Elsevier

The Lancet Neurology

Volume 6, Issue 12, December 2007, Pages 1086-1093
The Lancet Neurology

Review
Endovascular treatment of acute ischaemic stroke

https://doi.org/10.1016/S1474-4422(07)70269-7Get rights and content

Summary

The emphasis of treatments for acute ischaemic stroke during the past two decades has been on revascularisation. Endovascular treatment is a promising alternative for patients who are ineligible for standard intravenous thrombolytic therapy; however, its use is limited by the few randomised trials reported and the small number of practising neurointerventionalists. Although data are still being collected, important progress has been made. In this Review, we summarise the findings of the major clinical trials of endovascular treatment, and show that endovascular treatment of acute ischaemic stroke is a therapeutic option for patients who are disqualified from or do not improve on treatment with intravenous alteplase. Moreover, the American Heart Association has expanded its guidelines to include endovascular stroke therapies as a treatment option.

Introduction

Stroke therapy is in some ways similar to the treatment of coronary artery disease; for example, intravenous alteplase (tissue plasminogen activator; tPA) given within 3 hours for thrombolytic treatment of acute ischaemic stroke has been used for more than 10 years.1 However, although certain common features of occlusive vascular disease have enabled the extension of some of the treatments for acute myocardial infarction to acute ischaemic stroke, the differences have led to a fork in the road. Over the past decade, the treatment of acute myocardial infarction has moved away from systemic thrombolysis towards percutaneous coronary interventions.2, 3, 4, 5 By contrast, neuroendovascular interventions, which include procedures such as local intra-arterial thrombolysis and the mechanical removal of in situ thrombi, are still mostly reserved for patients with acute ischaemic stroke who cannot be safely given systemic thrombolysis. Alteplase might be less effective for treating occlusions of the large vessels, such as the internal carotid artery or middle cerebral artery, with estimated recanalisation rates of 0–33% based on transcranial Doppler of these vessels.6, 7, 8 Endovascular treatments for acute ischaemic stroke require validation from large-scale, randomised, controlled clinical trials; however, because these therapies are unproven, direct comparisons with alteplase for patients with acute ischaemic stroke in blinded studies are difficult—physicians are reluctant to randomly assign eligible patients away from a proven treatment. By contrast, in the specialty of cardiology, the success of angioplasty has helped the comparison of percutaneous coronary interventions with currently accepted treatment strategies.2, 5, 9 Despite these problems, investigations to validate endovascular therapies for acute ischaemic stroke are of paramount importance, in view of the low overall number of patients with acute ischaemic stroke who qualify for treatment with alteplase.10, 11

In this Review, we summarise randomised trials, some registries of local intra-arterial thrombolysis, mechanical thrombectomy and other mechanical treatments for the treatment of acute ischaemic stroke, and advanced imaging techniques as alternative ways to identify candidates for therapies based on widened therapeutic windows.

Section snippets

Local intra-arterial thrombolysis

An alternative regimen to systemic thrombolysis for use beyond 3 hours after the onset of symptoms is to give a lower dose of local intra-arterial thrombolysis, which gives targeted drug effects and clot dissolution without the risk of extracranial or intracranial haemorrhage associated with delayed systemic thrombolysis. Several case reports and series were published before the feasibility of this therapeutic option was assessed in large-scale studies,12, 13, 14, 15, 16, 17 and each of these

Systemic and local intra-arterial thrombolysis

In view of the resistance of proximal thrombi to intravenously given thrombolytics, combined therapy has the benefit of systemic thrombolysis with increased activity at the site of the clot. Since the publication of the NINDS tPA trial,1 which defined alteplase as an efficacious treatment for acute ischaemic stroke, recent studies seldom report the random assignment of patients away from this drug. However, the phase I Emergency Management of Stroke (EMS) trial,21 which tested the efficacy,

Mechanical or non-pharmacological methods of revascularisation

Devices have been developed to remove clots from the coronary vasculature, although they have mostly been replaced by angioplasty. However, in patients with acute ischaemic stroke, great emphasis has been placed on these interventions, which include mechanical thrombectomy (clot removal) and mechanical disruption of the clot. The Concentric retriever (Concentric Medical, Mountainview, CA, USA), which was granted approval by the US Food and Drug Administration in 2003, consists of a

Increased treatment windows

One of the greatest problems in the treatment of acute ischaemic stroke is the restricted time window during which reperfusion therapy can be safely given. Although early studies of systemic thrombolytics and local intra-arterial thrombolysis used triage criteria based on non-contrast CT data, MRI and perfusion imaging of the ischaemic penumbra might be an alternative means to identify candidates suitable for revascularisation therapy. When triage criteria based only on CT data are

Clinical criteria and selection of patients

Although there are no standardised guidelines for the endovascular treatment of acute ischaemic stroke, several studies have uniform inclusion and exclusion criteria. These criteria restrict endovascular treatment to patients who are ineligible for treatment with alteplase, such as those who present later than 3 hours after the onset of symptoms or those prevented from taking systemic thrombolysis.1 PROACT I, PROACT II, and the EMS bridging trial provide data on the safety of local

Practitioners of interventional neurology

The rapid progress in the interventional management of stroke is indicative of advances in the specialty in general. Clinicians who have previously provided only the more traditional modes of therapy have expressed interest in the new ways to treat diseases that previously could only be treated with medical or open surgical techniques. Although the first cerebral angiogram was done by the neurologist Egaz Moniz more than 50 years ago by direct carotid puncture, refinements in the transfemoral

Conclusions

A decade after the use of systemic thrombolysis for the treatment of acute ischaemic stroke, we now enter an era of newer endovascular treatments, in which intra-arterial thrombolysis and mechanical methods of thrombectomy and thrombus disruption are being investigated. Although these therapies have higher recanalisation rates compared with systemic thrombolysis, they are still limited by their availability, and we await the results of forthcoming randomised trials to validate these therapies.

Search strategy and selection criteria

References for this Review were identified by a search of PubMed with the terms “ischaemic stroke”, “MERCI”, “thrombectomy”, “thrombolysis”, “diffusion–perfusion mismatch”, “CT-perfusion”, and “clinical–diffusion mismatch”. Searches covered the period between 1966 and August, 2007. Only studies published in English were reviewed. Particular focus was given to reports of randomised clinical trials, safety and efficacy studies, and prospective registries that have been presented at multiple

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