title: Risk Related to Pre-Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction: Insights From Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial.
abstract: BACKGROUND
  The prevalence of pre-diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial.
  
  
  RESULTS
  We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: < 6.0% [< 42 mmol/mol], 6.0%-6.4% [42-47 mmol/mol; pre-diabetes mellitus], and ≥ 6.5% [≥ 48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n = 2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P < 0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre-diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, > 6.5%) and known diabetes mellitus compared with those with HbA1c < 6.0% was 1.39 (1.17-1.64); P < 0.001 and 1.64 (1.43-1.87); P < 0.001, respectively. Patients with pre-diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10-1.47]; P < 0.001) compared with those with HbA1c < 6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial.
  
  
  CONCLUSIONS
  In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre-diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c < 6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Søren L
authors.initials: SL
authors.lastname: Kristensen
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: David
authors.initials: D
authors.lastname: Preiss
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Pardeep S
authors.initials: PS
authors.lastname: Jhund
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Iain
authors.initials: I
authors.lastname: Squire
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: José Silva
authors.initials: JS
authors.lastname: Cardoso
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Bela
authors.initials: B
authors.lastname: Merkely
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Felipe
authors.initials: F
authors.lastname: Martinez
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Akshay S
authors.initials: AS
authors.lastname: Desai
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Martin P
authors.initials: MP
authors.lastname: Lefkowitz
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Adel R
authors.initials: AR
authors.lastname: Rizkala
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Jean L
authors.initials: JL
authors.lastname: Rouleau
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Victor C
authors.initials: VC
authors.lastname: Shi
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zile
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.). john.mcmurray@glasgow.ac.uk.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: From the British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (S.L.K., D.P., P.J., J.J.V.M.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (S.L.K.); Department of Cardiovascular Sciences, University of Leicester, Leicester, UK (I.S.); NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK (I.S.); Department of Cardiology, Porto Medical School, Porto, Portugal (J.S.C.); Heart and Vascular Center Semmelweiss University, Budapest, Hungary (B.M.); Instituo DAMIC, Cordoba National University, Cordoba, Argentina (F.M.); Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, OH (R.C.S.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.S.D); Novartis Pharmaceutical Corporation, East Hanover, NJ (M.P.L., A.R.R., V.C.S.); Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada (J.L.R.); Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden (K.S.); RHJ Department of Veterans Administration Medical Center, Medical University of South Carolina, Charleston (M.R.Z.); and Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas (M.P.).
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
mesh_terms: D000368:Aged; D000613:Aminobutyrates / Q000009:adverse effects / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds; D001786:Blood Glucose / Q000378:metabolism; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D018572:Disease-Free Survival; D004338:Drug Combinations; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016037:Single-Blind Method; D013318:Stroke Volume; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D000068756:Valsartan; D016277:Ventricular Function, Left
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D001713:Biphenyl Compounds; D001786:Blood Glucose; D004338:Drug Combinations; D004656:Enalapril; D006442:Glycated Hemoglobin; D013777:Tetrazoles; D000068756:Valsartan; C517652:hemoglobin A1c protein, human; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: clinical trial; diabetes mellitus; heart failure; prognosis; treatment outcome