Assessment of Optimal Patient Selection for Endovascular Thrombectomy Beyond 6 Hours After Symptom Onset
Authors: Gregory W. Albers, Maarten G. Lansberg, Scott Brown, Ashutosh P. Jadhav, Diogo C. Haussen, Sheila O. Martins, Leticia C. Rebello, Andrew M. Demchuk, Mayank Goyal, Marc Ribo, Aquilla S. Turk, David S. Liebeskind, Jeremy J. Heit, Michael P. Marks, Tudor G. Jovin, Raul G. Nogueira, Alain Bonafe, Ronald, F Budzik, Parita Bhuva, Soren Christensen, Christophe Cognard, Ricardo, A Hanel, Ameer, E Hassan, Michael Hill, Thabele Leslie-Mazwi, Ryan, A McTaggart, Monica Millán, Santiago Ortega-Gutierrez, Ashfaq Shuaib, Cathy, A Sila, Michel, T Torbey, May Kim-Tenser, Jenny, P Tsai, Dileep, R Yavagal
Journal: JAMA Neurology (2021)

<h3>Importance</h3> 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. <h3>Objective</h3> To assess the benefits of EVT among patients with 3 baseline imaging profiles using a pooled analysis of RCTs. <h3>Data Sources</h3> 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. <h3>Study Selection</h3> 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. <h3>Data Extraction/Synthesis</h3> 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. <h3>Main Outcomes and Measures</h3> 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]). <h3>Results</h3> 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;<i>P</i> &lt; .001; target perfusion mismatch subgroup, OR, 3.13; 95% CI, 2.10-4.66;<i>P</i> = .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;<i>P</i>&lt; .001; target perfusion mismatch subgroup, OR, 5.01; 95% CI, 2.37-10.60;<i>P</i>&lt; .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;<i>P</i> = .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;<i>P</i> = .03). <h3>Conclusions and Relevance</h3> 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.