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Background: Benefit of endovascular treatment (EVT) varies between individual patients with acute ischemic stroke. The MR PREDICTS decision tool, previously developed in the MR CLEAN trial, predicts outcome with and without EVT based on baseline patient characteristics and imaging characteristics (www.mrpredicts.com). We externally validated this model with data from recent EVT trials. Methods: Individual patient data was derived from the six other randomized controlled trials within the HERMES collaboration (ESCAPE, REVASCAT, SWIFT-PRIME, EXTEND-IA, THRACE and PISTE). Outcome of the ordinal logistic regression model was the modified Rankin Scale (mRS) at 90 days after stroke. Treatment benefit was defined as the difference between the predicted probability of achieving functional independence (mRS score 0-2) with and without EVT. Model performance was evaluated according to discrimination (measured with the c-statistic which ranges from 0.5 to 1) and calibration. Model coefficients were updated after calibration. Results: We included 1243 patients (633 assigned to EVT, 610 assigned to control). The c-statistic was 0.67 (95% confidence interval [CI] 0.65-0.69) for the ordinal mRS and 0.73 (95% CI 0.70-0.76) for functional independence, similar to previous performance. Outcomes were systematically better than predicted (calibration slope 0.89 and intercept 0.52). The observed probability of functional independence was higher than predicted for both treated patients (54% vs 40%) and controls (35% vs 26%), but the observed treatment benefit was similar (19% and 14%). Figure 1 shows a screenshot of the decision tool for use in clinical practice. Conclusion: Our model predicted outcome in a large representative trial population with discriminative value comparable to other well-known prediction tools. The decision tool can be used to support clinical decision making in ischemic stroke by selection of patients for EVT.

Introduction: We aimed to investigate the outcome of endovascular treatment (EVT) for acute ischemic stroke in patients with low Alberta Stroke Program Early CT Score (ASPECTS). Methods: This study reports on MR CLEAN Registry patients with available baseline ASPECTS (N=1423). ASPECTS was trichotomized in 0-4, 5, and 6-10 in order to create low ASPECTS groups of similar size. Primary outcome was modified Rankin Scale score (mRS) at 90 days. Secondary outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. Benefit of reperfusion (defined as extended thrombolysis in cerebral infarction [eTICI] score 2B-3) was assessed by multivariable ordinal logistic regression analysis, including an interaction term of reperfusion and ASPECTS, and it was expressed as an adjusted common odds ratio (acOR). A comparison with the MR CLEAN trial control arm was made to assess benefit of EVT. Results: Higher trichotomized ASPECTS was associated with improved mRS (acOR 1.4, 95%CI 1.2-1.7). For ASPECTS 0-4 (n=93) successful reperfusion was not associated with improved mRS (acOR 1.4, 95%CI 0.6-2.9). ASPECTS 5 (n=63) and ASPECTS 6-10 subgroups (n=1267) however, did show significant benefit of reperfusion (acOR 3.9, 95%CI 1.3-11.8; acOR 2.7, 95%CI 2.2-3.3, respectively)(Fig1). Interaction between trichotomized ASPECTS and reperfusion was not significant ( p =0.13). Comparison with the MR CLEAN trial control group showed that trichotomized ASPECTS did not modify the effect of EVT ( p =0.14). Patients with lower trichotomized ASPECTS had a higher risk of mortality (aOR 0.9, 95%CI 0.9-1.0), but not of sICH (aOR 1.0, 95%CI 0.9-1.1). Conclusion: ASPECTS does not modify effect of reperfusion or EVT on functional outcome after acute ischemic stroke. Patients with ASPECTS 5 or higher seem to benefit from successful reperfusion.

Background: The 90-day modified Rankin Scale (mRS) is the most commonly used primary outcome measure in stroke treatment trials, but has drawbacks, including the potential loss of subjects due to prolonged follow-up. An alternative may be the NIH Stroke Scale (NIHSS) early after stroke, which is frequently used as a secondary outcome measure. The aim of this study was to evaluate whether the NIHSS assessed within one week after trial inclusion could serve as a primary outcome measure for trials of acute ischaemic stroke treatment. Methods: We used the Prentice criteria to evaluate NIHSS 1 day and 5-7 days after trial inclusion as primary outcome measures in two trials of endovascular treatment (EVT): the positive MR CLEAN and the neutral IMS III. The four Prentice criteria evaluate a surrogate endpoint against a true endpoint (Figure). We adjusted for age, baseline NIHSS, collateral score, and time of symptom onset to randomization. Results: The Prentice criteria were met for NIHSS at 1 day and 5-7 days in MR CLEAN (n=500). We found a significant treatment effect of EVT on the mRS and on the NIHSS at 1 day and 5-7 days. After adjustment for NIHSS at 1 day and 5-7 days, the effect of EVT on mRS decreased from common odds ratio 1·69 (95%CI: 1·22-2·33) to respectively 1·33 (95%CI: 0·95-1·85) and 1·21 (95%CI: 0·86-1·72). In IMS III (n=656) there was no treatment effect on NIHSS at 1 day (p=0.56) and 5-7 days (p=0.28), coinciding with the absence of a treatment effect on mRS. Conclusion: NIHSS is able to replace the mRS at 90 days as a measure of treatment effect. NIHSS within one week after trial inclusion may be used as a primary outcome measure in trials of acute ischemic stroke treatment, particularly in phase II(b) trials. This could minimize loss to follow-up, and reduce trial duration and costs.

Background: Even when the revascularization and clinical status of a patient after endovascular treatment (EVT) for acute ischemic stroke is known, outcome is still highly variable and difficult to predict. We aimed to develop and externally validate a prognostic model that can be applied within one day after EVT to predict functional outcome at three months (MR PREDICTS@24H). Methods: For model development we used data from patients in the treatment arms of seven randomized controlled trials within the HERMES collaboration. For external validation we used data from the MR CLEAN Registry, a Dutch ongoing prospective multicenter study for consecutive patients treated with EVT between March 2014 and June 2016 (n=1526). Primary outcome was the ordinal modified Rankin Scale (mRS) score three months after EVT. Eighteen pre- and post-procedural variables, assessed within one day after EVT, were analyzed with univariable ordinal logistic regression analysis (p Results: The final model included nine variables: age, baseline stroke severity measured with the NIH Stroke Scale (NIHSS), diabetes mellitus, pre-stroke mRS, collateral score, occlusion location, revascularization grade, NIHSS 24 hours after EVT, and symptomatic intracranial hemorrhage. The model explained 62% of the variance in outcome and NIHSS 24 hours after EVT was the strongest predictor with 54% explained variance. The externally validated c-statistic was 0.84 for the prediction of the ordinal mRS and 0.91 for mRS 0-2, indicating very good model performance. Calibration for mRS 0-2 was also very good (intercept: 0.25 and slope: 0.99). Conclusion: MR PREDICTS@24H, which can be applied within one day after EVT, accurately predicts functional outcome at three months. It may provide physicians, patients, and family members with improved outcome expectations and could guide physicians in personalizing their patients’ treatment and rehabilitation plans.

We thank Freeman for his response to our article 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).1 We indeed assessed the effect of mean arterial pressure (MAP) on functional outcome in our analysis, which is shown in Figure IVB in the online-only Data Supplement (the supplements were updated because this figure was incorrectly showing Figure 1 of the article). The effect was U shaped; both low and high MAP were associated with poor …

Background & Purpose: Intra-arterial therapy (IAT) is being implemented worldwide as the main treatment option for acute ischemic stroke (AIS). We wondered whether effectiveness and safety results that have been reported in randomized clinical trials can be reproduced in everyday clinical practice. We will report results of the Dutch National post MR CLEAN IAT registry including work flow parameters, primary and secondary outcomes, as well as serious adverse events. Methods: The MR CLEAN Registry is a prospective registry of all patients undergoing IAT for AIS in the Netherlands, started after completion of the MR CLEAN trial in March 2014. Registration was required for reimbursement. A core set was defined, with inclusion criteria similar to those of the MR CLEAN trial, including a proven anterior circulation occlusion and treatment possible withing 6 hours from onset. The primary study outcome is the score on the modified Rankin Scale (mRS) at 90 days. The secondary clinical outcome is NIHSS after 24 to 48 hours. Secondary radiological outcomes include the mTICI score on DSA and final infarct volume and major bleeding on follow up NCCT. We used a propensity weighted and an unadjusted ordinal logistic regression model to compare outcomes in the MR CLEAN Registry core and total dataset with the treatment arm of MR CLEAN. Results: Between March 2014 and August 2016 the inclusion rate of the MR CLEAN Registry has been increasing steadily to an average of 79 (SD 22) per month for a cumulative inclusion of 1548 patients in July 2016 (Figure 1). Conclusions: The MR CLEAN registry data is now being analyzed. Results will be reported at the conference.