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.

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.

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.

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.

Reasons for Not Performing Mechanical Thrombectomy: A Population-Based Study of Stroke Codes.

Background and Purpose: Mechanical thrombectomy (MT) is effective for acute ischemic stroke (AIS) in selected patients with large intracranial vessel occlusion. A minority of patients with AIS receive MT. We aimed to describe the reasons for excluding patients with AIS for MT. Methods: We evaluated patients with AIS in a prospective population-based multicenter registry (Codi Ictus Catalunya registry) that includes all stroke code activations from January to June 2018 in Catalonia, Spain. We analyzed the major reasons for not treating with MT. Results: Stroke code was activated in 3060 patients. Excluding 355 intracranial hemorrhages and 502 stroke mimics, resulted in 2203 patients with AIS (mean age 72.8±13.8 years; 44.6% were women). Of the patients with AIS, 405 (18.4%) were treated with MT. We analyzed the reasons for not treating with MT. The following reasons were considered not modifiable: absence of large intracranial vessel occlusion (922, 41.9%), transient ischemic attack (206, 9.4%), and more than one cause (124, 5.6%). The potentially modifiable reasons for not performing MT by changing selection criteria were as follows: an intracranial artery occlusion that was considered inaccessible or not indicated (48, 2.2%); clinical presentation that was considered too mild to be treated (222, 10.1%); neuroimaging criteria (129, 5.9%), age/prior modified Rankin Scale score/medical comorbidities (129, 5.9%), and therapeutic time window >8 hours (16, 0.7%). Conclusions: In our area, considering all potentially modifiable causes for not performing MT, the percentage of patients with AIS eligible for MT could increase from 18.4% to a maximum of 43.1%. The clinical benefit of this increase is still uncertain and should be confirmed in future trials. Criteria for stroke code activation must be considered for the generalizability of these results.

Stroke Risk Analysis, a System With a High Detection Rate of Atrial Fibrillation in Stroke and Transient Ischemic Attack.

Background and Purpose- Stroke Risk Analysis (SRA) comprises an algorithm for automated analysis of ECG monitoring, enabling the detection of paroxysmal atrial fibrillation (pxAF) and identifying patterns indicating a high risk of atrial fibrillation (R_AF). We compared Holter-enabled continuous ECG monitoring in combination with SRA (hSRA) with standard continuous ECG monitoring for pxAF detection in patients with acute ischemic stroke. Also, we sought to identify whether the detection of R_AF patterns during the first cycle (first 2 hours) of hSRA recording was associated with the detection of pxAF during the Stroke Unit stay. Methods- We enrolled 524 consecutive patients admitted in the Stroke Unit with acute ischemic stroke or transient ischemic attack with neither history of AF nor AF at admission into a prospective multicentric observational analytic clinical study with intrapatient comparison, who received both continuous ECG monitoring as well as hSRA up to 7 days. Investigators were blinded to hSRA results unless pxAF was detected on SRA. Results- Of the 524 consecutive acute stroke patients (median age, 70.0 years; 60% male; acute ischemic stroke 93%, transient ischemic attack 7%), 462 were eligible and included in the study. Among 462 patients with hSRA available for 66 hours, AF was documented by hSRA in 79 patients (17.1%). From this group, 45 AF cases (9.7%) were confirmed after review by an independent and blinded cardiologist. continuous ECG monitoring detected 21 AF cases (4.3%; P<0.0001). hSRA detected R_AF patterns in 92 patients. 35 out of the 92 R_AF patients showed an episode of AF during the Stroke Unit stay. Predictive values of R_AF patterns within the first cycle of hSRA were: sensitivity 71%, specificity 86%, positive predictive value 38%, and negative predictive value 96%. Conclusions- Automated analysis using SRA technology strongly improves pxAF detection in acute ischemic stroke patients compared with continuous ECG monitoring. The predictive value of a R_AF pattern, as detected by hSRA during the first few hours after admission, deserves further investigation.

Vascular Occlusion Evolution in Endovascular Reperfusion Candidates Transferred from Primary to Comprehensive Stroke Centers.

BACKGROUND: The evolution of the symptomatic intracranial occlusion during transfers from primary stroke centers (PSCs) to comprehensive stroke centers (CSCs) for endovascular treatment (EVT) is not widely known. Our aim was to identify factors related to partial or complete recanalization (REC) at CSC arrival in patients with a documented large vessel occlusion (LVO) in PSC transferred for EVT evaluation to better define the workflow at CSC of this group of patients. METHODS: We conducted an observational, multicenter study from a prospective, government-mandated, population-based registry of stroke patients with documented LVO at PSC transferred to CSC for EVT from January 2017 to June 2019. The primary end point was defined as partial or complete REC that precluded EVT at CSC arrival (REC). We evaluated the association between baseline, treatment variables and time intervals with the presence of REC. RESULTS: From 589 patients, the rate of REC at CSC was 10.5% in all LVO patients transferred from PSC to CSC for EVT evaluation. On univariate analysis, lower PSC-NIHSS (median 12vs.16, p = 0.001), tPA treatment at PSC (13.7 vs. 5.0%; p = 0.001), presence of M2 occlusion on PSC (16.8 vs. 9%; p = 0.023), and clinical improvement at CSC arrival (21.7 vs. 9.6% p = 0.001) were associated with REC at CSC. On multivariate analysis, clinical improvement at CSC arrival (p < 0.001, OR: 5.96 95% CI: 2.5-13.9) and PSC tPA treatment predicted REC (p = 0.003, OR: 4.65, 95% CI: 1.73-12.4). CONCLUSION: REC at CSC arrival occurs exceptionally in patients with a documented LVO on PSC. Repeating a second vascular study before EVT would not be necessary in most patients. Despite its modest effect, tPA treatment at PSC was an independent predictor of REC.

Association of Socioeconomic Status With Ischemic Stroke Survival.

Background and Purpose- The aim of the study was to determine the impact of individuals' socioeconomic status and their Primary Care Service Area Socioeconomic Index on survival after ischemic stroke. Methods- We conducted a nationwide population-based cohort study in Catalonia, Spain. We included all patients with first ischemic stroke admitted to a public hospital between January 1, 2015, and December 31, 2016. We measured both individual socioeconomic status (categorized as exempts, <€18 000 [$US 20 468] income per year, and >€18 000 income per year) and Primary Care Service Area Socioeconomic Index (from 0 to 100 categorized in quartiles). We used mixed-effects logistic and survival models to estimate odds ratios and hazard ratios for the short- (30 days) and the long-term (3 years) all-cause case fatality rates by individuals' socioeconomic status groups. Results- The cohort consisted of 16 344 ischemic stroke patients with 24 638 person-years of follow-up. We did not find an association between the lowest socioeconomic individual status and short-term survival (odds ratio, 1.03; 95% CI, 0.76-1.40), although we found it in patients with <€18 000 income/year (odds ratio, 1.26; 95% CI, 1.10-1.45). At long-term, after adjustment, we observed a gradient in mortality risk with decreasing individual socioeconomic status (hazard ratio, 1.52; 95% CI, 1.30-1.77). The Primary Care Service Area Socioeconomic Index had only an influence on short-term survival (odds ratio, 1.19; 95% CI, 1.03-1.37). Conclusions- Individuals' socioeconomic status was associated with short- and long-term survival in patients with ischemic stroke. Conversely, Primary Care Service Area Socioeconomic Index measures had an influence only in short-term survival. A small fraction of this association is due to differences in comorbidity and cardiovascular risk factors. Interventions addressing both individuals' and primary care service socioeconomic aspects might eventually affect differently short- and long-term survival.

Predictors of Endovascular Treatment Among Stroke Codes Activated Within 6 Hours From Symptom Onset.

Background and Purpose- Prehospital stroke code activations help reducing workflow times during in-hospital triage. We aim to identify predictors of endovascular treatment (EVT) among stroke codes (SC) activated within 6 hours from symptom onset. Methods- CICAT (Codi Ictus Catalunya) is a prospective official mandatory registry of all SC in Catalunya. We studied all CICAT entries from 6 comprehensive stroke centers for 18 months. We recorded demographic, clinical, and imaging variables on admission. We explored the relationship between these variables and EVT Results- From 3944 SC, 2778 (70.4%) were admitted within 6 hours from symptom onset. Mean age was 72±15.3 years, median Rapid Arterial Occlusion Evaluation scale score 4 (interquartile range [IQR], 2-6), median onset-to-door time 89 minutes (IQR, 54-158), median National Institutes of Health Stroke Scale score 9 (IQR, 4-18), median Alberta Stroke Program Early CT Score 10 (IQR, 8-10). Final diagnosis was ischemic stroke in 1762 patients (63.4%), hemorrhagic stroke in 359 (13.0%), transient ischemic attack in 164 (5.9%), and stroke-mimic in 493 (17.7%). A large vessel occlusion was confirmed in 720 (25.6%) patients. Of all SC, 16% (n=444) received EVT, with a median door-to-groin time of 77 minutes (IQR, 55-102). Baseline variables associated with EVT were premorbid modified Rankin Scale score <2 ( P<0.001), prehospital Rapid Arterial Occlusion Evaluation scale score >4 ( P=0.003), and National Institutes of Health Stroke Scale on admission >8 ( P<0.001). National Institutes of Health Stroke Scale on admission was the only independent predictor of EVT. Although the rate of Alberta Stroke Program Early CT Score 10 progressively decreased over time (0-3 hours, 73.2% versus 3-6 hours, 57.1%; P<0.01), the rate of Alberta Stroke Program Early CT Score 6 remained >90% along time (0-3 hours, 95.1% versus 3-6 hours, 94.0%; P=0.25) and did not decrease over time. The chances to receive EVT and the presence of large vessel occlusion decreased over time. However, the rate of EVT was not different between patients admitted 0 to 3 hours (26.1%) and those admitted 3 to 6 hours (22.9%; P=0.2). Conclusions- Among SC within 6 hours from symptom onset, National Institutes of Health Stroke Scale on admission was the only factor independently associated with EVT. Only 5% of these patients show an Alberta Stroke Program Early CT Score <6 and this rate does not significantly increase over time. These data may be useful to generate direct transfer to angio-suite protocols based mainly on clinical severity.

Thrombectomy within 8 hours after symptom onset in ischemic stroke.

BACKGROUND: We aimed to assess the safety and efficacy of thrombectomy for the treatment of stroke in a trial embedded within a population-based stroke reperfusion registry. METHODS: During a 2-year period at four centers in Catalonia, Spain, we randomly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy (including intravenous alteplase when eligible) and endovascular therapy with the Solitaire stent retriever (thrombectomy group) or medical therapy alone (control group). All patients had confirmed proximal anterior circulation occlusion and the absence of a large infarct on neuroimaging. In all study patients, the use of alteplase either did not achieve revascularization or was contraindicated. The primary outcome was the severity of global disability at 90 days, as measured on the modified Rankin scale (ranging from 0 [no symptoms] to 6 [death]). Although the maximum planned sample size was 690, enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials. RESULTS: Thrombectomy reduced the severity of disability over the range of the modified Rankin scale (adjusted odds ratio for improvement of 1 point, 1.7; 95% confidence interval [CI], 1.05 to 2.8) and led to higher rates of functional independence (a score of 0 to 2) at 90 days (43.7% vs. 28.2%; adjusted odds ratio, 2.1; 95% CI, 1.1 to 4.0). At 90 days, the rates of symptomatic intracranial hemorrhage were 1.9% in both the thrombectomy group and the control group (P=1.00), and rates of death were 18.4% and 15.5%, respectively (P=0.60). Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals. CONCLUSIONS: Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset, stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence. (Funded by Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others; REVASCAT ClinicalTrials.gov number, NCT01692379.).

Telestroke in Catalonia: Increasing Thrombolysis Rate and Avoiding Interhospital Transfers.

OBJECTIVES: The study aimed to evaluate the impact of a telestroke network on acute stroke care in Catalonia, by measuring thrombolysis rates, access to endovascular treatment, and clinical outcome of telestroke patients in a population-based study. METHODS: Telestroke network was implemented on March 2013 and consists of 12 community hospitals and 1 expert stroke neurologist 24 h/7 day, covering a population of 1.3 million inhabitants. Rest of the population (6.2 million) of Catalonia is covered by 8 primary stroke centers (PSC) and 6 comprehensive stroke centers (CSC). After a 2-way videoconference and visualization of neuroimaging on a web platform, the stroke neurologist decides the therapeutic approach and/or to transfer the patient to another facility, entering these data in a mandatory registry. Simultaneously, all patients treated with reperfusion therapies in all centers of Catalonia are prospectively recorded in a mandatory and audited registry. RESULTS: From March 2013 to December 2015, 1,206 patients were assessed by telestroke videoconference, of whom 322 received intravenous thrombolysis (IVT; 33.8% of ischemic strokes). Baseline and 24 h NIHSS, rate of symptomatic hemorrhage, mortality, and good outcome at 3 months were similar compared to those who received IVT in PSC or CSC (2,897 patients in the same period). The door-to-needle time was longer in patients treated through telestroke, but was progressively reduced from 2013 to 2015. Percentage of patients receiving thrombectomy after IVT was similar in patients treated through telestroke circuit, compared to those treated in PSC or CSC (conventional circuit). Population rates of IVT*100,000 inhabitants in Catalonia increased from 2011 to 2015, especially in areas affected by the implementation of telestroke network, achieving rates as high as 16 per 100,000 inhabitants. Transfers to another facility were avoided after telestroke consultation in 46.8% of ischemic, 76.5% of transient ischemic attacks, and 23.5% of hemorrhages. CONCLUSIONS: Telestroke favors safe and effective thrombolysis, helps to increase the population rate of IVT, and avoids a large number of interhospital transfers.

Outcomes After Direct Thrombectomy or Combined Intravenous and Endovascular Treatment Are Not Different.

BACKGROUND AND PURPOSE: Whether intravenous thrombolysis adds a further benefit when given before endovascular thrombectomy (EVT) is unknown. Furthermore, intravenous thrombolysis delays time to groin puncture, mainly among drip and ship patients. METHODS: Using region-wide registry data, we selected cases that received direct EVT or combined intravenous thrombolysis+EVT for anterior circulation strokes between January 2011 and October 2015. Treatment effect was estimated by stratification on a propensity score. The average odds ratios for the association of treatment with good outcome and death at 3 months and symptomatic bleedings at 24 hours were calculated with the Mantel-Haenszel test statistic. RESULTS: We included 599 direct EVT patients and 567 patients with combined treatment. Stratification through propensity score achieved balance of baseline characteristics across treatment groups. There was no association between treatment modality and good outcome (odds ratio, 0.97; 95% confidence interval, 0.74-1.27), death (odds ratio, 1.07; 95% confidence interval, 0.74-1.54), or symptomatic bleedings (odds ratio, 0.56; 95% confidence interval, 0.25-1.27). CONCLUSIONS: This observational study suggests that outcomes after direct EVT or combined intravenous thrombolysis+EVT are not different. If confirmed by a randomized controlled trial, it may have a significant impact on organization of stroke systems of care.

Access to Endovascular Treatment in Remote Areas: Analysis of the Reperfusion Treatment Registry of Catalonia.

BACKGROUND AND PURPOSE: Since demonstration of the benefit of endovascular treatment (EVT) in acute ischemic stroke patients with proximal arterial occlusion, stroke care systems need to be reorganized to deliver EVT in a timely and equitable way. We analyzed differences in the access to EVT by geographical areas in Catalonia, a territory with a highly decentralized stroke model. METHODS: We studied 965 patients treated with EVT from a prospective multicenter population-based registry of stroke patients treated with reperfusion therapies in Catalonia, Spain (SONIIA). Three different areas were defined: (A) health areas primarily covered by Comprehensive Stroke Centers, (B) areas primarily covered by local stroke centers located less than hour away from a Comprehensive Stroke Center, and (C) areas primarily covered by local stroke centers located more than hour away from a Comprehensive Stroke Center. We compared the number of EVT×100 000 inhabitants/year and time from stroke onset to groin puncture between groups. RESULTS: Baseline characteristics were similar between groups. Throughout the study period, there were significant differences in the population rates of EVT across geographical areas. EVT rates by 100 000 in 2015 were 10.5 in A area, 3.7 in B, and 2.7 in C. Time from symptom onset to groin puncture was 82 minutes longer in group B (312 minutes [245-435]) and 120 minutes longer in group C (350 minutes [284-408]) compared with group A (230 minutes [160-407]; P<0.001). CONCLUSIONS: Accessibility to EVT from remote areas is hampered by lower rate and longer time to treatment compared with areas covered directly by Comprehensive Stroke Centers.

Remote Intracerebral Hemorrhage After Intravenous Thrombolysis: Results From a Multicenter Study.

BACKGROUND AND PURPOSE: Remote parenchymal hemorrhage (rPH) after intravenous thrombolysis with recombinant tissue-type plasminogen activator may be associated with cerebral amyloid angiopathy, although supportive data are limited. We aimed to investigate risk factors of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator. METHODS: This is an observational study of patients with ischemic stroke who were treated with intravenous thrombolysis with recombinant tissue-type plasminogen activator and were included in a multicenter prospective registry. rPH was defined as any extraischemic hemorrhage detected in the follow-up computed tomography. We collected demographic, clinical, laboratory, radiological, and outcome variables. In the subset of patients who underwent a magnetic resonance imaging examination, we evaluated the distribution and burden of cerebral microbleeds, cortical superficial siderosis, leukoaraiosis, and recent silent ischemia in regions anatomically unrelated to the ischemic lesion that caused the initial symptoms. We compared patients with rPH with those without rPH or parenchymal hemorrhage. Independent risk factors for rPH were obtained by multivariable logistic regression analyses. RESULTS: We evaluated 992 patients (mean age, 74.0±12.6 years; 52.9% were men), and 408 (41%) of them underwent a magnetic resonance imaging. Twenty-six patients (2.6%) had a rPH, 8 (0.8%) had both rPH and PH, 58 (5.8%) had PH, and 900 (90.7%) had no bleeding complication. Lobar cerebral microbleeds (odds ratio, 8.0; 95% confidence interval, 2.3-27.2) and recent silent ischemia (odds ratio, 4.8; 95% confidence interval, 1.6-14.1) increased the risk of rPH. CONCLUSIONS: The occurrence of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator in patients with ischemic stroke is associated with lobar cerebral microbleeds and multiple ischemic lesions in different regions.

Mechanical Thrombectomy in and Outside the REVASCAT Trial: Insights From a Concurrent Population-Based Stroke Registry.

BACKGROUND AND PURPOSE: Recent trials have shown the superiority of endovascular thrombectomy (EVT) over medical therapy alone in certain stroke patients with proximal arterial occlusion. Using data from the Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within 8-Hours of Symptom Onset (REVASCAT) and a parallel reperfusion treatment registry, we sought to assess the utilization of EVT in a defined patient population, comparing the outcomes of patients treated in and outside the REVASCAT trial. METHODS: SONIIA [Sistema Online d'Informació de l'Ictus Agut], a population-based, government-mandated, prospective registry of reperfusion therapies for stroke encompassing the entire population of Catalonia, was used as data source. The registry documents 5 key inclusion criteria of the REVASCAT trial: age, stroke severity, time to treatment, baseline functional status, and occlusion site. We compared procedural, safety, and functional outcomes in patients treated inside and outside the trial. RESULTS: From November 2012 to December 2014, out of 17596 ischemic stroke patients in Catalonia (population 7.5 million), 2576 patients received reperfusion therapies (17/100000 inhabitants-year), mainly intravenous thrombolysis only (2036). From the remaining 540 treated with EVT, 103 patients (out of 206 randomized) were treated within REVASCAT and 437 outside the trial. Of these, 399 did not fulfill some of the study criteria, and 38 were trial candidates (8 treated at REVASCAT centers and 30 at 2 non-REVASCAT centers). The majority of procedural, safety, and functional outcomes were similar in patients treated with EVT within and outside REVASCAT. CONCLUSIONS: REVASCAT enrolled nearly all eligible patients representing one third of all patients treated with EVT. Patients treated with EVT within and outside REVASCAT had similar outcomes, reinforcing the therapeutic value of EVT. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01692379.

Variations in acute hospital stroke care and factors influencing adherence to quality indicators in 6 European audits.

BACKGROUND AND PURPOSE: We compared compliance with standards of acute stroke care between 6 European audits and identified factors associated with delivery of appropriate care. METHODS: Data were derived from stroke audits in Germany, Poland, Scotland, Catalonia, Sweden, and England/Wales/Northern-Ireland participating within the European Implementation Score (EIS) collaboration. Associations between demographic and clinical characteristics with adherence to predefined quality indicators were investigated by hierarchical logistic regression analyses. RESULTS: In 2007/2008 data from 329 122 patients with stroke were documented. Substantial variations in adherence to quality indicators were found; older age was associated with a lower probability of receiving thrombolytic therapy, anticoagulant therapy, or stroke unit treatment and a higher probability of being tested for dysphagia. Women were less likely to receive anticoagulant or antiplatelet therapy or stroke unit treatment. No major weekend effect was found. CONCLUSIONS: Detected variations in performance of acute stroke services were found. Differences in adherence to quality indicators might indicate population subgroups with specific needs for improving care delivery.

Outcomes of a contemporary cohort of 536 consecutive patients with acute ischemic stroke treated with endovascular therapy.

BACKGROUND AND PURPOSE: We sought to assess outcomes after endovascular treatment/therapy of acute ischemic stroke, overall and by subgroups, and looked for predictors of outcome. METHODS: We used data from a mandatory, population-based registry that includes external monitoring of completeness, which assesses reperfusion therapies for consecutive patients with acute ischemic stroke since 2011. We described outcomes overall and by subgroups (age ≤ or >80 years; onset-to-groin puncture ≤ or >6 hours; anterior or posterior strokes; previous IV recombinant tissue-type plasminogen activator or isolated endovascular treatment/therapy; revascularization or no revascularization), and determined independent predictors of good outcome (modified Rankin Scale score ≤2) and mortality at 3 months by multivariate modeling. RESULTS: We analyzed 536 patients, of whom 285 received previous IV recombinant tissue-type plasminogen activator. Overall, revascularization (modified Thrombolysis In Cerebral Infarction scores, 2b and 3) occurred in 73.9%, 5.6% developed symptomatic intracerebral hemorrhages, 43.3% achieved good functional outcome, and 22.2% were dead at 90 days. Adjusted comparisons by subgroups systematically favored revascularization (lower proportion of symptomatic intracerebral hemorrhages and death rates and higher proportion of good outcome). Multivariate analyses confirmed the independent protective effect of revascularization. Additionally, age >80 years, stroke severity, hypertension (deleterious), atrial fibrillation, and onset-to-groin puncture ≤6 hours (protective) also predicted good outcome, whereas lack of previous disability and anterior circulation strokes (protective) as well as and hypertension (deleterious) independently predicted mortality. CONCLUSIONS: This study reinforces the role of revascularization and time to treatment to achieve enhanced functional outcomes and identifies other clinical features that independently predict good/fatal outcome after endovascular treatment/therapy.

Medical and endovascular treatment of patients with large vessel occlusion presenting with mild symptoms: an observational multicenter study.

BACKGROUND: A significant proportion of stroke patients presenting with mild symptoms does not have a successful recovery, especially when a large vessel is occluded. IV thrombolysis is safe and may benefit patients presenting with mild symptoms. In this study, we tested whether endovascular therapy (ET) is superior to medical therapy in these patients. METHODS: Observational, prospectively collected, multicenter study of 78 consecutive patients admitted from 2009 to 2012 within 6 h of stroke, with NIHSS≤5 at presentation or during initial diagnostic work-up and large vessel occlusion. Data for patients undergoing ET and/or IV thrombolysis were taken from the SONIIA registry of reperfusion therapies in Catalonia, or from our local stroke registry if no reperfusion therapy was delivered. We compared risk factors, clinical course, collateral circulation, revascularization rates, hemorrhagic complications, infarct volume, and the functional outcome at 3 months of patients treated with ET and those not receiving ET. Ordinal regression was used to assess the independent effect of ET on functional outcome. RESULTS: Baseline characteristics were similar for ET (n=34) and medically (n=44) treated patients, except for older age in the latter. The occlusions were located in the terminal internal carotid artery (1%), M1 segment of the middle cerebral artery (33%), M2 segment (30%), posterior circulation (31%), and 5% of the patients had tandem lesions, with no significant differences between groups. Most patients in both treatment groups had good collateral flow. The rate of successful revascularization (91.2 vs. 63.4%; p=0.006) and the risk of symptomatic intracranial hemorrhage (11.8 vs. 0%; p=0.033) were higher in the ET group. The NIHSS scores were similar at hospital arrival, after initial neuroimaging, and at 24 h in both treatment groups and there were no significant differences in the infarct volume in a follow-up MRI. At 3 months, 35.9% of the patients had some disability. The functional outcome was similar in both treatment groups in univariate analysis and also in models adjusted for age and initial NIHSS or for variables associated to functional outcome on univariate comparison. Conversely, IV thrombolysis was associated with significantly greater chances of full recovery after adjusting for baseline differences (OR 3.70, p=0.015). CONCLUSIONS: One third of stroke patients with mild symptoms and large vessel occlusions do not have a successful recovery. ET is effective to recanalize the occluded vessel but increases the risk of serious bleeding significantly without improving the functional outcome, and is therefore not justified routinely in these patients.

Functional outcome after primary endovascular therapy or IV thrombolysis alone for stroke. An observational, comparative effectiveness study.

BACKGROUND: Among the acute ischemic stroke patients with large vessel occlusions and contraindications for the use of IV thrombolysis, mainly on oral anticoagulation or presenting too late, primary endovascular therapy is often performed as an alternative to the standard therapy even though evidence supporting the use of endovascular reperfusion therapies is not yet established. Using different statistical approaches, we compared the functional independence rates at 3 months among patients undergoing primary endovascular therapy and patients treated only with IV thrombolysis. METHODS: We used data from a prospective, government-mandated and externally audited registry of reperfusion therapies for ischemic stroke (January 2011 to November 2012). Patients were selected if treated with either IV thrombolysis alone (n = 1,582) or primary endovascular thrombectomy (n = 250). A series of exclusions were made to homogenize the clinical characteristics among the two groups. We then carried out multivariate logistic regression and propensity score matching analyses on the final study sample (n = 1,179) to compare functional independence at 3 months, as measured by the modified Rankin scale scores 0-2, between the two groups. RESULTS: The unadjusted likelihood of good outcome was poorer among the endovascular group (OR: 0.69; 95% CI: 0.47-1.0). After adjustment, no differences by treatment modality were seen (OR: 1.51; 95% CI: 0.93-2.43 for primary endovascular therapy). Patients undergoing endovascular thrombectomy within 180-270 min (OR: 2.89; 95% CI: 1.17-7.15) and patients with severe strokes (OR: 1.84; 95% CI: 1.02-3.35) did better than their intravenous thrombolysis counterparts. The propensity score-matched analyses with and without adjustment by additional covariates showed that endovascular thrombectomy was as effective as intravenous thrombolysis alone in achieving functional independence (OR for unadjusted propensity score matched: 1.35; 95% CI: 0.9-2.02, OR for adjusted propensity score matched: 1.45; 95% CI: 0.91-2.32). CONCLUSION: This comparative effectiveness study shows that in ischemic stroke patients with contraindications for IV thrombolysis, primary endovascular treatment might be an alternative therapy at least as effective as IV thrombolysis alone. Randomized controlled trials are urgently needed.

Influence of vascular imaging acquisition at local stroke centers on workflows in the drip-n-ship model: a RACECAT post hoc analysis.

BACKGROUND: The influence of vascular imaging acquisition on workflows at local stroke centers (LSCs) not capable of performing thrombectomy in patients with a suspected large vessel occlusion (LVO) stroke remains uncertain. We analyzed the impact of performing vascular imaging (VI+) or not (VI- at LSC arrival on variables related to workflows using data from the RACECAT Trial. OBJECTIVE: To compare workflows at the LSC among patients enrolled in the RACECAT Trial with or without VI acquisition. METHODS: We included patients with a diagnosis of ischemic stroke who were enrolled in the RACECAT Trial, a cluster-randomized trial that compared drip-n-ship versus mothership triage paradigms in patients with suspected acute LVO stroke allocated at the LSC. Outcome measures included time metrics related to workflows and the rate of interhospital transfers and thrombectomy among transferred patients. RESULTS: Among 467 patients allocated to a LSC, vascular imaging was acquired in 277 patients (59%), of whom 198 (71%) had a LVO. As compared with patients without vascular imaging, patients in the VI+ group were transferred less frequently as thrombectomy candidates to a thrombectomy-capable center (58% vs 74%, P=0.004), without significant differences in door-indoor-out time at the LSC (median minutes, VI+ 78 (IQR 69-96) vs VI- 76 (IQR 59-98), P=0.6). Among transferred patients, the VI+ group had higher rate of thrombectomy (69% vs 55%, P=0.016) and shorter door to puncture time (median minutes, VI+ 41 (IQR 26-53) vs VI- 54 (IQR 40-70), P<0.001). CONCLUSION: Among patients with a suspected LVO stroke initially evaluated at a LSC, vascular imaging acquisition might improve workflow times at thrombectomy-capable centers and reduce the rate of futile interhospital transfers. These results deserve further evaluation and should be replicated in other settings and geographies.