Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke

K C J Compagne, A M M Boers, H A Marquering, O A Berkhemer, A J Yoo, L F M Beenen, R J van Oostenbrugge, W H van Zwam, Y B W E M Roos, C B Majoie, A C G M van Es, A van der Lugt, D W J Dippel, H Lingsma, MR CLEAN Investigators

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVE: The putative mechanism for the favourable effect of endovascular treatment (EVT) on functional outcome after acute ischaemic stroke is preventing follow-up infarct volume (FIV) progression. We aimed to assess to what extent difference in FIV explains the effect of EVT on functional outcome in a randomised trial of EVT versus no EVT (MR CLEAN).

METHODS: FIV was assessed on non-contrast CT scan 5-7 days after stroke. Functional outcome was the score on the modified Rankin Scale at 3 months. We tested the causal pathway from intervention, via FIV to functional outcome with a mediation model, using linear and ordinal regression, adjusted for relevant baseline covariates, including stroke severity. Explained effect was assessed by taking the ratio of the log odds ratios of treatment with and without adjustment for FIV.

RESULTS: Of the 500 patients included in MR CLEAN, 60 died and four patients underwent hemicraniectomy before FIV was assessed, leaving 436 patients for analysis. Patients in the intervention group had better functional outcomes (adjusted common odds ratio (acOR) 2.30 (95% CI 1.62-3.26) than controls and smaller FIV (median 53 vs. 81 ml) (difference 28 ml; 95% CI 13-41). Smaller FIV was associated with better outcome (acOR per 10 ml 0.60, 95% CI 0.52-0.68). After adjustment for FIV the effect of intervention on functional outcome decreased but remained substantial (acOR 2.05, 95% CI 1.44-2.91). This implies that preventing FIV progression explains 14% (95% CI 0-34) of the beneficial effect of EVT on outcome.

CONCLUSION: The effect of EVT on FIV explains only part of the treatment effect on functional outcome.

KEY POINTS: • Endovascular treatment in acute ischaemic stroke patients prevents progression of follow-up infarct volume on non-contrast CT at 5-7 days. • Follow-up infarct volume was related to functional outcome, but only explained a modest part of the effect of intervention on functional outcome. • A large proportion of treatment effect on functional outcome remains unexplained, suggesting FIV alone cannot be used as an early surrogate imaging marker of functional outcome.

Original languageEnglish
Pages (from-to)736-744
JournalEuropean Radiology
Volume29
Issue number2
DOIs
Publication statusPublished - Feb 2019

Cite this

Compagne, K. C. J., Boers, A. M. M., Marquering, H. A., Berkhemer, O. A., Yoo, A. J., Beenen, L. F. M., ... MR CLEAN Investigators (2019). Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke. European Radiology, 29(2), 736-744. https://doi.org/10.1007/s00330-018-5578-9
Compagne, K C J ; Boers, A M M ; Marquering, H A ; Berkhemer, O A ; Yoo, A J ; Beenen, L F M ; van Oostenbrugge, R J ; van Zwam, W H ; Roos, Y B W E M ; Majoie, C B ; van Es, A C G M ; van der Lugt, A ; Dippel, D W J ; Lingsma, H ; MR CLEAN Investigators. / Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke. In: European Radiology. 2019 ; Vol. 29, No. 2. pp. 736-744.
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title = "Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke",
abstract = "OBJECTIVE: The putative mechanism for the favourable effect of endovascular treatment (EVT) on functional outcome after acute ischaemic stroke is preventing follow-up infarct volume (FIV) progression. We aimed to assess to what extent difference in FIV explains the effect of EVT on functional outcome in a randomised trial of EVT versus no EVT (MR CLEAN).METHODS: FIV was assessed on non-contrast CT scan 5-7 days after stroke. Functional outcome was the score on the modified Rankin Scale at 3 months. We tested the causal pathway from intervention, via FIV to functional outcome with a mediation model, using linear and ordinal regression, adjusted for relevant baseline covariates, including stroke severity. Explained effect was assessed by taking the ratio of the log odds ratios of treatment with and without adjustment for FIV.RESULTS: Of the 500 patients included in MR CLEAN, 60 died and four patients underwent hemicraniectomy before FIV was assessed, leaving 436 patients for analysis. Patients in the intervention group had better functional outcomes (adjusted common odds ratio (acOR) 2.30 (95{\%} CI 1.62-3.26) than controls and smaller FIV (median 53 vs. 81 ml) (difference 28 ml; 95{\%} CI 13-41). Smaller FIV was associated with better outcome (acOR per 10 ml 0.60, 95{\%} CI 0.52-0.68). After adjustment for FIV the effect of intervention on functional outcome decreased but remained substantial (acOR 2.05, 95{\%} CI 1.44-2.91). This implies that preventing FIV progression explains 14{\%} (95{\%} CI 0-34) of the beneficial effect of EVT on outcome.CONCLUSION: The effect of EVT on FIV explains only part of the treatment effect on functional outcome.KEY POINTS: • Endovascular treatment in acute ischaemic stroke patients prevents progression of follow-up infarct volume on non-contrast CT at 5-7 days. • Follow-up infarct volume was related to functional outcome, but only explained a modest part of the effect of intervention on functional outcome. • A large proportion of treatment effect on functional outcome remains unexplained, suggesting FIV alone cannot be used as an early surrogate imaging marker of functional outcome.",
author = "Compagne, {K C J} and Boers, {A M M} and Marquering, {H A} and Berkhemer, {O A} and Yoo, {A J} and Beenen, {L F M} and {van Oostenbrugge}, {R J} and {van Zwam}, {W H} and Roos, {Y B W E M} and Majoie, {C B} and {van Es}, {A C G M} and {van der Lugt}, A and Dippel, {D W J} and H Lingsma and {MR CLEAN Investigators} and JCJ Bot",
year = "2019",
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language = "English",
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pages = "736--744",
journal = "European Radiology",
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Compagne, KCJ, Boers, AMM, Marquering, HA, Berkhemer, OA, Yoo, AJ, Beenen, LFM, van Oostenbrugge, RJ, van Zwam, WH, Roos, YBWEM, Majoie, CB, van Es, ACGM, van der Lugt, A, Dippel, DWJ, Lingsma, H & MR CLEAN Investigators 2019, 'Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke' European Radiology, vol. 29, no. 2, pp. 736-744. https://doi.org/10.1007/s00330-018-5578-9

Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke. / Compagne, K C J; Boers, A M M; Marquering, H A; Berkhemer, O A; Yoo, A J; Beenen, L F M; van Oostenbrugge, R J; van Zwam, W H; Roos, Y B W E M; Majoie, C B; van Es, A C G M; van der Lugt, A; Dippel, D W J; Lingsma, H; MR CLEAN Investigators.

In: European Radiology, Vol. 29, No. 2, 02.2019, p. 736-744.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke

AU - Compagne, K C J

AU - Boers, A M M

AU - Marquering, H A

AU - Berkhemer, O A

AU - Yoo, A J

AU - Beenen, L F M

AU - van Oostenbrugge, R J

AU - van Zwam, W H

AU - Roos, Y B W E M

AU - Majoie, C B

AU - van Es, A C G M

AU - van der Lugt, A

AU - Dippel, D W J

AU - Lingsma, H

AU - MR CLEAN Investigators

AU - Bot, JCJ

PY - 2019/2

Y1 - 2019/2

N2 - OBJECTIVE: The putative mechanism for the favourable effect of endovascular treatment (EVT) on functional outcome after acute ischaemic stroke is preventing follow-up infarct volume (FIV) progression. We aimed to assess to what extent difference in FIV explains the effect of EVT on functional outcome in a randomised trial of EVT versus no EVT (MR CLEAN).METHODS: FIV was assessed on non-contrast CT scan 5-7 days after stroke. Functional outcome was the score on the modified Rankin Scale at 3 months. We tested the causal pathway from intervention, via FIV to functional outcome with a mediation model, using linear and ordinal regression, adjusted for relevant baseline covariates, including stroke severity. Explained effect was assessed by taking the ratio of the log odds ratios of treatment with and without adjustment for FIV.RESULTS: Of the 500 patients included in MR CLEAN, 60 died and four patients underwent hemicraniectomy before FIV was assessed, leaving 436 patients for analysis. Patients in the intervention group had better functional outcomes (adjusted common odds ratio (acOR) 2.30 (95% CI 1.62-3.26) than controls and smaller FIV (median 53 vs. 81 ml) (difference 28 ml; 95% CI 13-41). Smaller FIV was associated with better outcome (acOR per 10 ml 0.60, 95% CI 0.52-0.68). After adjustment for FIV the effect of intervention on functional outcome decreased but remained substantial (acOR 2.05, 95% CI 1.44-2.91). This implies that preventing FIV progression explains 14% (95% CI 0-34) of the beneficial effect of EVT on outcome.CONCLUSION: The effect of EVT on FIV explains only part of the treatment effect on functional outcome.KEY POINTS: • Endovascular treatment in acute ischaemic stroke patients prevents progression of follow-up infarct volume on non-contrast CT at 5-7 days. • Follow-up infarct volume was related to functional outcome, but only explained a modest part of the effect of intervention on functional outcome. • A large proportion of treatment effect on functional outcome remains unexplained, suggesting FIV alone cannot be used as an early surrogate imaging marker of functional outcome.

AB - OBJECTIVE: The putative mechanism for the favourable effect of endovascular treatment (EVT) on functional outcome after acute ischaemic stroke is preventing follow-up infarct volume (FIV) progression. We aimed to assess to what extent difference in FIV explains the effect of EVT on functional outcome in a randomised trial of EVT versus no EVT (MR CLEAN).METHODS: FIV was assessed on non-contrast CT scan 5-7 days after stroke. Functional outcome was the score on the modified Rankin Scale at 3 months. We tested the causal pathway from intervention, via FIV to functional outcome with a mediation model, using linear and ordinal regression, adjusted for relevant baseline covariates, including stroke severity. Explained effect was assessed by taking the ratio of the log odds ratios of treatment with and without adjustment for FIV.RESULTS: Of the 500 patients included in MR CLEAN, 60 died and four patients underwent hemicraniectomy before FIV was assessed, leaving 436 patients for analysis. Patients in the intervention group had better functional outcomes (adjusted common odds ratio (acOR) 2.30 (95% CI 1.62-3.26) than controls and smaller FIV (median 53 vs. 81 ml) (difference 28 ml; 95% CI 13-41). Smaller FIV was associated with better outcome (acOR per 10 ml 0.60, 95% CI 0.52-0.68). After adjustment for FIV the effect of intervention on functional outcome decreased but remained substantial (acOR 2.05, 95% CI 1.44-2.91). This implies that preventing FIV progression explains 14% (95% CI 0-34) of the beneficial effect of EVT on outcome.CONCLUSION: The effect of EVT on FIV explains only part of the treatment effect on functional outcome.KEY POINTS: • Endovascular treatment in acute ischaemic stroke patients prevents progression of follow-up infarct volume on non-contrast CT at 5-7 days. • Follow-up infarct volume was related to functional outcome, but only explained a modest part of the effect of intervention on functional outcome. • A large proportion of treatment effect on functional outcome remains unexplained, suggesting FIV alone cannot be used as an early surrogate imaging marker of functional outcome.

U2 - 10.1007/s00330-018-5578-9

DO - 10.1007/s00330-018-5578-9

M3 - Article

VL - 29

SP - 736

EP - 744

JO - European Radiology

JF - European Radiology

SN - 0938-7994

IS - 2

ER -