Elsevier

The Lancet Neurology

Volume 14, Issue 8, August 2015, Pages 846-854
The Lancet Neurology

Rapid Review
Endovascular stent thrombectomy: the new standard of care for large vessel ischaemic stroke

https://doi.org/10.1016/S1474-4422(15)00140-4Get rights and content

Summary

Background

Results of initial randomised trials of endovascular treatment for ischaemic stroke, published in 2013, were neutral but limited by the selection criteria used, early-generation devices with modest efficacy, non-consecutive enrolment, and treatment delays.

Recent developments

In the past year, six positive trials of endovascular thrombectomy for ischaemic stroke have provided level 1 evidence for improved patient outcome compared with standard care. In most patients, thrombectomy was performed in addition to thrombolysis with intravenous alteplase, but benefits were also reported in patients ineligible for alteplase treatment. Despite differences in the details of eligibility requirements, all these trials required proof of major vessel occlusion on non-invasive imaging and most used some imaging technique to exclude patients with a large area of irreversibly injured brain tissue. The results indicate that modern thrombectomy devices achieve faster and more complete reperfusion than do older devices, leading to improved clinical outcomes compared with intravenous alteplase alone. The number needed to treat to achieve one additional patient with independent functional outcome was in the range of 3·2–7·1 and, in most patients, was in addition to the substantial efficacy of intravenous alteplase. No major safety concerns were noted, with low rates of procedural complications and no increase in symptomatic intracerebral haemorrhage.

Where next?

Thrombectomy benefits patients across a range of ages and levels of clinical severity. A planned meta-analysis of individual patient data might clarify effects in under-represented subgroups, such as those with mild initial stroke severity or elderly patients. Imaging-based selection, used in some of the recent trials to exclude patients with large areas of irreversible brain injury, probably contributed to the proportion of patients with favourable outcomes. The challenge is how best to implement imaging in clinical practice to maximise benefit for the entire population and to avoid exclusion of patients with smaller yet clinically important potential to benefit. Although favourable imaging identifies patients who might benefit despite long delays from symptom onset to treatment, the proportion of patients with favourable imaging decreases with time. Health systems therefore need to be reorganised to deliver treatment as quickly as possible to maximise benefits. On the basis of available trial data, intravenous alteplase remains the initial treatment for all eligible patients within 4·5 h of stroke symptom onset. Those patients with major vessel occlusion should, in parallel, proceed to endovascular thrombectomy immediately rather than waiting for an assessment of response to alteplase, because minimising time to reperfusion is the ultimate aim of treatment.

Introduction

In view of the strongly positive results of recent trials of endovascular thrombectomy for ischaemic stroke,1, 2, 3, 4, 5, 6 it seems remarkable that only 2 years ago, the reporting of three neutral endovascular trials7, 8, 9 led to widespread pessimism in the neurological community about the value of endovascular treatment. Although these early trials were state of the art when designed, in retrospect they had clear limitations: early-generation devices were relatively ineffective in achieving recanalisation; initiation of endovascular treatment was often delayed; non-consecutive enrolment occurred owing to lack of clinical equipoise, leading to open-label treatment for patients deemed to be good candidates, boosted by remuneration incentives for open-label therapy; and basic imaging selection to confirm major vessel occlusion was not routinely done.10, 11, 12 Some US insurance agencies stopped funding the procedure after these initial reports,7, 8, 9 and concerns were raised that the proliferation of new endovascular trials would fragment recruitment and delay results. Fortunately for patients with ischaemic stroke, this predicted outcome did not unfold. Indeed, neutral studies facilitated the recruitment of participants into subsequent trials by resetting the level of investigator equipoise.

Five positive randomised trials have now been published,1, 2, 3, 4, 5 which used predominantly stent retrievers in patients with occlusions in anterior circulation vessels only, and two more have reported interim outright positive results6 or a trend to positive results13 in the form of abstracts. The MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands)1 was the first to be completed. Investigators recruited rapidly, possibly in part because reimbursement for the procedure in the Netherlands was restricted to trial participants, which encouraged consecutive recruitment—an admirable model for the investigation of unproven treatments. Release of the MR CLEAN trial results1 at the 9th World Stroke Congress in October, 2014, prompted review of the ongoing trials. EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial),2 ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times),3 and SWIFT PRIME (Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment)4 were stopped by data safety monitoring committees after interim analyses crossed pre-specified efficacy boundaries. REVASCAT (Randomized Trial of Revascularization with Solitaire FR Device versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting within Eight Hours of Symptom Onset)5 was halted at a pre-planned interim analysis because of loss of equipoise in the trial population and because the intervention was associated with significantly improved functional outcome. The THRACE (Trial and Cost Effectiveness Evaluation of Intra-arterial Thrombectomy in Acute Ischemic Stroke) study6 ran to completion and has reported positive interim results, whereas the THERAPY (Assess the Penumbra System in the Treatment of Acute Stroke) trial,13 which used aspiration catheters, was terminated early, showing a trend to benefit. In this Rapid Review, we summarise the results of the latest trials and discuss the implications for stroke management.

Section snippets

Lessons learned from variation between trials

Although the recent endovascular trials1, 2, 3, 4, 5, 6, 13 differed in inclusion criteria, therapeutic time window, and the precise intervention used, great consistency can be seen in the clinical populations enrolled and the overall results (table, figure 1). All trials have shown a substantial reduction in disability at 90 days after treatment. The effect size in these trials is one of the largest across disciplines of medicine, with a number needed to treat (NNT) to achieve an additional

Role of intravenous thrombolysis

The recent endovascular trials all gave alteplase to eligible patients before endovascular thrombectomy. Those ineligible for alteplase also benefited from endovascular thrombectomy.3, 5 In view of the low rates of alteplase-induced recanalisation before angiogram, an argument might be made to omit alteplase if endovascular thrombectomy is immediately available.38 Indeed, some evidence suggests that alteplase independently increases the risk of symptomatic haemorrhage.39 However, this argument

Implementation

The European Stroke Organisation has released an updated guideline recommending endovascular stent thrombectomy for patients with large vessel occlusion within 6 h of stroke onset (level 1 evidence),42 with other organisations likely to follow shortly with similar guidance. Implementation of endovascular thrombectomy as a treatment for ischaemic stroke is expected to have a major effect on public health. During the completion of the REVASCAT trial5 in Catalonia, Spain, 4% of all patients

Conclusions and future directions

Evidence for endovascular stroke treatment is best established for stent retrievers with treatment started within 6 h of stroke symptom onset. Ongoing trials aim to extend this time window to 6–12 h (POSITIVE) and 6–24 h (DAWN) with the use of perfusion imaging selection. Patients with occlusion of the internal carotid and proximal middle cerebral artery (including tandem occlusions) clearly benefit from endovascular thrombectomy, but there is residual uncertainty in the case of more distal

Search strategy and selection criteria

We identified relevant articles published in English by searching PubMed, Embase, and ClinicalTrials.gov using search terms with synonyms and related terms in the title or abstract of “stroke” and “endovascular” and “randomised controlled trial”. We searched for articles from inception of the databases to May 30, 2015. We included reports of adult patients with stroke, those that used a randomised controlled trial design, in which the experimental intervention conformed to the definitions of

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