Food and Drug Association Approval Process for Devices Used in Endovascular Treatment of Stroke

Purpose of the ReviewThis article reviews the Food and Drug Administration's (FDA’s) process for approval of new medical devices and describes the evolution of endovascular devices used for the treatment of acute ischemic stroke.Recent FindingsSeveral recent studies have established the benefit of endovascular treatment of acute ischemic stroke from emergent large vessel occlusion. This has led to endovascular treatment becoming the usual care in acute stroke management and has generated greater-than-ever interest in the development of newer and more effective devices.SummaryIn the United States, the FDA is the regulatory authority that is empowered with the approval and monitoring of new medical devices for widespread use in the population. The FDA categorizes medical devices into 3 classes based mainly on their potential risks to patients and/or users; class I devices pose the least risk and have the least stringent approval process, while class III devices pose the highest risk and undergo the most stringent and time-consuming approval process. There are 4 main pathways to approval: premarket notification, also known as the 510(k) pathway; premarket approval (PMA), de novo, and Humanitarian Device Exemption pathway. These pathways are described in detail in the article. The FDA also mandates postmarketing surveillance to identify any untoward and unexpected long-term complications.

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Secondary Medium Vessel Occlusions

Stroke ◽

10.1161/strokeaha.120.032799 ◽

2021 ◽

Author(s):

Mayank Goyal ◽

Manon Kappelhof ◽

Rosalie McDonough ◽

Johanna Maria Ospel

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

De Novo ◽

Treatment Strategies ◽

Intravenous Thrombolysis ◽

Large Vessel ◽

Vessel Occlusion ◽

Different Types ◽

Underlying Mechanisms

Medium vessel occlusions (MeVOs, ie, M2, M3, A2, A3, P2, and P3 segment occlusions) are increasingly recognized as a target for endovascular treatment in acute ischemic stroke. It is important to note that not all MeVOs are equal. Primary MeVOs occur de novo with the underlying mechanisms being very similar to large vessel occlusion strokes. Secondary MeVOs arise from large vessel occlusions through clot migration or fragmentation, either spontaneously or following treatment with intravenous thrombolysis or endovascular treatment. Currently, there are little data on the prevalence, management, and prognosis of acute ischemic stroke due to secondary MeVOs. This type of stroke is, however, likely to become more relevant in the future as indications for endovascular treatment continue to broaden. In this article, we describe different types of secondary MeVOs, imaging findings associated with them, challenges related to the diagnosis of secondary MeVOs, and their potential implications for treatment strategies and clinical outcomes.

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Outcome of endovascular treatment within and beyond 6 h without perfusion software

Scientific Reports ◽

10.1038/s41598-021-84857-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhen Jing ◽

Hao Li ◽

Shengming Huang ◽

Min Guan ◽

Yongxin Li ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

General Anesthesia ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Symptom Onset ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Group A ◽

Group B

AbstractEndovascular treatment (EVT) has been accepted as the standard of care for patients with acute ischemic stroke. The aim of the present study was to compare clinical outcomes of patients who received EVT within and beyond 6 h from symptom onset to groin puncture without perfusion software in Guangdong district, China. Between March 2017 and May 2018, acute ischemic stroke patients who received EVT from 6 comprehensive stroke centers, were enrolled into the registry study. In this subgroup study, we included all patients who had acute proximal large vessel occlusion in the anterior circulation. The demographic, clinical and neuroimaging data were collected from each center. A total of 192 patients were included in this subgroup study. They were divided into two groups: group A (n = 125), within 6 h; group B (n = 67), 6–24 h from symptom onset to groin puncture. There were no substantial differences between these two groups in terms of 90 days favorable outcome (modified Rankin scale [mRS] ≤ 2, P = 0.051) and mortality (P = 0.083), and the risk of symptomatic intracranial hemorrhage at 24 h (P = 0.425). The NIHSS (median 16, IQR12-20, group A; median 12, IQR8-18, group B; P = 0.009) and ASPECTS (median 10, IQR8-10, group A; median 9, IQR8-10, group B; P = 0.034) at baseline were higher in group A. The anesthesia method (general anesthesia, 21.3%, group A vs. 1.5% group B, P = 0.001) were also statistically different between the two groups. The NIHSS and ASPECTS were higher, and general anesthesia was also more widely used in group A. Clinical outcomes were not significantly different within 6 h versus 6–24 h from symptom onset to groin puncture in this real world study.

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Effect of “drip-and-ship” and “drip-and-drive” on endovascular treatment of acute ischemic stroke with large vessel occlusion: a single-center retrospective study

Acta Radiologica ◽

10.1177/02841851211006897 ◽

2021 ◽

pp. 028418512110068

Author(s):

Yu Hang ◽

Zhen Yu Jia ◽

Lin Bo Zhao ◽

Yue Zhou Cao ◽

Huang Huang ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Vessel Occlusion ◽

Primary Stroke Center ◽

Secondary Endpoints ◽

Comprehensive Stroke Center ◽

Stroke Center

Background Patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) were usually transferred from a primary stroke center (PSC) to a comprehensive stroke center (CSC) for endovascular treatment (drip-and-ship [DS]), while driving the doctor from a CSC to a PSC to perform a procedure is an alternative strategy (drip-and-drive [DD]). Purpose To compare the efficacy and prognosis of the two strategies. Material and Methods From February 2017 to June 2019, 62 patients with LVO received endovascular treatment via the DS and DD models and were retrospectively analyzed from the stroke alliance based on our CSC. Primary endpoint was door-to-reperfusion (DTR) time. Secondary endpoints included puncture-to-recanalization (PTR) time, modified Thrombolysis in Cerebral Infarction (mTICI) rates at the end of the procedure, and modified Rankin Scale (mRS) at 90 days. Results Forty-one patients received the DS strategy and 21 patients received the DD strategy. The DTR time was significantly longer in the DS group compared to the DD group (315.5 ± 83.8 min vs. 248.6 ± 80.0 min; P < 0.05), and PTR time was shorter (77.2 ± 35.9 min vs. 113.7 ± 69.7 min; P = 0.033) compared with the DD group. Successful recanalization (mTICI 2b/3) was achieved in 89% (36/41) of patients in the DS group and 86% (18/21) in the DD group ( P = 1.000). Favorable functional outcomes (mRS 0–2) were observed in 49% (20/41) of patients in the DS group and 71% (15/21) in the DD group at 90 days ( P = 0.089). Conclusion Compared with the DS strategy, the DD strategy showed more effective and a trend of better clinical outcomes for AIS patients with LVO.

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Abstract TP1: The Promising System to Support Rural Area Where No Intervenitionists to Perform Embolectomy for Acute Ischemic Stroke "Drive and Retrieve Method"

Stroke ◽

10.1161/str.48.suppl_1.tp1 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Toshiya Osanai

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Rural Area ◽

Median Time ◽

Prospective Trial ◽

Large Vessel ◽

Full Time ◽

Large Vessel Occlusion ◽

Vessel Occlusion

Introduction: In Japan, endovascular treatment for acute ischemic stroke from large vessel occlusion should be performed by neurointerventionists. However, most hospitals in rural area , that offer treatment for cerebral vascular disease do not have access to a neurointerventionist; the rural areas are especially affected. Thus, Our University has offered support to institutions without a neurointerventionist, to perform endovascular treatment. The neurointerventionists stationed in other hospitals drive to retrieve the resultant clot since the acute ischemic stroke from large vessel occlusion. We called this the “drive and retrieve system” method, and launched the prospective trial to evaluate the validity and efficacy of this method. Herein, we report the initial results of this trial. Methods: Nine institutes across our affiliated hospitals within a one-hour drive from Sapporo City took part in this trial. Three of these 9 institutes that have a full-time neurointerventionist were registered as the source. When an episode of acute ischemic stroke requiring intervention occurred in the other 6 hospitals, the available neurointerventionist provided treatment based on the drive and retrieve method. The neurointerventionists’ schedules was updated and distributed to all participating units twice a week, so that the supported hospitals could immediately make contact when required. We analysis the data of 44 cases in this trial from July 2015 to April 2016. Results: For 41 out of 44 cases (93%), Neurointerventionaists were able to respond immediately. The median time from door-to-puncture was 90 min (interquartile range [IQR]: 72-125). The median time from puncture to recanalization was also 76 min (IQR: 57.5-99.5). The recanalization rate (TICI 2b/3) was 77 %. mRS 0-2 was 39%. Conclusion: The drive and retrieve system has the potential to support rural medical institutes that do not have access to a full-time neurointerventionist.

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Identification of Barriers to Access Endovascular Treatment for Acute Ischemic Stroke in the Health Care System of Mexico: Results From a National Survey Among Endovascular Neurologists

Frontiers in Neurology ◽

10.3389/fneur.2021.601328 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fernando Gongora-Rivera ◽

Alejandro Gonzalez-Aquines ◽

Juan Manuel Marquez-Romero ◽

Keyword(s):

Latin America ◽

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Medical Devices ◽

Public Funding ◽

National Health System ◽

Health Coverage ◽

Barriers To Access ◽

Barriers And Challenges

Background: Providing endovascular treatment (EVT) access for acute ischemic stroke (AIS) is a challenge in Latin America. Even though the Mexican Endovascular Reperfusion Registry (MERR) and the RESILIENT trial have demonstrated the feasibility of EVT of AIS in Latin America, the MERR has uncovered potential challenges to delivering EVT to AIS patients.Aim: To identify the perceived barriers to access EVT for AIS in Mexico.Methods: We surveyed endovascular neurologists in Mexico. The survey addressed the situation of thrombectomy in the country and the infrastructure and resources available in the participants' institutions. The questionnaire inquired about costs, barriers, and challenges to accessing EVT for AIS, emphasizing the prices and availability of medical devices needed for EVT.Results: We analyzed data from 21 hospitals. The most extreme identified barriers to access EVT were the lack of health coverage for EVT in the National Health System, the cost of the medical supplies for EVT, and inadequate knowledge of stroke symptoms in the general population. The median cost for EVT was USD 20,000 (IQR 7,500–20,000). From this amount, 60% (IQR 50–70%) corresponded to the costs involved with medical devices. EVT carried additional out-of-pocket costs in 90% of the hospitals, and in 57%, the costs exceed USD $10,000.Conclusion: Efforts at all government levels and society are required to tackle these barriers. An increase in and efficient use of public funding for EVT coverage and the deployment of continuous and targeted stroke education campaigns could reduce inequities in EVT access in Mexico.

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Predictors of parenchymal hemorrhage after endovascular treatment in acute ischemic stroke: data from ANGEL-ACT Registry

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2021-018292 ◽

2022 ◽

pp. neurintsurg-2021-018292

Author(s):

Dapeng Sun ◽

Baixue Jia ◽

Xu Tong ◽

Peter Kan ◽

Xiaochuan Huo ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Multivariable Analysis ◽

Serum Glucose ◽

Chinese Patients ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Atherosclerotic Stenosis

BackgroundParenchymal hemorrhage (PH) is a troublesome complication after endovascular treatment (EVT).ObjectiveTo investigate the incidence, independent predictors, and clinical impact of PH after EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO).MethodsSubjects were selected from the ANGEL-ACT Registry. PH was diagnosed according to the European Collaborative Acute Stroke Study classification. Logistic regression analyses were performed to determine the independent predictors of PH, as well as the association between PH and 90-day functional outcome assessed by modified Rankin Scale (mRS) score.ResultsOf the 1227 enrolled patients, 147 (12.0%) were diagnosed with PH within 12–36 hours after EVT. On multivariable analysis, low admission Alberta Stroke Program Early CT score (ASPECTS)(adjusted OR (aOR)=1.13, 95% CI 1.02 to 1.26, p=0.020), serum glucose >7 mmol/L (aOR=1.82, 95% CI 1.16 to 2.84, p=0.009), and neutrophil-to-lymphocyte ratio (NLR; aOR=1.05, 95% CI 1.02 to 1.09, p=0.005) were associated with a high risk of PH, while underlying intracranial atherosclerotic stenosis (ICAS; aOR=0.42, 95% CI 0.22 to 0.81, p=0.009) and intracranial angioplasty/stenting (aOR=0.37, 95% CI 0.15 to 0.93, p=0.035) were associated with a low risk of PH. Furthermore, patients with PH were associated with a shift towards to worse functional outcome (mRS score 4 vs 3, adjusted common OR (acOR)=2.27, 95% CI 1.53 to 3.38, p<0.001).ConclusionsIn Chinese patients with AIS caused by anterior circulation LVO, the risk of PH was positively associated with low admission ASPECTS, serum glucose >7 mmol/L, and NLR, but negatively related to underlying ICAS and intracranial angioplasty/stenting.Trial registration numberNCT03370939.

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Abstract TP19: Clinical Outcomes In Patients With Acute Ischemic Stroke Due To Large Vessel Occlusion In The Modern Era: 2010-2011 Experience With 423 Patients.

Stroke ◽

10.1161/str.44.suppl_1.atp19 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Maxim Mokin ◽

Tareq Kass-Hout ◽

Omar Kass-Hout ◽

Erol Veznedaroglu ◽

Fadi Nahab ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Medical Management ◽

Mortality Rates ◽

Artery Occlusion ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Vessel Occlusion

Background and Purpose: Acute ischemic stroke due to large vessel occlusion is associated with a poor prognosis. With no consensus about the best treatment option, various treatment modalities including conservative management, intravenous tissue plasminogen activator, and endovascular approach are currently being used. Methods: Retrospective data including demographic information, baseline NIHSS score, site of occlusion (based on CTA, MRA or angiogram), type of treatment and clinical outcomes were collected from 4 centers in the United States during the period of 2010-2011. Results: A total of 423 were included in final analysis: 175 patients received conservative medical management, 54 patients received intravenous (IV) thrombolysis alone, and 194 patients had endovascular treatment (with or without prior IV tPA). Younger patients were more likely to receive endovascular treatment (p<0.001). There was no statistically significant difference among the sex and co-morbid conditions among the three groups. Proximal middle cerebral artery was the most commonly involved vessel. Strokes due to basilar artery occlusion or internal carotid artery occlusion were associated with worst outcomes in all three groups. Conservative medical management had the lowest rates of symptomatic intracerebral hemorrhage but also the highest mortality rates at 3 months. Patients who received endovascular treatment within the first 3 hrs had better outcome and lower mortality rates as compared to patients with intervention during 3-8 hours or beyond 8 hrs. Conclusions: Our study represents real world experience on the management and outcomes of acute ischemic strokes due to large vessel occlusion. Our results help understand natural history of strokes with large vessel occlusion, as well as modern trends in managing these patients with intravenous and intraarterial treatment approaches.

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Abstract 3314: The Role of Bridging with Intravenous Thrombolysis in Endovascular Therapy of Acute Ischemic Stroke.

Stroke ◽

10.1161/str.43.suppl_1.a3314 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Omar Kass-Hout ◽

Tareq Kass-Hout ◽

Maxim Mokin ◽

David Orion ◽

Shadi Jahshan ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Endovascular Therapy ◽

Combined Therapy ◽

Large Vessel ◽

P Value ◽

Large Vessel Occlusion ◽

Vessel Occlusion ◽

Nihss Score

Background: Large vessel occlusions with a high clot burden are less likely to improve with the FDA-approved IV strategy. Endovascular therapy within the first 3 h of stroke symptom onset provides an effective alternative treatment in patients with large vessel occlusion. It is not clear if combination of IV thrombolysis and endovascular approach is superior to endovascular treatment alone. Methods: We retrospectively reviewed all cases of acute ischemic stroke with large vessel occlusion treated within the first 3 h stroke onset during the 2005-2010 period. First group received endovascular therapy within the first 3 h of stroke onset. Second group consisted of patients who received IV thrombolysis within the first 3 h followed by endovascular therapy. We compared the following outcomes: revascularization rates, NIHSS score at discharge, mRS at discharge and 3months, symptomatic hemorrhage rates and mortality. Results: Among 104 patients identified, 42 received combined therapy, and 62 received endovascular therapy only. The two groups had similar demographic (age and sex distribution) and vascular risk factors distribution, as well as NIHSS score on admission (14.8±4.7 and 16.0±5.3; p=0.23). We found no difference in TIMI recanalization rates (Thrombolysis in Myocardial Infarction scale score of 2 or 3) following combined or endovascular therapy alone (83.3% and 79.0%; p=0.59). A preferred outcome, defined as a mRS of 2 or less at 90 days also did not differ between the combined therapy group and the endovascular only group (37.5% and 34.5%; p=0.76). There was no difference in mortality rate (22.5% and 31.0%; p=0.36) and the rate of symptomatic intracranial hemorrhage (9.5% and 8.1%; p=0.73). There was a significant difference in mean time from symptom onset to endovascular treatment between the combined group (227±88 min) and endovascular only group (125±40 min; p<0.0001).Patients with good TIMI recanalization rate of 2 or 3 showed a trend of having a better mRS at 90 days in both bridging (16.67% vs. 41.18%, p-value: 0.3813) and endovascular groups (25% vs. 34.78%, p-value: 0.7326).When analyzing the correlation of mRS at 90 days with the site of occlusion, patients in the bridging group showed a trend of a better outcome when the site of occlusion was ICA (33.3% vs 30%) and MCA (66.67% vs. 27.59%) and worse outcome when the site of occlusion was in the posterior circulation (26.32% vs. 50%), however, these results were not statistically significant (p-values: 0.1735& 0.5366). Conclusion: Combining IV thrombolysis and endovascular therapy achieves similar rates of clinical outcomes, revascularization rates, complications and mortality rates, when compared with endovascular treatment alone. The combined therapy, however, significantly delays initiation of endovascular treatment. A randomized prospective trial comparing both treatment strategies in acute ischemic stroke is warranted

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Abstract TP18: Endovascular Treatment in the Elderly with Acute Ischemic Stroke - Is it Safe in Clinical Practice?

Stroke ◽

10.1161/str.48.suppl_1.tp18 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Thabele M Leslie-Mazwi ◽

Syed F Ali ◽

Sanjeeva R Onteddu ◽

Adewumi D Amole ◽

Mehmet S Akdol ◽

...

Keyword(s):

Ischemic Stroke ◽

Hospital Mortality ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Univariate Analysis ◽

The Elderly ◽

Stroke Patients ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Younger Patients

Introduction: An overwhelming benefit from endovascular treatment (EVT) of acute ischemic stroke (AIS) has been shown in recent trials, making it the new evidence-based standard of care for ischemic stroke due to anterior circulation large vessel occlusion. We sought to determine usage, safety and efficacy of EVT in patients ≥80 years of age. Methods: Using GWTG stroke registry data from MGH and UAMS, we analyzed 7,505 consecutive stroke admissions from 01/2009 - 06/2016. Univariate analysis was carried out to compare AIS patients < 80 vs. those ≥ 80yr. Results: Of the total 7,505 AIS patients, 3,722 presented within 12 hr of last known well and of these 334 (334/3722, 9%) underwent EVT. The majority of AIS patients undergoing EVT were younger than 80yr of age (264/334, 79%). Of the patients who underwent EVT, younger patients were more often male, Caucasian, and had stroke risk factors of atrial fibrillation, CAD, hypertension and smokers. The two groups were similar in NIHSS, initial clinical presentation, modified pre-stroke Rankin scale of ≤ 3, and initiation of tPA as a drip and ship or stroke center front-door administration. Higher rates of pneumonia were observed in younger patients while rates of sICH were similar. Younger patients were more often discharged to home/inpatient rehabilitation facility. On univariate analysis, in-hospital mortality was significantly higher in patients ≥ 80yr [Unadj. OR 2.50 (1.24, 5.03), p=0.01], however the strength of the association attenuated substantially after adjusting for significant covariates [Adj. OR 2.34 (0.99, 5.47), p=0.05] (Table). Conclusion: Elderly stroke patients are largely excluded from clinical trials and data are limited on the effectiveness of EVT in this cohort. Our results showed that rate of sICH and adjusted in-hospital mortality was not statistically different between those < 80yr vs. ≥ 80yr. Further studies are needed to explore the functional outcome of the elderly stroke patients undergoing EVT.

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Workflow Intervals of Endovascular Acute Stroke Therapy During On- Versus Off-Hours

Stroke ◽

10.1161/strokeaha.119.025381 ◽

2019 ◽

Vol 50 (10) ◽

pp. 2842-2850 ◽

Cited By ~ 3

Author(s):

Wouter H. Hinsenveld ◽

Inger R. de Ridder ◽

Robert J. van Oostenbrugge ◽

Jan A. Vos ◽

Adrien E. Groot ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Large Vessel ◽

Complication Rates ◽

Large Vessel Occlusion ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Significant Difference

Background and Purpose— Endovascular treatment (EVT) of patients with acute ischemic stroke because of large vessel occlusion involves complicated logistics, which may cause a delay in treatment initiation during off-hours. This might lead to a worse functional outcome. We compared workflow intervals between endovascular treatment–treated patients presenting during off- and on-hours. Methods— We retrospectively analyzed data from the MR CLEAN Registry, a prospective, multicenter, observational study in the Netherlands and included patients with an anterior circulation large vessel occlusion who presented between March 2014 and June 2016. Off-hours were defined as presentation on Monday to Friday between 17:00 and 08:00 hours, weekends (Friday 17:00 to Monday 8:00) and national holidays. Primary end point was first door to groin time. Secondary end points were functional outcome at 90 days (modified Rankin Scale) and workflow time intervals. We stratified for transfer status, adjusted for prognostic factors, and used linear and ordinal regression models. Results— We included 1488 patients of which 936 (62.9%) presented during off-hours. Median first door to groin time was 140 minutes (95% CI, 110–182) during off-hours and 121 minutes (95% CI, 85–157) during on-hours. Adjusted first door to groin time was 14.6 minutes (95% CI, 9.3–20.0) longer during off-hours. Door to needle times for intravenous therapy were slightly longer (3.5 minutes, 95% CI, 0.7–6.3) during off-hours. Groin puncture to reperfusion times did not differ between groups. For transferred patients, the delay within the intervention center was 5.0 minutes (95% CI, 0.5–9.6) longer. There was no significant difference in functional outcome between patients presenting during off- and on-hours (adjusted odds ratio, 0.92; 95% CI, 0.74–1.14). Reperfusion rates and complication rates were similar. Conclusions— Presentation during off-hours is associated with a slight delay in start of endovascular treatment in patients with acute ischemic stroke. This treatment delay did not translate into worse functional outcome or increased complication rates.

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