{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:31:33Z","timestamp":1787959893965,"version":"build-2784847793"},"reference-count":21,"publisher":"BMJ","issue":"19","funder":[{"name":"GSK"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Heart"],"accepted":{"date-parts":[[2017,3,9]]},"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) often coexist. We assessed the effect of inhaled COPD treatments on CVD outcomes and safety in patients with COPD and at heightened CVD risk.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The SUMMIT (Study to Understand Mortality and MorbidITy) was a multicentre, randomised, double-blind, placebo-controlled, event-driven trial in 16\u2009485 patients with moderate COPD who had or were at high risk of CVD. Here, we assessed the prespecified secondary endpoint of time to first on-treatment composite CVD event (CVD death, myocardial infarction, stroke, unstable angina or transient ischaemic attack (TIA)) by Cox regression and by clinician-reported CVD adverse events across the four groups: once-daily inhaled placebo (n=4111), long-acting beta<jats:sub>2<\/jats:sub>-agonist (vilanterol (VI) 25\u2009\u00b5g; n=4118), corticosteroid (fluticasone furoate (FF) 100\u2009\u00b5g; n=4135) and combination therapy (FF\/VI; n=4121).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Participants were predominantly middle-aged (mean 65 (SD 8) years) men (75%) with overt CVD (66%). The composite CVD endpoint occurred in 688 patients (first event: sudden death (35%), acute coronary syndrome (37%) and stroke or TIA (23%), and was not reduced in any treatment group versus placebo: VI (HR 0.99, 95% CI 0.80 to 1.22), FF (HR 0.90, 95%\u2009CI 0.72 to 1.11) and their combination (HR 0.93, 95%\u2009CI 0.75 to 1.14). Outcomes were similar among all subgroups. Adverse events, including palpitations and arrhythmias, did not differ by treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In patients with COPD with moderate airflow limitation and heightened CVD risk, treatment with inhaled VI, FF or their combination has an excellent safety profile and does not impact CVD outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>NCT01313676.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/heartjnl-2016-310897","type":"journal-article","created":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T20:35:19Z","timestamp":1492461319000},"page":"1536-1542","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Cardiovascular outcomes with an inhaled beta2-agonist\/corticosteroid in patients with COPD at high cardiovascular risk"],"prefix":"10.1136","volume":"103","clinical-trial-number":[{"clinical-trial-number":"nct01313676","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Robert D","family":"Brook","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A","family":"Anderson","sequence":"additional","affiliation":[{"name":"Research & Development, GlaxoSmithKline, Uxbridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter MA","family":"Calverley","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Liverpool, Liverpool, UK"},{"name":"Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartolome R","family":"Celli","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Division, Brigham and Womens Hospital, Harv\u2019ard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Crim","sequence":"additional","affiliation":[{"name":"Research & Development, GSK, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin A","family":"Denvir","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheldon","family":"Magder","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando J","family":"Martinez","sequence":"additional","affiliation":[{"name":"Joan and Sandy Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Rajagopalan","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen","family":"Vestbo","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Medicine and Allergy, Manchester Academic Health Science Centre, The University of Manchester and South Manchester University Hospital NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Yates","sequence":"additional","affiliation":[{"name":"Research & Development, GSK, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E","family":"Newby","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2017,4,17]]},"reference":[{"key":"2025092005263244000_103.19.1536.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61728-0"},{"key":"2025092005263244000_103.19.1536.2","doi-asserted-by":"publisher","DOI":"10.1159\/000281880"},{"key":"2025092005263244000_103.19.1536.3","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00012408"},{"key":"2025092005263244000_103.19.1536.4","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-010-9435-7"},{"key":"2025092005263244000_103.19.1536.5","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2009.128082"},{"key":"2025092005263244000_103.19.1536.6","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2010.136077"},{"key":"2025092005263244000_103.19.1536.7","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2014-307251"},{"key":"2025092005263244000_103.19.1536.8","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2015-007824","article-title":"Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis","volume":"5","author":"Rothnie","year":"2015","journal-title":"BMJ Open"},{"key":"2025092005263244000_103.19.1536.9","doi-asserted-by":"publisher","DOI":"10.1378\/chest.12-0938"},{"key":"2025092005263244000_103.19.1536.10","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2015-307739"},{"key":"2025092005263244000_103.19.1536.11","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1001\/jamainternmed.2013.1201","article-title":"Double-edged sword? Long-acting bronchodilators in chronic obstructive pulmonary disease","volume":"173","author":"Woodruff","year":"2013","journal-title":"JAMA Intern Med"},{"key":"2025092005263244000_103.19.1536.12","doi-asserted-by":"publisher","DOI":"10.1378\/chest.125.6.2309"},{"key":"2025092005263244000_103.19.1536.13","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1001\/jamainternmed.2013.1016","article-title":"Cardiovascular safety of inhaled long-acting bronchodilators in individuals with chronic obstructive pulmonary disease","volume":"173","author":"Gershon","year":"2013","journal-title":"JAMA Intern Med"},{"key":"2025092005263244000_103.19.1536.14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0137904","article-title":"Inhaled long-acting \u03b22-agonists do not increase fatal cardiovascular adverse events in COPD: a meta-analysis","volume":"10","author":"Xia","year":"2015","journal-title":"PLoS One"},{"key":"2025092005263244000_103.19.1536.15","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00087312"},{"key":"2025092005263244000_103.19.1536.16","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/S0140-6736(16)30069-1","article-title":"Fluticasone furoate and vilanterol in patients with chronic obstructive pulmonary disease at heightened cardiovascular risk","volume":"387","author":"Vestbo","year":"2016","journal-title":"Lancet"},{"key":"2025092005263244000_103.19.1536.17","doi-asserted-by":"publisher","DOI":"10.1001\/jama.300.12.1439"},{"key":"2025092005263244000_103.19.1536.18","first-page":"239","article-title":"Tiotropium HandiHaler(\u00ae) and Respimatrespimat(\u00ae) in COPD: a pooled safety analysis.","volume":"10","author":"Halpin","year":"2015","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"2025092005263244000_103.19.1536.19","first-page":"CD009285","article-title":"Tiotropium versus placebo for chronic obstructive pulmonary disease","volume":"(7)","author":"Karner","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"2025092005263244000_103.19.1536.20","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1303342"},{"key":"2025092005263244000_103.19.1536.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61215-4"}],"container-title":["Heart"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/heartjnl-2016-310897","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T12:26:38Z","timestamp":1758371198000},"score":1,"resource":{"primary":{"URL":"https:\/\/heart.bmj.com\/lookup\/doi\/10.1136\/heartjnl-2016-310897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,17]]},"references-count":21,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2017,9,11]]},"published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1136\/heartjnl-2016-310897"],"URL":"https:\/\/doi.org\/10.1136\/heartjnl-2016-310897","relation":{},"ISSN":["1355-6037","1468-201X"],"issn-type":[{"value":"1355-6037","type":"print"},{"value":"1468-201X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,17]]}}}