{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:52:08Z","timestamp":1791345128390,"version":"4.3.1"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100016304","name":"Medtronic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004320","name":"Philips","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004320","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate treatment effect heterogeneity across phenotypic clusters of patients with cryptogenic embolic stroke using causal inference methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>From a retrospective, multicenter cohort of patients with cryptogenic embolic stroke, we estimated the treatment effect of anticoagulation versus antiplatelet therapy in patients with ESUS in two ways: (1) Partitioning Around Medoids and (2) causal survival forest modeling. We assessed cluster\u2010level associations with time to primary outcome (recurrent stroke, major bleeding, or death) using Kaplan\u2013Meier survival analysis to assess cluster differences. We then extracted SHapley Additive exPlanations (SHAP) feature importances from the causal forest model to identify candidate effect modifiers from the causal forest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 1869 patients with ESUS, three phenotypically distinct clusters were extracted with significant differences in event\u2010free survival across clusters (log\u2010rank\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). There was no significant population\u2010level benefit of anticoagulation over antiplatelet therapy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.23). SHAP feature importance analysis identified several candidate effect modifiers; however, only higher LVEF (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u2212327, 95% CI: \u2212580 to \u221274,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.011) and cancer history (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u2212226, 95% CI: \u2212441 to \u221211,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.039) were independent predictors of response to antiplatelet over anticoagulation\u00a0using best linear projections. Phenotypic cluster assignment did not significantly predict treatment effect heterogeneity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Three distinct phenotypic clusters of cryptogenic stroke patients emerged with a differential risk of the composite outcome, but they did not predict responsiveness to anticoagulation. LVEF and cancer history, however, showed differential outcomes across antithrombotic strategies. These findings demonstrate the potential of causal inference methods for identifying effect heterogeneity and individualizing treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70542","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:41:10Z","timestamp":1791344470000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anticoagulation Treatment Response Among Phenotypic\n                    <scp>ESUS<\/scp>\n                    Clusters: Evidence From\n                    <scp>CASPR<\/scp>"],"prefix":"10.1002","author":[{"given":"Elena Badillo","family":"Goicoechea","sequence":"first","affiliation":[{"name":"Department of Neurology University of Chicago  Chicago Illinois 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