Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort

for the PERFECT-MILD Collaborators

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Abstract

OBJECTIVE: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch.

METHODS: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial, Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVT pri ) were compared to those who received primary MM (MM pri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality).

RESULTS: Of 540 patients, 286 (53%) received EVT pri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MM pri : 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MM pri : 3 [2-4], p < 0.001). Functional independence was similar (EVT pri : 77.4% vs MM pri : 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVT pri : 16.3% vs MM pri : 1.3%, p < 0.001) and neurological worsening (EVT pri : 19.6% vs MM pri : 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVT pri : 77.4% vs MM pri : 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVT pri : 77.4% vs MM pri : 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (p interaction = 0.06). Similar findings were observed in a propensity score-matched subpopulation.

INTERPRETATION: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378.

Original languageEnglish (US)
Pages (from-to)364-378
Number of pages15
JournalAnnals of Neurology
Volume92
Issue number3
DOIs
StatePublished - Sep 2022

Bibliographical note

Funding Information:
The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not‐for‐profit sectors. The EXTEND‐IA, EXTEND‐IA TNK, and EXTEND‐IA TNK Part II trials were supported by grants from the Australian National Health and Medical Research Council of Australia, Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation of Australia, and National Stroke Foundation of Australia, and by infrastructure funding from the state government of Victoria. For EXTEND‐IA, the Solitaire FR device and trial infrastructure were provided under an unrestricted grant from Covidien. The EXTEND‐IA TNK trial was also supported by an unrestricted grant from Medtronic. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

Funding Information:
The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. The EXTEND-IA, EXTEND-IA TNK, and EXTEND-IA TNK Part II trials were supported by grants from the Australian National Health and Medical Research Council of Australia, Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation of Australia, and National Stroke Foundation of Australia, and by infrastructure funding from the state government of Victoria. For EXTEND-IA, the Solitaire FR device and trial infrastructure were provided under an unrestricted grant from Covidien. The EXTEND-IA TNK trial was also supported by an unrestricted grant from Medtronic. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. We thank iSchemaView for processing of perfusion imaging for the purpose of analysis.

Publisher Copyright:
© 2022 American Neurological Association.

Keywords

  • Brain Ischemia/surgery
  • Cerebral Hemorrhage
  • Endovascular Procedures/methods
  • Humans
  • Prospective Studies
  • Stroke/drug therapy
  • Thrombectomy/methods
  • Treatment Outcome

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article

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