Effect of Bypassing the Closest Stroke Center in Patients with Intracerebral Hemorrhage: A Secondary Analysis of the RACECAT Randomized Clinical Trial.

Importance: Prehospital transfer protocols are based on rapid access to reperfusion therapies for patients with ischemic stroke. The effect of different protocols among patients receiving a final diagnosis of intracerebral hemorrhage (ICH) is unknown. Objective: To determine the effect of direct transport to an endovascular treatment (EVT)-capable stroke center vs transport to the nearest local stroke center. Design, Setting, and Participants: This was a prespecified secondary analysis of RACECAT, a multicenter, population-based, cluster-randomized clinical trial conducted from March 2017 to June 2020 in Catalonia, Spain. Patients were evaluated by a blinded end point assessment. All consecutive patients suspected of experiencing a large vessel occlusion stroke (Rapid Arterial Occlusion Evaluation Scale [RACE] score in the field >4 on a scale of 0 to 9, with lower to higher stroke severity) with final diagnosis of ICH were included. A total of 1401 patients were enrolled in RACECAT with suspicion of large vessel occlusion stroke. The current analysis was conducted in October 2022. Intervention: Direct transport to an EVT-capable stroke center (n = 137) or to the closest local stroke center (n = 165). Main Outcomes and Measures: The primary outcome was tested using cumulative ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI of the shift analysis of disability at 90 days as assessed by the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) in the intention-to-treat population. Secondary outcomes, included 90-day mortality, death or severe functional dependency, early neurological deterioration, early mortality, ICH volume and enlargement, rate of neurosurgical treatment, rate of clinical complications during initial transport, and rate of adverse events until day 5. Results: Of 1401 patients enrolled, 1099 were excluded from this analysis (32 rejected informed consent, 920 had ischemic stroke, 29 had transient ischemic attack, 12 had subarachnoid hemorrhage, and 106 had stroke mimic). Thus, 302 patients were included (204 [67.5%] men; mean [SD] age 71.7 [12.8] years; and median [IQR] RACE score, 7 [6-8]). For the primary outcome, direct transfer to an EVT-capable stroke center (mean [SD] mRS score, 4.93 [1.38]) resulted in worse functional outcome at 90 days compared with transfer to the nearest local stroke center (mean [SD] mRS score, 4.66 [1.39]; adjusted common OR, 0.63; 95% CI, 0.41-0.96). Direct transfer to an EVT-capable stroke center also suggested potentially higher 90-day mortality compared with transfer to the nearest local stroke center (67 of 137 [48.9%] vs 62 of 165 [37.6%]; adjusted hazard ratio, 1.40; 95% CI, 0.99-1.99). The rates of medical complications during the initial transfer (30 of 137 [22.6%] vs 9 of 165 patients [5.6%]; adjusted OR, 5.29; 95% CI, 2.38-11.73) and in-hospital pneumonia (49 of 137 patients [35.8%] vs 29 of 165 patients [17.6%]; OR, 2.61; 95% CI, 1.53-4.44) were higher in the EVT-capable stroke center group. Conclusions and Relevance: In this secondary analysis of the RACECAT randomized clinical trial, bypassing the closest stroke center resulted in reduced chances of functional independence at 90 days for patients who received a final diagnosis of ICH. Trial Registration: ClinicalTrials.gov Identifier: NCT02795962.

Prehospital care process and hospital outcomes in stroke-code cases: comparison of basic and advance life support ambulance attendance. / Proceso de atención prehospitalaria y resultados hospitalarios del código ictus: estudio comparativo entre unidades de soporte vital básico y avanzado.

OBJECTIVES: To study prehospital care process in relation to hospital outcomes in stroke-code cases first attended by 2 different levels of ambulance. To analyze factors associated with a satisfactory functional outcome at 3 months. MATERIAL AND METHODS: Prospective multicenter observational cohort study. All stroke-code cases attended by prehospital emergency services from January 2016 to April 2022 were included. Prehospital and hospital variables were collected. The classificatory variable was type of ambulance attending (basic vs advanced life support). The main outcome variables were mortality and functional status after ischemic strokes in patients who underwent reperfusion treatment 90 days after the ischemic episode. RESULTS: Out of 22 968 stroke-code activations, ischemic stroke was diagnosed in 12 467 patients (54.3%) whose functional status was good before the episode. Basic ambulances attended 93.1%; an advanced ambulance was ordered in 1.6% of the patients. Even though there were differences in patient and clinical characteristics recorded during the prehospital process, type of ambulance was not independently associated with mortality (adjusted odds ratio [aOR], 1.1; 95% CI, 0.77-1.59) or functional status at 3 months (aOR, 1.05; 95% CI, 0,72-1,47). CONCLUSION: The percentage of patient complications in stroke-code cases attended by basic ambulance teams is low. Type of ambulance responding was not associated with either mortality or functional outcome at 3 months in this study.

OBJETIVO: Comparar el proceso asistencial prehospitalario y los resultados hospitalarios de los pacientes categorizados como Código Ictus (CI) en función del tipo de ambulancia que realiza la primera valoración, y analizar los factores asociados con un buen resultado funcional y la mortalidad a los 3 meses. METODO: Estudio observacional de cohortes prospectivo multicéntrico. Incluyó todos los CI atendidos por un sistema de emergencias prehospitalario desde enero del 2016 a abril del 2022. Se recogieron variables prehospitalarias y hospitalarias. La variable de clasificación fue el tipo de ambulancia que asiste el CI: unidad de soporte vital básico (USVB) o avanzado (USVA). Las variables de resultado principal fueron la mortalidad y el estado funcional de los ictus isquémicos sometidos a tratamiento de reperfusión a los 90 días del episodio. RESULTADOS: Se incluyeron 22.968 pacientes, de los cuales 12.467 (54,3%) presentaron un ictus isquémico con un buen estado funcional previo. El 93,1% fueron asistidos por USVB y se solicitó una USVA en el 1,6% de los casos. A pesar de presentar diferencias en el perfil clínico del paciente atendido y en los tiempos del proceso CI prehospitalario, el tipo de unidad no mostró una asociación independiente con la mortalidad (OR ajustada 1,1; IC 95%: 0,77- 1,59) ni con el estado funcional a los 3 meses (OR ajustada 1,05; IC 95%: 0,72-1,47). CONCLUSIONES: El porcentaje de complicaciones de los pacientes con CI atendidos por USVB es bajo. El tipo de unidad que asistió al paciente inicialmente no se asoció ni con el resultado funcional ni con la mortalidad a los 3 meses.

Sex and gender differences in acute stroke care: metrics, access to treatment and outcome. A territorial analysis of the Stroke Code System of Catalonia.

INTRODUCTION: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. PATIENTS AND METHODS: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. RESULTS: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94-1.23; p = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97-1.22). DISCUSSION AND CONCLUSION: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself.

Association of Time of Day With Outcomes Among Patients Triaged for a Suspected Severe Stroke in Nonurban Catalonia.

BACKGROUND: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. METHODS: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am-8:59 pm) and nighttime (9:00 pm-7:59 am). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. RESULTS: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR], 1.620 [95% CI, 1.020-2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680-1.163]; P interaction=0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548-1.072]; nighttime, acOR, 1.785 [95% CI, 1.024-3.112] ; P interaction<0.01); no heterogeneity was observed for other stroke subtypes (P interaction>0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. CONCLUSIONS: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02795962.

First pass effect in posterior circulation occlusions: Analysis from the CICAT registry.

BACKGROUND: The first pass effect (FPE) is an independent predictor of functional independence in patients with large vessel occlusion in anterior circulation ischemic strokes. However, whether it predicts outcome in posterior circulation large vessel occlusion (PC-LVO) is uncertain. We aimed to study the frequency, characteristics, and predictors of FPE and its association with clinical outcomes in PC-LVO. METHOD: We performed an analysis from the prospective CICAT Registry. All patients with PC-LVO who underwent endovascular therapy between January 2016 and January 2020 were included. A centrally assessed clinical follow-up was performed at 3 months by blinded investigators. FPE was defined as the achievement of modified Thrombolysis In Cerebral Infarction 3 in a single pass of the endovascular thrombectomy device, and multi-pass effect (MPE) if it was achieved in more than one pass. A multivariable analysis was performed to identify whether FPE is an independent predictor of functional independence defined as a modified Rankin Score of 0-2. RESULTS: We analyzed data from 265 patients in who FPE was achieved in 105 (39.6%). Patients with FPE were more likely to achieve functional independence compared to the non-FPE group (52.4% vs 25.1%, p < .001) and the MPE group (52.4% vs 26.7%, p < .001). FPE was independently associated with functional independence (adjusted odds ratio (aOR): 2.10, 95% confidence interval (CI) 1.01-4.37) but MPE was not (aOR: 0.92, 95% CI 0.40-2.13). Independent predictors of FPE were the use of direct aspiration, embolic mechanism of stroke, and the absence of general anesthesia (GA) use. CONCLUSIONS: FPE is an independent predictor of functional independence in PC-LVO and was associated with a significantly better outcome than MPE.

Workflows and Outcomes in Patients With Suspected Large Vessel Occlusion Stroke Triaged in Urban and Nonurban Areas.

BACKGROUND: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion). METHODS: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics. RESULTS: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2-5] versus 3 [1-5], common odds ratio, 1.25 [95% CI, 1.06-1.48]); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08-1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81-1.28]). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16-1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51-0.75]), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25-52]) and thrombectomy(mean difference 66 minutes [95% CI, 37-95]). CONCLUSIONS: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02795962.

Workflow Times and Outcomes in Patients Triaged for a Suspected Severe Stroke.

INTRODUCTION: Current recommendations for regional stroke destination suggest that patients with severe acute stroke in non-urban areas should be triaged based on the estimated transport time to a referral thrombectomy-capable center. METHODS: We performed a post hoc analysis to evaluate the association of pre-hospital workflow times with neurological outcomes in patients included in the RACECAT trial. Workflow times evaluated were known or could be estimated before transport allocation. Primary outcome was the shift analysis on the modified Rankin score at 90 days. RESULTS: Among the 1,369 patients included, the median time from onset to emergency medical service (EMS) evaluation, the estimated transport time to a thrombectomy-capable center and local stroke center, and the estimated transfer time between centers were 65 minutes (interquartile ratio [IQR] = 43-138), 61 minutes (IQR = 36-80), 17 minutes (IQR = 9-27), and 62 minutes (IQR = 36-73), respectively. Longer time intervals from stroke onset to EMS evaluation were associated with higher odds of disability at 90 days in the local stroke center group (adjusted common odds ratio (acOR) for each 30-minute increment = 1.03, 95% confidence interval [CI] = 1.01-1.06), with no association in the thrombectomy-capable center group (acOR for each 30-minute increment = 1.01, 95% CI = 0.98-1.01, pinteraction  = 0.021). No significant interaction was found for other pre-hospital workflow times. In patients evaluated by EMS later than 120 minutes after stroke onset, direct transport to a thrombectomy-capable center was associated with better disability outcomes (acOR = 1.49, 95% CI = 1.03-2.17). CONCLUSION: We found a significant heterogeneity in the association between initial transport destination and neurological outcomes according to the elapse of time between the stroke onset and the EMS evaluation (ClinicalTrials.gov: NCT02795962). ANN NEUROL 2022;92:931-942.

Determinants and Trends of the Use of Intravenous Thrombolysis for Minor Stroke: A Population-Based Study, 2016 to 2020.

BACKGROUND: We analyzed the main factors associated with intravenous thrombolysis (IVT) in patients with minor ischemic stroke. METHODS: Data were obtained from a prospective, government-mandated, population-based registry of stroke code patients in Catalonia (6 Comprehensive Stroke Centers, 8 Primary Stroke Centers, and 14 TeleStroke Centers). We selected patients diagnosed with ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) ≤5 at hospital admission from January 2016 to December 2020. We excluded patients with a baseline modified Rankin Scale score of ≥3, absolute contraindication for IVT, unknown stroke onset, or admitted to hospital beyond 4.5 after stroke onset. The main outcome was treatment with IVT. We performed univariable and binary logistic regression analyses to identify the most important factors associated with IVT. RESULTS: We included 2975 code strokes; 1433 (48.2%) received IVT of which 30 (2.1%) had a symptomatic hemorrhagic transformation. Patients treated with IVT as compared to patients who did not receive IVT were more frequently women, had higher NIHSS, arrived earlier to hospital, were admitted to a Comprehensive Stroke Centers, and had large vessel occlusion. After binary logistic regression, NIHSS score 4 to 5 (odds ratio, 40.62 [95% CI, 31.73-57.22]; P<0.001) and large vessel occlusion (odds ratio, 16.39 [95% CI, 7.25-37.04]; P<0.001) were the strongest predictors of IVT. Younger age, female sex, baseline modified Rankin Scale score of 0, earlier arrival to hospital (<120 minutes after stroke onset), and the type of stroke center were also independently associated with IVT. The weight of large vessel occlusion on IVT was higher in patients with lower NIHSS. CONCLUSIONS: Minor stroke female patients, with higher NIHSS, arriving earlier to the hospital, presenting with large vessel occlusion and admitted to a Comprehensive Stroke Centers were more likely to receive intravenous thrombolysis.

Effect of Direct Transportation to Thrombectomy-Capable Center vs Local Stroke Center on Neurological Outcomes in Patients With Suspected Large-Vessel Occlusion Stroke in Nonurban Areas: The RACECAT Randomized Clinical Trial.

Importance: In nonurban areas with limited access to thrombectomy-capable centers, optimal prehospital transport strategies in patients with suspected large-vessel occlusion stroke are unknown. Objective: To determine whether, in nonurban areas, direct transport to a thrombectomy-capable center is beneficial compared with transport to the closest local stroke center. Design, Setting, and Participants: Multicenter, population-based, cluster-randomized trial including 1401 patients with suspected acute large-vessel occlusion stroke attended by emergency medical services in areas where the closest local stroke center was not capable of performing thrombectomy in Catalonia, Spain, between March 2017 and June 2020. The date of final follow-up was September 2020. Interventions: Transportation to a thrombectomy-capable center (n = 688) or the closest local stroke center (n = 713). Main Outcomes and Measures: The primary outcome was disability at 90 days based on the modified Rankin Scale (mRS; scores range from 0 [no symptoms] to 6 [death]) in the target population of patients with ischemic stroke. There were 11 secondary outcomes, including rate of intravenous tissue plasminogen activator administration and thrombectomy in the target population and 90-day mortality in the safety population of all randomized patients. Results: Enrollment was halted for futility following a second interim analysis. The 1401 enrolled patients were included in the safety analysis, of whom 1369 (98%) consented to participate and were included in the as-randomized analysis (56% men; median age, 75 [IQR, 65-83] years; median National Institutes of Health Stroke Scale score, 17 [IQR, 11-21]); 949 (69%) comprised the target ischemic stroke population included in the primary analysis. For the primary outcome in the target population, median mRS score was 3 (IQR, 2-5) vs 3 (IQR, 2-5) (adjusted common odds ratio [OR], 1.03; 95% CI, 0.82-1.29). Of 11 reported secondary outcomes, 8 showed no significant difference. Compared with patients first transported to local stroke centers, patients directly transported to thrombectomy-capable centers had significantly lower odds of receiving intravenous tissue plasminogen activator (in the target population, 229/482 [47.5%] vs 282/467 [60.4%]; OR, 0.59; 95% CI, 0.45-0.76) and significantly higher odds of receiving thrombectomy (in the target population, 235/482 [48.8%] vs 184/467 [39.4%]; OR, 1.46; 95% CI, 1.13-1.89). Mortality at 90 days in the safety population was not significantly different between groups (188/688 [27.3%] vs 194/713 [27.2%]; adjusted hazard ratio, 0.97; 95% CI, 0.79-1.18). Conclusions and Relevance: In nonurban areas in Catalonia, Spain, there was no significant difference in 90-day neurological outcomes between transportation to a local stroke center vs a thrombectomy-capable referral center in patients with suspected large-vessel occlusion stroke. These findings require replication in other settings. Trial Registration: ClinicalTrials.gov Identifier: NCT02795962.

Effectiveness of Thrombectomy in Stroke According to Baseline Prognostic Factors: Inverse Probability of Treatment Weighting Analysis of a Population-Based Registry.

BACKGROUND AND PURPOSE:  In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. METHODS:  Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score <6, proximal vertebrobasilar occlusion, supratherapeutic international normalized ratio >3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria). RESULTS:  Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). CONCLUSIONS:  Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors.

Innovation in Systems of Care in Acute Phase of Ischemic Stroke. The Experience of the Catalan Stroke Programme.

Stroke, and mainly ischemic stroke, is the second cause of death and disability. To confront the huge burden of this disease, innovative stroke systems of care are mandatory. This requires the development of national stroke plans to offer the best treatment to all patients eligible for reperfusion therapies. Key elements for success include a high level of organization, close cooperation with emergency medical services for prehospital assessment, an understanding of stroke singularity, the development of preassessment tools, a high level of commitment of all stroke teams at Stroke Centres, the availability of a disease-specific registry, and local government involvement to establish stroke care as a priority. In this mini review, we discuss recent evidence concerning different aspects of stroke systems of care and describe the success of the Catalan Stroke Programme as an example of innovation. In Catalonia, reperfusion treatment rates have increased in recent years and currently are among the highest in Europe (17.3% overall, 14.3% for IVT, and 6% for EVT in 2016).