Top

Published in:

Open Access 01-02-2019 | Neuro

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

Authors: 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, for the MR CLEAN Investigators

Published in: European Radiology | Issue 2/2019

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.

Available only for authorised users

Goyal M, Menon BK, van Zwam WH et al (2016) Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomized trials. Lancet 387(10029):1723–1731

Berkhemer OA, Fransen PS, Beumer D et al (2015) A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 372(1):11–20

Jovin TG, Chamorro A, Cobo E et al (2015) Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 372(24):2296–2306

Yoo AJ, Chaudhry ZA, Nogueira RG et al (2012) Infarct volume is a pivotal biomarker after intra-arterial stroke therapy. Stroke 43(5):1323–1330

Barrett KM, Ding YH, Wagner DP, Kallmes DF, Johnston KC, Investigators A (2009) Change in diffusion-weighted imaging infarct volume predicts neurologic outcome at 90 days: results of the Acute Stroke Accurate Prediction (ASAP) trial serial imaging substudy. Stroke 40(7):2422–2427

Al-Ajlan FS, Goyal M, Demchuk AM et al (2016) Intra-Arterial Therapy and Post-Treatment Infarct Volumes: Insights From the ESCAPE Randomized Controlled Trial. Stroke 47(3):777–781

Quinn TJ, Dawson J, Walters MR, Lees KR (2009) Exploring the reliability of the modified rankin scale. Stroke 40(3):762–766CrossRef

Quinn TJ, Dawson J, Walters MR, Lees KR (2008) Variability in modified Rankin scoring across a large cohort of international observers. Stroke 39(11):2975–2979CrossRef

Bucker A, Boers AM, Bot JCJ et al (2017) Associations of Ischemic Lesion Volume With Functional Outcome in Patients With Acute Ischemic Stroke: 24-Hour Versus 1-Week Imaging. Stroke 48(5):1233–1240

10.

Lansberg MG, Lee J, Christensen S et al (2011) RAPID automated patient selection for reperfusion therapy: a pooled analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study. Stroke 42(6):1608–1614

11.

Saver JL, Johnston KC, Homer D et al (1999) Infarct volume as a surrogate or auxiliary outcome measure in ischemic stroke clinical trials. The RANTTAS Investigators. Stroke 30(2):293–298

12.

Ebinger M, Christensen S, De Silva DA et al (2009) Expediting MRI-based proof-of-concept stroke trials using an earlier imaging end point. Stroke 40(4):1353–1358

13.

Barber PA, Parsons MW, Desmond PM et al (2004) The use of PWI and DWI measures in the design of "proof-of-concept" stroke trials. J Neuroimaging 14(2):123–132

14.

Baron RM, Kenny DA (1986) The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 51(6):1173–1182CrossRef

15.

Prentice RL (1989) Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med 8(4):431–440CrossRef

16.

Al-Ajlan FS, Al Sultan AS, Minhas P et al (2018) Posttreatment Infarct Volumes when Compared with 24-Hour and 90-Day Clinical Outcomes: Insights from the REVASCAT Randomized Controlled Trial. AJNR Am J Neuroradiol 39(1):107–110

17.

Boers AM, Marquering HA, Jochem JJ et al (2013) Automated cerebral infarct volume measurement in follow-up noncontrast CT scans of patients with acute ischemic stroke. AJNR Am J Neuroradiol 34(8):1522–1527

18.

Moons KG, Donders RA, Stijnen T, Harrell FE Jr (2006) Using the outcome for imputation of missing predictor values was preferred. J Clin Epidemiol 59(10):1092–1101CrossRef

19.

Vanderweele TJ, Vansteelandt S (2010) Odds ratios for mediation analysis for a dichotomous outcome. Am J Epidemiol 172(12):1339–1348CrossRef

20.

Freedman LS, Graubard BI, Schatzkin A (1992) Statistical validation of intermediate endpoints for chronic diseases. Stat Med 11(2):167–178CrossRef

21.

Valeri L, Vanderweele TJ (2013) Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros. Psychol Methods 18(2):137–150CrossRef

22.

Dong Y, Peng CY (2013) Principled missing data methods for researchers. Springerplus 2(1):222CrossRef

23.

van der Heijden GJ, Donders AR, Stijnen T, Moons KG (2006) Imputation of missing values is superior to complete case analysis and the missing-indicator method in multivariable diagnostic research: a clinical example. J Clin Epidemiol 59(10):1102–1109CrossRef

24.

Payabvash S, Souza LC,Wang Y et al (2011) Regional ischemic vulnerability of the brain to hypoperfusion: the need for location specific computed tomography perfusion thresholds in acute stroke patients. Stroke 42(5):1255–1260CrossRef

25.

Marcoux FW, Morawetz RB, Crowell RM, DeGirolami U, Halsey JH Jr (1982) Differential regional vulnerability in transient focal cerebral ischemia. Stroke 13(3):339–346CrossRef

26.

Ernst M, Boers AMM, Aigner A et al (2017) Association of Computed Tomography Ischemic Lesion Location With Functional Outcome in Acute Large Vessel Occlusion Ischemic Stroke. Stroke 48(9):2426–2433

27.

Rangaraju S, Streib C, Aghaebrahim A, Jadhav A, Frankel M, Jovin TG (2015) Relationship Between Lesion Topology and Clinical Outcome in Anterior Circulation Large Vessel Occlusions. Stroke 46(7):1787–1792CrossRef

28.

Simonsen CZ, Yoo AJ, Sorensen LH et al (2018) Effect of general anesthesia and conscious sedation during endovascular therapy on infarct growth and clinical outcomes in acute ischemic stroke: a randomized clinical trial. JAMA Neurol 75(4):470–477

29.

Brott T, Adams HP Jr, Olinger CP et al (1989) Measurements of acute cerebral infarction: a clinical examination scale. Stroke 20(7):864–870

30.

Adams HP Jr, Davis PH, Leira EC et al (1999) Baseline NIH Stroke Scale score strongly predicts outcome after stroke: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 53(1):126–131

31.

Frankel MR, Morgenstern LB, Kwiatkowski T et al (2000) Predicting prognosis after stroke: a placebo group analysis from the National Institute of Neurological Disorders and Stroke rt-PA Stroke Trial. Neurology 55(7):952–959

32.

Lansberg MG, O'Brien MW, Tong DC, Moseley ME, Albers GW (2001) Evolution of cerebral infarct volume assessed by diffusion-weighted magnetic resonance imaging. Arch Neurol 58(4):613–617CrossRef

Title: Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke
Authors: 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
for the MR CLEAN Investigators
Publication date: 01-02-2019
Publisher: Springer Berlin Heidelberg
Published in: European Radiology / Issue 2/2019
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-018-5578-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Objective

Methods

Results

Conclusion

Key Points

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

Key Points

Please log in to get access to this content

Other articles of this Issue 2/2019

Correction to: National survey on dose data analysis in computed tomography

The MR radiomic signature can predict preoperative lymph node metastasis in patients with esophageal cancer

Prognostic value of radiomic analysis of iodine overlay maps from dual-energy computed tomography in patients with resectable lung cancer

Shear wave elastography for liver fibrosis in chronic hepatitis B: Adapting the cut-offs to alanine aminotransferase levels improves accuracy

Magnetic resonance elastography can predict development of hepatocellular carcinoma with longitudinally acquired two-point data

BOLD cardiac MRI for differentiating reversible and irreversible myocardial damage in ST segment elevation myocardial infarction