IMS-III: Endovascular Therapy Benefits Severe Stroke

Daniel M. Keller, PhD

October 28, 2014

ISTANBUL, Turkey — Endovascular therapy combined with intravenous (IV) recombinant tissue plasminogen activator (tPA) appears to benefit patients with severe acute ischemic stroke more than does IV tPA alone when assessed 12 months after stroke, a subgroup analysis of the results of the Interventional Management of Stroke III trial (IMS-III) shows.

And although patients with moderate acute ischemic stroke did better than those with severe stroke, there was no evidence that adding endovascular therapy improved their outcomes compared with IV tPA alone.

The intervention consisted of thrombectomy or endovascular delivery of tPA, depending on lesion characteristics and training and experience of the interventionalist.

Previously presented results of the trial showed no benefit of the endovascular intervention when measured at 3 months. There was only a 2.1% difference in the proportion of patients with a modified Rankin Scale (mRS) score of 0 to 2 between the endovascular and IV tPA groups (40.8% vs 38.7%, respectively), and the trial was stopped early for futility.

Speaking here at the 9th World Stroke Congress (WSC), Yuko Palesch, PhD, a professor in the Department of Public Health Sciences at the Medical University of South Carolina in Charleston, said that although the primary endpoint of IMS-III was the 3-month favorable functional outcome (mRS score, 0 to 2) among patients with acute ischemic strokes, additional functional and quality-of-life outcome measures were planned out to 12 months.

Patients were randomly assigned 2:1 to IV tPA plus endovascular therapy or to IV tPA alone and were stratified by stroke severity, with moderate severity (n = 452) defined as National Institutes of Health Stroke Scale (NIHSS) score of 8 to 19 and severe (n = 204) defined as a score of 20 or greater.

The present analysis examined outcome profiles between the endovascular and IV tPA-alone groups over 12 months.

As expected, the moderate stroke cohort fared better overall compared with the severe cases, "but there's no evidence of benefit of the endovascular treatment in the percentage of good outcome or in the quality adjusted days," Dr Palesch reported. For moderate stroke, the IV tPA-alone group consistently did better, by 2% out to 12 months, and there was a 4% to 5% improvement for each treatment group during the year.

The severe stroke cohort showed more benefit from adding endovascular therapy compared with the IV tPA-alone group, with an 8% vs 2% improvement over time, respectively. The treatment benefits between the two interventions increased over time after 3 months.

The odds ratio for the treatment effect on an outcome of mRS score 0 to 2 was 0.95 for the moderate stroke group after adjustment for baseline NIHSS score, time from symptom onset to IV tPA, and age. For the severe stroke group, the adjusted odds ratio was 2.37.

Table. Good Outcomes at 12 Months (mRS Score of 0 to 2)

Group Endovascular + IV tPA (%) IV tPA Alone (%) P Value
Moderate stroke cohort 55.6 57.7
Severe stroke cohort 32.5 18.6 .037


The number of quality-adjusted days in 12 months was measured by using the EQ-5D-3L questionnaire and weighting the measurements by the number of days between assessment periods.

For moderate stroke, the quality-adjusted days were very similar for the endovascular and IV tPA-alone groups (212.6 vs 211.1 days, respectively), but the severe group had a statistically significant greater number of quality-adjusted days with the combined therapy (145.8 vs 110.6 days, respectively).

Dr Palesch concluded that improvement may continue after 3 months for patients with mild stroke and for patients with severe stroke if they are given endovascular therapy in addition to IV tPA.

The moderate stroke group continued to improve in both function and quality of life for a year, but endovascular therapy did not add any benefit over IV tPA alone. She advised that any benefits seen in this trial need to be confirmed by other ongoing and future endovascular trials.

Still Unknown

Peter Sandercock, MD, professor of neurology at the University of Edinburgh, United Kingdom, commented that he thinks that IMS-III is a very important study because it shows that it is still unknown whether endovascular therapy is superior.

"The other interesting piece of information that emerged here at WSC in Istanbul is that maybe the people who are likely to benefit are the severe strokes, and what we see in IMS-III is that the benefit from therapy emerges late, after 3 months, when the curves continue to diverge," he told Medscape Medical News. "If a therapy has a small impact on disability at, say, 3 months, that may be amplified subsequently and be expressed in better long-term survival."

He noted that in stroke epidemiologic studies, as well as in the Oxford Community Stroke Project in the United Kingdom, survival differed greatly between mRS scores of 0 and 1 and between scores of 2 and 3 when one looks at longer-term survival.

Therefore, he strongly advises that endovascular trials need longer-term follow-up because important mortality differences may not show up for 3, 6, or 12 months. In addition, severe strokes are the ones likely to benefit, supported by evidence from the Third International Stroke Trial (IST-3) of intravenous thrombolysis, in which a mortality benefit emerged after about a month or two. Patients with severe strokes treated with tPA had improved survival by 12 to 18 months.

Dr Sandercock emphasized that "stroke survivors are interested in survival, so this is an endpoint I think we need to take more notice of." Furthermore, quality of life is increasingly being recognized as an important endpoint.

"We need to be sure that treatments don't just prolong survival but they improve quality of survival. So there's work to be done in this field," Dr Sandercock suggested.

The IMS-III trial was funded by the National Institutes of Health and others. Genentech supplied the tPA used for intra-arterial administration. EKOS, Concentric, and Cardis Neurovascular supplied study catheters, and Genentech, EKOS, Concentric, and Boehringer Ingelheim provided investigator meeting support. Dr Palesch reported receiving honoraria and/or expenses from Brainsgate, Ltd. and Biogen Idec, Inc. Dr Sandercock has disclosed no relevant financial relationships.

9th World Stroke Congress (WSC). Abstract 159. Presented October 23, 2014.


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