Meta-analysis Confirms Endovascular Benefits in Stroke

November 03, 2015

The benefit of endovascular therapy for certain patients with acute ischemic stroke has been confirmed in a new meta-analysis of recent trials.

The meta-analysis, published in the November 3 issue of JAMA, included eight trials with both positive and negative primary outcomes published since 2013.

"We wanted to look at the overall effect in all the studies and then to look more closely at the heterogeneity and how to explain it from subgroup and sensitivity analyses," senior author, Saleh A. Almenawer, MD, McMaster University, Hamilton, Ontario, Canada, told Medscape Medical News.

"The main message is the quality of the evidence in support of endovascular treatment is high for patients with moderate-severity strokes with a confirmed proximal occlusion treated within 6 hours," Dr Almenawer added. "While we may have heard these messages before when the more recent individual trials have been reported, this is statistical confirmation from the largest meta-analysis of recent trials."

The main finding from the meta-analysis was that functional independence was markedly improved with endovascular treatment: from 31% in those receiving tissue plasminogen activator (tPA) alone to 45% in those given endovascular therapy as well. This was achieved without a major safety hazard with similar rates of intracranial hemorrhage (ICH) and all-cause mortality in the two groups.

But the results also showed a large variability in improvement of functional outcomes, and the researchers performed subgroup analysis to identify the groups of patients who benefited the most or least.

"In these analyses, we found that patients who did not undergo CT [computed tomographic] angiography to confirm the presence of a proximal occlusion did not show benefit," Dr Almenawer commented. "We also showed that endovascular treatment was associated with more benefit when given after tPA rather than alone, and the best results were achieved when stent retrievers were used rather than other devices."

For the current meta-analysis, the researchers included eight randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, including use of intravenous tPA published between 2013 and 2015. The trials included were SYNTHESIS, MR RESCUE, IMS III, MR CLEAN, ESCAPE, EXTEND-IA, SWIFT-PRIME, and REVASCAT.

The studies involved a total of 2423 patients with a mean age of 67 years, of whom 47% were women. Of these, 1313 underwent endovascular thrombectomy and 1110 received standard medical care with tPA.

Results showed that after pooling of all the trials, endovascular therapy was associated with a significant proportional treatment benefit across modified Rankin Scale (mRS) scores (odds ratio [OR], 1.56; P = .005).

Other results showed significant increase in patients with functional independence at 90 days (mRS score, 0 to 2) and in angiographic revascularization at 24 hours in the endovascular group.

There was no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.

Table. Meta-analysis Main Results

Endpoint Endovascular (%) Standard Care (%) OR P Value
Functional independence at 90 d (mRS score, 0 - 2) 44.6 31.8 1.71 .005
Angiographic revascularization at 24 h 75.8 34.1 6.49 <.001
Symptomatic intracranial hemorrhage at 90 d 5.7 5.1 1.12 .56
All-cause mortality at 90 d 15.8 17.8 0.87 .27


Subgroup analysis showed that functional outcomes were significantly better among patients with angiographic imaging that confirmed proximal arterial occlusion (OR, 2.24; P for interaction < .001), among patients who received the combined therapy of intravenous tPA and endovascular intervention (OR, 2.07; P for interaction = .018), and when stent retriever devices were used for mechanical thrombectomy (OR, 2.39; P for interaction <.001).

The researchers say more work is needed to identify the ideal patient to undergo endovascular therapy, with limits on age, Alberta Stroke Program Early Computed Tomography Score, National Institutes of Health Stroke Scale score, and time to treatment to be explored.

They suggest that it may be beneficial for medical personnel involved in the early care of patients with acute ischemic stroke, such as paramedics and emergency physicians, to be trained to identify candidate patients who may benefit from endovascular therapy, so that neurointerventional resources can be mobilized quickly and the time from stroke onset to recanalization and reperfusion can be reduced.

In an accompanying editorial, Joanna M. Wardlaw, MD, and Martin S. Dennis, MD, from the Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom, suggest that additional rigorous trials would help to define which additional patients might benefit from thrombectomy and by how much. They say that factors to be considered include the effects of comorbidities, advanced age, limits of extractable thrombus location or extent, and the latest time window.

They add that studies are also needed to determine how to implement thrombectomy in routine practice, "including testing the thorny question of who should perform the procedure, and whether the balance of benefit, cost, and service efficiency favor treating just those patients who individually will gain most or treating all patients with a reasonable chance of some worthwhile benefit."

The study authors and editorialists have disclosed no relevant financial relationships.

JAMA. 2015;314:1832-1843, 1803-1805. Abstract Editorial


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