eprintid: 10206587 rev_number: 12 eprint_status: archive userid: 699 dir: disk0/10/20/65/87 datestamp: 2025-03-28 12:00:56 lastmod: 2025-03-28 12:04:52 status_changed: 2025-03-28 12:00:56 type: article metadata_visibility: show sword_depositor: 699 creators_name: Gregson, John creators_name: Donners, Simone JA creators_name: Dippel, Diederik creators_name: Lingsma, Hester creators_name: Dea Hazewinkel, Audinga creators_name: Brown, Martin M creators_name: Bonati, Leo H creators_name: Nederkoorn, Paul J title: Use of the Win Ratio for Analysis of Stroke Trials: Description, Illustration, and Planned Use in the Second European Carotid Surgery Trial (ECST-2) ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. abstract: Randomized trials in stroke often focus on outcomes beyond a single clinical event. Trials of stroke prevention commonly use composite outcomes that include multiple components (eg, death, stroke, or myocardial infarction). A major limitation is that all events count equally but may differ markedly in terms of clinical severity. Trials in acute stroke often use ordinal outcomes or scale scores. Limitations include the requirement for statistical assumptions and the difficulty of handling the competing risk of death. We introduce the win ratio as an alternative method. It works by placing components of a composite into a hierarchy, whereby clinically more important outcomes take priority over less important ones. We illustrate how it works using data from 2 major stroke trials: the ICSS (International Carotid Stenting Study, a trial in stroke prevention) and the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Potential benefits of the win ratio approach include the possibility to (1) emphasize the clinically most important outcomes, (2) combine components of different outcome types into a composite (eg, a mixture of time-to-event, continuous, and categorical), and (3) naturally handle the competing risk of death in analyses of quantitative outcomes. The win ratio will be used in the upcoming analysis of the ECST-2 (Second European Carotid Surgery Trial), which has a hierarchical primary outcome of (1) time to perioperative death, fatal stroke, or fatal myocardial infarction (most important); (2) time to nonfatal stroke; (3) time to nonfatal myocardial infarction (excluding silent infarcts); and (4) new silent cerebral infarct on brain imaging (least important). The win ratio provides a useful clinically relevant method for analyzing trial outcomes. It has some advantages over conventional methods, and we recommend its wider application in future stroke trials. date: 2025-01 date_type: published publisher: LIPPINCOTT WILLIAMS & WILKINS official_url: https://doi.org/10.1161/strokeaha.124.048689 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2325050 doi: 10.1161/STROKEAHA.124.048689 medium: Print-Electronic lyricists_name: Brown, Martin lyricists_id: MMBRO52 actors_name: Brown, Martin actors_id: MMBRO52 actors_role: owner funding_acknowledgements: FS/20/25/34983 [British Heart Foundation]; PB-PG-0609-19216 [National Institute for Health and Care Research]; TSA 2013/04 [Stroke Association]; 32003B-156658 [Swiss National Science Foundation]; [Leeds Neurology Foundation]; 843004107 [Netherlands Organisation for Scientific Research] full_text_status: restricted publication: Stroke volume: 56 number: 1 pagerange: 230-238 pages: 9 event_location: United States citation: Gregson, John; Donners, Simone JA; Dippel, Diederik; Lingsma, Hester; Dea Hazewinkel, Audinga; Brown, Martin M; Bonati, Leo H; Gregson, John; Donners, Simone JA; Dippel, Diederik; Lingsma, Hester; Dea Hazewinkel, Audinga; Brown, Martin M; Bonati, Leo H; Nederkoorn, Paul J; - view fewer <#> (2025) Use of the Win Ratio for Analysis of Stroke Trials: Description, Illustration, and Planned Use in the Second European Carotid Surgery Trial (ECST-2). Stroke , 56 (1) pp. 230-238. 10.1161/STROKEAHA.124.048689 <https://doi.org/10.1161/STROKEAHA.124.048689>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10206587/4/Brown_Use%20of%20the%20Win%20Ratio%20for%20Analysis%20of%20Stroke%20Trials_AAM.pdf