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

Treatment in patients who are not eligible for intravenous alteplase: MR CLEAN subgroup analysis

Patients with acute ischemic stroke due to intracranial large vessel occlusion benefit from intra-arterial therapy. Uncertainty exists about the effect of intra-arterial therapy in patients with contraindications for treatment with intravenous alteplase treatment. Our aim was to describe the clinical characteristics of this subgroup of patients and whether intra-arterial therapy is as safe and effective as it is after intravenous alteplase treatment. All 500 MR CLEAN patients were included and we distinguished between patients who were and were not treated with intravenous alteplase treatment. We estimated the effect of intra-arterial therapy on the shift on the modified Rankin Scale score with ordinal logistic regression analysis and tested for interaction of intravenous alteplase treatment with intra-arterial therapy on outcome. Furthermore, safety parameters and serious adverse events were analyzed. Fifty-five patients (11%) were not treated with intravenous alteplase treatment, mostly because of prolonged coagulation time tests or recent surgery. These patients were older and more often had atrial fibrillation or other vascular comorbidity. There was no interaction between intravenous alteplase treatment and intervention effect (p = 0.927). Intra-arterial therapy effect size in patients without intravenous alteplase treatment was 2.06 [95% CI: 0.69-6.13] and in patients with intravenous alteplase treatment 1.71 [95% CI: 1.22-2.40]. There were no safety issues. For patients with acute ischemic anterior circulation stroke caused by intracranial large vessel occlusion, who have contraindications for intravenous alteplase, intra-arterial treatment is not less effective or less safe than in patients who receive the treatment after intravenous alteplase. Clinical trial registration-URL: http://www.trialregister.nl. Unique identifier: (NTR)1804.Clinical trial registration-URL: http://www.controlled-trials.com. Unique identifier: ISRCTN1088875

Reader response: Comparative safety and efficacy of combined IVT and MT with direct MT in large vessel occlusion

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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

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