BackgroundAlthough CT perfusion (CTP) is often incorporated in acute stroke workflows, it remains largely unclear what the associated costs and health implications are in the long run of CTP-based... Show moreBackgroundAlthough CT perfusion (CTP) is often incorporated in acute stroke workflows, it remains largely unclear what the associated costs and health implications are in the long run of CTP-based patient selection for endovascular treatment (EVT) in patients presenting within 6 hours after symptom onset with a large vessel occlusion.MethodsPatients with a large vessel occlusion were included from a Dutch nationwide cohort (n=703) if CTP imaging was performed before EVT within 6 hours after stroke onset. Simulated cost and health effects during 5 and 10 years follow-up were compared between CTP based patient selection for EVT and providing EVT to all patients. Outcome measures were the net monetary benefit at a willingness-to-pay of euro80 000 per quality-adjusted life year, incremental cost-effectiveness ratio), difference in costs from a healthcare payer perspective (Delta Costs) and quality-adjusted life years (Delta QALY) per 1000 patients for 1000 model iterations as outcomes.ResultsCompared with treating all patients, CTP-based selection for EVT at the optimised ischaemic core volume (ICV >= 110 mL) or core-penumbra mismatch ratio (MMR <= 1.4) thresholds resulted in losses of health (median Delta QALYs for ICV >= 110 mL: -3.3 (IQR: -5.9 to -1.1), for MMR <= 1.4: 0.0 (IQR: -1.3 to 0.0)) with median Delta Costs for ICV >= 110 mL of -euro348 966 (IQR: -euro712 406 to -euro51 158) and for MMR <= 1.4 of euro266 513 (IQR: euro229 403 to euro380 110)) per 1000 patients. Sensitivity analyses did not yield any scenarios for CTP-based selection of patients for EVT that were cost-effective for improving health, including patients aged >= 80 yearsConclusionIn EVT-eligible patients presenting within 6 hours after symptom onset, excluding patients based on CTP parameters was not cost-effective and could potentially harm patients. Show less
Background: Endovascular thrombectomy (EVT) through femoral access is difficult to perform in some patients with acute ischemic stroke due to challenging vasculature. We compared outcomes of EVT... Show moreBackground: Endovascular thrombectomy (EVT) through femoral access is difficult to perform in some patients with acute ischemic stroke due to challenging vasculature. We compared outcomes of EVT through femoral versus alternative arterial access. Methods: In this observational study, we included patients from the MR CLEAN Registry who underwent EVT for acute ischemic stroke in the anterior circulation between 2014 and 2019 in the Netherlands. Patients who underwent EVT through alternative and femoral access were matched on propensity scores in a 1:3 ratio. The primary endpoint was favorable functional outcome (modified Rankin Scale score ≤ 2) at 90 days. Secondary endpoints were early neurologic recovery, mortality, successful intracranial reperfusion and puncture related complications. Results: Of the 5197 included patients, 17 patients underwent EVT through alternative access and were matched to 48 patients who underwent EVT through femoral access. Alternative access was obtained through the common carotid artery (n = 15/17) and brachial artery (n = 2/17). Favorable functional outcome was less often observed after EVT through alternative than femoral access (18% versus 27%; aOR, 0.36; 95% CI, 0.05–2.74). The rate of successful intracranial reperfusion was higher for alternative than femoral access (88% versus 58%), although mortality (59% versus 31%) and puncture related complications (29% versus 0%) were more common after alternative access. Conclusions: EVT through alternative arterial access is rarely performed in the Netherlands and seems to be associated with worse outcomes than standard femoral access. A next step would be to compare the additional value of EVT through alternative arterial access after failure of femoral access. Show less
Background Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment... Show moreBackground Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA).Methods MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220. Findings Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1 center dot 67 [95% CI 1 center dot 20-2 center dot 32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0 center dot 72 [95% CI 0 center dot 44-1 center dot 18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4 center dot 59 [95% CI 1 center dot 49-14 center dot 10]). Interpretation In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow.Funding Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.Copyright (c) 2023 Elsevier Ltd. All rights reserved. Show less
Steen, W. van der; Ende, N.A.M. van der; Kranendonk, K.R. van; Chalos, V.; Oostenbrugge, R.J. van; Zwam, W.H. van; ... ; MR CLEAN Trial MR CLEAN Registry 2022
BACKGROUND: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location... Show moreBACKGROUND: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location.METHODS: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue.RESULTS: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06-2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02-1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI 1.16-2.78]).CONCLUSIONS: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms.[GRAPHICS]. Show less
Background: In patients with large vessel occlusion stroke of the anterior circulation, underlying cause is a determinant of outcome. Whether this is the case for posterior circulation large vessel... Show moreBackground: In patients with large vessel occlusion stroke of the anterior circulation, underlying cause is a determinant of outcome. Whether this is the case for posterior circulation large vessel occlusion stroke has yet to be determined. We aimed to report on cause in patients with posterior circulation stroke treated with endovascular thrombectomy and to analyze the association with functional outcome. Methods: We used data of patients with posterior circulation stroke included in the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) registry, a prospective multicenter observational study, between 2014 and 2018. Stroke cause was categorized into large artery atherosclerosis (LAA), cardioembolism, arterial dissection, embolic stroke of undetermined source (ESUS), other determined cause, or undetermined cause. For primary analysis on the association between cause and outcome, we used multivariable ordinal logistic regression analysis to estimate the adjusted common odds ratio for a shift towards a better functional outcome on the modified Rankin Scale at 90 days with LAA as a reference group. Secondary outcomes included favorable functional outcome (modified Rankin Scale score 0-3), National Institutes of Health Stroke Scale score at 24 to 48 hours, reperfusion on digital subtraction angiography, and stroke progression. Results: Of 264 patients with posterior circulation stroke, 84 (32%) had LAA, 48 (18%) cardioembolism, 31 (12%) dissection, and 14 (5%) ESUS. Patients with a dissection were younger (48 [interquartile range, 43-60] years) and had a lower National Institutes of Health Stroke Scale at baseline (12 [interquartile range, 6-31]) than patients with other cause. Functional outcome was better for patients with cardioembolism and ESUS compared to LAA (modified Rankin Scale adjusted common odds ratio, 2.4 [95% CI, 1.1-5.2], respectively adjusted common odds ratio, 3.1 [95% CI, 1.0-9.3]). Patients with a dissection had a lower chance of successful reperfusion compared with LAA (adjusted odds ratio, 0.20 [95% CI, 0.06-0.70]). Conclusions: Unlike the anterior circulation, most frequent cause in our posterior large vessel occlusion stroke cohort is LAA followed by cardioembolism, dissection, and ESUS. Patients with cardioembolism and ESUS have a better prognosis for functional outcome after endovascular thrombectomy than patients with LAA. Show less
Background The effects of thrombus imaging characteristics on procedural and clinical outcomes after ischemic stroke are increasingly being studied. These thrombus characteristics - for eg, size,... Show moreBackground The effects of thrombus imaging characteristics on procedural and clinical outcomes after ischemic stroke are increasingly being studied. These thrombus characteristics - for eg, size, location, and density - are commonly analyzed as separate entities. However, it is known that some of these thrombus characteristics are strongly related. Multicollinearity can lead to unreliable prediction models. We aimed to determine the distribution, correlation and clustering of thrombus imaging characteristics based on a large dataset of anterior-circulation acute ischemic stroke patients. Methods We measured thrombus imaging characteristics in the MR CLEAN Registry dataset, which included occlusion location, distance from the intracranial carotid artery to the thrombus (DT), thrombus length, density, perviousness, and clot burden score (CBS). We assessed intercorrelations with Spearman's coefficient (rho) and grouped thrombi based on 1) occlusion location and 2) thrombus length, density and perviousness using unsupervised clustering. Results We included 934 patients, of which 22% had an internal carotid artery (ICA) occlusion, 61% M1, 16% M2, and 1% another occlusion location. All thrombus characteristics were significantly correlated. Higher CBS was strongly correlated with longer DT (rho=0.67, p<0.01), and moderately correlated with shorter thrombus length (rho=-0.41, p<0.01). In more proximal occlusion locations, thrombi were significantly longer, denser, and less pervious. Unsupervised clustering analysis resulted in four thrombus groups; however, the cohesion within and distinction between the groups were weak. Conclusions Thrombus imaging characteristics are significantly intercorrelated - strong correlations should be considered in future predictive modeling studies. Clustering analysis showed there are no distinct thrombus archetypes - novel treatments should consider this thrombus variability. Show less
Compagne, K.C.J.; Kappelhof, M.; Hinsenveld, W.H.; Brouwer, J.; Goldhoorn, R.J.B.; Uyttenboogaart, M.; ... ; MR CLEAN Registry Investigators 2022
Background: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to... Show moreBackground: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes. Methods: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days). Results: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; PP<0.001, respectively). Successful reperfusion was achieved more often in the second than in the first cohort (72% versus 66%; P<0.001). Functional outcome significantly improved (adjusted common odds ratio 1.23 [95% CI, 1.07-1.40]). This effect was attenuated by adjustment for time from onset to reperfusion (adjusted common odds ratio, 1.12 [95% CI, 0.98-1.28]) and successful reperfusion (adjusted common odds ratio, 1.13 [95% CI, 0.99-1.30]). Outcomes were consistent in the analysis per chronological quartile. Conclusions: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates. Show less
Thrombus volume in posterior circulation stroke (PCS) has been associated with outcome, through recanalization. Manual thrombus segmentation is impractical for large scale analysis of image... Show moreThrombus volume in posterior circulation stroke (PCS) has been associated with outcome, through recanalization. Manual thrombus segmentation is impractical for large scale analysis of image characteristics. Hence, in this study we develop the first automatic method for thrombus localization and segmentation on CT in patients with PCS. In this multi-center retrospective study, 187 patients with PCS from the MR CLEAN Registry were included. We developed a convolutional neural network (CNN) that segments thrombi and restricts the volume-of-interest (VOI) to the brainstem (Polar-UNet). Furthermore, we reduced false positive localization by removing small-volume objects, referred to as volume-based removal (VBR). Polar-UNet is benchmarked against a CNN that does not restrict the VOI (BL-UNet). Performance metrics included the intra-class correlation coefficient (ICC) between automated and manually segmented thrombus volumes, the thrombus localization precision and recall, and the Dice coefficient. The majority of the thrombi were localized. Without VBR, Polar-UNet achieved a thrombus localization recall of 0.82, versus 0.78 achieved by BL-UNet. This high recall was accompanied by a low precision of 0.14 and 0.09. VBR improved precision to 0.65 and 0.56 for Polar-UNet and BL-UNet, respectively, with a small reduction in recall to 0.75 and 0.69. The Dice coefficient achieved by Polar-UNet was 0.44, versus 0.38 achieved by BL-UNet with VBR. Both methods achieved ICCs of 0.41 (95% CI: 0.27-0.54). Restricting the VOI to the brainstem improved the thrombus localization precision, recall, and segmentation overlap compared to the benchmark. VBR improved thrombus localization precision but lowered recall. Show less
Introduction: Computed tomography perfusion (CTP) is variably considered to assess eligibility for endovascular thrombectomy (EVT) in acute ischemic (AIS) stroke patients. Although CTP is... Show moreIntroduction: Computed tomography perfusion (CTP) is variably considered to assess eligibility for endovascular thrombectomy (EVT) in acute ischemic (AIS) stroke patients. Although CTP is recommended for patient selection in later (6-24 h) time window, it is currently not recommended in the earlier (0-6 h) time window and the costs and health effects of including CTP for EVT selection remain unknown. We aim to estimate the costs and health effects of using CTP for EVT selection in AIS patients compared to conventional selection. Patients and methods: CLEOPATRA is a healthcare evaluation study using clinical and imaging data from multiple, prospective EVT trials and registries in both the earlier and later time windows. To study the long-term health and cost effects, we will construct a ("Markov") health state transition model simulating the clinical outcome over a 5-year follow-up period for CTP-based and conventional selection for EVT. Clinical data acquired within the current study and estimates from the literature will be used as input for probabilities of events, costs, and Quality-Adjusted Life Years (QALYs) per modified Rankin Scale (mRS) subscore. Primary outcome for the cost-effectiveness analysis will be the Incremental Cost-Effectiveness Ratio (ICER) in terms of costs per QALY gained over the simulated follow-up period. Study outcomes: Outcome measures will be reported as cumulative values over a 5-year follow-up period. Discussion: This study will provide preliminary insight into costs and health effects of including CTP in the selection for EVT for AIS patients, presenting between 0 and 24 h after time last known well. The results may be used to develop recommendations and inform further implementation projects and studies. Show less
Background Pre-stroke dependent patients (modified Rankin Scale score (mRS) >= 3) were excluded from most trials on endovascular treatment (EVT) for acute ischemic stroke (AIS) in the anterior... Show moreBackground Pre-stroke dependent patients (modified Rankin Scale score (mRS) >= 3) were excluded from most trials on endovascular treatment (EVT) for acute ischemic stroke (AIS) in the anterior circulation. Therefore, little evidence exists for EVT in those patients. We aimed to investigate the safety and benefit of EVT in pre-stroke patients with mRS score 3. Methods We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic stroke in the Netherlands (MR CLEAN) Registry. All patients treated with EVT for anterior circulation AIS with pre-stroke mRS 3 were included. We assessed causes for dependence and compared patients with successful reperfusion (defined as expanded Thrombolysis in Cerebral Ischemia scale (eTICI) 2b-3) to patients without successful reperfusion. We used regression analyses with pre-specified adjustments. Our primary outcome was 90-day mRS 0-3 (functional improvement or return to baseline). Results A total of 192 patients were included, of whom 82 (43%) had eTICI <2b and 108 (56%) eTICI >= 2b. The median age was 80 years (IQR 73-87). Fifty-one of the 192 patients (27%) suffered from previous stroke and 36/192 (19%) had cardiopulmonary disease. Patients with eTICI >= 2b more often returned to their baseline functional state or improved (n=26 (26%) vs n=15 (19%); adjusted odds ratio (aOR) 2.91 (95% CI 1.08 to 7.82)) and had lower mortality rates (n=49 (49%) vs n=50 (64%); aOR 0.42 (95% CI 0.19 to 0.93)) compared with patients with eTICI Conclusions Although patients with AIS with pre-stroke mRS 3 comprise a heterogenous group of disability causes, we observed improved outcomes when patients achieved successful reperfusion after EVT. Show less
Ramos, L.A.; Os, H. van; Hilbert, A.; Olabarriaga, S.D.; Lugt, A. van der; Roos, Y.B.W.E.M.; ... ; Marquering, H.A. 2022
Background: Accurate prediction of clinical outcome is of utmost importance for choices regarding the endovascular treatment (EVT) of acute stroke. Recent studies on the prediction modeling for... Show moreBackground: Accurate prediction of clinical outcome is of utmost importance for choices regarding the endovascular treatment (EVT) of acute stroke. Recent studies on the prediction modeling for stroke focused mostly on clinical characteristics and radiological scores available at baseline. Radiological images are composed of millions of voxels, and a lot of information can be lost when representing this information by a single value. Therefore, in this study we aimed at developing prediction models that take into account the whole imaging data combined with clinical data available at baseline. Methods: We included 3,279 patients from the MR CLEAN Registry; a prospective, observational, multicenter registry of patients with ischemic stroke treated with EVT. We developed two approaches to combine the imaging data with the clinical data. The first approach was based on radiomics features, extracted from 70 atlas regions combined with the clinical data to train machine learning models. For the second approach, we trained 3D deep learning models using the whole images and the clinical data. Models trained with the clinical data only were compared with models trained with the combination of clinical and image data. Finally, we explored feature importance plots for the best models and identified many known variables and image features/brain regions that were relevant in the model decision process. Results: From 3,279 patients included, 1,241 (37%) patients had a good functional outcome [modified Rankin Scale (mRS) <= 2] and 1,954 (60%) patients had good reperfusion [modified Thrombolysis in Cerebral Infarction (eTICI) >= 2b]. There was no significant improvement by combining the image data to the clinical data for mRS prediction [mean area under the receiver operating characteristic (ROC) curve (AUC) of 0.81 vs. 0.80] above using the clinical data only, regardless of the approach used. Regarding predicting reperfusion, there was a significant improvement when image and clinical features were combined (mean AUC of 0.54 vs. 0.61), with the highest AUC obtained by the deep learning approach. Conclusions: The combination of radiomics and deep learning image features with clinical data significantly improved the prediction of good reperfusion. The visualization of prediction feature importance showed both known and novel clinical and imaging features with predictive values. Show less
Terreros, N.A.; Bruggeman, A.A.E.; Voorst, H. van; Konduri, P.R.; Jansen, I.G.H.; Kappelhof, M.; ... ; Majoie, C.B.L.M. 2022
Background: A thrombus in the M1 segment of the middle cerebral artery (MCA) can occlude this main stem only or extend into the M1-M2 bifurcation. The occlusion pattern may affect endovascular... Show moreBackground: A thrombus in the M1 segment of the middle cerebral artery (MCA) can occlude this main stem only or extend into the M1-M2 bifurcation. The occlusion pattern may affect endovascular treatment (EVT) success, as a bifurcated thrombus may be more prone to fragmentation during retrieval.Objective: To investigate whether bifurcated thrombus patterns are associated with EVT procedural and clinical outcomes.Methods: Occlusion patterns of MCA thrombi on CT angiography from MR CLEAN Registry patients were classified into three groups: main stem occlusion, bifurcation occlusion extending into one M2 branch, and bifurcation occlusion extending into both M2 branches. Procedural parameters, procedural outcomes (reperfusion grade and embolization to new territory), and clinical outcomes (24-48 hour National Institutes of Health Stroke Scale [NIHSSFU] score, change in NIHSS scores between 24 and 48 hours and baseline Delta[NIHSS], and 90-day modified Rankin Scale [mRS] scores) were compared between occlusion patterns.Results: We identified 1023 patients with an MCA occlusion of whom 370 (36%) had a main stem occlusion, 151 (15%) a single branch, and 502 (49%) a double branch bifurcation occlusion. There were no statistically significant differences in retrieval method, procedure time, number of retrieval attempts, reperfusion grade, and embolization to new territory between occlusion patterns. Patients with main stem occlusions had lower NIHSSFU scores than patients with single (7 vs 11, p=0.01) or double branch occlusions (7 vs 9, p=0.04). However, there were no statistically significant differences in Delta NIHSS or in 90-day mRS scores. Conclusions: In our population, EVT procedural and long-term clinical outcomes were similar for MCA bifurcation occlusions and MCA main stem occlusions. Show less
BACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of... Show moreBACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of this study was to assess whether endovascular therapy plus usual care is cost-effective in comparison to usual care alone in acute ischemic stroke patients. METHODS: An economic evaluation was performed from a societal perspective with a 2-year time horizon. Empirical data on health outcomes and the use of resources following endovascular treatment were gathered parallel to the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and its 2-year follow-up study. Incremental cost-effectiveness ratios were calculated as the extra costs per additional patient with functional independence (modified Rankin Scale score 0-2) and the extra cost per quality-adjusted life year gained. RESULTS: The mean costs per patient in the intervention group were $126 494 versus $143 331 in the control group (mean difference, -$16 839 [95% CI, -$38 113 to $5456]). Compared with patients in the control group, more patients in the intervention group achieved functional independence, 37.2% versus 23.9% (absolute difference, 13.3% [95% CI, 4.0%-22.0%]) and they generated more quality-adjusted life years, 0.99 versus 0.83 (mean difference of 0.16 [95% CI, 0.04-0.29]). Endovascular treatment dominated standard treatment with $18 233 saved per extra patient with a good outcome and $105 869 saved per additional quality-adjusted life year. CONCLUSIONS: Endovascular treatment added to usual care is clinically effective, and cost saving in comparison to usual care alone in patients with acute ischemic stroke. Registration: URL: ; Unique identifier: NL695. URL: ; Unique identifier: ISRCTN10888758. Show less
Background and Purpose: The benefit of endovascular treatment (EVT) for posterior circulation stroke (PCS) remains uncertain, and little is known on treatment outcomes in clinical practice. This... Show moreBackground and Purpose: The benefit of endovascular treatment (EVT) for posterior circulation stroke (PCS) remains uncertain, and little is known on treatment outcomes in clinical practice. This study evaluates outcomes of a large PCS cohort treated with EVT in clinical practice. Simultaneous to this observational study, several intervention centers participated in the BASICS trial (Basilar Artery International Cooperation Study), which tested the efficacy of EVT for basilar artery occlusion in a randomized setting. We additionally compared characteristics and outcomes of patients treated outside BASICS in trial centers to those from nontrial centers. Methods: We included patients with PCS from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry: a prospective, multicenter, observational study of patients who underwent EVT in the Netherlands between 2014 and 2018. Primary outcome was a score of 0 to 3 on the modified Rankin Scale at 90 days. Secondary outcomes included reperfusion status and symptomatic intracranial hemorrhage. For outcome comparison between patients treated in trial versus nontrial centers, we used ordinal logistic regression analysis. Results: We included 264 patients of whom 135 (51%) had received intravenous thrombolysis. The basilar artery was most often involved (77%). Favorable outcome (modified Rankin Scale score 0-3) was observed in 115/252 (46%) patients, and 109/252 (43%) patients died. Successful reperfusion was achieved in 178/238 (75%), and symptomatic intracranial hemorrhage occurred in 9/264 (3%). The 154 nontrial patients receiving EVT in BASICS trial centers had similar characteristics and outcomes as the 110 patients treated in nontrial centers (modified Rankin Scale adjusted cOR: 0.77 [95% CI, 0.5-1.2]). Conclusions: Our study shows that high rates of favorable clinical outcome and successful reperfusion can be achieved with EVT for PCS, despite high mortality. Characteristics and outcomes of patients treated in trial versus nontrial centers were similar indicating that our cohort is representative of clinical practice in the Netherlands. Randomized studies using modern treatment approaches are needed for further insight in the benefit of EVT for PCS. Show less
Background Higher expanded Treatment In Cerebral Ischemia (eTICI) reperfusion scores after endovascular treatment (EVT) are associated with better outcomes. However, the influence of the number of... Show moreBackground Higher expanded Treatment In Cerebral Ischemia (eTICI) reperfusion scores after endovascular treatment (EVT) are associated with better outcomes. However, the influence of the number of passes on this association is unclear. We aimed to compare outcomes of single-pass good reperfusion (eTICI 2B) with multiple-pass excellent/complete reperfusion (eTICI 2C/3) in daily clinical practice. Methods We compared outcomes of patients in the MR CLEAN Registry with good reperfusion (eTICI 2B) in a single pass to those with excellent/complete reperfusion (eTICI 2C/3) in multiple passes. Regression models were used to investigate the association of single-pass eTICI 2B versus multiple-pass eTICI 2C/3 reperfusion with 90-day functional outcome (modified Rankin Scale (mRS)), functional independence (mRS 0-2), per-procedural complications and safety outcomes. Results We included 699 patients: 178 patients with single-pass eTICI 2B, and 242 and 279 patients with eTICI 2C/3 after 2 and >= 3 passes, respectively. Patients with eTICI 2C/3 after 2 or >= 3 passes did not achieve significantly better functional outcomes compared with patients with single-pass eTICI 2B (adjusted common OR (acOR) 1.06, 95% CI 0.75 to 1.50 and acOR 0.88, 95% CI 0.74 to 1.05 for 90-day mRS, and adjusted OR (aOR) 1.24, 95% CI 0.78 to 1.97 and aOR 0.79, 95% CI 0.52 to 1.22 for functional independence). Conclusions Our results did not show better outcomes for patients who achieved eTICI 2C/3 in multiple, that is, two or more, passes when compared with patients with single-pass eTICI 2B. However, this concerns observational data. Further research is necessary to investigate the per-pass effect in relation to reperfusion and functional outcome. Show less
Introduction We investigated the impact of the Corona Virus Disease 2019 (COVID-19) pandemic and the resulting lockdown on reperfusion treatments and door-to-treatment times during the first surge... Show moreIntroduction We investigated the impact of the Corona Virus Disease 2019 (COVID-19) pandemic and the resulting lockdown on reperfusion treatments and door-to-treatment times during the first surge in Dutch comprehensive stroke centers. Furthermore, we studied the association between COVID-19-status and treatment times. Methods We included all patients receiving reperfusion treatment in 17 Dutch stroke centers from May 11th, 2017, until May 11th, 2020. We collected baseline characteristics, National Institutes of Health Stroke Scale (NIHSS) at admission, onset-to-door time (ODT), door-to-needle time (DNT), door-to-groin time (DGT) and COVID-19-status at admission. Parameters during the lockdown (March 15th, 2020 until May 11th, 2020) were compared with those in the same period in 2019, and between groups stratified by COVID-19-status. We used nationwide data and extrapolated our findings to the increasing trend of EVT numbers since May 2017. Results A decline of 14% was seen in reperfusion treatments during lockdown, with a decline in both IVT and EVT delivery. DGT increased by 12 min (50 to 62 min, p-value of < 0.001). Furthermore, median NIHSS-scores were higher in COVID-19 - suspected or positive patients (7 to 11, p-value of 0.004), door-to-treatment times did not differ significantly when stratified for COVID-19-status. Conclusions During the first surge of the COVID-19 pandemic, a decline in acute reperfusion treatments and a delay in DGT was seen, which indicates a target for attention. It also appeared that COVID-19-positive or -suspected patients had more severe neurologic symptoms, whereas their EVT-workflow was not affected. Show less
Background and Purpose: Acute ischemic stroke due to large vessel occlusion is uncommon in young adults. We assessed stroke cause in young patients and compared their outcomes after endovascular... Show moreBackground and Purpose: Acute ischemic stroke due to large vessel occlusion is uncommon in young adults. We assessed stroke cause in young patients and compared their outcomes after endovascular thrombectomy with older patients. Methods: We used data (March 2014 until November 2017) of patients with an anterior circulation large vessel occlusion stroke from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a nationwide, prospective study on endovascular thrombectomy in the Netherlands. We compared young patients (18-49 years) with older patients (>= 50 years). Outcomes included modified Rankin Scale score after 90 days (both shift and dichotomized analyses), expanded Thrombolysis in Cerebral Infarction score, and symptomatic intracranial hemorrhage. Analyses were adjusted for confounding. Results: We included 3256 patients, 310 (10%) were 18 to 49 years old. Young patients had lower median National Institutes of Health Stroke Scale scores (14 versus 16, P<0.001) and less cardiovascular comorbidities than older patients. Stroke etiologies in young patients included carotid dissection (16%), cardio-embolism (15%), large artery atherosclerosis (10%), and embolic stroke of undetermined source (31%). Clinical outcome was better in young than older patients (acOR for modified Rankin Scale shift: 1.8 [95% CI, 1.5-2.2]; functional independence [modified Rankin Scale score 0-2] 61 versus 39% [adjusted odds ratio, 2.1 [95% CI, 1.6-2.8]); mortality 7% versus 32%, adjusted odds ratio, 0.2 [95% CI, 0.1-0.3]). Symptomatic intracranial hemorrhage occurred less frequently in young patients (3% versus 6%, adjusted odds ratio, 0.5 [95% CI, 0.2-1.00]). Successful reperfusion (expanded Thrombolysis in Cerebral Infarction Score 2b-3) did not differ between groups. Onset to reperfusion time was shorter in young patients (253 versus 255 minutes, adjusted B in minutes 12.4 [95% CI, 2.4-22.5]). Conclusions: Ten percent of patients with acute ischemic stroke undergoing endovascular thrombectomy were younger than 50. Cardioembolism and carotid dissection were common underlying causes in young patients. In one-third of cases, no cause was identified, indicating the need for more research on stroke cause in young patients. Young patients had better prognosis and lower risk of symptomatic intracranial hemorrhage than older patients. Show less
Voorst, H. van; Kunz, W.G.; Berg, L.A. van den; Kappelhof, M.; Pinckaers, F.M.E.; Goyal, M.; ... ; Majoie, C.B.L.M. 2021
Background The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster... Show moreBackground The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population. Methods A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of euro80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs. Results EVT administered 1 min faster resulted in a median NMB of euro309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -euro15, IQR: -65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs. Conclusion One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs. Show less
LeCouffe, N.E.; Kappelhof, M.; Treurniet, K.M.; Rinkel, L.A.; Bruggeman, A.E.; Berkhemer, O.A.; ... ; MR CLEAN-NO IV Investigators 2021
Alteplase with EVT versus EVT Alone for Stroke Trials involving Asian patients with acute stroke have suggested that endovascular treatment alone is not inferior to the usual practice of... Show moreAlteplase with EVT versus EVT Alone for Stroke Trials involving Asian patients with acute stroke have suggested that endovascular treatment alone is not inferior to the usual practice of thrombolysis before endovascular treatment. This trial involving European patients did not show noninferiority or superiority of endovascular treatment alone.Background The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations. Methods We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points. Results The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P=0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81). Conclusions In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by the Collaboration for New Treatments of Acute Stroke consortium and others; MR CLEAN-NO IV ISRCTN number, .) Show less
OBJECTIVE Calcified cerebral emboli (CCE) are a rare cause of acute ischemic stroke. The authors aimed to assess the association of CCE with functional outcome, successful reperfusion, and... Show moreOBJECTIVE Calcified cerebral emboli (CCE) are a rare cause of acute ischemic stroke. The authors aimed to assess the association of CCE with functional outcome, successful reperfusion, and mortality. Furthermore, they aimed to assess the effectiveness of intravenous alteplase treatment and endovascular treatment (EVT), as well as the best first-line EVT approach in patients with CCE. METHODS The Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry is a prospective, observational multicenter registry of patients treated with EVT for acute ischemic stroke in 16 intervention hospitals in the Netherlands. The association of CCE with functional outcome, reperfusion, and mortality was evaluated using logistic regression models. Univariable comparisons were made to determine the effectiveness of intravenous alteplase treatment and the best first-line EVT approach in CCE patients. RESULTS The study included 3077 patients from the MR CLEAN Registry. Fifty-five patients (1.8%) had CCE. CCE were not significantly associated with worse functional outcome (adjusted common OR 0.71, 95% CI 0.44-1.15), and 29% of CCE patients achieved functional independence. An extended Thrombolysis in Cerebral Infarction score >= 2B was significantly less often achieved in CCE patients compared to non-CCE patients (adjusted OR [aOR] 0.52, 95% CI 0.28- 0.97). Symptomatic intracranial hemorrhage occurred in 8 CCE patients (15%) vs 171 of 3022 non-CCE patients (6%; p = 0.01). The median improvement on the National Institutes of Health Stroke Scale (NIHSS) was 2 in CCE patients versus 4 in non-CCE patients (p = 0.008). CCE were not significantly associated with mortality (aOR 1.16, 95% CI 0.64-2.12). Intravenous alteplase use in CCE patients was not associated with functional outcome or reperfusion. In CCE patients with successful reperfusion, stent retrievers were more often used as the primary treatment device (p = 0.04). CONCLUSIONS While patients with CCE had significantly lower reperfusion rates and less improvement on the NIHSS after EVT, CCE were not significantly associated with worse functional outcome or higher mortality rates. Therefore, EVT should still be considered in this specific group of patients. Show less
