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Selection of patients for intra-arterial treatment for acute ischaemic stroke: development and validation of a clinical decision tool in two randomised trials

BMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j1710 (Published 03 May 2017) Cite this as: BMJ 2017;357:j1710
  1. Esmee Venema, PhD candidate1 2,
  2. Maxim J H L Mulder, PhD candidate2 3,
  3. Bob Roozenbeek, physician and researcher2,
  4. Joseph P Broderick, professor4,
  5. Sharon D Yeatts, associate professor5,
  6. Pooja Khatri, professor4,
  7. Olvert A Berkhemer, physician and researcher3 6 7,
  8. Bart J Emmer, physician and researcher3,
  9. Yvo B W E M Roos, professor8,
  10. Charles B L M Majoie, professor6,
  11. Robert J van Oostenbrugge, professor9,
  12. Wim H van Zwam, professor7,
  13. Aad van der Lugt, professor3,
  14. Ewout W Steyerberg, professor1 10,
  15. Diederik W J Dippel, professor2,
  16. Hester F Lingsma, assistant professor1
  1. 1Department of Public Health, Erasmus MC University Medical Centre Rotterdam, PO Box 2040, 3000 CA Rotterdam, Netherlands
  2. 2Department of Neurology, Erasmus MC University Medical Centre Rotterdam, Rotterdam, Netherlands
  3. 3Department of Radiology, Erasmus MC University Medical Centre Rotterdam, Rotterdam, Netherlands
  4. 4Department of Neurology and Rehabilitation Medicine, University of Cincinnati Gardner Neuroscience Institute, Cincinnati, OH, USA
  5. 5Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA
  6. 6Department of Radiology, Academic Medical Centre, Amsterdam, Netherlands
  7. 7Department of Radiology, Maastricht University Medical Centre, Maastricht, Netherlands
  8. 8Department of Neurology, Academic Medical Centre, Amsterdam, Netherlands
  9. 9Department of Neurology, Maastricht University Medical Centre, Maastricht, Netherlands
  10. 10Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, Netherlands
  1. Correspondence to: E Venema e.venema{at}erasmusmc.nl
  • Accepted 27 March 2017

Abstract

Objective To improve the selection of patients with acute ischaemic stroke for intra-arterial treatment using a clinical decision tool to predict individual treatment benefit.

Design Multivariable regression modelling with data from two randomised controlled clinical trials.

Setting 16 hospitals in the Netherlands (derivation cohort) and 58 hospitals in the United States, Canada, Australia, and Europe (validation cohort).

Participants 500 patients from the Multicenter Randomised Clinical Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands trial (derivation cohort) and 260 patients with intracranial occlusion from the Interventional Management of Stroke III trial (validation cohort).

Main outcome measures The primary outcome was the modified Rankin Scale (mRS) score at 90 days after stroke. We constructed an ordinal logistic regression model to predict outcome and treatment benefit, defined as the difference between the predicted probability of good functional outcome (mRS score 0-2) with and without intra-arterial treatment.

Results 11 baseline clinical and radiological characteristics were included in the model. The externally validated C statistic was 0.69 (95% confidence interval 0.64 to 0.73) for the ordinal model and 0.73 (0.67 to 0.79) for the prediction of good functional outcome, indicating moderate discriminative ability. The mean predicted treatment benefit varied between patients in the combined derivation and validation cohort from −2.3% to 24.3%. There was benefit of intra-arterial treatment predicted for some individual patients from groups in which no treatment effect was found in previous subgroup analyses, such as those with no or poor collaterals.

Conclusion The proposed clinical decision tool combines multiple baseline clinical and radiological characteristics and shows large variations in treatment benefit between patients. The tool is clinically useful as it aids in distinguishing between individual patients who may experience benefit from intra-arterial treatment for acute ischaemic stroke and those who will not.

Trial registration clinicaltrials.gov NCT00359424 (IMS III) and isrctn.com ISRCTN10888758 (MR CLEAN).

Footnotes

  • Contributors: BR, HFL, EWS, DWJD, BJE, JPB, SDY, PK, OAB, YBWEMR, RJO, WHZ, CBLMM, and AL conceived the study. MJHLM, EV, BR, HFL, EWS, and DWJD designed the study. MJHLM and EV performed the literature search, data analysis, and statistical modelling. They contributed equally to the study. MJHLM, EV, BR, and HFL drafted the manuscript. EWS, DWJD, BJE, JPB, SDY, PK, OAB, YBWEMR, RJO, WHZ, CBLMM, and AL performed a critical review of the manuscript. HFL is the guarantor.

  • Funding: This study was funded by the Erasmus MC Cost-Effectiveness Research. The Interventional Management of Stroke III (IMS III) trial was funded by National Institutes of Health and National Institute of Neurological Disorders and Stroke grant numbers: University of Cincinnati (U01NS052220) and Medical University of South Carolina (U01NS054630 and U01NS077304). Genentech supplied the study drug used for intra-arterial tissue-type plasminogen activator treatment in the endovascular group. EKOS, Concentric Medical, and Cordis supplied study catheters during protocol versions 1 to 3. In the United States, IMS III investigator meeting support was provided in part by Genentech, EKOS, and Concentric Medical. In Europe, IMS III investigator meeting support was provided in part by Boehringer Ingelheim. The Multicenter Randomised Clinical Trial of Endovascular Therapy for Acute Ischaemic Stroke in the Netherlands (MR CLEAN) was partly funded by the Dutch Heart Foundation and by unrestricted grants from Angiocare BV, Covidien, medac , Lamepro Benelux, Penumbra, Stryker, TOP Medical, and Concentric Medical.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form. JPB received study medication for intra-arterial tissue type plasminogen activator from Genentech and catheters were supplied by EKOS Corporation, Concentric Medical, and Cordis. His research is funded by the Department of Neurology and Rehabilitation Medicine. He is remunerated by Genentech for his role on the Steering Committee for A Study of the Efficacy and Safety of Activase (Alteplase) in Patients With Mild Stroke (PRISMS) trial. SDY is remunerated by Genentech for her statistical role in the PRISMS trial. PK is remunerated by Genentech for her role as lead principal investigator of the PRISMS trial and by Penumbra for her role as neurology principal investigator of the Assess the Penumbra System in the Treatment of Acute Stroke trial. She has also received royalties from UpToDate and consulted for Grand Rounds, St Jude Medical, and Biogen. BJE is remunerated for his role as CE mark reviewer by DEKRA and by Novartis for educational lectures. Erasmus MC received funds from Stryker for consultations by DWJD and AL and for training courses by BJE, and from Bracco Imaging for consultations by DWJD. The Academic Medical Centre received funds from Stryker for consultations by CBLMM and YBWEMR. Maastricht University Medical Centre received funds from Stryker and Codman for consultations by WHZ.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

  • Transparency: The lead authors (MJHLM and EV) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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