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Optimal Patient Selection for EVT Beyond 6 Hours After Symptom Onset
abstract
This abstract is available on the publisher's site.
Access this abstract nowImportance
The optimal imaging approach for identifying patients who may benefit from endovascular thrombectomy (EVT) beyond 6 hours after they were last known well is unclear. Six randomized clinical trials (RCTs) have evaluated the efficacy of EVT vs standard medical care among patients with ischemic stroke.
Objective
To assess the benefits of EVT among patients with 3 baseline imaging profiles using a pooled analysis of RCTs.
Data Sources
The AURORA (Analysis of Pooled Data from Randomized Studies of Thrombectomy More Than 6 Hours After Last Known Well) Collaboration pooled patient-level data from the included clinical trials.
Study Selection
An online database search identified RCTs of endovascular stroke therapy published between January 1, 2010, and March 1, 2021, that recruited patients with ischemic stroke who were randomized between 6 and 24 hours after they were last known well.
Data Extraction/Synthesis
Data from the final locked database of each study were provided. Data were pooled, and analyses were performed using mixed-effects modeling with fixed effects for parameters of interest.
Main Outcomes and Measures
The primary outcome was reduction in disability measured by the modified Rankin Scale at 90 days. An evaluation was also performed to examine whether the therapeutic response differed based on imaging profile among patients who received treatment based on the time they were last known well. Treatment benefits were assessed among a clinical mismatch subgroup, a target perfusion mismatch subgroup, and an undetermined profile subgroup. The primary end point was assessed among these subgroups and during 3 treatment intervals (tercile 1, 360-574 minutes [6.0-9.5 hours]; tercile 2, 575-762 minutes [9.6-12.7 hours]; and tercile 3, 763-1440 minutes [12.8-24.0 hours]).
Results
Among 505 eligible patients, 266 (mean [SD] age, 68.4 [13.8] years; 146 women [54.9%]) were assigned to the EVT group and 239 (mean [SD] age, 68.7 [13.7] years; 126 men [52.7%]) were assigned to the control group. Among 295 patients in the clinical mismatch subgroup and 359 patients in the target perfusion mismatch subgroup, EVT was associated with reductions in disability at 90 days vs no EVT (clinical mismatch subgroup, odds ratio [OR], 3.57; 95% CI, 2.29-5.57; P < .001; target perfusion mismatch subgroup, OR, 3.13; 95% CI, 2.10-4.66; P = .001). Statistically significant benefits were observed in all 3 terciles for both subgroups, with the highest OR observed for tercile 3 (clinical mismatch subgroup, OR, 4.95; 95% CI, 2.20-11.16; P < .001; target perfusion mismatch subgroup, OR, 5.01; 95% CI, 2.37-10.60; P < .001). A total of 132 patients (26.1%) had an undetermined imaging profile and no significant treatment benefit (OR, 1.59; 95% CI, 0.82-3.06; P = .17). The interaction between treatment effects for the clinical and target perfusion mismatch subgroups vs the undetermined profile subgroup was significant (OR, 2.28; 95% CI, 1.11-4.70; P = .03).
Conclusions and Relevance
In this study, EVT was associated with similar benefit among patients in the clinical mismatch and target perfusion mismatch subgroups during the 6- to 24-hour treatment interval. These findings support EVT as a treatment for patients meeting the criteria for either of the imaging mismatch profiles within the 6- to 24-hour interval.
Additional Info
Assessment of Optimal Patient Selection for Endovascular Thrombectomy Beyond 6 Hours After Symptom Onset: A Pooled Analysis of the AURORA Database
JAMA Neurol 2021 Sep 01;78(9)1064-1071, GW Albers, MG Lansberg, S Brown, AP Jadhav, DC Haussen, SO Martins, LC Rebello, AM Demchuk, M Goyal, M Ribo, AS Turk, DS Liebeskind, JJ Heit, MP Marks, TG Jovin, RG NogueiraFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The results from the two randomized controlled trials for endovascular therapy in the extended time window, Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE3)1 and Diffusion-Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention (DAWN),2 made performing endovascular therapy on large-vessel occlusions (LVO) in the anterior circulation standard of care in the expanded time window from 6 to 24 hours from last known well (LKW).3 Both studies excluded patients with large cores and used perfusion imaging for patient selection. DEFUSE3 used a target perfusion imaging mismatch to include patients with a core <70 mL 6 to 16 hours from LKW,1 whereas DAWN used the more restrictive clinical mismatch 6 to 24 hours from LKW.2 Replicating the clinical trial selection criteria in clinical practice requires all eligible patients to have perfusion imaging. Also, the pool of patients eligible for endovascular therapy 16 to 24 hours from LKW would include only patients screened by the DAWN clinical mismatch criteria, resulting in a more conservative subset of patients who would be eligible 16 to 24 hours of LKW in comparison with patients who would be eligible 6 to 16 hours from LKW.3,4 This highlights two important questions: 1) Could a target perfusion mismatch also select patients who would benefit from endovascular therapy between 16 to 24 hours of LKW?4; and 2) Could patients with an LVO in the anterior circulation be effectively selected for endovascular therapy without quantitative perfusion imaging if the ischemic burden on CT or MRI was not large enough to have otherwise precluded enrollment in DEFUSE3 or DAWN?4
By pooling the data from five endovascular trials that included patients randomized to receive a thrombectomy 6 to 24 hours from LKW, the authors of the “Analysis of Pooled Data from Randomized Studies of Thrombectomy More Than 6 Hours After Last Known Well (AURORA)” were able to perform analysis to address these questions using an expanded dataset.4 The authors compared the likelihood of a patient having a good functional outcome at 90 days in comparison with control if taken for thrombectomy based on the target perfusion mismatch used in DEFUSE3, the clinical mismatch used in DAWN, and enrolled patients taken for endovascular therapy without perfusion imaging.4 There was a clear benefit with both the clinical mismatch and the target perfusion mismatch up to 24 hours from LKW.4 However, no significant benefit was found in patients taken for endovascular therapy without perfusion imaging. It is important to note that the subgroup without perfusion imaging was underpowered.4
The results of this study suggest that the DEFUSE3 target perfusion mismatch can also be used to select patients who may benefit from endovascular therapy even 16 to 24 hours from LKW.4 Identifying how to select patients for endovascular therapy for anterior circulation LVO in the absence of perfusion imaging up to 24 hours will need to be addressed with future studies.4,5
References