Elsevier

The Lancet Neurology

Volume 17, Issue 10, October 2018, Pages 895-904
The Lancet Neurology

Articles
Imaging features and safety and efficacy of endovascular stroke treatment: a meta-analysis of individual patient-level data

https://doi.org/10.1016/S1474-4422(18)30242-4Get rights and content

Summary

Background

Evidence regarding whether imaging can be used effectively to select patients for endovascular thrombectomy (EVT) is scarce. We aimed to investigate the association between baseline imaging features and safety and efficacy of EVT in acute ischaemic stroke caused by anterior large-vessel occlusion.

Methods

In this meta-analysis of individual patient-level data, the HERMES collaboration identified in PubMed seven randomised trials in endovascular stroke that compared EVT with standard medical therapy, published between Jan 1, 2010, and Oct 31, 2017. Only trials that required vessel imaging to identify patients with proximal anterior circulation ischaemic stroke and that used predominantly stent retrievers or second-generation neurothrombectomy devices in the EVT group were included. Risk of bias was assessed with the Cochrane handbook methodology. Central investigators, masked to clinical information other than stroke side, categorised baseline imaging features of ischaemic change with the Alberta Stroke Program Early CT Score (ASPECTS) or according to involvement of more than 33% of middle cerebral artery territory, and by thrombus volume, hyperdensity, and collateral status. The primary endpoint was neurological functional disability scored on the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included symptomatic intracranial haemorrhage, parenchymal haematoma type 2 within 5 days of randomisation, and mortality within 90 days. For the primary analysis, we used mixed-methods ordinal logistic regression adjusted for age, sex, National Institutes of Health Stroke Scale score at admission, intravenous alteplase, and time from onset to randomisation, and we used interaction terms to test whether imaging categorisation at baseline modifies the association between treatment and outcome. This meta-analysis was prospectively designed by the HERMES executive committee but has not been registered.

Findings

Among 1764 pooled patients, 871 were allocated to the EVT group and 893 to the control group. Risk of bias was low except in the THRACE study, which used unblinded assessment of outcomes 90 days after randomisation and MRI predominantly as the primary baseline imaging tool. The overall treatment effect favoured EVT (adjusted common odds ratio [cOR] for a shift towards better outcome on the mRS 2·00, 95% CI 1·69–2·38; p<0·0001). EVT achieved better outcomes at 90 days than standard medical therapy alone across a broad range of baseline imaging categories. Mortality at 90 days (14·7% vs 17·3%, p=0·15), symptomatic intracranial haemorrhage (3·8% vs 3·5%, p=0·90), and parenchymal haematoma type 2 (5·6% vs 4·8%, p=0·52) did not differ between the EVT and control groups. No treatment effect modification by baseline imaging features was noted for mortality at 90 days and parenchymal haematoma type 2. Among patients with ASPECTS 0–4, symptomatic intracranial haemorrhage was seen in ten (19%) of 52 patients in the EVT group versus three (5%) of 66 patients in the control group (adjusted cOR 3·94, 95% CI 0·94–16·49; pinteraction=0·025), and among patients with more than 33% involvement of middle cerebral artery territory, symptomatic intracranial haemorrhage was observed in 15 (14%) of 108 patients in the EVT group versus four (4%) of 113 patients in the control group (4·17, 1·30–13·44, pinteraction=0·012).

Interpretation

EVT achieves better outcomes at 90 days than standard medical therapy across a broad range of baseline imaging categories, including infarcts affecting more than 33% of middle cerebral artery territory or ASPECTS less than 6, although in these patients the risk of symptomatic intracranial haemorrhage was higher in the EVT group than the control group. This analysis provides preliminary evidence for potential use of EVT in patients with large infarcts at baseline.

Funding

Medtronic.

Introduction

Randomised clinical trials from the past 3 years have established the safety and efficacy of endovascular thrombectomy (EVT) in the treatment of patients with acute ischaemic stroke and proximal anterior circulation occlusion.1, 2, 3, 4, 5, 6, 7, 8 Because the clinical benefit observed in these trials was time dependent, the need for fast and efficient patient selection is well recognised.9 Imaging is widely used to determine prognosis and to select patients for EVT.10, 11, 12 After the results of five trials were reported in 2015, the new American Heart Association guidelines13 recommended EVT as standard of care (level I, class A evidence) in patients with a baseline non-contrast Alberta Stroke Program Early CT Score (ASPECTS) between 6 and 10.

Imaging features are strong predictors of clinical outcome.10 Large infarcts at baseline, large thrombi in proximal arteries, and poor collateral circulation identified with imaging are associated with overall lower likelihood of functional independence and increased risk of intracranial haemorrhage after reperfusion therapies.14, 15, 16, 17, 18, 19 However, evidence regarding whether these imaging features are useful for selecting patients for EVT is scarce. This patient-level meta-analysis by the highly effective reperfusion evaluated in multiple endovascular stroke trials (HERMES) collaboration aims to determine safety and efficacy of EVT compared with standard medical therapy, by baseline imaging features.

Section snippets

Search strategy and selection criteria

In this individual patient-level meta-analysis, we searched PubMed for randomised trials published between Jan 1, 2010, and Oct 31, 2017, which compared EVT predominantly done with stent retrievers with standard care in patients with anterior circulation ischaemic stroke. The PubMed search string was ((“randomized controlled trial”[Publication Type]) AND ((thrombectomy [Title/Abstract]) OR (clot retrieval [Title/Abstract]) OR intraarterial[Title/Abstract]) AND (stroke[Title/Abstract]) AND

Results

We obtained data from 1764 randomised participants, of whom 871 were assigned to receive EVT and 893 to receive standard medical treatment (control group). Pre-randomisation brain imaging features were evaluated in 1388 patients on CT and in 364 patients on MRI (appendix). Clinical characteristics and imaging features at baseline were balanced between the two treatment groups, but treatment with intravenous alteplase was more common in the control group (table 1). Risk of bias was low except in

Discussion

Our patient-level meta-analysis lends support to a benefit of EVT for acute ischaemic stroke across a broad range of imaging subgroups. Our results add to previous work from the HERMES collaboration that showed benefit of EVT across a broad range of clinical subgroups.8 Our analysis is larger than this previous work (seven trials instead of five and 1764 patients instead of 1287), uses more rigorous imaging analysis (HERMES core laboratory uniform rereading of all scans from all trials), and

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