{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:35:57Z","timestamp":1791920157488,"version":"4.3.4"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2018,7,31]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure (HF) and cardiovascular death overall, in those with and without a baseline history of HF, and in other participant subgroups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10\u2009142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks. The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Participants with a history of HF at baseline (14.4%) were more frequently women, white, and hypertensive and had a history of prior cardiovascular disease (all\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system, diuretics, and \u03b2-blockers at baseline (all\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Overall, cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67\u20130.91), as was fatal or hospitalized HF (HR, 0.70; 95% CI, 0.55\u20130.89) and hospitalized HF alone (HR, 0.67; 95% CI, 0.52\u20130.87). The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF (HR, 0.61; 95% CI, 0.46\u20130.80) compared with those without HF at baseline (HR, 0.87; 95% CI, 0.72\u20131.06;\n              <jats:italic>P<\/jats:italic>\n              interaction =0.021). The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline (all interaction\n              <jats:italic>P<\/jats:italic>\n              values &gt;0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF (\n              <jats:italic>P<\/jats:italic>\n              =0.03).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease, canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups. Benefits may be greater in those with a history of HF at baseline.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifiers: NCT01032629 and NCT01989754.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.118.034222","type":"journal-article","created":{"date-parts":[[2018,3,11]],"date-time":"2018-03-11T20:55:14Z","timestamp":1520801714000},"page":"458-468","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":443,"title":["Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus"],"prefix":"10.1161","volume":"138","author":[{"given":"Karin","family":"R\u00e5dholm","sequence":"first","affiliation":[{"name":"Department of Medicine and Health Sciences, Division of Community Medicine, Primary Care, Faculty of Health Sciences, Department of Local Care West, County Council of \u00d6terg\u00f6tland, Link\u00f6ping University, Sweden (K.R.)."},{"name":"The George Institute for Global Health (K.R., V.P., B.N.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Figtree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlado","family":"Perkovic","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health (K.R., V.P., B.N.)"},{"name":"University of New South Wales, Sydney, Australia. Royal North Shore Hospital (G.F., V.P., G.F.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"University of Sydney, Australia. Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, MA (S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Mahaffey","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick","family":"de Zeeuw","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, The Netherlands (D.d.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Fulcher","sequence":"additional","affiliation":[{"name":"University of New South Wales, Sydney, Australia. Royal North Shore Hospital (G.F., V.P., G.F.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrance D.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC, Raritan, NJ (T.D.B., W.S., M.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Shaw","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC, Raritan, NJ (T.D.B., W.S., M.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehul","family":"Desai","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC, Raritan, NJ (T.D.B., W.S., M.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, United Kingdom (D.R.M)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Neal","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health (K.R., V.P., B.N.)"},{"name":"Faculty of Medicine (B.N.)"},{"name":"Charles Perkins Centre (B.N.)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61601-9"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.030209"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(14)70219-0"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2017.05.014"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12350-016-0622-0"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-0755"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht386"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/1479164112471064"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.633"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2014.01.017"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2016.09.005"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv728"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12924"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.319.7223.1492"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.19.2534"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2017.04.009"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.11.082"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.017355"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2017.08.005"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.2337\/db15-1356"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.029166"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00055.2009"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-018097"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.021887"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.933"},{"key":"e_1_3_4_29_2","unstructured":"National Institutes of Health. EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced). Identifier: NCT03057977. https:\/\/www.clinicaltrials.gov. Accessed March 26 2018."},{"key":"e_1_3_4_30_2","unstructured":"National Institutes of Health. EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved). Identifier: NCT03057951. https:\/\/www.clinicaltrials.gov. Accessed March 26 2018."},{"key":"e_1_3_4_31_2","unstructured":"National Institutes of Health. Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure (Dapa-HF). Identifier: NCT03036124. https:\/\/www.clinicaltrials.gov. Accessed March 26 2018."}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.118.034222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T08:24:44Z","timestamp":1715588684000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.118.034222"}},"subtitle":["Results From the CANVAS Program"],"short-title":[],"issued":{"date-parts":[[2018,7,31]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,7,31]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.118.034222"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.118.034222","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,31]]},"assertion":[{"value":"2018-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}