{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T21:12:57Z","timestamp":1776114777079,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"44","license":[{"start":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research & Development LLC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Stroke is often a devastating event among patients with heart failure with reduced ejection (HFrEF). In COMMANDER HF, rivaroxaban 2.5\u2009mg b.i.d. did not reduce the composite of first occurrence of death, stroke, or myocardial infarction compared with placebo in patients with HFrEF, coronary artery disease (CAD), and sinus rhythm. We now examine the incidence, timing, type, severity, and predictors of stroke or a transient ischaemic attack (TIA), and seek to establish the net clinical benefit of treatment with low-dose rivaroxaban.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>In this double-blind, randomized trial, 5022 patients who had HFrEF(\u226440%), elevated natriuretic peptides, CAD, and who were in sinus rhythm were treated with rivaroxaban 2.5\u2009mg b.i.d. or placebo in addition to antiplatelet therapy, after an episode of worsening HF. The primary neurological outcome for this post hoc analysis was time to first event of any stroke or TIA. Over a median follow-up of 20.5 (25th\u201375th percentiles 20.0\u201320.9) months, 150 all-cause stroke (127) or TIA (23) events occurred (ischaemic stroke in 82% and haemorrhagic stroke in 11% of stroke events). Overall, 47.5% of first-time strokes were either disabling (16.5%) or fatal (31%). Prior stroke, low body mass index, geographic region, and the CHA2DS2-VASc score were predictors of stroke\/TIA. Rivaroxaban significantly reduced the primary neurological endpoint of all-cause stroke or TIA compared with placebo by 32% (1.29 events vs. 1.90 events per 100 patient-years), adjusted for the time from index HF event to randomization and stratified by geographic region (adjusted hazard ratio 0.68, 95% confidence interval 0.49\u20130.94), with a number needed to treat of 164 patients per year to prevent one stroke\/TIA event. The principal safety endpoint of fatal bleeding or bleeding into a critical space, occurred at a similar rate on rivaroxaban and placebo (0.44 events vs. 0.55 events per 100 patient-years).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Patients with HFrEF and CAD are at risk for stroke or TIA in the period following an episode of worsening heart failure in the absence of atrial fibrillation. Most strokes are of ischaemic origin and nearly half are either disabling or fatal. Rivaroxaban at a dose of 2.5\u2009mg b.i.d. reduced rates of stroke or TIA compared with placebo in this population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial Registration<\/jats:title>\n                  <jats:p>COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure); ClinicalTrials.gov NCT01877915.<\/jats:p>\n                  <jats:p\/>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehz427","type":"journal-article","created":{"date-parts":[[2019,6,8]],"date-time":"2019-06-08T19:09:26Z","timestamp":1560020966000},"page":"3593-3602","source":"Crossref","is-referenced-by-count":90,"title":["A comprehensive analysis of the effects of rivaroxaban on stroke or transient ischaemic attack in patients with heart failure, coronary artery disease, and sinus rhythm: the COMMANDER HF trial"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-7044","authenticated-orcid":false,"given":"Mandeep R","family":"Mehra","sequence":"first","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0885-1953","authenticated-orcid":false,"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA, USA"}]},{"given":"Min","family":"Fu","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Spring House , PA, USA"}]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universite de Lorraine, INSERM Unite 1116 , Vandoeuvre les Nancy, France"},{"name":"Clinical Investigation Center 1433, French Clinical Research Infrastructure Network, Investigation Network Initiative\u2013Cardiovascular and Renal Clinical Trialists , Centre Hospitalier Regional et Universitaire de Nancy, Vandoeuvre les Nancy, France"}]},{"given":"Stefan D","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK); and Berlin Institute of Health Center for Regenerative Therapies (BCRT) ; German Centre for Cardiovascular Research (DZHK) partner site Berlin; Charit\u00e9 Universit\u00e4tsmedizin Berlin, Germany"}]},{"given":"John G F","family":"Cleland","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow , Glasgow, Scotland"},{"name":"National Heart and Lung Institute, Imperial College London , London, England"}]},{"given":"Carolyn S P","family":"Lam","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore , Singapore"},{"name":"Duke-National University of Singapore , Singapore"},{"name":"The George Institute for Global Health , Australia"},{"name":"Department of Cardiology, University Medical Center Groningen , University of Groningen, Groningen, the Netherlands"}]},{"given":"Dirk J","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen , University of Groningen, Groningen, the Netherlands"}]},{"given":"William M","family":"Byra","sequence":"additional","affiliation":[{"name":"Janssen Research and Development , Raritan, NJ, USA"}]},{"given":"Theodore E","family":"Spiro","sequence":"additional","affiliation":[{"name":"Research and Development, Pharmaceuticals, Thrombosis and Hematology Therapeutic Area , Bayer US, LLC, Whippany, NJ, USA"}]},{"given":"Hsiaowei","family":"Deng","sequence":"additional","affiliation":[{"name":"Janssen Research and Development , Raritan, NJ, USA"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universite de Lorraine, INSERM Unite 1116 , Vandoeuvre les Nancy, France"},{"name":"Clinical Investigation Center 1433, French Clinical Research Infrastructure Network, Investigation Network Initiative\u2013Cardiovascular and Renal Clinical Trialists , Centre Hospitalier Regional et Universitaire de Nancy, Vandoeuvre les Nancy, France"}]},{"given":"Barry","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of California , San Diego, La Jolla, CA, USA"}]}],"member":"286","published-online":{"date-parts":[[2019,6,25]]},"reference":[{"key":"2022102609282443000_ehz427-B1","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1161\/CIRCULATIONAHA.113.006588","article-title":"Rethinking composite end points in clinical trials: insights from patients and 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