Mediation of the Relationship Between Endovascular Therapy and Functional Outcome by Follow-up Infarct Volume in Patients With Acute Ischemic Stroke

Anna M. M. Boers*, Ivo G. H. Jansen, Scott Brown, Hester F. Lingsma, Ludo F. M. Beenen, Thomas G. Devlin, Luis San Roman, Ji-Hoe Heo, Marc Ribo, Mohammed A. Almekhlafi, David S. Liebeskind, Jeanne Teitelbaum, Patricia Cuadras, Richard du Mesnil de Rochemont, Marine Beaumont, Martin M. Brown, Albert J. Yoo, Geoffrey A. Donnan, Jean Louis Mas, Catherine OppenheimRichard J. Dowling, Thierry Moulin, Nelly Agrinier, Demetrius K. Lopes, Lucia Aja Rodriguez, Kars C. J. Compagne, Fahad S. Al-Ajlan, Jeremy Madigan, Gregory W. Albers, Sebastien Soize, Jordi Blasco, Stephen M. Davis, Raul G. Nogueira, Antoni Davalos, Bijoy K. Menon, Aad van der Lugt, Keith W. Muir, Yvo B. W. E. M. Roos, Phil White, Peter J. Mitchell, Andrew M. Demchuk, Wim H. van Zwam, Tudor G. Jovin, Robert J. van Oostenbrugge, Diederik W. J. Dippel, Bruce C. V. Campbell, Francis Guillemin, Serge Bracard, Michael D. Hill, Mayank Goyal, Henk A. Marquering, Charles B. L. M. Majoie

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

IMPORTANCE The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction in follow-up infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke.

OBJECTIVE To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke.

DESIGN, SETTING, AND PARTICIPANTS Patient data from 7 randomized multicenter trialswere pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography ormagnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017.

MAIN OUTCOME AND MEASURE The 90-day functional outcome via the modified Rankin Scale (mRS).

RESULTS Among 1665 patients, the median (interquartile range [IQR]) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median [IQR] FIV, 33 [11-99] vs 51 [18-134] mL; P =.007) and lower mRS scores at 90 days (median [IQR] score, 3 [1-4] vs 4 [2-5]). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P

CONCLUSIONS AND RELEVANCE In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.

Original languageEnglish
Pages (from-to)194-202
Number of pages9
JournalJAMA Neurology
Volume76
Issue number2
DOIs
Publication statusPublished - Feb 2019

Keywords

  • CT SCANS
  • THROMBECTOMY
  • RECANALIZATION
  • REPERFUSION
  • INSIGHTS
  • 24-HOUR

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