LOS ANGELES – The final results of the DEFUSE 3 trial are in, and the results are unequivocal: Thrombectomy performed 6-16 hours after the stroke patient was last known to be well was associated with dramatically improved outcomes in 90-day death and disability.
It has long been said that time is brain. Time is still vital, but some strokes progress at a slower rate. “We have the opportunity to treat these patients in a time window that we never thought was possible,”, said in presenting the findings at the International Stroke Conference sponsored by the American Heart Association.
The subjects included those with proximal middle-cerebral artery or internal-carotid artery occlusion and infarcts of 70 mL or less in size, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct tissue of 1.8 or higher. Both DAWN and DEFUSE 3 used the RAPID software from iSchemaView to assess infarct volume.
The DEFUSE 3 results aren’t a surprise, as the trial was stopped early after an interim analysis showed efficacy. But they are immediately practice changing. “This will perhaps be a once in a lifetime situation where a study gets published and within 2 hours gets incorporated into new guidelines,” said Dr. Albers, lead author of the study, who is the Coyote Foundation Professor, neurology and neurological sciences, and professor, by courtesy, of neurosurgery at the Stanford (Calif.) University Medical Center. Minutes later at the press conference, it was announced that the results of both DEFUSE 3 and DAWN had indeed been included in the guidelines.
The DEFUSE (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) 3 trial included 182 patients from 38 U.S. centers who were recruited during May 2016–May 2017. Of these, 92 were randomized to thrombectomy and standard medical therapy, and 90 to standard medical therapy only.
Patients who underwent thrombectomy were more likely to have a favorable distribution of disability scores on the modified Rankin scale at 90 days (unadjusted odds ratio, 2.77; adjusted OR, 3.36; both P less than .001). “The odds ratio [of 2.77] was the largest ever reported for a thrombectomy study,” Dr. Albers said, and the ISC audience erupted into spontaneous applause. “We couldn’t be happier,” he responded.
Nearly half (45%) of patients in the thrombectomy group scored as functionally independent at 90 days (Rankin score 0-2), compared with 17% in the medical-therapy group (risk ratio, 2.67; P less than .001). Mortality was also lower in the intervention group (14% vs. 26%; P = .05).
The rates of symptomatic intracranial hemorrhage (7% thrombectomy, 4% medical therapy only) did not differ significantly between the two groups. Serious complications occurred in 43% of patients in the thrombectomy group, compared with 53% in the medical therapy–only group (P = .018).
A subanalysis showed consistent benefit of thrombectomy, even in patients with a longer elapsed time between stroke onset and randomization, while the patients who received medical therapy had worse outcomes as more time passed. In 50 patients in the under 9-hour group, 40% of those who received thrombectomy were functionally independent at 9 weeks, compared with 28% in the medical therapy–only group. Among 72 patients in the 9- to 12-hour group, 50% were functionally independent (vs. 17%), and in the greater than 12-hour group, 42% (7%).
The study filled up rapidly, at about twice the rate that the researchers anticipated, and that suggests that the procedure could find broad use. “It shows that these patients are not difficult to find,” said Dr. Albers.
The National Institutes of Health funded the study. Dr. Albers has a financial stake in iSchemaView and is on the scientific advisory board for iSchemaView and Medtronic.
The DEFUSE 3 results were published online concurrently with Dr. Albers’s presentation (N Engl J Med. 2018 Jan 24;).
SOURCE: Albers G et al.