{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:11:51Z","timestamp":1790259111898,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2020,12,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>In patients with type 2 diabetes mellitus, sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure (HHF). We assessed the effect of ertugliflozin on HHF and related outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial), a double-blind, placebo-controlled trial, randomly assigned patients with type 2 diabetes mellitus and atherosclerotic cardiovascular (CV) disease to once-daily ertugliflozin 5 mg, 15 mg, or placebo. Prespecified secondary analyses compared ertugliflozin (pooled doses) versus placebo on time to first event of HHF and composite of HHF\/CV death, overall and stratified by prespecified characteristics. Cox proportional hazards modeling was used with the Fine and Gray method to account for competing mortality risk, and Andersen-Gill modeling to analyze total (first+recurrent) HHF and total HHF\/CV death events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A total of 8246 patients were randomly assigned to ertugliflozin (n=5499) or placebo (n=2747); n=1958 (23.7%) had a history of heart failure (HF) and n=5006 (60.7%) had pretrial ejection fraction (EF) available, including n=959 with EF \u226445%. Ertugliflozin did not significantly reduce first HHF\/CV death (hazard ratio [HR], 0.88 [95% CI, 0.75\u20131.03]). Overall, ertugliflozin reduced risk for first HHF (HR, 0.70 [95% CI, 0.54\u20130.90];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.006). Previous HF did not modify this effect (HF: HR, 0.63 [95% CI, 0.44\u20130.90]; no HF: HR, 0.79 [95% CI, 0.54\u20131.15];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction=0.40). In patients with HF, the risk reduction for first HHF was similar for those with reduced EF \u226445% versus preserved EF &gt;45% or unknown. However, in the overall population, the risk reduction tended to be greater for those with EF \u226445% (HR, 0.48 [95% CI, 0.30\u20130.76]) versus EF &gt;45% (HR, 0.86 [95% CI, 0.58\u20131.29]). Effect on risk for first HHF was consistent across most subgroups, but greater benefit of ertugliflozin was observed in 3 populations: baseline estimated glomerular filtration rate &lt;60 mL\u00b7min\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b71.73 m\n                      <jats:sup>\u20132<\/jats:sup>\n                      , albuminuria, and diuretic use (each\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction &lt;0.05). Ertugliflozin reduced total events of HHF (rate ratio, 0.70 [95% CI, 0.56\u20130.87]) and total HHF\/CV death (rate ratio, 0.83 [95% CI, 0.72\u20130.96]).\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, ertugliflozin reduced the risk for first and total HHF and total HHF\/CV death, adding further support for the use of sodium-glucose cotransporter 2 inhibitors in primary and secondary prevention of HHF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>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 identifier: NCT01986881.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.120.050255","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T11:00:19Z","timestamp":1602068419000},"page":"2205-2215","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":218,"title":["Efficacy of Ertugliflozin on Heart Failure\u2013Related Events in Patients With Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease"],"prefix":"10.1161","volume":"142","clinical-trial-number":[{"clinical-trial-number":"nct01986881","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6967-5685","authenticated-orcid":true,"given":"Francesco","family":"Cosentino","sequence":"first","affiliation":[{"name":"Unit of Cardiology, Karolinska Institute and Karolinska University Hospital Solna, Stockholm, Sweden (F.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (C.P.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4164-0429","authenticated-orcid":true,"given":"David Z.I.","family":"Cherney","sequence":"additional","affiliation":[{"name":"University of Toronto, Ontario, Canada (D.Z.I.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula","family":"Masiukiewicz","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Groton, CT (U.M., J.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2912-1389","authenticated-orcid":true,"given":"Richard","family":"Pratley","sequence":"additional","affiliation":[{"name":"AdventHealth Translational Research Institute, Orlando, FL (R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Dagogo-Jack","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science Center, Memphis (S.D.-J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Frederich","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Collegeville, PA (R.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Charbonnel","sequence":"additional","affiliation":[{"name":"University of Nantes, France (B.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Groton, CT (U.M., J.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weichung J.","family":"Shih","sequence":"additional","affiliation":[{"name":"Rutgers School of Public Health and Rutgers Cancer Institute of New Jersey, New Brunswick (W.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Terra","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Andover, MA (S.G.T)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilo B.","family":"Cater","sequence":"additional","affiliation":[{"name":"Pfizer Inc, New York (N.B.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8572-5614","authenticated-orcid":true,"given":"Ira","family":"Gantz","sequence":"additional","affiliation":[{"name":"Merck &amp; Co Inc, Kenilworth, NJ (I.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren K.","family":"McGuire","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, and Parkland Health and Hospital System, Dallas (D.K.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"On behalf of the VERTIS CV Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(14)70031-2"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800256"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14042"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2016.0103"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2016.08.001"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.014796"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.679"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.306924"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2004967"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-S009"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz486"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/cir.0000000000000691"},{"key":"e_1_3_6_19_2","unstructured":"European Medicines Agency. 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