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Current endovascular treatment of acute stroke and future aspects

https://doi.org/10.1016/j.drudis.2010.04.007Get rights and content

Acute ischemic stroke remains a condition of high morbidity and mortality. Until now, the only established therapy has been intravenous (IV) tissue-type plasminogen activator (tPA). Only 3–10% of patients with acute ischemic stroke receive this treatment.

On the basis of data from part 3 of the European Collaborative Acute Stroke Study (ECASS III), the time window for beneficial treatment of ischemic stroke with IV tPA has been extended from 3 to 4.5 h after the onset of stroke symptoms. Beyond that window of opportunity, and additionally to IV treatment, interventional stroke therapy has assumed an important role for the treatment of acute ischemic stroke.

Currently, new promising pharmacological and mechanical treatment options are being established as routine procedures to achieve a further improved outcome for stroke patients.

Introduction

After myocardial infarction and cancer, stroke is the third most common cause of death in the western world, affecting an estimated 700,000 Americans each year, and is the most common cause of severe disability [1]. Some 30–50% of stroke survivors do not regain functional independence and 15–30% of these remain permanently disabled. Thus, stroke is a massive financial and personal burden on our society [2]. For someone who is having a stroke ‘Time is Brain’. Earlier treatment is associated with better outcome. To achieve this, acute stroke protocols are initiated to identify patients within the therapeutic time window for thrombolytic and mechanical recanalization therapies.

In 1996, as a result of the National Institute of Neurological Disorder and Stroke (NINDS) and rtPA Stroke Study Group trial, the US Food and Drug Administration (FDA) approved IV thrombolysis with recombinant tissue plasminogen activator (rtPA, alteplase) for the treatment of ischemic stroke within 3 h of onset [3]. Thus, IV rtPA thrombolysis was the first approved treatment that attacks the acute vessel occlusion directly. It is now accepted as a class 1A level of evidence intervention for acute ischemic stroke [4].

Analysis of major randomized placebo-controlled IV rtPA stroke trials, as ATLANTIS I and II (Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke), ECASS I and II (European Cooperative Acute Stroke Study), and NINDS I and II showed a benefit up to 3 h from the onset of stroke symptoms and suggested a potential benefit beyond 3 h for some patients 5, 6. The ECASS-III trial confirmed a treatment window up to 4.5 h for IV rtPA therapy [7].

Despite its promise and the use of different drugs, the recanalization rates of IV rtPA for proximal arterial occlusion range from only 10% to 30% and the NINDS trial data showed a 12% increase at 3 months in better outcomes between the placebo and rtPA groups [8].

Section snippets

Drugs used in acute stroke therapy

Drug therapy is a relatively recent approach to the treatment of stroke, and a large amount of research is focused on finding effective new drugs that can minimize stroke damage. The most relevant drugs evaluated for acute stroke therapy are summarized in Table 1.

Endovascular therapy of acute stroke

The relatively high haemorrhage rates, in combination with the low complete recanalization rates, demonstrate the imitations of treatment solely with pharmacological agents. Especially in carotid terminus or basilar artery occlusions with large clot burden, the procedure takes time and may not achieve meaningful recanalization. Platelet-rich clots, old clots and calcified clots or fat emboli cannot be addressed. These factors substantiate the assumption that faster and more complete reperfusion

Intraarterial mechanical therapies

The limitations to IA lysis are related to clot characteristics. The response to the pharmacological agent may vary according to the source and type of clot. White platelet rich clots are more resistant to lytics than fresh red blood cell rich clots. De novo cardiac clots and paradoxial venous clots respond better than calcified clots from atherosclerotic plaques.

The therapeutic approach concerning these limitations changed dramatically in 2004 with the US Food and Drug Administration approval

Alternative reperfusion strategies

The alternative reperfusion strategies use the collateral vasculature of the brain as well as retrograde and reversed flow.

Retrograde reperfusion and flow reversal are experimental treatment techniques that cause total reversal of the cerebral circulation and perfusion of the venous system with arterial blood into the capillary bed, which is then physiologically proximal to the occluded artery.

Limitations

Delayed symptomatic reocclusion after initial endovascular stroke therapy can lead to sudden clinical deterioration and has been linked to poor clinical outcomes [59]. The rate of reocclusion after endovascular treatments is 18% [60]. This may be underestimated as many patients present with large clinical deficits at time of presentation and explain the low rate of good clinical outcome despite of a high rate of revascularization.

Conclusions

The advantages of pharmacological thrombolysis over mechanical means are: The drugs are easier to administer and – ‘Time is Brain’: they can be started faster. Future newer generation lytics and platelet inhibitors may be even more faster, effective and specific. The disadvantages are that often no success can be achieved, and although the therapy can be initiated quickly, the effect occurs slowly and the risk of local and systemic hemorrhagic complications is evident.

The major disadvantages of

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