in-hospital stroke (n = 39), and patients treated with EVT through randomization in a large core clinical trial (n = 3). Intervention: Artificial intelligence (AI)-enabled automated LVO detection from CT angiogram coupled with secure messaging was activated at the 4 CSCs in a random-stepped fashion. Once activated, clinicians and radiologists received real-time alerts to their mobile phones notifying them of possible LVO within minutes of CT imaging completion. Main Outcomes and Measures: Primary outcome was the effect of AI-enabled LVO detection on door-to-groin (DTG) time and was measured using a mixed-effects linear regression model, which included a random effect for cluster (CSC) and a fixed effect for exposure status (pre-AI vs post-AI). Secondary outcomes included time from hospital arrival to intravenous tissue plasminogen activator (IV tPA) bolus in eligible patients, time from initiation of CT scan to start of EVT, and hospital length of stay. In exploratory analysis, the study team evaluated the impact of AI implementation on 90-day modified Rankin Scale disability outcomes. Results: Among 243 patients who met inclusion criteria, 140 were treated during the unexposed period and 103 during the exposed period. Median age for the complete cohort was 70 (IQR, 58-79) years and 122 were female (50%). Median National Institutes of Health Stroke Scale score at presentation was 17 (IQR, 11-22) and the median DTG preexposure was 100 (IQR, 81-116) minutes. In mixed-effects linear regression, implementation of the AI algorithm was associated with a reduction in DTG time by 11.2 minutes (95% CI, -18.22 to -4.2). Time from CT scan initiation to EVT start fell by 9.8 minutes (95% CI, -16.9 to -2.6). There were no differences in IV tPA treatment times nor hospital length of stay. In multivariable logistic regression adjusted for age, National Institutes of Health Stroke scale score, and the Alberta Stroke Program Early CT Score, there was no difference in likelihood of functional independence (modified Rankin Scale score, 0-2; odds ratio, 1.3; 95% CI, 0.42-4.0). Conclusions and Relevance: Automated LVO detection coupled with secure mobile phone application-based communication improved in-hospital acute ischemic stroke workflows. Software implementation was associated with clinically meaningful reductions in EVT treatment times. Trial Registration: ClinicalTrials.gov Identifier: NCT05838456.
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Arteriopatias Oclusivas , Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Ativador de Plasminogênio Tecidual/uso terapêutico , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Inteligência Artificial , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/cirurgia , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Arteriopatias Oclusivas/tratamento farmacológico , Software , Resultado do TratamentoRESUMO
INTRODUCTION: 4-F PCC is administered for reversal of factor Xa inhibitor-associated coagulopathy despite a lack of quality evidence demonstrating hemostatic efficacy. The aim of this study was to evaluate the hemostatic efficacy of 4-F PCC in intracerebral hemorrhage patients who received factor Xa inhibitors versus warfarin. MATERIALS AND METHODS: This was a multi-center, retrospective, observational cohort study at a large healthcare system. Patients taking warfarin received 4-F PCC 25-50 units/kg based on the presenting INR, while patients taking a factor Xa inhibitor received 35 units/kg. The primary outcome was the percentage of patients with good or excellent hemostatic efficacy as assessed by modified Sarode scale, with neurologic outcomes assessed as a secondary endpoint. Patients were included in the primary outcome population if they had a repeat CT scan within 24 h. RESULTS: One hundred fifty-seven patients were included in the primary outcome population; [warfarin (n = 76), factor Xa inhibitors (n = 81)]. Hemostatic efficacy was 83 % in the warfarin group versus 75 % in the factor Xa inhibitor group (p = 0.24). The hemostatic efficacy risk difference between the groups was 7.6 % (95 % CI 5.1 %, 20.2 %). Good neurologic outcome (mRS 0-2) at discharge was 17 % in warfarin patients versus 12 % in the factor Xa inhibitor patients (p = 0.40). CONCLUSIONS: There was no significant difference in hemostatic efficacy or clinical outcomes between patients taking warfarin or a factor Xa inhibitor following reversal with 4-F PCC. This study provides further support that 4-F PCC can be used for the reversal of factor Xa inhibitor-associated coagulopathy.
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Transtornos da Coagulação Sanguínea , Hemostáticos , Humanos , Varfarina/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Hemostáticos/uso terapêutico , Estudos Retrospectivos , Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/farmacologia , Fatores de Coagulação Sanguínea/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Fator IX , Fator Xa/farmacologia , Fator Xa/uso terapêuticoRESUMO
Randomized clinical trials of acute stroke have led to major advances in acute stroke therapy over the past decade. Despite these successes, recruitment in acute trials is often difficult. We outline challenges in recruitment for acute stroke trials and present potential solutions, which can increase the speed and decrease the cost of identifying new treatments for acute stroke. One of the largest opportunities to increase the speed of enrollment and make trials more generalizable is expansion of inclusion criteria whose impact on expected recruitment can be assessed by epidemiologic and registry databases. Another barrier to recruitment besides the number of eligible patients is availability of study investigators limited to business hours, which may be helped by financial support for after-hours call. The wider use of telemedicine has accelerated quicker stroke treatment at many hospitals and has the potential to accelerate research enrollment but requires training of clinical investigators who are often inexperienced with this approach. Other potential solutions to enhance recruitment include rapid prehospital notification of clinical investigators of potential patients, use of mobile stroke units, advances in the process of emergency informed consent, storage of study medication in the emergency department, simplification of study treatments and data collection, education of physicians to improve equipoise and enthusiasm for randomization of patients within a trial, and clear recruitment plans, and even potentially coenrollment, when there are competing trials at sites. Without successful recruitment, scientific advances and clinical benefit for acute stroke patients will lag.
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Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/terapia , Hospitais , Consentimento Livre e EsclarecidoRESUMO
BACKGROUND: Recent studies have shown that tPA can be safely administered past the standard 4.5 h window with good outcomes when selected with multi-model imaging, which is often lacking outside of comprehensive stroke centers. AIM: We aim to analyze the safety and outcomes of wake up/unknown onset (WUS/UNK) patients treated based on non-contrast head CT (NCCT) at our institution and in the literature. METHODS: Suspected stroke patients from January 2015 to December 2018 receiving tPA within 4.5 h (standard window-SW) and with WUS/UNK based on NCCT and clinical-imaging mismatch were identified. We compared baseline characteristics, tPA metrics, and outcome data, with primary outcome as symptomatic intracerebral hemorrhage (sICH). A meta-analysis was performed evaluating NCCT-based treatment of WUS/UNK patients. RESULTS: Of 1827 patients treated at our hub or through telestroke, 93 underwent WUS/UNK-based treatment. There was no statistical difference in sICH between WUS/UNK and SW: 1% vs. 4% (OR 0.3; 95% confidence interval 0.0-1.9). 90-day modified Rankin scale outcomes were similar between SW and WUS/UNK-treated patients. Seven studies encompassing 485 WUS/UNK patients were included in a pooled analysis with a 2.1% incidence of sICH. In our meta-analysis, three studies compared NCCT-based treated WUS/UNK patients with SW patients with no difference in rate of hemorrhage: 2.1% vs 3.4% (OR 1.01; 95% confidence interval 0.45-2.28). INTERPRETATION: Our single-center analysis and meta-analysis suggest that tPA can be safely administered based on NCCT with comparable rates of sICH for select WUS/UNK stroke patients.
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Acidente Vascular Cerebral , Ativador de Plasminogênio Tecidual , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
INTRODUCTION: Prior retrospective and case-control studies have shown that the use of general anesthesia (GA) during endovascular therapy (EVT) for acute ischemic stroke with large vessel occlusion (AIS-LVO) was independently associated with poor clinical outcomes compared with cases performed under conscious sedation (CS). Conversely, recent small randomized clinical trials (RCT) demonstrated a trend toward better outcome in cases performed under GA. METHODS: We submitted an online survey to 193 Society of Vascular Interventional Neurology and 78 American Association of Neurological Surgeons and Congress of Neurological Surgeons - Cerebrovascular Section neuroendovascular practitioners. Questions were aimed at understanding the current state of anesthesia practice during EVT, and to determine if there is clinical equipoise for a large multicenter RCT comparing GA versus CS during EVT. RESULTS: Between March and May of 2017, we received 116 (43%) responses. Anesthesiologists were responsible for managing 96% of the GA cases as compared to only 51% of the CS cases (P < 0.0001). Notable 56% of providers reported performing less than a quarter of their cases under GA. Only 7% performed all cases under GA compared with 17% who used solely CS (P = 0.048). More than half of respondents thought a new RCT was necessary, of whom 61% were interested in participating. Among interested responders, 59% were located in centers with 3 or more neurointerventionalists. CONCLUSION: The significant variation among neuroendovascular providers, added with the lack of consensus among recent trials and meta-analyses, demonstrate clinical equipoise for further studies to explore the effects of anesthesia during EVT in AIS-LVO.
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BACKGROUND: Social inequities affecting minority populations after Hurricane Katrina led to an expansion of environmental justice literature. In August 2017, Hurricane Harvey rainfall was estimated as a 3000- to 20,000-year flood event, further affecting minority populations with disproportionate stroke prevalence. The Stomp Out Stroke initiative leveraged multimedia engagement, creating a patient-centered cerebrovascular health intervention. OBJECTIVE: This study aims to address social inequities in cerebrovascular health through the identification of race- or ethnicity-specific health needs and the provision of in-person stroke prevention screening during two community events (May 2018 and May 2019). METHODS: Stomp Out Stroke recruitment took place through internet-based channels (websites and social networking). Exclusively through web registration, Stomp Out Stroke participants (aged >18 years) detailed sociodemographic characteristics, family history of stroke, and stroke survivorship. Participant health interests were compared by race or ethnicity using Kruskal-Wallis or chi-square test at an α=.05. A Bonferroni-corrected P value of .0083 was used for multiple comparisons. RESULTS: Stomp Out Stroke registrants (N=1401) were 70% (973/1390) female (median age 45 years) and largely self-identified as members of minority groups: 32.05% (449/1401) Hispanic, 25.62% (359/1401) African American, 13.63% (191/1401) Asian compared with 23.63% (331/1401) non-Hispanic White. Stroke survivors comprised 11.55% (155/1401) of our population. A total of 124 stroke caregivers participated. Approximately 36.81% (493/1339) of participants had a family history of stroke. African American participants were most likely to have Medicare or Medicaid insurance (84/341, 24.6%), whereas Hispanic participants were most likely to be uninsured (127/435, 29.2%). Hispanic participants were more likely than non-Hispanic White participants to obtain health screenings (282/449, 62.8% vs 175/331, 52.9%; P=.03). Asian (105/191, 54.9%) and African American (201/359, 55.9%) participants were more likely to request stroke education than non-Hispanic White (138/331, 41.6%) or Hispanic participants (193/449, 42.9%). African American participants were more likely to seek overall health education than non-Hispanic White participants (166/359, 46.2% vs 108/331, 32.6%; P=.002). Non-Hispanic White participants (48/331, 14.5%) were less likely to speak to health care providers than African American (91/359, 25.3%) or Asian participants (54/191, 28.3%). During the 2018 and 2019 events, 2774 health screenings were completed across 12 hours, averaging four health screenings per minute. These included blood pressure (1031/2774, 37.16%), stroke risk assessment (496/2774, 17.88%), bone density (426/2774, 15.35%), carotid ultrasound (380/2774, 13.69%), BMI (182/2774, 6.56%), serum lipids (157/2774, 5.65%), and hemoglobin A1c (102/2774, 3.67%). Twenty multimedia placements using the Stomp Out Stroke webpage, social media, #stompoutstroke, television, iQ radio, and web-based news reached approximately 849,731 people in the Houston area. CONCLUSIONS: Using a combination of internet-based recruitment, registration, and in-person assessments, Stomp Out Stroke identified race- or ethnicity-specific health care needs and provided appropriate screenings to minority populations at increased risk of urban flooding and stroke. This protocol can be replicated in Southern US Stroke Belt cities with similar flood risks.
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Multimídia , Participação do Paciente , Negro ou Afro-Americano , Idoso , Feminino , Hispânico ou Latino , Humanos , Medicare , Pessoa de Meia-Idade , Estados UnidosRESUMO
BACKGROUND AND PURPOSE: Evidence about the utility of ultrasound-enhanced thrombolysis (sonothrombolysis) in patients with acute ischemic stroke (AIS) is conflicting. We aimed to evaluate the safety and efficacy of sonothrombolysis in patients with AIS with large vessel occlusion, by analyzing individual patient data of available randomized-controlled clinical trials. METHODS: We included all available randomized-controlled clinical trials comparing sonothrombolysis with or without addition of microspheres (treatment group) to intravenous thrombolysis alone (control group) in patients with AIS with large vessel occlusion. The primary outcome measure was the rate of complete recanalization at 1 to 36 hours following intravenous thrombolysis initiation. We present crude odds ratios (ORs) and ORs adjusted for the predefined variables of age, sex, baseline stroke severity, systolic blood pressure, and onset-to-treatment time. RESULTS: We included 7 randomized controlled clinical trials that enrolled 1102 patients with AIS. A total of 138 and 134 confirmed large vessel occlusion patients were randomized to treatment and control groups respectively. Patients randomized to sonothrombolysis had increased odds of complete recanalization compared with patients receiving intravenous thrombolysis alone (40.3% versus 22.4%; OR, 2.17 [95% CI, 1.03-4.54]; adjusted OR, 2.33 [95% CI, 1.02-5.34]). The likelihood of symptomatic intracranial hemorrhage was not significantly different between the 2 groups (7.3% versus 3.7%; OR, 2.03 [95% CI, 0.68-6.11]; adjusted OR, 2.55 [95% CI, 0.76-8.52]). No differences in the likelihood of asymptomatic intracranial hemorrhage, 3-month favorable functional and 3-month functional independence were documented. CONCLUSIONS: Sonothrombolysis was associated with a nearly 2-fold increase in the odds of complete recanalization compared with intravenous thrombolysis alone in patients with AIS with large vessel occlusions. Further study of the safety and efficacy of sonothrombolysis is warranted.
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AVC Isquêmico/terapia , Trombólise Mecânica/métodos , Resultado do Tratamento , Terapia por Ultrassom/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To evaluate the comparative safety and efficacy of direct endovascular thrombectomy (dEVT) compared to bridging therapy (BT; IV tissue plasminogen activator + EVT) and to assess whether BT potential benefit relates to stroke severity, size, and initial presentation to EVT vs non-EVT center. METHODS: In a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke [SELECT]), patients with anterior circulation large vessel occlusion (LVO) presenting to EVT-capable centers within 4.5 hours from last known well were stratified into BT vs dEVT. The primary outcome was 90-day functional independence (modified Rankin Scale [mRS] score 0-2). Secondary outcomes included a shift across 90-day mRS grades, mortality, and symptomatic intracranial hemorrhage. We also performed subgroup analyses according to initial presentation to EVT-capable center (direct vs transfer), stroke severity, and baseline infarct core volume. RESULTS: We identified 226 LVOs (54% men, mean age 65.6 ± 14.6 years, median NIH Stroke Scale [NIHSS] score 17, 28% received dEVT). Median time from arrival to groin puncture did not differ in patients with BT when presenting directly (dEVT 1.43 [interquartile range (IQR) 1.13-1.90] hours vs BT 1.58 [IQR 1.27-2.02] hours, p = 0.40) or transferred to EVT-capable centers (dEVT 1.17 [IQR 0.90-1.48] hours vs BT 1.27 [IQR 0.97-1.87] hours, p = 0.24). BT was associated with higher odds of 90-day functional independence (57% vs 44%, adjusted odds ratio [aOR] 2.02, 95% confidence interval [CI] 1.01-4.03, p = 0.046) and functional improvement (adjusted common OR 2.06, 95% CI 1.18-3.60, p = 0.011) and lower likelihood of 90-day mortality (11% vs 23%, aOR 0.20, 95% CI 0.07-0.58, p = 0.003). No differences in any other outcomes were detected. In subgroup analyses, patients with BT with baseline NIHSS scores <15 had higher functional independence likelihood compared to those with dEVT (aOR 4.87, 95% CI 1.56-15.18, p = 0.006); this association was not evident for patients with NIHSS scores ≥15 (aOR 1.05, 95% CI 0.40-2.74, p = 0.92). Similarly, functional outcomes improvements with BT were detected in patients with core volume strata (ischemic core <50 cm3: aOR 2.10, 95% CI 1.02-4.33, p = 0.044 vs ischemic core ≥50 cm3: aOR 0.41, 95% CI 0.01-16.02, p = 0.64) and transfer status (transferred: aOR 2.21, 95% CI 0.93-9.65, p = 0.29 vs direct to EVT center: aOR 1.84, 95% CI 0.80-4.23, p = 0.15). CONCLUSIONS: BT appears to be associated with better clinical outcomes, especially with milder NIHSS scores, smaller presentation core volumes, and those who were "dripped and shipped." We did not observe any potential benefit of BT in patients with more severe strokes. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02446587. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with ischemic stroke from anterior circulation LVO within 4.5 hours from last known well, BT compared to dEVT leads to better 90-day functional outcomes.
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Arteriopatias Oclusivas/terapia , Doenças Arteriais Cerebrais/terapia , Fibrinolíticos/administração & dosagem , AVC Isquêmico/terapia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Trombectomia/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/tratamento farmacológico , Doenças Arteriais Cerebrais/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , AVC Isquêmico/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
Acute ischemic stroke (AIS) is a time sensitive medical emergency and a leading cause of morbidity and mortality worldwide. Intravenous (IV) recombinant tissue plasminogen activator (IV alteplase) is currently the only proven effective medication for the treatment of AIS with promising adjuvant medications currently under investigation. Recent advances in endovascular thrombectomy have broadened therapeutic options in specific patient populations, with modern treatment strategies utilizing advanced imaging modalities to extend the window for treatment. In all cases, rapid treatment remains a priority. The future of IV alteplase and the changing standard for treatment of AIS remain unwritten with the increasing evidence for imaging selection for both endovascular thrombectomy and IV alteplase, while novel adjuncts are under investigation. In this article, we review the history of IV alteplase investigations for stroke, evidence for thrombectomy as an adjunct to IV alteplase, and the potential of novel adjuvant therapeutics currently under investigation.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia , Ativador de Plasminogênio Tecidual , Resultado do TratamentoRESUMO
INTRODUCTION: Patients with acute ischemic stroke (AIS) and neurologic deficits are often unable to provide consent and excluded from emergency research participation. Experiences with exception from informed consent (EFIC) to facilitate research on potentially life-saving emergency interventions are limited. Here, we describe our multifaceted approach to EFIC approval for an ongoing randomized clinical trial that compares sedation versus general anesthesia (SEGA) approaches for endovascular thrombectomy during AIS. METHODS: We published a university clinical trial website with EFIC information. We initiated a social media campaign on Facebook within a 50 mile radius of Texas Medical Center. Advertisements were linked to our website, and a press release was issued with information about the trial. In-person community consultations were performed, and voluntary survey information was collected. RESULTS: A total of 193 individuals (65% female, age 46.7 ± 16.6 years) participated in seven focus group community consultations. Of the 144 (75%) that completed surveys, 88.7% agreed that they would be willing to have themselves or family enrolled in this trial under EFIC. Facebook advertisements had 134,481 (52% females; 60% ≥45 years old) views followed by 1,630 clicks to learn more. The website had 1130 views (56% regional and 44% national) with an average of 3.85 min spent. Our Institutional Review Board received zero e-mails requesting additional information or to optout. CONCLUSION: Our social media campaign and community consultation methods provide a significant outreach to potential stroke patients. We hope that our experience will inform and help future efforts for trials seeking EFIC.
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BACKGROUND: Large pituitary adenomas can rarely cause compression of the cavernous internal carotid artery (ICA) due to chronic tumor compression or invasion. Here, the authors present a case of pituitary apoplexy causing acute bilateral ICA occlusion with resultant stroke. Our middle-aged patient presented with sudden vision loss and experienced rapid deterioration requiring intubation. Computed tomography (CT) angiography revealed a large pituitary mass causing severe stenosis of the bilateral ICAs. CT perfusion revealed a significant perfusion delay in the anterior circulation. The patient was taken for cerebral angiography, and balloon angioplasty was attempted with no improvement in arterial flow. Resection of the tumor was then performed, with successful restoration of blood flow. Despite restoration of luminal patency, the patient experienced bilateral ICA infarcts. OBSERVATIONS: Pituitary apoplexy can present as an acute stroke due to flow-limiting carotid compression. Balloon angioplasty is ineffective for the treatment of this type of compression. Surgical removal of the tumor restores the flow and luminal caliber of the ICA. LESSONS: Pituitary apoplexy can be a rare presentation of acute stroke and should be managed with immediate surgical decompression rather than attempted angioplasty in order to restore blood flow and prevent the development of cerebral ischemia.
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BACKGROUND: Intravenous recombinant tissue plasminogen activator is the only proven effective medication for the treatment of acute ischemic stroke. Two approaches that may augment recombinant tissue plasminogen activator thrombolysis and prevent arterial reocclusion are direct thrombin inhibition with argatroban and inhibition of the glycoprotein 2b/3a receptor with eptifibatide. AIM: The multi-arm optimization of stroke thrombolysis trial aims to determine the safety and efficacy of intravenous therapy with argatroban or eptifibatide as compared with placebo in acute ischemic stroke patients treated with intravenous recombinant tissue plasminogen activator within 3 h of symptom onset. SAMPLE SIZE ESTIMATE: A maximum of 1200 randomized subjects to test the superiority of argatroban or eptifibatide to placebo in improving 90-day modified Rankin scores. METHODS AND DESIGN: Multiarm optimization of stroke thrombolysis is a multicenter, multiarm, adaptive, single blind, randomized controlled phase 3 clinical trial conducted within the National Institutes of Health StrokeNet clinical trial network. Patients treated with 0.9 mg/kg intravenous recombinant tissue plasminogen activator within 3 h of stroke symptom onset are randomized to receive intravenous argatroban (100 µg/kg bolus followed by 3 µg/kg/min for 12 h), intravenous eptifibatide (135 µg/kg bolus followed by 0.75 µg/kg/min infusion for 2 h) or IV placebo. Patients may receive endovascular thrombectomy per usual care. STUDY OUTCOMES: The primary efficacy outcome is improved modified Rankin score assessed at 90 days post-randomization. DISCUSSION: Multiarm optimization of stroke thrombolysis is an innovative and collaborative project that is the culmination of many years of dedicated efforts to improve outcomes for stroke patients.
Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Fibrinolíticos/uso terapêutico , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
OBJECTIVE: To investigate the association of blood pressure BP excursions, defined as greater than 185 SBP or greater than 105 DBP, with the probability of intracranial hemorrhage (ICH) and worse functional outcomes in patients with acute ischemic stroke (AIS) treated with tissue plasminogen activator (tPA). METHODS: We performed a post hoc analysis of the CLOTBUST-ER trial. Serial BP measurements were conducted using automated cuff recording according to the recommended BP protocol guidelines for tPA administration. The outcomes were prespecified efficacy and safety endpoints of CLOTBUST-ER. RESULTS: The mean number of serial BP recordings per patient was 37. Of the 674 patients, 227 (34%) had at least one BP excursion (>185/105âmmHg) during the first 24âh following tPA-bolus. The majority of BP excursions (46%) occurred within the first 75âmin from tPA-bolus. Patients with at least one BP excursion in the first 24âh following tPA bolus had significantly lower rates of independent functional outcome at 90 days (31 vs. 40.1%, Pâ=â0.028). The total number of BP excursions was associated with decreased odds of 24-h clinical recovery (ORâ=â0.88, 95% CI:0.80-0.96), 24-h neurological improvement (ORâ=â0.87, 95% CI: 0.81-0.94), 7-day functional improvement (common ORâ=â0.92, 95% CI: 0.87-0.97), 90-day functional improvement (common ORâ=â0.94, 95% CI: 0.88-0.98) and 90-day independent functional outcome (ORâ=â0.90, 95% CI: 0.82-0.98) in analyses adjusted for potential confounders. DBP excursions were independently associated with increased odds of any intracranial hemorrhage (ORâ=â1.26, 95% CI: 1.04-1.53). CONCLUSION: BP excursions above guideline thresholds during the first 24âh following tPA administration for AIS are common and are independently associated with adverse clinical outcomes.
Assuntos
Pressão Sanguínea , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Terapia Trombolítica , Pressão Sanguínea/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/farmacologia , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoRESUMO
COVID-19 has been associated with a hypercoagulable state causing cardiovascular and neurovascular complications. To further characterize cerebrovascular disease (CVD) in COVID-19, we review the current literature of published cases and additionally report the clinical presentation, laboratory and diagnostic testing results of 12 cases with COVID-19 infection and concurrent CVD from two academic medical centers in Houston, TX, USA, between March 1 and May 10, 2020. To date, there are 12 case studies reporting 47 cases of CVD in COVID-19. However, only 4 small case series have described the clinical and laboratory findings in patients with COVID-19 and concurrent stroke. Viral neurotropism, endothelial dysfunction, coagulopathy and inflammation are plausible proposed mechanisms of CVD in COVID-19 patients. In our case series of 12 patients, 10 patients had an ischemic stroke, of which 1 suffered hemorrhagic transformation and two had intracerebral hemorrhage. Etiology was determined to be embolic without a clear cause identified in 6 ischemic stroke patients, while the remaining had an identifiable source of stroke. The majority of the patients had elevated inflammatory markers such as D-dimer and interleukin-6. In patients with embolic stroke of unclear etiology, COVID-19 may have played a direct or indirect role in the processes that eventually led to the strokes while in the remaining cases, it is unclear if infection contributed partially or was an incidental finding.
Assuntos
Infecções por Coronavirus , National Institute of Neurological Disorders and Stroke (USA) , Pandemias , Pneumonia Viral , Acidente Vascular Cerebral/terapia , COVID-19 , Ensaios Clínicos como Assunto , Educação Médica , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Reabilitação do Acidente Vascular Cerebral/estatística & dados numéricos , Telemedicina , Estados UnidosRESUMO
OBJECTIVE: The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are noncontrast computed tomography (CT) and CT perfusion (CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes. METHODS: A phase 2, multicenter, prospective cohort study of large-vessel occlusions presented up to 24 hours from last known well was conducted. Patients received a unified prespecified imaging evaluation (CT, CT angiography, and CTP with Rapid Processing of Perfusion and Diffusion software mismatch determination). The treatment decision, EVT versus medical management, was nonrandomized and at the treating physicians' discretion. An independent, blinded, neuroimaging core laboratory adjudicated favorable profiles based on predefined criteria (CT:Alberta Stroke Program Early CT Score ≥ 6, CTP:regional cerebral blood flow (<30%) < 70ml with mismatch ratio ≥ 1.2 and mismatch volume ≥ 10ml). RESULTS: Of 4,722 patients screened from January 2016 to February 2018, 361 patients were included. Two hundred eighty-five (79%) received EVT, of whom 87.0% had favorable CTs, 91% favorable CTPs, 81% both favorable profiles, 16% discordant, and 3% both unfavorable. Favorable profiles on the 2 modalities correlated similarly with 90-day functional independence rates (favorable CT = 56% vs favorable CTP = 57%, adjusted odds ratio [aOR] = 1.91, 95% confidence interval [CI] = 0.40-9.01, p = 0.41). Having a favorable profile on both modalities significantly increased the odds of receiving thrombectomy as compared to discordant profiles (aOR = 3.97, 95% CI = 1.97-8.01, p < 0.001). Fifty-eight percent of the patients with favorable profiles on both modalities achieved functional independence as compared to 38% in discordant profiles and 0% when both were unfavorable (p < 0.001 for trend). In favorable CT/unfavorable CTP profiles, EVT was associated with high symptomatic intracranial hemorrhage (sICH) (24%) and mortality (53%) rates. INTERPRETATION: Patients with favorable imaging profiles on both modalities had higher odds of receiving EVT and high functional independence rates. Patients with discordant profiles achieved reasonable functional independence rates, but those with an unfavorable CTP had higher adverse outcomes. Ann Neurol 2020;87:419-433.
Assuntos
Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/cirurgia , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Seleção de Pacientes , Estudos Prospectivos , Método Simples-Cego , Trombectomia/métodos , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the utility of IV thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS) with unclear symptom onset time or outside the 4.5-hour time window selected by advanced neuroimaging. METHODS: We performed random-effects meta-analyses on the unadjusted and adjusted for potential confounders associations of IVT (alteplase 0.9 mg/kg) with the following outcomes: 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores 0-1), 3-month functional independence (FI; mRS scores 0-2), 3-month mortality, 3-month functional improvement (assessed with ordinal analysis on the mRS scores), symptomatic intracranial hemorrhage (sICH), and complete recanalization (CR). RESULTS: We identified 4 eligible randomized clinical trials (859 total patients). In unadjusted analyses, IVT was associated with a higher likelihood of 3-month FFO (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.12-1.96), FI (OR 1.42, 95% CI 1.07-1.90), sICH (OR 5.28, 95% CI 1.35-20.68), and CR (OR 3.29, 95% CI 1.90-5.69), with no significant difference in the odds of all-cause mortality risk at 3 months (OR 1.75, 95% CI 0.93-3.29). In the adjusted analyses, IVT was also associated with higher odds of 3-month FFO (adjusted OR [ORadj] 1.62, 95% CI 1.20-2.20), functional improvement (ORadj 1.42, 95% CI 1.11-1.81), and sICH (ORadj 6.22, 95% CI 1.37-28.26). There was no association between IVT and FI (ORadj 1.61, 95% CI 0.94-2.75) or all-cause mortality (ORadj 1.75, 95% CI 0.93-3.29) at 3 months. No evidence of heterogeneity was evident in any of the analyses (I 2 = 0). CONCLUSION: IVT in patients with AIS with unknown symptom onset time or elapsed time from symptom onset >4.5 hours selected with advanced neuroimaging results in a higher likelihood of CR and functional improvement at 3 months despite the increased risk of sICH.