International Stroke Conference
International Stroke Conference
January 24, 2018
5 min read

Thrombectomy improved outcomes in patients with stroke, salvageable brain tissue

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In patients with evidence of salvageable brain tissue on perfusion imaging, endovascular thrombectomy initiated up to 16 hours after stroke appeared to be safe and resulted in better functional outcomes than treatment with medical therapy alone, according to data from the DEFUSE trial.

Specifically, results from the trial, which were presented at the International Stroke Conference and simultaneously published in The New England Journal of Medicine, showed that patients with stroke and ischemic brain tissue that was not yet infarcted had less disability and were more likely to be functionally independent at 90 days after initiation of endovascular thrombectomy between 6 and 16 hours after the patient was last known to be well.

These findings are in keeping with those from the recent DAWN trial, which showed that endovascular thrombectomy was safe and effective when initiated outside the currently recommended 6-hour time window in patients with a mismatch between clinical deficit and infarct, according to Gregory W. Albers, MD, from the Stanford Stroke Center.

“DEFUSE 3 is the culmination of a 20-year effort to establish that every ischemic stroke evolves in a unique manner and that treatment decisions need to be personalized rather than based on arbitrary time windows,” Albers said during a press conference.

New data

In the randomized, multicenter, open-label DEFUSE 3 trial, Albers and colleagues sought to determine whether endovascular therapy would be beneficial outside the 6-hour time window in patients with stroke who had evidence of salvageable tissue on the basis of a formula that incorporated early infarct size and the volume of hypoperfused tissue on perfusion imaging.

The trial, which was conducted at 38 centers in the United States, randomly assigned 92 patients to endovascular therapy plus standard medical therapy and 90 to medical therapy alone. The patient population included those with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size less than 70 mL, a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more and an absolute penumbra of 15 mL or more. The researchers used RAPID software, an automated image postprocessing system, that allowed them to see how much brain tissue was irreversibly injured when the patient arrived.

The primary efficacy outcome was ordinal score on the modified Rankin scale at 90 days and the secondary efficacy outcome was functional independence, defined as a score of 0 to 2 on the modified Rankin scale, at 90 days. The primary safety outcomes included death within 90 days and symptomatic intracranial hemorrhage within 36 hours, defined as an increase of at least four points on the NIH Stroke Scale that was associated with brain hemorrhage on imaging within 36 hours after symptom onset.

Results showed a more favorable distribution of disability scores on the modified Rankin scale at 90 days among patients randomly assigned to endovascular thrombectomy plus medical therapy vs. medical therapy alone (unadjusted common OR = 2.77; 95% CI, 1.63-4.7), a finding that held true after adjustment for stratification factors (adjusted OR = 3.36; 95% CI, 1.96-5.77).

Similarly, at 90 days, more patients in the endovascular-treatment group compared with the medical-therapy group were functionally independent (45% vs. 17%; P < .001). Moreover, fewer patients in the endovascular-treatment group experienced severe disability or death, defined as a modified Rankin scale score of 5 to 6 (22% vs. 42%; P = .0048).

Patients who underwent endovascular plus medical therapy, compared with medical therapy alone, also had higher rates of reperfusion (79% vs. 18%; P < .0001) and recanalization (78% vs. 18%; P < .0001).

The trial was terminated early for efficacy after enrollment of 182 patients, which limited the ability to perform subgroup analyses. However, the researchers noted that the results were also significant for the primary and secondary efficacy outcomes for both patients who did and did not meet the DAWN enrollment criteria. For the primary efficacy outcome, the ORs were 2.66 (95% CI, 1.36-5.23) for those who did meet the criteria and 2.96 (95% CI, 1.26-6.97) for those who did not meet the criteria.

In terms of safety, 90-day mortality was 14% in the endovascular-treatment group vs. 26% in the medical-therapy group (P = .05), according to the data. There were no significant differences in the rates of symptomatic intracranial hemorrhage (7% vs. 4%; P = .75) or parenchymal hematoma type 2 (9% vs. 3%; P = .21).

Two patients experienced complications related to thrombectomy, including a vessel perforation resulting in subarachnoid hemorrhage that was associated with a three-point increase in the NIH Stroke Scale score at 90 days and device-related vasospasm that did not lead to neurologic worsening. Serious adverse effects were experienced by 43% of patients in the endovascular group and 53% in the medical-therapy group (P = .18).

Subgroup analyses

Additionally, Maarten Lansberg, MD, also from the Stanford Stroke Center, presented preliminary results from two subgroup analyses based on patient age and treatment effect over time.

Previous trials, such as SWIFT-PRIME and REVASCAT, excluded patients aged older than 80 years due to a presumed lack of treatment benefit. DEFUSE 3 enrolled patients up to age 90 years. Age appeared to be an important predictor of functional independence in the endovascular therapy arm, with the probability of functional independence at 90 days decreasing from 80% in the youngest patients to 20% in the oldest. The researchers also observed a downward trend with declining age in the medical therapy arm, but there was a floor effect as the probability of functional independence approached 0 in the elderly and endovascular therapy remained associated with better outcomes throughout the entire age spectrum. Comparing 90-day outcomes of older patients with those of younger patients, results showed no difference in the treatment effect for patients aged younger than 80 years (OR = 2.9; 95% CI, 1.6-5.3) vs. those aged older than 80 years (OR = 2.3; 95% CI, 0.8-6.7; P = .7).

DEFUSE 3 also enrolled patients over a broad time window to evaluate whether the effect of treatment wanes during the later time window, Lansberg said. The researchers observed no tapering in treatment effect over time in the endovascular arm.

“Regardless of time, the endovascular arm did much better, and there was no indication that this would change with longer times from symptom onset to randomization,” Lansberg said. “As long as the patients were selected with perfusion imaging and had evidence of salvageable brain tissue, they were going to benefit the same as those who were treated earlier.”

‘Time is brain’

In a comment published in Stroke, Albers noted that the “time is brain” treatment concept paints stroke as a time-critical emergency. “Late-window” trials such as DAWN and DEFUSE 3, however, indicate that there may be a need for a paradigm shift in the approach to treatment.

“The ‘time is brain’ concept requires a 2018 revision that is more generous than the original and provides a reprieve for the fortunate patients who have favorable collaterals and slow infarct growth,” he wrote. “However, because it is not possible to immediately determine the growth rate of the ischemic core, it remains critical to evaluate all stroke patients as urgently as possible.”

According to Albers, more research, such as data on the need for repeat imaging, is still needed, though imaging will likely play an important role in stroke treatment.

“As more primary stroke centers begin to perform advanced imaging, these data should be rapidly shared with the comprehensive center to help optimize triage decisions,” Albers wrote. – by Melissa Foster


Albers GW. LB1. Presented at: International Stroke Conference; Jan. 24-26, 2018; Los Angeles.

Albers GW, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1713973.

Albers GW. Stroke. 2018;doi:10.1161/STROKEAHA.117.020200.

Lansberg M. LB6. Presented at: International Stroke Conference; Jan. 24-26, 2018; Los Angeles.

Disclosures: Albers reports he has ownership interest in iSchemaView and is a consultant or an advisory board member for iSchemaView and Medtronic. Lansberg reports no relevant financial disclosures.

Editor’s note: This article was updated on Jan. 30 with additional information about subgroup analyses of DEFUSE 3 presented at ISC 2018.