Budget impact of endovascular treatment for acute ischaemic stroke patients in the Netherlands for 2015-2021.

INTRODUCTION: Endovascular treatment (EVT) has been proven to be both effective and cost-effective for patients with acute ischaemic stroke. We investigated the budget impact of large-scale implementation of EVT for acute ischaemic stroke patients in the Netherlands for 2015-2021. METHODS: An analysis was performed from a healthcare perspective as a preplanned substudy of the Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN). Estimated yearly costs during follow-up after stroke for patients who had or had not been treated with EVT as add-on to usual care were linked to numbers of new patients retrieved from 2 Dutch registries of EVT that started after the last inclusion in MR CLEAN (2014). Aggregated costs and costs per care sector were calculated based on prevalence using a population dynamic tool. RESULTS: From 2015, the yearly number of new acute ischaemic stroke patients receiving EVT increased almost threefold, from 812 in 2015 to 2,370 in 2021. The introduction of EVT plus usual care resulted in estimated net annual savings that increased from €â€¯2.9 million in 2015 to €â€¯58 million in 2021. CONCLUSION: Offering EVT as add-on to usual care for acute ischaemic stroke patients was increasingly cost saving from a national healthcare perspective but affected distinct healthcare sectors differently.

Economic Evaluation of Endovascular Treatment for Acute Ischemic Stroke.

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 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: https://www.trialregister.nl/trial/695; Unique identifier: NL695. URL: https://www.isrctn.com; Unique identifier: ISRCTN10888758.

Two-Year Outcome after Endovascular Treatment for Acute Ischemic Stroke.

BACKGROUND: Several trials involving patients with acute ischemic stroke have shown better functional outcomes with endovascular treatment than with conventional treatment at 90 days after initiation of treatment. However, results on long-term clinical outcomes are lacking. METHODS: We assessed clinical outcomes 2 years after patients were randomly assigned to receive either endovascular treatment (intervention group) or conventional treatment (control group) for acute ischemic stroke. The primary outcome was the score on the modified Rankin scale at 2 years; this scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). Secondary outcomes included all-cause mortality and the quality of life at 2 years, as measured by means of a health utility index that is based on the European Quality of Life-5 Dimensions questionnaire (scores range from -0.329 to 1, with higher scores indicating better health). RESULTS: Of the 500 patients who underwent randomization in the original trial, 2-year data for this extended follow-up trial were available for 391 patients (78.2%) and information on death was available for 459 patients (91.8%). The distribution of outcomes on the modified Rankin scale favored endovascular treatment over conventional treatment (adjusted common odds ratio, 1.68; 95% confidence interval [CI], 1.15 to 2.45; P=0.007). There was no significant difference between the treatment groups in the percentage of patients who had an excellent outcome (i.e., a modified Rankin scale score of 0 or 1). The mean quality-of-life score was 0.48 among patients randomly assigned to endovascular treatment as compared with 0.38 among patients randomly assigned to conventional treatment (mean difference, 0.10; 95% CI, 0.03 to 0.16; P=0.006). The cumulative 2-year mortality rate was 26.0% in the intervention group and 31.0% in the control group (adjusted hazard ratio, 0.9; 95% CI, 0.6 to 1.2; P=0.46). CONCLUSIONS: In this extended follow-up trial, the beneficial effect of endovascular treatment on functional outcome at 2 years in patients with acute ischemic stroke was similar to that reported at 90 days in the original trial. (Funded by the Netherlands Organization for Health Research and Development and others; MR CLEAN Current Controlled Trials number, ISRCTN10888758 , and Netherlands Trial Register number, NTR1804 , and MR CLEAN extended follow-up trial Netherlands Trial Register number, NTR5073 .).

Clinical and Imaging Markers Associated With Hemorrhagic Transformation in Patients With Acute Ischemic Stroke.

Background and Purpose- Hemorrhagic transformation (HT) after acute ischemic stroke may cause severe neurological deterioration and affects functional outcome. Identifying patients most likely to suffer from this complication could potentially be used for future treatment selection. Reperfusion after endovascular therapy could be associated with different risk factors for HT than intravenous thrombolytics as these treatments largely differ. In this study, we aimed to identify clinical and imaging markers that are associated with HT subtypes in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) population. Methods- In this post hoc analysis, all patients with follow-up imaging were included. HT was classified according to ECASS II (European Cooperative Acute Stroke Study). Variables with an association of P<0.1 were included in the multivariable logistic regression to identify clinical and radiological variables associated with petechial hemorrhagic infarction, parenchymal hematoma (PH), and symptomatic intracranial hemorrhage. Results- Of the 478 out of 500 included patients in this subanalysis, 46% had HT (n=222). Of these, 66% had hemorrhagic infarction (n=147) and 34% PH (n=75). Symptomatic intracranial hemorrhage was observed in 7.3% (n=35) of all patients. Baseline National Institutes of Health Stroke Scale (odds ratio [OR], 1.05,95% CI, 1.01-1.09 per point) and absent/poor collaterals (OR, 1.90; 95% CI, 1.05-3.42) were significantly associated with hemorrhagic infarction. Increased systolic blood pressure (OR, 1.17; 95% CI, 1.05-1.31 per 10 mm Hg) and atrial fibrillation (OR, 1.94; 95% CI, 1.08-3.48) were associated with PH. Increased systolic blood pressure (OR, 1.28; 95% CI, 1.12-1.48) and antiplatelet use (OR, 2.6; 95% CI, 1.08-6.3) were associated with symptomatic intracranial hemorrhage. Conclusions- Clinical and imaging stroke severity parameters were associated with HT, both in hemorrhagic infarction and PH, whereas baseline patients characteristics like systolic blood pressure, atrial fibrillation, and antiplatelet use were only associated with PH or symptomatic intracranial hemorrhage. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN10888758.

A randomized trial of intraarterial treatment for acute ischemic stroke.

BACKGROUND: In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. METHODS: We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). RESULTS: We enrolled 500 patients at 16 medical centers in The Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. CONCLUSIONS: In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).

Extracranial Carotid Disease and Effect of Intra-arterial Treatment in Patients With Proximal Anterior Circulation Stroke in MR CLEAN.

Background: The presence of extracranial carotid disease (ECD) is associated with less favorable clinical outcomes in patients with acute ischemic stroke caused by intracranial proximal occlusion. Acute intra-arterial treatment (IAT) in the setting of extracranial and intracranial lesions is considered challenging, and whether it yields improved outcomes remains uncertain. Objective: To examine whether the presence of ECD modified the effect of IAT for intracranial proximal anterior circulation occlusion. Design: Prespecified subgroup analysis of a randomized clinical trial of endovascular treatment for acute ischemic stroke in the Netherlands. (Trial registrations: NTR1804 [Netherlands Trial Register] and ISRCTN10888758). Setting: 16 hospitals in the Netherlands. Patients: Acute ischemic stroke caused by proximal intracranial arterial occlusion of the anterior circulation. Extracranial carotid disease was defined as cervical internal carotid artery stenosis (>50%) or occlusion. Intervention: IAT treatment versus no IAT. Measurements: The primary outcome was functional outcome, as measured by the modified Rankin Scale at 90 days and reported as adjusted common odds ratio (acOR) for a shift in direction of a better outcome. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by ECD. Results: The overall acOR was 1.67 (95% CI, 1.21 to 2.30) in favor of the intervention. The acOR was 3.1 (CI, 1.7 to 5.8) in the prespecified subgroup of patients with ECD versus 1.3 (CI, 0.9 to 1.9) in patients presenting without ECD. Both acORs are in favor of the intervention (P for interaction = 0.07). Limitation: The study was not powered for subgroup analysis. Conclusion: Intra-arterial treatment may be at least as effective in patients with ECD as in those without ECD, and it should not be withheld in these complex patients with acute ischemic stroke. Primary Funding Source: Dutch Heart Foundation, AngioCare BV, Medtronic/Covidien/EV3, MEDAC Gmbh/LAMEPRO, Penumbra, Stryker, and Top Medical/Concentric.

Baseline Blood Pressure Effect on the Benefit and Safety of Intra-Arterial Treatment in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands).

BACKGROUND AND PURPOSE: High blood pressure (BP) is associated with poor outcome and the occurrence of symptomatic intracranial hemorrhage in acute ischemic stroke. Whether BP influences the benefit or safety of intra-arterial treatment (IAT) is not known. We aimed to assess the relation of BP with functional outcome, occurrence of symptomatic intracranial hemorrhage and effect of IAT. METHODS: This is a post hoc analysis of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). BP was measured at baseline, before IAT or stroke unit admission. We estimated the association of baseline BP with the score on the modified Rankin Scale at 90 days and safety parameters with ordinal and logistic regression analysis. Effect of BP on the effect of IAT was tested with multiplicative interaction terms. RESULTS: Systolic BP (SBP) had the best correlation with functional outcome. This correlation was U-shaped; both low and high baseline SBP were associated with poor functional outcome. Higher SBP was associated with symptomatic intracranial hemorrhage (adjusted odds ratio, 1.25 for every 10 mm Hg higher SBP [95% confidence interval, 1.09-1.44]). Between SBP and IAT, there was no interaction for functional outcome, symptomatic intracranial hemorrhage, or other safety parameters; the absolute benefit of IAT was evident for the whole SBP range. The same was found for diastolic BP. CONCLUSIONS: BP does not affect the benefit or safety of IAT in patients with acute ischemic stroke caused by proximal intracranial vessel occlusion. Our data provide no arguments to withhold or delay IAT based on BP. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758.

Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.

BACKGROUND: In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included. METHODS: We formed the HERMES collaboration to pool patient-level data from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) done between December, 2010, and December, 2014. In these trials, patients with acute ischaemic stroke caused by occlusion of the proximal anterior artery circulation were randomly assigned to receive either endovascular thrombectomy within 12 h of symptom onset or standard care (control), with a primary outcome of reduced disability on the modified Rankin Scale (mRS) at 90 days. By direct access to the study databases, we extracted individual patient data that we used to assess the primary outcome of reduced disability on mRS at 90 days in the pooled population and examine heterogeneity of this treatment effect across prespecified subgroups. To account for between-trial variance we used mixed-effects modelling with random effects for parameters of interest. We then used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in subgroups after adjustment for age, sex, baseline stroke severity (National Institutes of Health Stroke Scale score), site of occlusion (internal carotid artery vs M1 segment of middle cerebral artery vs M2 segment of middle cerebral artery), intravenous alteplase (yes vs no), baseline Alberta Stroke Program Early CT score, and time from stroke onset to randomisation. FINDINGS: We analysed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control). Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control (adjusted cOR 2.49, 95% CI 1.76-3.53; p<0.0001). The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2.6. Subgroup analysis of the primary endpoint showed no heterogeneity of treatment effect across prespecified subgroups for reduced disability (pinteraction=0.43). Effect sizes favouring endovascular thrombectomy over control were present in several strata of special interest, including in patients aged 80 years or older (cOR 3.68, 95% CI 1.95-6.92), those randomised more than 300 min after symptom onset (1.76, 1.05-2.97), and those not eligible for intravenous alteplase (2.43, 1.30-4.55). Mortality at 90 days and risk of parenchymal haematoma and symptomatic intracranial haemorrhage did not differ between populations. INTERPRETATION: Endovascular thrombectomy is of benefit to most patients with acute ischaemic stroke caused by occlusion of the proximal anterior circulation, irrespective of patient characteristics or geographical location. These findings will have global implications on structuring systems of care to provide timely treatment to patients with acute ischaemic stroke due to large vessel occlusion. FUNDING: Medtronic.

Influence of Device Choice on the Effect of Intra-Arterial Treatment for Acute Ischemic Stroke in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands).

BACKGROUND AND PURPOSE: Intra-arterial treatment by means of retrievable stents has been proven safe and effective. In MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), the choice of the type of thrombectomy device was left to the discretion of the interventionist. The aim of this study was to explore the differences in functional outcome, neurological recovery, reperfusion, extent of infarction, and adverse events according to stent type and make. METHODS: The primary outcome was functional outcome at 90 days, assessed with the modified Rankin Scale (mRS). Neuroimaging outcomes included occlusion on computed tomographic angiography at 24 hours, infarct volume at 5 to 7 days, and modified thrombolysis in cerebral infarction scores. Safety outcomes included death within 90 days and any symptomatic intracerebral hemorrhage. We analyzed possible interactions between stent type and treatment with multiple regression models. Treatment effects were adjusted for patient age, stroke severity, and collateral score. RESULTS: Of the 500 patients included in the trial, 233 were allocated to intervention. Of these, 124 (53%) were first treated with Trevo (adjusted common odds ratio for shift on the mRS [acOR, 1.98; 95% confidence interval, 1.30-2.92]), 31 (13%) with Solitaire (acOR, 1.90; 95% confidence interval, 0.97-3.73), 40 (17%) with other retrievable stents or mechanical devices (acOR, 0.96; 95% confidence interval, 0.51-3.93], and 38 (16%) could not be treated. There was no interaction between device and treatment effect on functional outcome and all other secondary and safety outcomes. CONCLUSIONS: We found no evidence for a differential effect of thrombectomy for acute ischemic stroke by type of stent. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758.

Clot Burden Score on Baseline Computerized Tomographic Angiography and Intra-Arterial Treatment Effect in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: A high clot burden score (CBS) is associated with favorable outcome after intravenous treatment for acute ischemic stroke. The added benefit of intra-arterial treatment might be less in these patients. The aim of this exploratory post hoc analysis was to assess the relation of CBS with neurological improvement and endovascular treatment effect. METHODS: For 499 of 500 patients in the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), the CBS was determined. Ordinal logistic regression models with and without main baseline prognostic variables were used to assess the association between CBS (continuous or dichotomized at CBS of 6) and a shift toward better outcome on the modified Rankin Scale. The model without main baseline prognostic variables only included treatment allocation and CBS. Models with and without a multiplicative interaction term of CBS and treatment were compared using the χ2 test to assess treatment effect modification by CBS. RESULTS: Higher CBS was associated with a shift toward better outcome on the modified Rankin Scale; adjusted common odds ratio per point CBS was 1.12 (95% confidence interval, 1.04-1.20]. Dichotomized CBS had an adjusted common odds ratio of 1.67 (95% confidence interval, 1.12-2.51). Both effect estimates were slightly attenuated by adding baseline prognostic variables. The addition of the interaction terms did not significantly improve the fit of the models. There was a small and insignificant increase of intra-arterial treatment efficacy in the high CBS group. CONCLUSIONS: A higher CBS is associated with improved outcome and may be used as a prognostic marker. We found no evidence that CBS modifies the effect of intra-arterial treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR1804. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN10888758.

Collateral Status on Baseline Computed Tomographic Angiography and Intra-Arterial Treatment Effect in Patients With Proximal Anterior Circulation Stroke.

BACKGROUND AND PURPOSE: Recent randomized trials have proven the benefit of intra-arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN). METHODS: MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status. RESULTS: We found a significant modification of treatment effect by collaterals (P=0.038). The strongest benefit (adjusted common odds ratio 3.2 [95% confidence intervals 1.7-6.2]) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 [95% confidence intervals 1.0-2.7] for moderate collaterals (grade 2), 1.2 [95% confidence intervals 0.7-2.3] for poor collaterals (grade 1), and 1.0 [95% confidence intervals 0.1-8.7] for patients with absent collaterals (grade 0). CONCLUSIONS: In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl and http://www.controlled-trials.com. Unique identifier: (NTR)1804 and ISRCTN10888758, respectively.

Type of anesthesia and differences in clinical outcome after intra-arterial treatment for ischemic stroke.

BACKGROUND AND PURPOSE: Intra-arterial treatment (IAT) in patients with acute ischemic stroke (AIS) can be performed with or without general anesthesia (GA). Previous studies suggested that IAT without the use of GA (non-GA) is associated with better clinical outcome. Nevertheless, no consensus exists about the anesthetic management during IAT of AIS patients. This study investigates the association between type of anesthesia and clinical outcome in a large cohort of patients with AIS treated with IAT. METHODS: All consecutive patients with AIS of the anterior circulation who received IAT between 2002 and 2013 in 16 Dutch hospitals were included in the study. Primary outcome was functional outcome on the modified Rankin Scale at discharge. Difference in primary outcome between GA and non-GA was estimated using multiple ordinal regression analysis, adjusting for age, stroke severity, occlusion of the internal carotid artery terminus, previous stroke, atrial fibrillation, and diabetes mellitus. RESULTS: Three hundred forty-eight patients were included in the analysis; 70 patients received GA and 278 patients did not receive GA. Non-GA was significantly associated with good clinical outcome (odds ratio 2.1, 95% confidence interval 1.02-4.31). After adjusting for prespecified prognostic factors, the point estimate remained similar; statistical significance, however, was lost (odds ratio 1.9, 95% confidence interval 0.89-4.24). CONCLUSIONS: Our study suggests that patients with AIS of the anterior circulation undergoing IAT without GA have a higher probability of good clinical outcome compared with patients treated with general anesthesia.

Assessment of Recurrent Stroke Risk in Patients With a Carotid Web.

Importance: A carotid web (CW) is a shelf-like lesion along the posterior wall of the internal carotid artery bulb and an underrecognized cause of young stroke. Several studies suggest that patients with symptomatic CW have a high risk of recurrent stroke, but high-quality data are lacking. Objective: To assess the 2-year risk of recurrent stroke in patients with a symptomatic CW. Design, Setting, and Participants: A comparative cohort study used data from the MR CLEAN trial (from 2010-2014) and MR CLEAN Registry (from 2014-2017). Data were analyzed in September 2020. The MR CLEAN trial and MR CLEAN Registry were nationwide prospective multicenter studies on endovascular treatment (EVT) of large vessel occlusion (LVO) stroke in the Netherlands. Baseline data were from 3439 consecutive adult patients with anterior circulation LVO stroke and available computed tomography (CT)-angiography of the carotid bulb. Two neuroradiologists reevaluated CT-angiography images for presence or absence of CW and identified 30 patients with CW ipsilateral to the index stroke. For these 30 eligible CW participants, detailed follow-up data regarding stroke recurrence within 2 years were acquired. These 30 patients with CW ipsilateral to the index stroke were compared with 168 patients without CW who participated in the MR CLEAN extended follow-up trial and who were randomized to the EVT arm. Main Outcomes and Measures: The primary outcome was recurrent stroke occurring within 2 years after the index stroke. Cox proportional hazards regression models were used to compare recurrent stroke rates within 2 years for patients with and without CW, adjusted for age and sex. The research question was formulated prior to data collection. Results: Of 3439 patients with baseline CT-angiography assessed, the median age was 72 years (interquartile range, 61-80 years) and 1813 (53%) were men. Patients with CW were younger (median age, 57 [interquartile range, 46-66] years vs 66 [interquartile range, 56-77] years; P = .02 and more often women (22 of 30 [73%] vs 67 of 168 [40%]; P = .001) than patients without CW. Twenty-eight of 30 patients (93%) received medical management after the index stroke (23 with antiplatelet therapy and 5 with anticoagulant therapy). During 2 years of follow-up, 5 of 30 patients (17%) with CW had a recurrent stroke compared with 5 of 168 patients (3%) without CW (adjusted hazard ratio, 4.9; 95% CI, 1.4-18.1). Conclusions and Relevance: In this study, 1 of 6 patients with a symptomatic CW had a recurrent stroke within 2 years, suggesting that medical management alone may not provide sufficient protection for patients with CW.

Quantified health and cost effects of faster endovascular treatment for large vessel ischemic stroke patients in the Netherlands.

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 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 €80 000 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 €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, 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.

Hemorrhagic transformation is associated with poor functional outcome in patients with acute ischemic stroke due to a large vessel occlusion.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a complication that may cause neurological deterioration in patients with acute ischemic stroke. Various radiological subtypes of HT can be distinguished. Their influence on functional outcome is currently unclear. The purpose of this study was to assess the associations between HT subtypes and functional outcome in acute ischemic stroke patients with proven large vessel occlusion included in the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic stroke in The Netherlands). METHODS: All patients with follow-up imaging were included. HT was classified on follow-up CT scans according to the European Cooperative Acute Stroke Study II classification. Functional outcome was assessed using the modified Rankin Scale (mRS) 90 days after stroke onset. Ordinal logistic regression analysis with adjustment for potential confounders was used to determine the association of HT subtypes with functional outcome. RESULTS: Of 478 patients, 222 had HT. Of these, 76 (16%) patients were classified as hemorrhagic infarction type 1, 71 (15%) as hemorrhagic infarction type 2, 36 (8%) as parenchymal hematoma type 1, and 39 (8%) as parenchymal hematoma type 2. Hemorrhagic infarction type 2 (adjusted common OR (acOR) 0.54, 95% CI: 0.32 to 0.89) and parenchymal hematoma type 2 (acOR 0.37, 95% CI 0.17 to 0.78) were significantly associated with a worse functional outcome. Hemorrhagic infarction type 1 and parenchymal hematoma type 1 were not significantly associated, although their point estimates pointed in the direction of worse outcome. CONCLUSION: This study suggests that parenchymal hematoma type 2 is relevant for functional outcome after an acute ischemic stroke, and smaller HTs might also influence long term functional outcome. TRAIL REGISTRATION NUMBER: ISRCTN10888758.

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data.

BACKGROUND: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. METHODS: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. FINDINGS: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14-2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. INTERPRETATION: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons. FUNDING: Medtronic.

Quality of life after intra-arterial treatment for acute ischemic stroke in the MR CLEAN trial-Update.

Background Health-related quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire was one of the secondary outcomes in the Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN). We reported no statistically significant difference in EuroQol Group 5-Dimension Self-Report Questionnaire score between the intervention and control groups, but deaths were not included. Aims Reanalyze the effect of intra-arterial treatment for large vessel occlusion in acute ischemic stroke patients on health-related quality of life in more detail. We now include patients who died during follow-up. Methods The EuroQol Group 5-Dimension Self-Report Questionnaire questionnaires were obtained 90 days after treatment. We used the Dutch tariff to derive a utility index from the EuroQol Group 5-Dimension Self-Report Questionnaire score. Treatment effect was estimated with the Mann-Whitney U test and linear regression. The effect of treatment on the distribution of EuroQol Group 5-Dimension Self-Report Questionnaire dimension scores was assessed with ordinal logistic regression. Results We obtained EuroQol Group 5-Dimension Self-Report Questionnaire scores from 457 (91.7%) of the 500 patients, including 108 who died before follow-up. Median EuroQol Group 5-Dimension Self-Report Questionnaire score in the intervention group was 0.57, and 0.39 in the control group (p = 0.03). Treatment effect estimated with linear regression was 0.07 (95%CI: -0.001 to 0.143). Treatment specifically affected EuroQol Group 5-Dimension Self-Report Questionnaire dimensions "mobility" (OR: 0.43, 95%CI: 0.29-0.66), "self-care" (OR: 0.60, 95%CI: 0.41-0.89), and "usual activities" (OR: 0.53, 95%CI: 0.36-0.79). Conclusion Treatment had a limited effect on quality of life, as measured with the EuroQol Group 5-Dimension Self-Report Questionnaire. Nevertheless, patients with acute ischemic stroke caused by an intracranial occlusion in the anterior circulation, who had intra-arterial treatment, experience better health-related quality of life than patients without intra-arterial treatment. Trial Registration URL: http://www.isrctn.com/ISRCTN10888758 Unique identifier: ISRCTN10888758.