{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T21:13:15Z","timestamp":1768425195171,"version":"3.49.0"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>To analyse whether the benefits and risks of rivaroxaban plus aspirin vary in patients with comorbidities and receiving multiple drugs. In patients with coronary or peripheral artery disease, adding low-dose rivaroxaban to aspirin reduces cardiovascular events and mortality. Polypharmacy and multimorbidity are frequent in such patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We describe ischaemic events (cardiovascular death, stroke, or myocardial infarction) and major bleeding in participants from the randomized, double-blind COMPASS study by number of cardiovascular medications and concomitant medical conditions. We compared event rates and hazard ratios (HRs) for rivaroxaban plus aspirin vs. aspirin alone by the number of medications and concomitant conditions, and tested for interaction between polypharmacy or multimorbidity and the antithrombotic regimen. The risk of ischaemic events was higher in patients with more concomitant drugs (HR 1.7, 95% confidence interval 1.5\u20132.1 for &amp;gt;4\u00a0vs. 0\u20132) and with more comorbidities (HR 2.3, 1.8\u20132.1 for &amp;gt;3\u00a0vs. 0\u20131). Multimorbidity, but not polypharmacy, was associated with a higher risk of major bleeding. The relative efficacy, safety, and net clinical benefit of rivaroxaban were not affected by the number of drugs or comorbidities. Patients taking more concomitant medications derived the largest absolute reduction in the net clinical outcome with added rivaroxaban (1.1%\u00a0vs. 0.4% reduction with &amp;gt;4\u00a0vs. 0\u20132 cardiovascular drugs, number needed to treat 91\u00a0vs. 250).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Adding low-dose rivaroxaban to aspirin resulted in benefits irrespective of the number of concomitant drugs or comorbidities. Multiple comorbidities and\/or polypharmacy should not dissuade the addition of rivaroxaban to aspirin in otherwise eligible patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjcvp\/pvab050","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T19:18:58Z","timestamp":1624907938000},"page":"462-473","source":"Crossref","is-referenced-by-count":13,"title":["Low-dose rivaroxaban plus aspirin in patients with polypharmacy and multimorbidity: an analysis from the COMPASS trial"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7404-8918","authenticated-orcid":false,"given":"Thomas","family":"Vanassche","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Sciences, University Hospitals Leuven, KU Leuven , Herestraat 49, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Verhamme","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University Hospitals Leuven, KU Leuven , Herestraat 49, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia S","family":"Anand","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University and Hamilton Health Sciences , Hamilton, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Shestakovska","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University and Hamilton Health Sciences , Hamilton, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darryl P","family":"Leong","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University and Hamilton Health Sciences , Hamilton, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A A","family":"Fox","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh , Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak L","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School , Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3073-6890","authenticated-orcid":false,"given":"Alvaro","family":"Avezum","sequence":"additional","affiliation":[{"name":"International Research Center, Hospital Alem\u00e3o Oswaldo Cruz , S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2090-4683","authenticated-orcid":false,"given":"Marco","family":"Alings","sequence":"additional","affiliation":[{"name":"Amphia Ziekenhuis and Werkgroep Cardiologische Centra Nederland , Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Aboyans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Dupuytren University Hospital, and INSERM 1094 & IRD, Limoges University , Limoges, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aldo P","family":"Maggioni","sequence":"additional","affiliation":[{"name":"Associazione Nazionale Medici Cardiologi Ospedalieri Research Center , Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-7752","authenticated-orcid":false,"given":"Petr","family":"Widimsky","sequence":"additional","affiliation":[{"name":"Cardiocenter, University Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University , Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Muehlhofer","sequence":"additional","affiliation":[{"name":"Bayer AG , Wuppertal, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott D","family":"Berkowitz","sequence":"additional","affiliation":[{"name":"Bayer U.S. LLC , Whippany, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salim","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University and Hamilton Health Sciences , Hamilton, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart J","family":"Connolly","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University and Hamilton Health Sciences , Hamilton, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4126-1285","authenticated-orcid":false,"given":"John W","family":"Eikelboom","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University and Hamilton Health Sciences , Hamilton, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6292-4207","authenticated-orcid":false,"given":"Jackie","family":"Bosch","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University and Hamilton Health Sciences , Hamilton, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"2022081109085714100_bib1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/eurheartj\/ehz425","article-title":"2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes","volume":"41","author":"Knuuti","year":"2020","journal-title":"Eur Heart J"},{"key":"2022081109085714100_bib2","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/eurheartj\/ehx095","article-title":"2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. Endorsed by the European Stroke Organization (ESO), the Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS)","volume":"39","author":"Aboyans","year":"2018","journal-title":"Eur Heart J"},{"key":"2022081109085714100_bib3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk","volume":"41","author":"Mach","year":"2020","journal-title":"Eur Heart J"},{"key":"2022081109085714100_bib4","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1016\/j.jacc.2018.03.022","article-title":"Multimorbidity in older adults with cardiovascular disease","volume":"71","author":"Forman","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2022081109085714100_bib5","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/gerona\/gly110","article-title":"Frailty and multimorbidity: a systematic review and meta-analysis","volume":"74","author":"Vetrano","year":"2019","journal-title":"J Gerontol A: Biol Sci Med Sci"},{"key":"2022081109085714100_bib6","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1056\/NEJMoa1709118","article-title":"Rivaroxaban with or without aspirin in stable cardiovascular disease","volume":"377","author":"Eikelboom","year":"2017","journal-title":"N Engl J Med"},{"key":"2022081109085714100_bib7","doi-asserted-by":"crossref","first-page":"e015089","DOI":"10.1161\/JAHA.119.015089","article-title":"Polypharmacy, adverse outcomes, and treatment effectiveness in patients \u226575 with atrial fibrillation","volume":"9","author":"Chen","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"2022081109085714100_bib8","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2174\/1871525715666170529093442","article-title":"Polypharmacy in cardiovascular medicine: problems and promises!","volume":"15","author":"Abolbashari","year":"2017","journal-title":"Cardiovasc Hematol Agents Med Chem"},{"key":"2022081109085714100_bib9","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1089\/rej.2019.2268","article-title":"Prevalence and correlates of statin underuse for secondary prevention of cardiovascular disease in older adults 65\u201379 years of age: the Italian Health Examination Survey 2008\u20132012","volume":"23","author":"Viscogliosi","year":"2020","journal-title":"Rejuvenation Res"},{"key":"2022081109085714100_bib10","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.cjca.2017.06.001","article-title":"Rationale, design and baseline characteristics of participants in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial","volume":"33","author":"Bosch","year":"2017","journal-title":"Can J Cardiol"},{"key":"2022081109085714100_bib11","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1001\/jama.2015.0809","article-title":"Association of NSAID use with risk of bleeding and cardiovascular events in patients receiving antithrombotic therapy after myocardial infarction","volume":"313","author":"Schjerning Olsen","year":"2015","journal-title":"JAMA"},{"key":"2022081109085714100_bib12","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1097\/HJR.0b013e3283383f30","article-title":"EUROASPIRE III. Management of cardiovascular risk factors in asymptomatic high-risk patients in general practice: cross-sectional survey in 12 European countries","volume":"17","author":"Kotseva","year":"2010","journal-title":"Eur J Cardiovasc Prev Rehabil"},{"key":"2022081109085714100_bib13","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1056\/NEJMoa1815359","article-title":"Polypill for cardiovascular disease prevention in an underserved population","volume":"381","author":"Munoz","year":"2019","journal-title":"N Engl J Med"},{"key":"2022081109085714100_bib14","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1056\/NEJMoa2028220","article-title":"Polypill with or without aspirin in persons without cardiovascular disease","volume":"384","author":"Yusuf","year":"2021","journal-title":"N Engl J Med"},{"key":"2022081109085714100_bib15","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/S0140-6736(19)31791-X","article-title":"Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial","volume":"394","author":"Roshandel","year":"2019","journal-title":"Lancet"}],"container-title":["European Heart Journal - Cardiovascular Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ehjcvp\/advance-article-pdf\/doi\/10.1093\/ehjcvp\/pvab050\/39622661\/pvab050.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article-pdf\/8\/5\/462\/45328971\/pvab050.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article-pdf\/8\/5\/462\/45328971\/pvab050.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T09:09:58Z","timestamp":1660208998000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article\/8\/5\/462\/6311809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,30]]},"references-count":15,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,6,30]]},"published-print":{"date-parts":[[2022,8,11]]}},"URL":"https:\/\/doi.org\/10.1093\/ehjcvp\/pvab050","relation":{},"ISSN":["2055-6837","2055-6845"],"issn-type":[{"value":"2055-6837","type":"print"},{"value":"2055-6845","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9]]},"published":{"date-parts":[[2021,6,30]]}}}