{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T18:32:00Z","timestamp":1740162720732,"version":"3.37.3"},"reference-count":23,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000},"content-version":"unspecified","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>COMMANDER-HF was a randomised trial comparing rivaroxaban 2.5\u2009mg two times a day to placebo, in addition to antiplatelet therapy, in patients hospitalised for worsening heart failure with coronary artery disease and sinus rhythm. Patients with diabetes are at increased risk of cardiovascular events and therefore have more to gain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>In this post-hoc analysis, we evaluated the efficacy and safety of rivaroxaban in patients with (n=2052) and without diabetes (n=2970). The primary outcome was the composite of cardiovascular death, myocardial infarction (MI) or ischaemic stroke. HRs and 95% CIs with interaction analyses were used to describe event-rates and treatment effects. Patients with diabetes had a higher prevalence of cardiovascular comorbidities (eg, hypertension, obesity) and increased incidence of cardiovascular events. Adjusted HRs for events in people with versus without diabetes were 1.34 (95% CI 1.19 to 1.50) for the primary outcome, 1.21 (95% CI 0.84 to 1.75) for stroke, 1.51 (95% CI 1.14 to 1.99) for MI, 1.17 (95% CI 1.05 to 1.31) for heart failure hospitalisation and 1.06 (95% CI 0.56 to 2.01) for major bleeding. Rivaroxaban had no significant effect on event-rates in patients with and without diabetes (all interaction p values &gt;0.05). Low-dose rivaroxaban was associated with an overall reduction in ischaemic stroke (HR 0.66; 95%\u2009CI 0.47 to 0.95), with no apparent subgroup interaction according to diabetes status (p-int=0.93).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In COMMANDER-HF a diagnosis of diabetes conferred higher rates of cardiovascular events that, with exception of ischaemic stroke, was not substantially reduced by rivaroxaban. Rivaroxaban was associated with reduced risk of ischaemic stroke for patients with and without diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial post-results\" xlink:href=\"NCT01877915\">NCT01877915<\/jats:ext-link>; Post-results.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2022-068865","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T15:45:16Z","timestamp":1691768716000},"page":"e068865","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Cardiovascular effects of rivaroxaban in heart failure patients with sinus rhythm and coronary disease with and without diabetes: a retrospective international cohort study from COMMANDER-HF"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct01877915","registry":"10.18810\/clinical-trials-gov","type":"postResults"}],"author":[{"given":"Abhinav","family":"Sharma","sequence":"first","affiliation":[]},{"given":"Daniel","family":"Caldeira","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8397-7949","authenticated-orcid":false,"given":"Amir","family":"Razaghizad","sequence":"additional","affiliation":[]},{"given":"Fausto J","family":"Pinto","sequence":"additional","affiliation":[]},{"given":"Dirk J","family":"van Veldhuisen","sequence":"additional","affiliation":[]},{"given":"Mandeep R","family":"Mehra","sequence":"additional","affiliation":[]},{"given":"Carolyn S P","family":"Lam","sequence":"additional","affiliation":[]},{"given":"John","family":"Cleland","sequence":"additional","affiliation":[]},{"given":"Stefan D","family":"Anker","sequence":"additional","affiliation":[]},{"given":"Barry","family":"Greenberg","sequence":"additional","affiliation":[]},{"given":"Joao Pedro","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[]}],"member":"239","published-online":{"date-parts":[[2023,8,11]]},"reference":[{"key":"2023081108450996000_13.8.e068865.1","doi-asserted-by":"crossref","unstructured":"Sharma A , Zhao X , Hammill BG , et al . Trends in noncardiovascular comorbidities among patients hospitalized for heart failure. Circ Heart Failure 2018;11:e004646. doi:10.1161\/CIRCHEARTFAILURE.117.004646","DOI":"10.1161\/CIRCHEARTFAILURE.117.004646"},{"key":"2023081108450996000_13.8.e068865.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112277"},{"key":"2023081108450996000_13.8.e068865.3"},{"key":"2023081108450996000_13.8.e068865.4","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1056\/NEJMoa2000052","article-title":"Rivaroxaban in peripheral artery disease after revascularization","volume":"382","author":"Bonaca","year":"2020","journal-title":"N Engl J Med"},{"key":"2023081108450996000_13.8.e068865.5","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1161\/CIRCULATIONAHA.119.039609","article-title":"Rivaroxaban with or without aspirin in patients with heart failure and chronic coronary or peripheral artery disease","volume":"140","author":"Branch","year":"2019","journal-title":"Circulation"},{"key":"2023081108450996000_13.8.e068865.6","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1056\/NEJMoa1808848","article-title":"Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease","volume":"379","author":"Zannad","year":"2018","journal-title":"N Engl J Med"},{"key":"2023081108450996000_13.8.e068865.7","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1001\/jamacardio.2019.1049","article-title":"Association of rivaroxaban with thromboembolic events in patients with heart failure, coronary disease, and sinus rhythm: a post hoc analysis of the COMMANDER HF trial","volume":"4","author":"Greenberg","year":"2019","journal-title":"JAMA Cardiol"},{"key":"2023081108450996000_13.8.e068865.8","doi-asserted-by":"crossref","first-page":"3593","DOI":"10.1093\/eurheartj\/ehz427","article-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","volume":"40","author":"Mehra","year":"2019","journal-title":"Eur Heart J"},{"key":"2023081108450996000_13.8.e068865.9","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.266"},{"key":"2023081108450996000_13.8.e068865.10","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.12.3333"},{"key":"2023081108450996000_13.8.e068865.11","doi-asserted-by":"publisher","DOI":"10.1001\/2012.jama.11467"},{"key":"2023081108450996000_13.8.e068865.12","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.amjcard.2018.09.014","article-title":"Prevalence and outcomes of polyvascular (coronary, peripheral, or cerebrovascular) disease in patients with diabetes mellitus (from the SAVOR-TIMI 53 trial)","volume":"123","author":"Gutierrez","year":"2019","journal-title":"Am J Cardiol"},{"key":"2023081108450996000_13.8.e068865.13","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(74)90089-7"},{"key":"2023081108450996000_13.8.e068865.14","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000691"},{"key":"2023081108450996000_13.8.e068865.15","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ahj.2007.08.002","article-title":"Influence of diabetes on characteristics and outcomes in patients hospitalized with heart failure: a report from the organized program to initiate lifesaving treatment in hospitalized patients with heart failure (OPTIMIZE-HF)","volume":"154","author":"Greenberg","year":"2007","journal-title":"Am Heart J"},{"key":"2023081108450996000_13.8.e068865.16","doi-asserted-by":"crossref","unstructured":"Tabata N , Yamamoto E , Hokimoto S , et al . Prognostic value of the CHADS2 score for adverse cardiovascular events in coronary artery disease patients without atrial fibrillation-a multi-center observational cohort study. J Am Heart Assoc 2017;6:e006355. doi:10.1161\/JAHA.117.006355","DOI":"10.1161\/JAHA.117.006355"},{"key":"2023081108450996000_13.8.e068865.17","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.10725"},{"key":"2023081108450996000_13.8.e068865.18","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1161\/CIRCULATIONAHA.120.046448","article-title":"Role of combination antiplatelet and anticoagulation therapy in diabetes mellitus and cardiovascular disease: insights from the COMPASS trial","volume":"141","author":"Bhatt","year":"2020","journal-title":"Circulation"},{"key":"2023081108450996000_13.8.e068865.19","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/ehf2.13688","article-title":"Aspirin use is associated with increased risk for incident heart failure: a patient-level pooled analysis","volume":"9","author":"Mujaj","year":"2022","journal-title":"ESC Heart Fail"},{"key":"2023081108450996000_13.8.e068865.20","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1055\/s-0041-1740639","article-title":"Aspirin for primary and secondary prevention of cardiovascular disease: time to stop?","volume":"122","author":"Cleland","year":"2022","journal-title":"Thromb Haemost"},{"key":"2023081108450996000_13.8.e068865.21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2010.03159.x"},{"key":"2023081108450996000_13.8.e068865.22","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1366"},{"key":"2023081108450996000_13.8.e068865.23","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041022"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2022-068865","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T15:45:41Z","timestamp":1691768741000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2022-068865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":23,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,11]]},"published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1136\/bmjopen-2022-068865"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2022-068865","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2023,8]]}}}