Updates In Neurology | Stroke | Neurology 2018 | Abstracts Invited |

Thrombectomy beyond the conventional therapeutic window and in unwitnessed strokes

Abstract Submission at https://neurology.cmesociety.com/abstract-submission

Recently two trials reported results about the effectiveness of thrombectomy for patients with acute ischemic stroke with large-vessel occlusion of intracranial arteries who can be treated beyond the conventional 6 hours therapeutic window or who have unwitnessed strokes.

In the DAWN trial (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo) patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group) (Nogueira et al., 2018). The trial included patients with occlusion of a large cerebral vessel who presented between 6 and 24 hours after the onset of stroke; approximately 60% of the patients had had their first stroke symptoms when they woke up. To be included, “tissue window” criteria were required to detect evidence of ischemic but not yet infarcted brain tissue. Patients were included if evidence of a small infarct core on magnetic resonance imaging (MRI) or perfusion computed tomography (CT) in addition to evidence of a clinical deficit that was disproportionately severe relative to the infarct. The trial was halted on the basis of results of a prespecified interim analysis, which suggested a high probability of success. Results indicated that for every 2 patients who underwent thrombectomy, 1 additional patient had a better score for disability at 90 days (as compared with the results in the control group); for every 2.8 patients who underwent thrombectomy, 1 additional patient had functional independence at 90 days. The safety profile for thrombectomy did not differ significantly from the rates seen with standard medical care.

In the DEFUSE 3 (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group) (Albers et al., 2018). The trial included patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, who could undergo initiation of endovascular therapy between 6 and 16 hours after the time that they had last been known to be well, including if they had awakened from sleep with symptoms of a stroke. Patients were eligible if they had 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 as estimated by CT perfusion or MRI diffusion and perfusion scans with the use of a dedicated software. Even this trial was halted on the basis of results of a prespecified interim analysis, which suggested a high probability of success. Results indicated that the thrombectomy group, as compared to the control group, had 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 functionally 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 thrombectomy group and 26% in the control group (P = 0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P = 0.75) or of serious adverse events (43% and 53%, respectively; P = 0.18).

Taken together the results of those trials support that, in selected patients with acute ischemic stroke due to the occlusion of a large vessel, endovascular treatment may be associated with benefits even when performed beyond the 6-hour therapeutic window. Implementation of this treatment strategy requires advanced neuroimaging studies and expertise.

key points

• For patients with acute ischemic stroke and occlusion of a large vessel who present late after the onset of stroke but who have small infarct core and a large volume of tissue at risk late thrombectomy appears beneficial.
• The results of the DAWN and the DEFUSE 3 trials do not support a general extension of the time window for thrombectomy.
• Selection of patients who may benefit from late thrombectomy can be done using magnetic resonance imaging or perfusion computed tomography to identify the presence of viable tissue at risk; the role of the evaluation of collateral circulation which may be more easily available in some centers requires further evaluation.

Nogueira RG, Jadhav AP , Haussen DC et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018 ;378(1):11-21.

Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG; DEFUSE 3 Investigators. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018 Jan 24. doi: 10.1056/NEJMoa1713973.