DAWN: Thrombectomy Effective Up to 24 Hours After Stroke

Sue Hughes            

May 17, 2017

PRAGUE, Czech Republic — Removal of a clot by endovascular thrombectomy reduced disability in selected stroke patients presenting up to 24 hours after symptom onset, in a new study.

The results of the DAWN trial, presented here at the 3rd European Stroke Organisation Conference (ESOC) 2017, was hailed by experts as "ground breaking" and "a major step forward" in that it will significantly expand the population eligible for thrombectomy.

The investigators selected patients arriving after 6 hours from symptom onset for inclusion in the trial by using imaging and clinical scores to identify those with "target mismatch" — a small core infarct volume but a large area of brain at risk for ischemia yet still potentially salvageable.

Results showed a 2-point difference in the 90-day weighted modified Rankin Scale (mRS) score in favor of the thrombectomy group, which translated into a 73% relative reduction of dependency in activities of daily living and a number needed to treat for any lower disability of 2.0.

In addition, there was a 35% absolute increase in the number of patients achieving functional independence (mRS score, 0 to 2), with a number need to treat for this endpoint of 2.8.

The study's lead investigator, Tudor Jovin, MD, University of Pittsburgh School of Medicine, Pennsylvania, stated: "Our results show that for every 100 patients treated with endovascular therapy, 49 will have a less disabled outcome as a result of treatment, including 36 who will be functionally independent."

"These results greatly expand the population of patients who can benefit from mechanical thrombectomy for stroke, to significantly reduce functional impairment in the mostly severely affected patients," he added.  

"Time is still obviously very important and the earlier the treatment is given the better the results, but we have shown in this trial that it shouldn't be the only factor that determines whether we consider endovascular therapy."

Jeffrey Saver, MD, University of California Los Angeles, who was part of the DAWN steering committee, said, "These are very exciting results. It is another paradigm shift for acute stroke care. We can now help many more patients."

Outside experts were also impressed with the results.

"These are enormously interesting results," Yvo Roos, MD, Department of Neurology, Academic Medical Center, Amsterdam, the Netherlands, lead investigator of the MR CLEAN trial — the first thrombectomy study to show a benefit in stroke — told Medscape Medical News

"I will need to see the details when published but it is very exciting," Dr Roos said. "We already know from the previous data that some patients benefit after 6 hours, but now this trial shows definitely that we can select out these patients. We thought that would be the case, but this is the first trial to prove it." 

He said he would like to see more data on the subgroups and whether there are any that benefit more than others, particularly on the different time points, and whether there really was benefit right out to 24 hours. 

"But this trial will have huge implications for clinical practice especially for countries where there are long travel distances to comprehensive stroke centers," he said.

Andrew Demchuk, MD, University of Calgary, Alberta, Canada, called these findings "a breakthrough trial in every way shape and form. A number needed to treat of between 2 and 3 is quite amazing."

"Stroke is a very heterogeneous disease and so in order to be successful in treatment we have to classify patients into the correct subtypes who may benefit the most and they did a masterful job of doing that in this trial," he added. "Patients with a poor clinical score have had large strokes, but if they have a small core infarct size they tend to have a long time window — the stroke expands very slowly. By selecting patients this way, they have achieved a large effect size with thrombectomy."

"This has major implications," Dr Demchuk noted. "We're going to have to screen every stroke patient with a large-vessel occlusion for this therapy as the window now is pretty much everyone. This is fairly immediately feasible in most developed countries, but it will have a cost, of course. "

Experts were unsure exactly how many more patients would now become eligible for thrombectomy as a result of this trial.

"It's hard to know how many of these patients there are as they are currently not being identified," Dr Jovin said. "But in our center we have a culture of looking at this, and we estimate that about one third of patients with a large-vessel occlusion presenting after 6 hours would meet DAWN criteria."

Dr Demchuck added: "We estimate that between 10% and 15% of stroke patients are eligible for thrombectomy based on the original trials. That number may have now been boosted by another 2% to 5% with these results."

Alastair Webb, MD, University of Oxford, United Kingdom, noted that the results will add to pressure on hospitals to provide a 24-hour thrombectomy service.   

"As well as having an endovascular team available all hours, hospitals will have to have a 24-hour perfusion imaging service available too," Dr Webb noted. "There are ways of doing that, although it will take a lot of resources.  But these results showed a large degree of disability was prevented so it will probably be worthwhile."

DAWN Trial

For the DAWN trial, patients with a large-vessel occlusion stroke presenting between 6 and 24 hours (average, 13 hours) underwent computed tomographic (CT) perfusion or magnetic resonance diffusion weighted imaging. Patients were selected for inclusion and randomization to thrombectomy or control if they had a small infarct core in relation to their National Institutes of Health Stroke Scale (NIHSS) score. The exact requirements varied with age.

Patients aged over 80 had to have an NIHSS score over 10 and a core volume less than 21 mL. For patients younger than 80 years, requirements were an NIHSS score of over 10 and a core less than 31 mL or an NIHSS score over 20 and a core less than 51 mL. 

"Imaging is necessary to tell us how much of the brain is already dead, but the clinical score can give us an estimate of how much of the brain is not functioning and is therefore at risk of dying," coinvestigator Raul Nogueira, MD, Emory University School of Medicine, Atlanta, Georgia, explained.   

"We can also use imaging to assess the area of brain at risk, but the results of this trial prove that the clinical score is also a valid method, and at least as good as imaging, for identifying suitable patients for later treatment."

He noted that the area at risk may continuously change, and by using the NIHSS score it is possible to reassess the situation easily at any point. In contrast, imaging only gives a snapshot of what is happening at one particular timepoint.

Thrombectomy in this trial was performed by using the Trevo device, a product of Stryker Medical, which also funded the DAWN trial.

The data safety monitoring board recommended that the study be stopped early on the basis of a preplanned interim review of data from the first 206 patients (of a planned 500) because of benefit in the thrombectomy group.

Results showed significant benefit of thrombectomy in both of the co-primary endpoints.

Table 1. DAWN: Co-primary Endpoints

Endpoint Thrombectomy Group n = 107 Control Group (n = 99) Treatment Benefit (95% Confidence Interval) Bayesian Probability of Superiority
Day 90 weighted mRS score 5.5 3.4 2.1 (1.20 - 3.12) >.9999a
Day 90 mRS score (0 - 2) (%) 48.6 13.1 35.5 (23.9 - 47.0) >.9999a
aSimilar to P < .0001.


Dr Jovin reported that thrombectomy was still beneficial throughout the 24 hours from the time the patient was last known well, but as expected earlier treatment was associated with more chance of an independent functional outcome.

Table 2. DAWN: Patients Achieving Functional Independence (mRS Score, 0 - 2) by Time of Presentation 

Endpoint Thrombectomy Group (%) Control Group (%) P Value
6 - 12 h 55.1 20.0 <.001
12 - 24 h 43.1 7.4 <.001


"The treatment effect size in DAWN is the highest out of any stroke trial to date and suggests that the presence of clinical-core mismatch is a critical predictor of treatment effect independent of time to presentation," Dr Jovin concluded.

Implications for Other Trials  

Other trials underway or planned are also looking at thrombectomy in later-presenting stroke patients. One is the US National Institutes of Health–sponsored DEFUSE-3 trial.  Exerts were unsure how the results of DAWN would affect other similar ongoing trials.

"Usually I would say we always need at least two trials, but these results are so strong," Dr Demchuk said. "We'll have to see how the community reflects on this data once it is published."         

Professor Roos and his group are also planning a "MR CLEAN LATE" trial. "We will certainly have to adapt plans for that trial because of these results," he said.

He suggested that future studies could evaluate easier ways of selecting patients who present late.  "We are very pragmatic. We would like to think we could select patients for thrombectomy based on data from CT angiography [CTA], which has to be done anyway to identify the large-vessel occlusion." 

CTA can be used to assess the collateral circulation and may be a simpler, faster, and cheaper method of identifying patients who will still benefit later on, he noted. "If that works, then this would be more feasible to use in smaller hospitals to decide which patients to transfer urgently to a comprehensive stroke center for endovascular therapy."

The DAWN trial was funded by Stryker Neurovascular. Dr Jovin has acted as a consultant for Stryker (unpaid).  

3rd European Stroke Organisation Conference (ESOC) 2017. Session PL01. Presented May 16, 2017.

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