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
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
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 Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this... Show moreBackground Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke.Methods We did an open-label, multicentre, randomised controlled trial with a 2 x 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, >= 18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621.Findings Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1.95 [95% CI 1.13-3.35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1.98 [1.14-3.46]). Both aspirin (adjusted common OR 0.91 [95% CI 0.69-1.21]) and unfractionated heparin (0.81 [0.61-1.08]) led to a non-significant shift towards worse modified Rankin Scale scores.Interpretation Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome. Copyright (C) 2022 Published by Elsevier Ltd. All rights reserved. Show less
Background Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this... Show moreBackground Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke.Methods We did an open-label, multicentre, randomised controlled trial with a 2 x 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, >= 18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621.Findings Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1.95 [95% CI 1.13-3.35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1.98 [1.14-3.46]). Both aspirin (adjusted common OR 0.91 [95% CI 0.69-1.21]) and unfractionated heparin (0.81 [0.61-1.08]) led to a non-significant shift towards worse modified Rankin Scale scores.Interpretation Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome. Copyright (C) 2022 Published by Elsevier Ltd. All rights reserved. Show less
Background Approximately one-third of patients with ischemic stroke treated with endovascular treatment do not recover to functional independence despite rapid and successful recanalization. We... Show moreBackground Approximately one-third of patients with ischemic stroke treated with endovascular treatment do not recover to functional independence despite rapid and successful recanalization. We aimed to quantify the importance of predictors of poor functional outcome despite successful reperfusion. Methods We analyzed patients from the MR CLEAN Registry between March 2014 and November 2017 with successful reperfusion (extended Thrombolysis In Cerebral Infarction >= 2B). First, predictors were selected based on expert opinion and were clustered according to acquisition over time (ie, baseline patient factors, imaging factors, treatment factors, and postprocedural factors). Second, several models were constructed to predict 90-day functional outcome (modified Rankin Scale (mRS)). The relative importance of individual predictors in the most extensive model was expressed by the proportion of unique added chi(2) to the model of that individual predictor. Results Of 3180 patients, 1913 (60%) had successful reperfusion. Of these 1913 patients, 1046 (55%) were functionally dependent at 90 days (mRS >2). The most important predictors for mRS were baseline patient factors (ie, pre-stroke mRS, added chi(2) 0.16; National Institutes of Health Stroke Scale score at baseline, added chi(2) 0.12; age, added chi(2) 0.10), and postprocedural factors (ie, symptomatic intracranial hemorrhage (sICH), added chi(2) 0.12; pneumonia, added chi(2) 0.09). The probability of functional independence for a typical stroke patient with sICH was 54% (95% CI 36% to 72%) lower compared with no sICH, and 21% (95% CI 4% to 38%) for pneumonia compared with no pneumonia. Conclusion Baseline patient factors and postprocedural adverse events are important predictors of poor functional outcome in successfully reperfused patients with ischemic stroke. This implies that prevention of postprocedural adverse events has the greatest potential to further improve outcomes in these patients. Show less
Background The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied.Methods We randomly assigned patients within 6 hours after... Show moreBackground The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied.Methods We randomly assigned patients within 6 hours after the estimated time of onset of a stroke due to basilar-artery occlusion, in a 1:1 ratio, to receive endovascular therapy or standard medical care. The primary outcome was a favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death) at 90 days. The primary safety outcomes were symptomatic intracranial hemorrhage within 3 days after the initiation of treatment and mortality at 90 days.Results A total of 300 patients were enrolled (154 in the endovascular therapy group and 146 in the medical care group). Intravenous thrombolysis was used in 78.6% of the patients in the endovascular group and in 79.5% of those in the medical group. Endovascular treatment was initiated at a median of 4.4 hours after stroke onset. A favorable functional outcome occurred in 68 of 154 patients (44.2%) in the endovascular group and 55 of 146 patients (37.7%) in the medical care group (risk ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.50). Symptomatic intracranial hemorrhage occurred in 4.5% of the patients after endovascular therapy and in 0.7% of those after medical therapy (risk ratio, 6.9; 95% CI, 0.9 to 53.0); mortality at 90 days was 38.3% and 43.2%, respectively (risk ratio, 0.87; 95% CI, 0.68 to 1.12).Conclusions Among patients with stroke from basilar-artery occlusion, endovascular therapy and medical therapy did not differ significantly with respect to a favorable functional outcome, but, as reflected by the wide confidence interval for the primary outcome, the results of this trial may not exclude a substantial benefit of endovascular therapy. Larger trials are needed to determine the efficacy and safety of endovascular therapy for basilar-artery occlusion. (Funded by the Dutch Heart Foundation and others; BASICS ClinicalTrials.gov number, NCT01717755; Netherlands Trial Register number, NL2500.)Endovascular Therapy for Basilar-Artery Stroke In a randomized trial involving 300 patients with basilar-artery stroke, endovascular thrombectomy was not significantly different from medical therapy with respect to a favorable functional outcome (modified Rankin scale score of 0 to 3) at 90 days, but a clinically significant benefit could not be excluded. Show less
Background and Purpose:Ischemic brain tissue damage in patients with acute ischemic stroke, as measured by the Alberta Stroke Program Early CT Score (ASPECTS) may be more impactful in older than in... Show moreBackground and Purpose:Ischemic brain tissue damage in patients with acute ischemic stroke, as measured by the Alberta Stroke Program Early CT Score (ASPECTS) may be more impactful in older than in younger patients, although this has not been studied. We aimed to investigate a possible interaction effect between age and ASPECTS on functional outcome in acute ischemic stroke patients undergoing endovascular treatment, and compared reperfusion benefit across age and ASPECTS subgroups.Methods:Patients with ischemic stroke from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; March 2014-November 2017) were included. Multivariable ordinal logistic regression was performed to obtain effect size estimates (adjusted common odds ratio) on functional outcome (modified Rankin Scale score) for continuous age and granular ASPECTS, with a 2-way multiplicative interaction term (agexASPECTS). Outcomes in four patient subgroups based on age (< versus >= median age [71.8 years]) and baseline ASPECTS (6-10 versus 0-5) were assessed.Results:We included 3279 patients. There was no interaction between age and ASPECTS on modified Rankin Scale (P=0.925). The highest proportion of modified Rankin Scale 5 to 6 was observed in patients >71.8 years with baseline ASPECTS 0 to 5 (68/107, 63.6%). There was benefit of reperfusion in all age-ASPECTS subgroups. Although the adjusted common odds ratio was lower in patients >71.8 years with ASPECTS 0 to 5 (adjusted common odds ratio, 1.60 [95% CI, 0.66-3.88], n=110), there was no significant difference from the main effect (P=0.299).Conclusions:Although the proportion of poor outcomes following endovascular treatment was highest in older patients with low baseline ASPECTS, outcomes did not significantly differ from the main effect. These results do not support withholding endovascular treatment based n a combination of high age and low ASPECTS. Show less
BackgroundThe Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer... Show moreBackgroundThe Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer-dependent, which may result in suboptimal prediction of patient outcome and inconsistent reperfusion grading.AimsWe present a semi-automated quantitative reperfusion measure (quantified TICI (qTICI)) using image processing techniques based on the TICI methodology.MethodsWe included patients with an intracranial proximal large vessel occlusion with complete, good quality runs of anteroposterior and lateral digital subtraction angiography from the MR CLEAN Registry. For each vessel occlusion, we identified the target downstream territory and automatically segmented the reperfused area in the target downstream territory on final digital subtraction angiography. qTICI was defined as the percentage of reperfused area in target downstream territory. The value of qTICI and extended TICI (eTICI) in predicting favorable functional outcome (modified Rankin Scale 0-2) was compared using area under receiver operating characteristics curve and binary logistic regression analysis unadjusted and adjusted for known prognostic factors.ResultsIn total, 408 patients with M1 or internal carotid artery occlusion were included. The median qTICI was 78 (interquartile range 58-88) and 215 patients (53%) had an eTICI of 2C or higher. qTICI was comparable to eTICI in predicting favorable outcome with area under receiver operating characteristics curve of 0.63 vs. 0.62 (P = 0.8) and 0.87 vs. 0.86 (P = 0.87), for the unadjusted and adjusted analysis, respectively. In the adjusted regression analyses, both qTICI and eTICI were independently associated with functional outcome.ConclusionqTICI provides a quantitative measure of reperfusion with similar prognostic value for functional outcome to eTICI score. Show less
Background and Purpose- The location of the thrombus as observed on first digital subtraction angiography during endovascular treatment may differ from the initial observation on initial... Show moreBackground and Purpose- The location of the thrombus as observed on first digital subtraction angiography during endovascular treatment may differ from the initial observation on initial noninvasive imaging. We studied the incidence of thrombus dynamics, its impact on patient outcomes, and its association with intravenous thrombolytics. Methods- We included patients from the MR CLEAN registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke) with an initial target occlusion on computed tomography angiography located in the intracranial internal carotid artery, M1, or M2. The conventional angiography target occlusion was defined during endovascular treatment. Thrombus dynamics were classified as growth, stability, migration, and resolution. The primary outcome was functional outcome at 90 days (modified Rankin Scale). The secondary outcomes were successful and complete reperfusion (extended treatment in cerebral infarction scores of 2b-3 and 3, respectively). Results- The analysis included 1349 patients. Thrombus migration occurred in 302 (22%) patients, thrombus growth in 87 (6%), and thrombus resolution in 39 (3%). Intravenous treatment with alteplase was associated with more thrombus migration (adjusted odds ratio, 2.01; CI, 1.29-3.11) and thrombus resolution (adjusted odds ratio, 1.85; CI, 1.22-2.80). Thrombus migration was associated with a lower chance of complete reperfusion (adjusted odds ratio, 0.57; CI, 0.42-0.78) and successful reperfusion (adjusted odds ratio, 0.74; CI, 0.55-0.99). In the subgroup of patients with M1 initial target occlusion, thrombus migration was associated with better functional outcome (adjusted common odds ratio, 1.49; CI, 1.02-2.17), and there was a trend towards better functional outcome in patients with thrombus resolution (adjusted common odds ratio, 2.23; CI, 0.93-5.37). Conclusions- In patients with acute ischemic stroke, thrombus location regularly changes between computed tomography angiography and digital subtraction angiography. Administration of intravenous alteplase increases the chance of thrombus migration and resolution. Thrombus migration is associated with better functional outcome but reduces the rate of complete reperfusion. Show less
