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Outcomes of Thrombectomy in Transferred Patients With Ischemic Stroke in the Late WindowA Subanalysis From the DEFUSE 3 Trial

Educational Objective
To determine whether patients with ischemic stroke with large-vessel occlusion in the anterior circulation who were transferred from outside facilities for endovascular thrombectomy have similar outcomes in the late window compared with patients who were directly admitted to thrombectomy-capable hospitals.
1 Credit CME
Key Points

Question  Do patients with ischemic stroke with large-vessel occlusion in the anterior circulation who were transferred from outside facilities and had penumbral imaging mismatch prior to endovascular thrombectomy have similar outcomes with thrombectomy in the late window as those who were directly admitted to thrombectomy-capable hospitals?

Findings  In this secondary analysis of a randomized clinical trial, transfer and direct patients had comparable rates of functional independence and similar treatment effect with endovascular thrombectomy as well as similar symptomatic intracranial hemorrhage and mortality.

Meaning  Transferring patients for late-window thrombectomy may be associated with substantial clinical benefits and should be encouraged.

Abstract

Importance  Although thrombectomy benefit was maintained in transfer patients with ischemic stroke in early-window trials, overall functional independence rates were lower in thrombectomy and medical management–only groups.

Objective  To evaluate whether the imaging-based selection criteria used in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) trial would lead to comparable outcome rates and treatment benefits in transfer vs direct-admission patients.

Design, Setting, and Participants  Subgroup analysis of DEFUSE 3, a prospective, randomized, multicenter, blinded–end point trial. Patients were enrolled between May 2016 and May 2017 and were followed up for 90 days. The trial comprised 38 stroke centers in the United States and 182 patients with stroke with a large-vessel anterior circulation occlusion and initial infarct volume of less than 70 mL, mismatch ratio of at least 1.8, and mismatch volume of at least 15 mL, treated within 6 to 16 hours from last known well. Patients were stratified based on whether they presented directly to the study site or were transferred from a primary center. Data were analyzed between July 2018 and October 2018.

Interventions or Exposures  Endovascular thrombectomy plus standard medical therapy vs standard medical therapy alone.

Main Outcomes and Measures  The primary outcome was the distribution of 90-day modified Rankin Scale scores.

Results  Of the 296 patients who consented, 182 patients were randomized (66% were transfer patients and 34% directly presented to a study site). Median age was 71 years (interquartile range [IQR], 60-79 years) vs 70 years (IQR, 59-80 years); 69 transfer patients were women (57%) and 23 of the direct group were women (37%). Transfer patients had longer median times from last known well to study site arrival (9.43 vs 9 hours) and more favorable collateral profiles (based on hypoperfusion intensity ratio): median for transfer, 0.35 (IQR, 0.18-0.47) vs 0.42 (IQR, 0.25-0.56) for direct (P = .05). The primary outcome (90-day modified Rankin Scale score shift) did not differ in the direct vs transfer groups (direct OR, 2.9; 95% CI, 1.2-7.2; P = .01; transfer OR, 2.6; 95% CI, 1.3-4.8; P = .009). The overall functional independence rate (90-day modified Rankin Scale score 0-2) in the thrombectomy group did not differ (direct 44% vs transfer 45%) nor did the treatment effect (direct OR, 2.0; 95% CI, 0.9-4.4 vs transfer OR, 3.1; 95% CI, 1.6-6.1). Thrombectomy reperfusion rates, mortality, and symptomatic intracranial hemorrhage rates did not differ.

Conclusions and Relevance  In late-window patients selected by penumbral mismatch criteria, both the favorable outcome rate and treatment effect did not decline in transfer patients. These results have health care implications indicating transferring potential candidates for late-window thrombectomy is associated with substantial clinical benefits and should be encouraged.

Trial Registration  ClinicalTrials.gov identifier: NCT02586415

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Article Information

Corresponding Author: Amrou Sarraj, MD, University of Texas at Houston Stroke Center, University of Texas Health Foundation, 6431 Fannin St, MSB 7.044, Houston, TX 77030 (amrou.sarraj@uth.tmc.edu).

Accepted for Publication: January 10, 2019.

Published Online: February 7, 2019. doi:10.1001/jamaneurol.2019.0118

Author Contributions: Drs Albers and Mlynash had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Sarraj, Savitz, Lansberg, Albers.

Acquisition, analysis, or interpretation of data: Sarraj, Mlynash, Heit, Lansberg, Marks, Albers.

Drafting of the manuscript: Sarraj, Albers.

Critical revision of the manuscript for important intellectual content: Mlynash, Savitz, Heit, Lansberg, Marks, Albers.

Statistical analysis: Mlynash.

Obtained funding: Lansberg, Albers.

Administrative, technical, or material support: Sarraj, Lansberg.

Supervision: Lansberg, Albers.

Conflict of Interest Disclosures: Dr Sarraj is the principal investigator of the SELECT and SELECT 2 trials, with an unrestricted grant from Stryker Neurovascular, and of the DEFUSE 3 trial and is a consultant, speakers bureau, and advisory board member for Stryker Neurovascular. Dr Marks received honoraria from Medtronic and ThrombX Medical. Dr Albers has an ownership interest in iSchemiaView and is a consultant to iSchemiaView and Medtronic. No other disclosures were reported

Funding/Support: This study was supported by grants from the National Institute of Neurological Disorders and Stroke (U10NS086487 and U01NS092076).

Role of the Funder/Sponsor: The funding source did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

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