MR CLEAN: Time Crucial for Endovascular Benefit in Stroke

February 26, 2015

NASHVILLE, TENNESSEE — A new analysis of the MR CLEAN trial of endovascular therapy for acute ischemic stroke highlights the importance of fast treatment times — the chance of good outcomes decreases rapidly with every hour of treatment delay.

Presenting the time-to-treatment analysis at the recent International Stroke Conference (ISC) 2015, MR CLEAN investigator Puck Fransen, MD, Erasmus Medical Center, Rotterdam, The Netherlands, concluded, "Patients with acute ischemic stroke should have vessel imaging and appropriate treatment as soon as possible."

The MR CLEAN trial showed for the first time that patients with an acute ischemic stroke caused by a blockage of a major cerebral artery have a better outcome when the clot is removed with intra-arterial endovascular therapy — mainly using the new stent retrievers. This was performed in most cases in patients who had already received tissue plasminogen activator (tPA) and were then taken straight to the catheterization laboratory for the intervention.

For entry into the study, treatment had to be started within 6 hours from stroke onset, although a few patients were included after this time limit.

The main results of MR CLEAN showed a significant favorable effect for intra-arterial intervention that was consistent in almost all subgroups.

The primary outcome was the odds ratio of achieving a lower score on the modified Rankin Scale (shift analysis) at 90 days with endovascular therapy. This was achieved with an odds ratio of 1.67.

Presenting the time data, Dr Fransen said there was a "strong interaction" of time from symptom onset to reperfusion (when thrombolysis in cerebral infarction 2b/3 flow was reached) with the effect of endovascular treatment, with a much greater chance of a good outcome if reperfusion occurred early. However, because there was still a benefit at 6 hours, "there is no reason to withhold treatment within the 6-hour time window," she added.

The confidence intervals crossed unity at 6:19 hours, suggesting that the benefit of repersuion is not significant after this point.

When analyzed by time to treatment (the moment the catheter entered the groin), results showed a similar trend, although this did not reach significance.

The confidence intervals crossed unity at 5:13 hours, suggesting that the benefit of starting endovascular treatment was not significant after this timepoint.

Table. Absolute Difference in Chances of Good Outcome Between Treated and Untreated Patients

Time Risk Difference: 2 Hours (%) Risk Difference: 6 Hours (%) Reduction per Hour Delay (%) P Value
By time to reperfusion 33 6.6 7 .038
By time to treatment 19 3 4 .26


Senior MR CLEAN investigator, Diederik Dippel, MD, Erasmus MC University Medical Center, Rotterdam, The Netherlands, said, "This analysis suggests that interventional treatment is much less effective at 6 hours than it is at 2 or 3 hours."

Commenting for Medscape Medical News, Larry Goldstein, MD, from Duke University in Durham, North Carolina, said there's "a clear benefit of the intervention at earlier times and it becomes less clear as time progresses. It looks from this data that the cutoff point might be somewhere between 5 and 6 hours."

Dr Goldstein added that the researchers for the other endovascular trials reported at ISC — ESCAPE, EXTEND-IA, and SWIFT PRIME — will all probably do similar analyses, and then some general guidelines will need to be drafted on when to draw the line on intervening.

"Hospitals need good systems in place and operators need to be doing high volumes so times are reduced. It can be done. We get patients coming in from other hospitals who have already had CT [computed tomographic] angiogram [CTA] and they are in the cath lab in 15 minutes. If arriving at our hospital first we can get the CTA done and tPA started at the same time and they can easily be in the lab within an hour of arrival," said Dr Dippel.

But ISC vice chair, Bruce Ovbiagele, MD, Medical University of South Carolina, Charleston, pointed out that this is not generally the case in the real world.

"We now have to address how we can modify systems of care to approximate the speed seen in MR CLEAN, and the other new trials, which were all done in specialist centers. In the real world it is going to be a challenge to meet these targets," he told Medscape Medical News.

In the MR CLEAN study, the median time from symptom onset to start of endovascular treatment was 256 minutes. Breaking down times further, 11.5% of patients were treated within 3 hours, 45% between 3 and 4.5 hours, and 44% between 4.5 and 6 hours.

In trems of reperfusion, the medium time was 332 minutes from symptom onset, with just 1.5% of patients reperfusing within 3 hours; 22% within 3 and 4.5 hours, 40% between 4.5 and 6 hours, and 36% over 6 hours.

International Stroke Conference (ISC) 2015. Presented February 12, 2014. Abstract LB18


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