PracticeUpdate Neurology Best of 2018

EDITOR’S PICKS 9

Thrombectomy for Stroke at 6 to 16 Hours With Selection by Perfusion Imaging The New England Journal of Medicine

Take-home message • The authors of this randomized open-label trial with blinded assessment evaluated the effectiveness of endovascular thrombectomy plus standard medical therapy vs standard medical therapy alone for the treatment of ischemic stroke in patients who had MCA or ICA occlusion, were 6 to 16 hours from last known normal, and had ischemic tissue on perfusion imaging. Compared with the standard care alone group, the thrombectomy group had significantly better 90-day functional outcomes on the modified Rankin scale and lower 90-day mortality. There was no difference in serious adverse events between the groups. • Endovascular therapy plus standard treatment was more effective than standard treatment alone in patients with ischemic stroke who were 6 to 16 hours from last known normal and who had ischemic, but not infarcted, tissue on perfusion imaging. Abstract

middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard med- ical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90.

BACKGROUND Thrombectomy is currently rec- ommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms. METHODS We conducted a multicenter, rand- omized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal COMMENT By Jean-Claude Baron MD, ScD, FMedSci T he DEFUSE 3 randomized controlled trial documents that patients with large-vessel occlusion (LVO) andclear mismatch between at-risk but salvageable tissue and already irreversibly damaged tis- sue (ie, penumbra and core, respectively) treated with mechanical thrombectomy (MT) 6 to 16 hours from last-time-seen-well (LTSW; ie, including wake-up and unknown time-of-onset strokes) enjoyed markedly improved functional outcomes relative to best medical therapy. Only a few weeks ago, the DAWN trial reported similar results in patients with small-core but dispropor- tionate neurological deficit – suggestive of mismatch – treated 6 to 24 hours from LTSW. Showing that a subgroup of patients can strongly benefit fromMT up to 24 hours after stroke is the third major revolution in acute stroke management, occurring only 3 years after the second revolution demon- strating that MT added on to intravenous thrombolysis (IVT) using tPA up to 6 hours post onset in patients with LVO and small- core infarct improved outcome over IVT alone. And it occurred 22 years after the

RESULTS The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular-therapy group and 90 to the medical-therapy group). Endovascular ther- apy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were function- ally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P=0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemor- rhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respec- tively; P=0.18). CONCLUSIONS Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical ther- apy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or inter- nal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. Thrombectomy for Stroke at 6 to 16 Hours With Selection by Perfusion Imaging. N Engl J Med 2018 Jan 24;[EPub Ahead of Print], GW Albers, MP Marks, S Kemp, et al. www.practiceupdate.com/c/63459

first, which showed that tPA ≤3 hours (sub- sequently extended to ≤4.5 hours) afforded better outcomes than placebo. Both trials being highly positive, the AHA/ ASA guidelines changed the same day, recommending MT alone in imaging- based selected patients up to 24 hours post onset – a fourfold extension relative to previous guidelines published only 3 years ago! Although this breakthrough will increase the overall number of patients benefitting from MT, exerting pressure on the care systems given the relative scarcity of MT-capable centers, the emphasis that the earlier recanalization is achieved, the better the outcome (ie, that “time is brain”) remains unchanged.

Dr. Baron is Director of Research and Deputy- Director of the Inserm/Paris Descartes University Research Centre for Psychiatry and Neuroscience, and Honorary Neurology Consultant at

Sainte-Anne Hospital in Paris, France.

VOL. 3 • NO. 4 • 2018