{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:59:01Z","timestamp":1791593941633,"version":"4.3.4"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2019,11,5]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing heart failure. Sodium-glucose cotransporter-2 inhibitors reduce the risk of hospitalization for heart failure (HHF) in patients with T2DM. We aimed to develop and validate a practical clinical risk score for HHF in patients with T2DM and assess whether this score can identify high-risk patients with T2DM who have the greatest reduction in risk for HHF with a sodium-glucose cotransporter-2 inhibitor.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              We developed a clinical risk score for HHF in 8212 patients with T2DM in the placebo arm of SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus\u2013Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using multivariable Cox regression, and independent clinical risk indicators achieving statistical significance of\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001 were included in the risk score. We externally validated the score in 8578 patients with T2DM in the placebo arm of DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events\u2013Thrombolysis in Myocardial Infarction 58). The relative and absolute risk reductions in HHF with the sodium-glucose cotransporter-2 inhibitor dapagliflozin were assessed by baseline HHF risk.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Five clinical variables were independent risk predictors of HHF: prior heart failure, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. A simple integer-based score (0\u20137 points) using these predictors identified a &gt;20-fold gradient of HHF risk (\n              <jats:italic>P<\/jats:italic>\n              for trend &lt;0.001) in both the derivation and validation cohorts, with C indices of 0.81 and 0.78, respectively. Although relative risk reductions with dapagliflozin were similar for patients across the risk scores (25%\u201334%), absolute risk reductions were greater in those at higher baseline risk (1-sided\n              <jats:italic>P<\/jats:italic>\n              for trend=0.04), with high-risk (2 points) and very-high-risk (\u22653 points) patients having 1.5% and 2.7% absolute reductions in Kaplan-Meier estimates of HHF risk at 4 years, respectively.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Risk stratification using a novel clinical risk score for HHF in patients with T2DM identifies patients at higher risk for HHF who derive greater absolute benefit from sodium-glucose cotransporter-2 inhibition.<\/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: NCT01107886 and NCT01730534.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.119.042685","type":"journal-article","created":{"date-parts":[[2019,8,31]],"date-time":"2019-08-31T11:45:08Z","timestamp":1567251908000},"page":"1569-1577","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":139,"title":["Heart Failure Risk Stratification and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes Mellitus"],"prefix":"10.1161","volume":"140","author":[{"given":"David D.","family":"Berg","sequence":"first","affiliation":[{"name":"TIMI Study Group, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (D.D.B., S.D.W., B.M.S., Y.G., S.A.M., D.L.B., E.B., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Wiviott","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (D.D.B., S.D.W., B.M.S., Y.G., S.A.M., D.L.B., E.B., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin M.","family":"Scirica","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (D.D.B., S.D.W., B.M.S., Y.G., S.A.M., D.L.B., E.B., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yared","family":"Gurmu","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (D.D.B., S.D.W., B.M.S., Y.G., S.A.M., D.L.B., E.B., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofri","family":"Mosenzon","sequence":"additional","affiliation":[{"name":"Hadassah Hebrew University Hospital, Jerusalem, Israel (O.M., I.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina A.","family":"Murphy","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (D.D.B., S.D.W., B.M.S., Y.G., S.A.M., D.L.B., E.B., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (D.D.B., S.D.W., B.M.S., Y.G., S.A.M., D.L.B., E.B., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence A.","family":"Leiter","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St Michael\u2019s Hospital, University of Toronto, Canada (L.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren K.","family":"McGuire","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas (D.K.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.H.","family":"Wilding","sequence":"additional","affiliation":[{"name":"University of Liverpool, United Kingdom (J.P.H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Johanson","sequence":"additional","affiliation":[{"name":"AstraZeneca, Gothenburg, Sweden (P.J., P.A.J., A.M.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Johansson","sequence":"additional","affiliation":[{"name":"AstraZeneca, Gothenburg, Sweden (P.J., P.A.J., A.M.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Langkilde","sequence":"additional","affiliation":[{"name":"AstraZeneca, Gothenburg, Sweden (P.J., P.A.J., A.M.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itamar","family":"Raz","sequence":"additional","affiliation":[{"name":"Hadassah Hebrew University Hospital, Jerusalem, Israel (O.M., 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