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