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

Anna Boers 1, 2 Ivo Jansen 1 Scott Brown 3 Hester Lingsma 4 Ludo Beenen 1 Thomas Devlin 5 Luis Román 6 Ji-Hoe Heo 7 Marc Ribó 8 Mohammed Almekhlafi 9 David Liebeskind 10 Jeanne Teitelbaum 11 Patricia Cuadras 12 Richard Du Mesnil de Rochemont 13 Marine Beaumont 14, 15 Martin Brown 16 Albert Yoo 17 Geoffrey Donnan 18 Jean Mas 19 Catherine Oppenheim 19 Richard Dowling 18 Thierry Moulin 20 Nelly Agrinier 21 Demetrius Lopes 22 Lucía Aja Rodríguez 23 Kars Compagne 24 Fahad Al-Ajlan 25 Jeremy Madigan 26 Gregory Albers 27 Sebastien Soize 28 Jordi Blasco 6 Stephen Davis 18 Raul Nogueira 29 Antoni Dávalos 12 Bijoy Menon 30 Aad van der Lugt 24 Keith Muir 31 Yvo Roos 1 Phil White 32 Peter Mitchell 18 Andrew Demchuk 30 Wim van Zwam 33 Tudor Jovin 34 Robert van Oostenbrugge 33 Diederik Dippel 24 Bruce Campbell 18 Francis Guillemin 21 Serge Bracard 15, 35 Michael Hill 30 Mayank Goyal 30 Henk Marquering 1 Charles Majoie 1
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 trials were 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 or magnetic 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 < .001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P < .001). Treatment-reduced FIV explained 12% (95% CI, 1-19) of the relationship between EVT and functional outcome. 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.
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Submitted on : Thursday, May 20, 2021 - 12:08:42 PM
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Anna Boers, Ivo Jansen, Scott Brown, Hester Lingsma, Ludo Beenen, et al.. Mediation of the Relationship Between Endovascular Therapy and Functional Outcome by Follow-up Infarct Volume in Patients With Acute Ischemic Stroke. JAMA neurology, American Medical Association, 2019, 76 (2), pp.194-202. ⟨10.1001/jamaneurol.2018.3661⟩. ⟨hal-03225408⟩

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