Endovascular Treatment for Acute Ischemic Stroke

Arnold, Marcel; Schroth, Gerhard; Gralla, Jan

doi:10.1056/nejmc1304759

Cited by 32 publications

(33 citation statements)

References 31 publications

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“…This association was also identified in the overall IMS III cohort (TICI 0 12.7%, 1 27.6%, 2A 34.3%, 2B 47.9%, and 3 71.4%; p<0.001). 3 This finding must be interpreted with caution because confounding factors can lead patients with reperfusion to have better outcomes as well. Only randomized trials with intention-to-treat analyses can determine the true benefit of endovascular therapy.…”

Section: Discussionmentioning

confidence: 98%

“…3 Time to angiographic reperfusion was defined as time from stroke onset to procedure termination. Procedure end was deemed to be a reasonable surrogate for reperfusion timing since angiographic assessments were required after successive 15-minute infusions of IA rt-PA or after each device deployment, and investigators were encouraged to abort the procedure upon achieving TICI 2b reperfusion (i.e., half or more of the vascular distribution of the occluded artery).…”

Section: Methodsmentioning

confidence: 99%

“…The trial was stopped after crossing a prespecified futility boundary (primary outcome ≤2: 41% endovascularvs 39% IV rt-PA; p=0.70). 3 One reason for the neutral result mRS = may have been angiographic reperfusion that occurredtoo late to salvage brain tissue.…”

Section: Introductionmentioning

confidence: 99%

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Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial

Khatri

Yeatts

Mazighi

et al. 2014

The Lancet Neurology

376

247

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BACKGROUND The IMS III Trial did not demonstrate clinical benefit of the endovascular approach compared to IV rt-PA alone for moderate or severe ischemic strokes (NIHSS≥8) enrolled within three hours of stroke onset. Late reperfusion of tissue that is no longer salvageable may be one explanation, as suggested by prior exploratory studies showing an association between time to reperfusion and good clinical outcome. We sought to validate this relationship in the large-scale IMS III trial, and consider its implications for future endovascular trials. METHODS The analysis consisted of the endovascular cohort with proximal arterial occlusions in the anterior circulation that achieved angiographic reperfusion (TICI 2–3) during the endovascular procedure (within 7 hours from the onset of symptoms). Logistic regression was used to model good clinical outcome (90-day modified Rankin 0–2) as a function of the time to reperfusion, and prespecified variables were considered for adjustment. FINDINGS Among 240 proximal vessel occlusions, angiographic reperfusion (TICI 2–3) was achieved in 182 (76%). Mean time to reperfusion was 325 minutes (range 180–418 minutes). Longer time for reperfusion was associated with a decreased likelihood of good clinical outcome (RR [95% CI] for every 30 minute delay: unadjusted 0·85 [0·77–0·94]; adjusted 0·88 [0·80–0·98]). INTERPRETATION We confirm that delay in time to angiographic reperfusion leads to a decreased likelihood of good clinical outcome. Achieving rapid reperfusion may be critical for the successes of future acute endovascular trials. FUNDING: NIH/NINDS (study sponsor), Genentech Inc. (study drug - intra-arterial t-PA), EKOS Corp. (device), Concentric Inc. (device), Cordis Neurovascular, Inc. (device), and Boehringer Ingelheim (European Investigator Meeting support).

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

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Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial

Khatri

Yeatts

Mazighi

et al. 2014

The Lancet Neurology

376

247

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“…Despite some recent negative results [63,64,65], delayed intervention with clot retrieval remains an attractive strategy given the strong correlations between recanalization, reperfusion and favourable clinical outcome. The early trials used the MERCI device with more recent studies using the more effective stentriever devices [66].…”

Section: Part 2: Using Penumbral Imaging In Trials For the Selection mentioning

confidence: 99%

Time Is Penumbra: Imaging, Selection and Outcome

Davis

Donnan

2014

Cerebrovasc Dis

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The foundation of modern therapy for ischaemic stroke involves reperfusion of the ischaemic penumbra and salvage of threatened but potentially viable brain tissue. Work on imaging of the penumbra and clinical trials using penumbral evaluation or selection have been a major focus of our collaborative work over several decades. We review the original description of the ischaemic penumbra, its measurement using a variety of imaging techniques, the duration of the penumbra and its potential salvage up to 48 h after stroke onset. The penumbra can now be accurately measured using automated thresholded techniques in real time with MRI or CT perfusion (CTP). Particular advances include more precise definitions of mismatch with validation of the measures for the ischaemic core and exclusion of benign oligaemia. While there has been greater trial experience with MRI perfusion/diffusion mismatch, CTP mismatch using a similar thresholded perfusion metric (T_max 6 s) and relative blood flow (around 31%) to estimate the ischaemic core is generally more available and practicable in our experience. We review the completed clinical trials, which generally demonstrate the clinical benefits of acute reperfusion in penumbral patients, provided that large ischaemic cores are excluded. Our EPITHET trial was the first randomized controlled trial of tissue plasminogen activator (tPA) versus placebo at delayed times to test the concept of penumbral selection. We showed that in patients with a penumbra receiving thrombolysis, there was substantially increased reperfusion. Major reperfusion times were associated with reduced growth of the ischaemic core and improved clinical outcomes. Our current trial programme involves the application of penumbral imaging to attempt to extend the time window for intravenous tPA and treat wake-up strokes, to test the benefits of endovascular therapy in patients who have already received tPA but still have both substantial penumbra and an occluded vessel, and, finally, to use penumbral imaging to define a responder population in a phase III trial testing intravenous tenecteplase versus tPA within the current 4.5-hour time window. We believe that confirmation of these trial hypotheses will substantiate the role of multimodal imaging of the penumbra as a routine part of acute stroke management.

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“…Subsequently, the endovascular approach was pioneered as treatment for acute LVO. The first 3 clinical randomized trials of endovascular approach in LVO (SYNTHESIS Expansion, IMS III and MR RESCUE) failed to demonstrate superiority of the endovascular approach over standard IV tPA therapy [11-13]. There were several drawbacks in these trials, in particular the use of first generation thrombectomy devices that likely prevented them from showing benefit because of extended time needed for revascularization.…”

Section: Recanalization As a Predictor Of Good Outcome For Acute Ischmentioning

confidence: 99%

Improving Reperfusion Therapies in the Era of Mechanical Thrombectomy

Linfante

Cipolla

2016

Transl. Stroke Res.

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Recent positive clinical trials using mechanical thrombectomy proved that endovascular recanalization is an effective treatment for patients with acute stroke secondary to large vessel occlusions. The trials offer definite evidence that in acute ischemia recanalization is a powerful predictor of good outcome. However, even in the era of rapid and effective recanalization using endovascular approaches, the percentage of patients with good outcomes varies between 33% and 71%. In addition, the number of patients who are eligible for endovascular thrombectomy is small and usually based on having salvageable tissue on imaging. There is therefore room for improvement to both enhance the effectiveness of current practice and expand treatment to a larger subset of stroke patients. In this review, we highlight some of the most promising approaches to improve endovascular therapy by combining with strategies to enhance collateral perfusion and vascular protection.

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Endovascular Treatment for Acute Ischemic Stroke

Cited by 32 publications

References 31 publications

Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial

Time to angiographic reperfusion and clinical outcome after acute ischaemic stroke: an analysis of data from the Interventional Management of Stroke (IMS III) phase 3 trial

Time Is Penumbra: Imaging, Selection and Outcome

Improving Reperfusion Therapies in the Era of Mechanical Thrombectomy

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