Stroke Rounds: Q&A with MR CLEAN

— How old is too old for thrombectomy? What's an okay window? Subanalyses aim to provide answers.

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As mechanical thrombolysis in large vessel ischemic strokes gains clinical momentum, the MR CLEAN trialists delved into their data for answers to key clinical issues.

Diederik W. Dippel, MD, PhD, of Erasmus MC University Medical Center in Rotterdam, the Netherlands, presented subanalyses at the American Academy of Neurology meeting in Washington.

Q: How many patients stand to be good candidates for this treatment?

A: About 200 per 1 million population each year, Dippel suggested. The rough calculation was that about 2,000 new strokes would be expected per million annually; about a third present within 6 hours and one-third have a proximal occlusion.

Q: Should patients over age 80 get endovascular thrombectomy?

A: MR CLEAN treated patients as old as 96 with no upper age limit on enrollment.

Although the rate of mortality or functional dependence after stroke rose with age in the trial as expected, the advantage of adding the procedure to standard medical treatment was seen at every age, Dippel noted.

The odds ratio for a thrombectomy advantage was 1.60 for those under age 80 and 3.24 for those 80 and older, both significant albeit with a wider confidence interval in the older age group.

Q: Is it too late to treat if a patient presents beyond the 3- to 4.5-hour window?

A: No, Dippel suggested. While the trials have supported a need for speed to gain the greatest benefit, there's still an advantage if patients present further out.

MR CLEAN and the other recent positive endovascular thrombectomy trials enrolled patients out to 6, 8, and even 12 hours after stroke onset, although the vast majority were randomized within 6 hours because late presenters were less likely to be candidates for thrombectomy.

A prior MR CLEAN subanalysis had shown a nonsignificant trend for declining advantage of mechanical clot removal with greater treatment delay in initiating the procedure but a significant effect with time from stroke onset to reperfusion.

In the update, Dippel showed that the advantage persisted out to nearly 6.5 hours time from onset to reperfusion, based on the lower bound for the confidence interval hitting the point of unity.

Q: Should patients with minor deficits get endovascular treatment?

A: Subanalysis of MR CLEAN showed a similar odds ratio for benefit of thrombectomy versus medical therapy alone across the National Institutes of Health Stroke Scale score ranges -- 1.71 at scores of 2 to 15, 1.50 at 16 to 19, and 1.85 for 20 or greater -- although only the highest severity range came in statistically significant.

Q: Should patients with low ASPECTS score be treated?

A: While the odds ratios for outcome favored thrombectomy at least as much for scores in the 5 to 7 range as in the 8 to 10 range (1.97 and 1.61), the lower range had a wide confidence interval that crossed into nonsignificance. For the lowest ASPECTS score range of 0 to 4, thrombectomy had a neutral effect (OR 1.09, 95% CI 0.14-8.46).

Q: What about patients with poor collateral blood flow in the brain?

A: The odds of an advantage to thrombectomy were best for patients with a Collateral Score System score of 3 but remained statistically significant even in the 0 to 1 score range, Dippel pointed out.

The good news is that the treatment works, and many patients are eligible, he concluded.

The bottom-line message is to get CT angiography in all patients within 6 hours to find candidates, and then transfer and treat quickly without waiting to see whether thrombolytics will do the job, Dippel added.

From the American Heart Association:

Disclosures

The trial was funded by the Dutch Heart Foundation with and by unrestricted grants from AngioCare Covidien/ev3, Medac/Lamepro, and Penumbra.

Dippel disclosed no relevant relationships with industry.

Primary Source

American Academy of Neurology

Source Reference: Dippel D, et al "The Multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke in the Netherlands (MR CLEAN): Update and clinical implications" AAN 2015.