Differential Effect of Endovascular Treatment in Medium or Distal Vessel Occlusion: A Distal Secondary Analysis

BACKGROUND: Patients with medium or distal vessel occlusion stroke are heterogeneous. Randomized trials show no net benefit of endovascular treatment (EVT) over best medical treatment (BMT) alone, which may mask heterogeneity of treatment effect. We used an externally developed machine learning model to predict excellent early neurological outcome (EENO) with BMT alone and examined whether the effect of EVT differed across predicted risk. METHODS: A Tabular Prior-Data Fitted Network (TabPFN) model was trained to predict EENO (24-hour National Institutes of Health Stroke Scale [NIHSS] score of 0–2) in patients with medium or distal vessel occlusion treated with BMT alone in a local Bernese Stroke Registry. This model was applied to patients from the DISTAL randomized trial (55 centers and 11 countries), who were randomized to EVT plus BMT or BMT alone. We tested for interaction between predicted EENO and treatment allocation on the primary outcome (90-day modified Rankin Scale shift), repeating this using admission NIHSS alone. RESULTS: In the development cohort (n=257, 42% female, and mean age 70.4±14.8 years), 54% achieved EENO. In the DISTAL cohort (270 BMT alone, 269 EVT plus BMT, 44% female, and mean age 74.9±12.0 years), the model showed moderate external discrimination (area under the receiver operating characteristic curve 0.73). A significant interaction was found between predicted EENO and treatment effect ( P interaction =0.012): in 152 patients predicted to achieve EENO, EVT was associated with worse 90-day modified Rankin Scale score (common odds ratio, 0.48 [95% CI, 0.27–0.84]), whereas no treatment effect was seen in 387 patients predicted not to achieve EENO (common odds ratio 1.13 [95% CI, 0.79–1.60]). A model using admission NIHSS alone showed comparable discrimination (area under the receiver operating characteristic curve 0.71) and a common odds ratio for EVT of 0.47 (95% CI, 0.25–0.89) in patients with an NIHSS score of ≤4 and a common odds ratio of 1.05 (95% CI, 0.75–1.47) in patients with an NIHSS score of >4 ( P interaction =0.029). CONCLUSIONS: EVT was harmful in patients with medium or distal vessel occlusion predicted to achieve EENO with BMT alone, and an NIHSS-alone model performed comparably to the multivariable model. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05029414.

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Journal
Stroke
Published
2026-10-30
DOI
https://doi.org/10.1161/strokeaha.126.057558
Primary Topic
Acute Ischemic Stroke Management
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article
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article

Differential Effect of Endovascular Treatment in Medium or Distal Vessel Occlusion: A Distal Secondary Analysis

Alex Brehm, Elmar Lobsien, Urs Fischer, Benjamin Wagner et al.
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Stroke
Acute Ischemic Stroke Management
article

Differential Effect of Endovascular Treatment in Medium or Distal Vessel Occlusion: A Distal Secondary Analysis

Alex Brehm, Elmar Lobsien, Urs Fischer, Benjamin Wagner, Pasquale Mordasini, Lehel-Barna Lakatos, Elias Auer, Tobias Djamsched Faizy, Christian Philip Thaler, Giovanni Bianco, Daniel Pielenz, Nikki Rommers, Jan Gralla, Christian Commodaro, Johannes Kaesmacher, Guillaume Saliou, Christian Maegerlein, Hani Ridwan, Bastian Cheng, Arno Reich, Noah Ayadi, Casjupea Knispel, Tilman B. Schubert, Alexander Salerno, Lars‐Peder Pallesen, Maximilian Rauch, Ala Jamous, Vera Aebischer, Fabian Flottmann, Davide Strambo, Ioannis Tsogkas, Maximillian Schell, Benedikt Kügelgen, Florian Eff, Hendrik Lesch, Mohamed Elsharkawy, Gianmarco Bernava, Bruno Mario Bartolini, Annahita Sedghi, Jérémy Hofmeister, Eike Immo I Piechowiak, Grzegorz Marek Karwacki, Jürgen Den Hollander, Fabio Capilli, Victor Schulze-Zachau, Christoph C. Kurmann, Dennis Martin Hedderich, Marco Pileggi, Jawid Madjidyar, Tobias Boeckh‐Behrens, Philipp Erdmann, Francesco Puccinelli, Ida Rangus, Marios‐Nikos Psychogios, Christoph Globas, Martin Renz, Gian Marco De Marchis, Eckhard Schlemm, Franziska Lieschke, Bruce C.V. Campbell, Fabiano Cavalcante, David Julian Seiffge, Ioannis Farah, Sara Magdalena Pilgram-Pastor, Christoph Riegler, Wolfram Schwindt, Guillaume Thévoz, Eva Neumaier‐Probst, Pia Niederau, Jochen Vehoff, Timo Kahles, Johannes C. Gerber, Patrick Felix Samp, Rüdiger Lange, ELKE LEINISCH, Kristina Szabo, Charlotte S. Weyland, Jan-Hendrik Schäfer, Johanna Härtl, Tatjana Wittenberg, Janis Patricia Rauch, Martin Arndt, Maria Alexandrou, João Pinho, Marton D. Gyurko, Luca Remonda, Christian Hartmann, Johanna Herget, Martin Schlösser, Guillaume Marie, Andreea Gottschalk, Rimpal Patoliya, Maria Messe, Friedericke Austein, Stephanie Pflugi, Carmen-Alexandra Vieriu, Eilsabeth Dirren, Sherif Mohamed, Christian Roth, Kristine-Ann Blackham
article en

Abstract

BACKGROUND: Patients with medium or distal vessel occlusion stroke are heterogeneous. Randomized trials show no net benefit of endovascular treatment (EVT) over best medical treatment (BMT) alone, which may mask heterogeneity of treatment effect. We used an externally developed machine learning model to predict excellent early neurological outcome (EENO) with BMT alone and examined whether the effect of EVT differed across predicted risk. METHODS: A Tabular Prior-Data Fitted Network (TabPFN) model was trained to predict EENO (24-hour National Institutes of Health Stroke Scale [NIHSS] score of 0–2) in patients with medium or distal vessel occlusion treated with BMT alone in a local Bernese Stroke Registry. This model was applied to patients from the DISTAL randomized trial (55 centers and 11 countries), who were randomized to EVT plus BMT or BMT alone. We tested for interaction between predicted EENO and treatment allocation on the primary outcome (90-day modified Rankin Scale shift), repeating this using admission NIHSS alone. RESULTS: In the development cohort (n=257, 42% female, and mean age 70.4±14.8 years), 54% achieved EENO. In the DISTAL cohort (270 BMT alone, 269 EVT plus BMT, 44% female, and mean age 74.9±12.0 years), the model showed moderate external discrimination (area under the receiver operating characteristic curve 0.73). A significant interaction was found between predicted EENO and treatment effect ( P interaction =0.012): in 152 patients predicted to achieve EENO, EVT was associated with worse 90-day modified Rankin Scale score (common odds ratio, 0.48 [95% CI, 0.27–0.84]), whereas no treatment effect was seen in 387 patients predicted not to achieve EENO (common odds ratio 1.13 [95% CI, 0.79–1.60]). A model using admission NIHSS alone showed comparable discrimination (area under the receiver operating characteristic curve 0.71) and a common odds ratio for EVT of 0.47 (95% CI, 0.25–0.89) in patients with an NIHSS score of ≤4 and a common odds ratio of 1.05 (95% CI, 0.75–1.47) in patients with an NIHSS score of >4 ( P interaction =0.029). CONCLUSIONS: EVT was harmful in patients with medium or distal vessel occlusion predicted to achieve EENO with BMT alone, and an NIHSS-alone model performed comparably to the multivariable model. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05029414.

Stroke
University of Bern (CH), The Royal Melbourne Hospital (AU), The University of Melbourne (AU), University of Basel (CH), University Hospital of Bern (CH), University Hospital of Basel (CH), Amsterdam Neuroscience (NL), Amsterdam University Medical Centers (NL), University of Amsterdam (NL)
Good health and well-being
Openalex Percentile: Top 12%
Acute Ischemic Stroke Management
DOISourceOpenAlex
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