Long-term results from the MR CLEAN trial of endovascular intervention for patients with ischemic stroke, showing that the improvement in functional recovery at 3 months is still maintained at 2 years, have now been published in the New England Journal of Medicine.
The trial was the first of several ground-breaking studies to validate endovascular therapy with stent retrievers for stroke patients with an occluded major cerebral artery, showing a clinically significant increase in functional independence in daily life by 3 months.
Of the 500 patients who underwent randomization in the original MR CLEAN trial, 2-year data for this extended follow-up trial were available for 391 patients (78.2%) and information on death was available for 459 patients (91.8%).
These latest results show that the increase in functional independence is still apparent at 2 years. The odds ratio for better scores on the modified Rankin Scale (mRS) in the endovascular group than in the conventional treatment group was 1.67 at 90 days, as compared with an odds ratio of 1.68 at 2 years.
The percentage of patients in the intervention group who were functionally independent (mRS score of 0 to 2) at 2 years (37.1%) was also similar to the results at 90 days (32.6%).
The longer-term results also show a trend toward a reduction in mortality at 2 years in the endovascular group, whereas this was not seen at the 3-month mark.
The cumulative 2-year mortality rates were 26.0% in the intervention group and 31.0% in the control group (adjusted hazard ratio, 0.9; 95% confidence interval [CI], 0.6 - 1.2; P = .46).
The 2-year results also looked at quality of life and showed an improvement in the endovascular group. The mean quality-of-life score was 0.48 among those given endovascular therapy compared with 0.38 for the control group (mean difference, 0.10; 95% CI, 0.03 - 0.16; P = .006). The difference in the treatment effect between the two groups was attributable mainly to the EQ-5D-3L dimensions of "mobility," "self-care," and "usual activities."
The preliminary 2-year results were first reported at last year's European Stroke Organisation Conference (ESOC), but more detailed data are now available in the publication.
Commenting on the results for Medscape Medical News, senior author Yvo B.W.E.M. Roos, MD, PhD, Department of Neurology, Academic Medical Center, Amsterdam, the Netherlands, said the long-term data were reassuring on many levels.
"At 2 years, patients are doing as well as they were at 3 months," he said. "Some who had mRS scores of 4 or 5 at 3 months have now died, and others who had moderate functional deficits have improved. The overall difference between the endovascular and control groups is exactly the same as it was at 2 years."
He noted that because the patients included in the trial had had a major stroke and were therefore at high cardiovascular risk, there was a concern about a high rate of further events — stroke or myocardial infarction (MI) — in the months and years after the initial event.
"Funders were worried that the endovascular therapy may just be helping with the first event, but these high-risk patients would go on to have further events quite quickly," he said. "But this hasn't been the case."
Dr Roos believes the low number of recurrent events in the long-term follow-up is probably due to good secondary prevention. "These patients will have been taking statins, antiplatelet agents, and if they have atrial fibrillation they will be on anticoagulants. This can really dramatically lower the risk of further events. Only 8 patients in our cohort had a new stroke or MI in the 2-year follow-up. That is really very low."
He added: "As the benefit at 2 years is similar to that at 3 months, this will be very reassuring to everyone — patients, doctors, and funders. As a doctor it helps us to be able to tell patients and relatives that the benefits of this procedure will likely remain in the long term. It will also help healthcare policymakers to see that it is worth investing funds to make this acute therapy available as it will likely save healthcare funds in the long term."
More information on this will be available from a cost-effectiveness analysis based on these 2-year results, which will be presented at the upcoming ESOC meeting in Prague in May.
Commenting on the latest MR CLEAN data, Michael Hill, MD, who led another of the endovascular stroke trials — ESCAPE — welcomed the long-term outcome data.
"This reflects stroke as an episodic condition; if disability is prevented and subsequent stroke prevented, the long-term outcome is good," Dr Hill said. "I think this is generally already known about stroke, but this data is helpful in so far as we can now really accept the 90-day outcome as definitive and predictive of longer-term survival and favorable outcome after endovascular therapy."
Mortality Curves Separating
On the observation of a trend toward lower mortality in the endovascular group at 2 years, which wasn't there at 3 months, Dr Roos suggested this may reflect the more disabled patients' dying.
"We are seeing a separation of the mortality curves over longer-term follow-up," he said. "A possible explanation for this could be that in the control group there were a lot of patients with poor functional status at the 3-month mark — mRS scores of 4 or 5 — and by 2 years there were fewer patients in this condition, but more deaths, suggesting that many of these patients have now died. However, in the treated group there were fewer patients left with mRS scores of 4 or 5 at 3 months, so there is less of a shift to death."
He pointed out that in some of the other endovascular trials they did see some differences in mortality by 90 days, but this was not the case in MR CLEAN.
"We think this is because some of the other trials used sophisticated imaging to select patients who would benefit most from the procedure. When you do that, you are going to get a higher percentage of patients recovering and a bigger contrast between the treated and control arms. However, the MR CLEAN and REVASCAT trials had the widest inclusion criteria and neither showed an effect on early mortality. It is reassuring, however, that we are seeing this now at 2 years."
One peculiar observation in the latest data is a reduction in patients with an "excellent outcome" — the least disability (mRS score, 0 to 1) — at 2 years compared with at 3 months.
Dr Roos suggested that a possible reason for this could be patients having unrealistic expectations in the early months.
"Patients can sometimes believe they can do more than they really can in the first few months, when they have a lot of support and are in more of a protected environment," he said. "They are often undergoing rehabilitation therapy and have significant family support in the first few months and feel enthusiastic about their progress. But by 2 years they will be back to getting on with life on their own and may be encountering problems in daily life activities, such as cooking, shopping, or working, that they didn't realize they would have earlier on. Our nurses who do the telephone interviews with the patients heard this quite frequently."
Dr Hill suggested that the mRS scores of 0 to 1 may be an artefact because more patients in the control were lost to follow-up. But Dr Roos said he did not believe this to be the case. "We did a lot of work to follow up, especially in the mRS 0 to 1 category as they are the easiest group to keep in touch with."
The study was supported by the Netherlands Organization for Health Research and Development. The MR CLEAN trial was partly supported by the Dutch Heart Foundation and through unrestricted grants from AngioCare BV, Covidien/EV3, MEDAC/LAMEPRO, Stryker, and Penumbra.
N Engl J Med. 2017;376:1341-1349. Abstract
Medscape Medical News © 2017
Cite this: MR CLEAN at 2 Years: Endovascular Benefit Maintained in Stroke - Medscape - Apr 06, 2017.