Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials
Abstract Background Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failu...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-022-01545-1 |
| _version_ | 1818555382508814336 |
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| author | Magnus O. Wijkman Brian Claggett Muthiah Vaduganathan Jonathan W. Cunningham Rasmus Rørth Alice Jackson Milton Packer Michael Zile Jean Rouleau Karl Swedberg Martin Lefkowitz Sanjiv J. Shah Marc A. Pfeffer John J. V. McMurray Scott D. Solomon |
| author_facet | Magnus O. Wijkman Brian Claggett Muthiah Vaduganathan Jonathan W. Cunningham Rasmus Rørth Alice Jackson Milton Packer Michael Zile Jean Rouleau Karl Swedberg Martin Lefkowitz Sanjiv J. Shah Marc A. Pfeffer John J. V. McMurray Scott D. Solomon |
| author_sort | Magnus O. Wijkman |
| collection | DOAJ |
| description | Abstract Background Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes. Methods We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF. Results Among 2395 patients with HFpEF and diabetes in PARAGON-HF, sacubitril/valsartan compared with valsartan reduced HbA1c (baseline-adjusted between-group difference in HbA1c change at 48 weeks: − 0.24%, 95% CI − 0.33 to − 0.16%, P < 0.001). Numerically, new insulin treatment was initiated less often in the sacubitril/valsartan group than in the valsartan group, but the difference was not statistically significant (12.8% vs. 16.1%; HR: 0.80, 95% CI 0.62–1.02, P = 0.07). Hypoglycemia adverse event reports were low, but more frequent in those receiving sacubitril/valsartan than in the valsartan group (4.2% vs. 2.6%; HR: 1.64, 95% CI 1.05–2.56, P = 0.030). In a pooled analysis of PARAGON-HF and PARADIGM-HF, the effect of sacubitril/valsartan on change in HbA1c was not significantly modified by LVEF (Pinteraction = 0.56). Across the spectrum of LVEF, sacubitril/valsartan reduced new insulin therapy (HR: 0.75, 95% CI 0.63–0.89, P = 0.001), compared with enalapril or valsartan. Conclusions Sacubitril/valsartan reduced HbA1c and new insulin therapy in patients with heart failure and diabetes across the spectrum of LVEF but may be associated with a slightly higher risk for hypoglycemia. Trial registration ClinicalTrials.gov NCT01920711 |
| first_indexed | 2024-12-12T09:52:44Z |
| format | Article |
| id | doaj.art-20fcdeb88347412ba1316850ab84980a |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-12-12T09:52:44Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-20fcdeb88347412ba1316850ab84980a2022-12-22T00:28:14ZengBMCCardiovascular Diabetology1475-28402022-06-0121111110.1186/s12933-022-01545-1Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trialsMagnus O. Wijkman0Brian Claggett1Muthiah Vaduganathan2Jonathan W. Cunningham3Rasmus Rørth4Alice Jackson5Milton Packer6Michael Zile7Jean Rouleau8Karl Swedberg9Martin Lefkowitz10Sanjiv J. Shah11Marc A. Pfeffer12John J. V. McMurray13Scott D. Solomon14Cardiovascular Division, Brigham & Women’s Hospital, Harvard Medical SchoolCardiovascular Division, Brigham & Women’s Hospital, Harvard Medical SchoolCardiovascular Division, Brigham & Women’s Hospital, Harvard Medical SchoolCardiovascular Division, Brigham & Women’s Hospital, Harvard Medical SchoolRigshospitalet Copenhagen University HospitalBritish Heart Foundation Cardiovascular Research Centre, University of GlasgowBaylor Heart and Vascular Institute, Baylor University Medical CenterMedical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical CenterMontreal Heart Institute, University of MontrealDepartment of Molecular and Clinical Medicine, University of GothenburgNovartisDivision of Cardiology, Department of Medicine, Northwestern University Feinberg School of MedicineCardiovascular Division, Brigham & Women’s Hospital, Harvard Medical SchoolBritish Heart Foundation Cardiovascular Research Centre, University of GlasgowCardiovascular Division, Brigham & Women’s Hospital, Harvard Medical SchoolAbstract Background Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes. Methods We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF. Results Among 2395 patients with HFpEF and diabetes in PARAGON-HF, sacubitril/valsartan compared with valsartan reduced HbA1c (baseline-adjusted between-group difference in HbA1c change at 48 weeks: − 0.24%, 95% CI − 0.33 to − 0.16%, P < 0.001). Numerically, new insulin treatment was initiated less often in the sacubitril/valsartan group than in the valsartan group, but the difference was not statistically significant (12.8% vs. 16.1%; HR: 0.80, 95% CI 0.62–1.02, P = 0.07). Hypoglycemia adverse event reports were low, but more frequent in those receiving sacubitril/valsartan than in the valsartan group (4.2% vs. 2.6%; HR: 1.64, 95% CI 1.05–2.56, P = 0.030). In a pooled analysis of PARAGON-HF and PARADIGM-HF, the effect of sacubitril/valsartan on change in HbA1c was not significantly modified by LVEF (Pinteraction = 0.56). Across the spectrum of LVEF, sacubitril/valsartan reduced new insulin therapy (HR: 0.75, 95% CI 0.63–0.89, P = 0.001), compared with enalapril or valsartan. Conclusions Sacubitril/valsartan reduced HbA1c and new insulin therapy in patients with heart failure and diabetes across the spectrum of LVEF but may be associated with a slightly higher risk for hypoglycemia. Trial registration ClinicalTrials.gov NCT01920711https://doi.org/10.1186/s12933-022-01545-1Heart failureDiabetesSacubitril/valsartanHypoglycemia |
| spellingShingle | Magnus O. Wijkman Brian Claggett Muthiah Vaduganathan Jonathan W. Cunningham Rasmus Rørth Alice Jackson Milton Packer Michael Zile Jean Rouleau Karl Swedberg Martin Lefkowitz Sanjiv J. Shah Marc A. Pfeffer John J. V. McMurray Scott D. Solomon Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials Cardiovascular Diabetology Heart failure Diabetes Sacubitril/valsartan Hypoglycemia |
| title | Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials |
| title_full | Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials |
| title_fullStr | Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials |
| title_full_unstemmed | Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials |
| title_short | Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials |
| title_sort | effects of sacubitril valsartan on glycemia in patients with diabetes and heart failure the paragon hf and paradigm hf trials |
| topic | Heart failure Diabetes Sacubitril/valsartan Hypoglycemia |
| url | https://doi.org/10.1186/s12933-022-01545-1 |
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