Baseline kidney function and the effects of dapagliflozin on health status in heart failure in DEFINE‐HF and PRESERVED‐HF
Abstract Aims Sodium–glucose co‐transporter‐2 (SGLT2) inhibitors improve health status and outcomes in the setting of heart failure (HF) across the range of ejection fraction (EF). Baseline kidney disease is common in HF, complicates HF management and is strongly linked to worse health status. This...
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| Language: | English |
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Wiley
2025-06-01
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| Series: | ESC Heart Failure |
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| Online Access: | https://doi.org/10.1002/ehf2.15184 |
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| author | Andrew P. Ambrosy Andrew J. Sauer Shachi Patel Sheryl L. Windsor Barry A. Borlaug Mansoor Husain Silvio E. Inzucchi Dalane W. Kitzman Darren K. McGuire Sanjiv J. Shah Kavita Sharma Guillermo Umpierrez Mikhail N. Kosiborod |
| author_facet | Andrew P. Ambrosy Andrew J. Sauer Shachi Patel Sheryl L. Windsor Barry A. Borlaug Mansoor Husain Silvio E. Inzucchi Dalane W. Kitzman Darren K. McGuire Sanjiv J. Shah Kavita Sharma Guillermo Umpierrez Mikhail N. Kosiborod |
| author_sort | Andrew P. Ambrosy |
| collection | DOAJ |
| description | Abstract Aims Sodium–glucose co‐transporter‐2 (SGLT2) inhibitors improve health status and outcomes in the setting of heart failure (HF) across the range of ejection fraction (EF). Baseline kidney disease is common in HF, complicates HF management and is strongly linked to worse health status. This study aimed to assess whether the treatment effects of dapagliflozin on health status vary based on estimated glomerular filtration rate (eGFR). Methods and Results We conducted a pooled participant‐level analysis of two double‐blind, randomized trials, DEFINE‐HF (n = 236) and PRESERVED‐HF (n = 324), which evaluated dapagliflozin versus placebo. Both multicentre studies enrolled adults with HF, New York Heart Association Class II or higher, elevated natriuretic peptides, and an EF < 40% in DEFINE‐HF or >45% in PRESERVED‐HF. The primary exposure was eGFR. The main outcome was the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ‐CSS) at 12 weeks. Across both trials, there were 583 (99.3%) participants with a baseline eGFR. The median (25th, 75th) eGFR was 59 (46, 77) mL/min/1.73 m2. Dapagliflozin improved KCCQ‐CSS at 12 weeks [placebo‐adjusted difference, +5.0 points, 95% confidence interval (CI) 2.6–7.5; P < 0.001], and this was consistent in participants with an eGFR ≥ 60 (+6.0 points, 95% CI 2.4–9.7; P = 0.001) and eGFR < 60 (+4.1 points, 95% CI 0.5–7.7; P = 0.025) (P interaction = 0.46). The benefits of dapagliflozin on KCCQ‐CSS remained robust across eGFR when modelled as a continuous variable (P interaction = 0.48). Conclusions Dapagliflozin led to early and clinically meaningful improvements in health status in HF patients, regardless of EF or baseline eGFR. |
| format | Article |
| id | doaj-art-e2dbf941f01d4581a38fe7f23fe77850 |
| institution | DOAJ |
| issn | 2055-5822 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj-art-e2dbf941f01d4581a38fe7f23fe778502025-08-20T03:11:21ZengWileyESC Heart Failure2055-58222025-06-011231676168110.1002/ehf2.15184Baseline kidney function and the effects of dapagliflozin on health status in heart failure in DEFINE‐HF and PRESERVED‐HFAndrew P. Ambrosy0Andrew J. Sauer1Shachi Patel2Sheryl L. Windsor3Barry A. Borlaug4Mansoor Husain5Silvio E. Inzucchi6Dalane W. Kitzman7Darren K. McGuire8Sanjiv J. Shah9Kavita Sharma10Guillermo Umpierrez11Mikhail N. Kosiborod12Department of Cardiology Kaiser Permanente San Francisco California USASaint Luke's Mid America Heart Institute Kansas City Missouri USASaint Luke's Mid America Heart Institute Kansas City Missouri USASaint Luke's Mid America Heart Institute Kansas City Missouri USADepartment of Cardiovascular Medicine Mayo Clinic Rochester Minnesota USATed Rogers Centre for Heart Research, Peter Munk Cardiac Centre University of Toronto Toronto CanadaYale School of Medicine New Haven Connecticut USASections on Cardiovascular Medicine and Geriatrics, Department of Internal Medicine Wake Forest University School of Medicine Winston‐Salem North Carolina USASouthwestern Medical Center and Parkland Health and Hospital System University of Texas Dallas Texas USADivision of Cardiology, Department of Medicine, and Bluhm Cardiovascular Institute Northwestern University Feinberg School of Medicine Chicago Illinois USASchool of Medicine Johns Hopkins University Baltimore Maryland USAEmory University Atlanta Georgia USASaint Luke's Mid America Heart Institute Kansas City Missouri USAAbstract Aims Sodium–glucose co‐transporter‐2 (SGLT2) inhibitors improve health status and outcomes in the setting of heart failure (HF) across the range of ejection fraction (EF). Baseline kidney disease is common in HF, complicates HF management and is strongly linked to worse health status. This study aimed to assess whether the treatment effects of dapagliflozin on health status vary based on estimated glomerular filtration rate (eGFR). Methods and Results We conducted a pooled participant‐level analysis of two double‐blind, randomized trials, DEFINE‐HF (n = 236) and PRESERVED‐HF (n = 324), which evaluated dapagliflozin versus placebo. Both multicentre studies enrolled adults with HF, New York Heart Association Class II or higher, elevated natriuretic peptides, and an EF < 40% in DEFINE‐HF or >45% in PRESERVED‐HF. The primary exposure was eGFR. The main outcome was the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ‐CSS) at 12 weeks. Across both trials, there were 583 (99.3%) participants with a baseline eGFR. The median (25th, 75th) eGFR was 59 (46, 77) mL/min/1.73 m2. Dapagliflozin improved KCCQ‐CSS at 12 weeks [placebo‐adjusted difference, +5.0 points, 95% confidence interval (CI) 2.6–7.5; P < 0.001], and this was consistent in participants with an eGFR ≥ 60 (+6.0 points, 95% CI 2.4–9.7; P = 0.001) and eGFR < 60 (+4.1 points, 95% CI 0.5–7.7; P = 0.025) (P interaction = 0.46). The benefits of dapagliflozin on KCCQ‐CSS remained robust across eGFR when modelled as a continuous variable (P interaction = 0.48). Conclusions Dapagliflozin led to early and clinically meaningful improvements in health status in HF patients, regardless of EF or baseline eGFR.https://doi.org/10.1002/ehf2.15184dapagliflozinejection fractionhealth statusheart failurerenal function |
| spellingShingle | Andrew P. Ambrosy Andrew J. Sauer Shachi Patel Sheryl L. Windsor Barry A. Borlaug Mansoor Husain Silvio E. Inzucchi Dalane W. Kitzman Darren K. McGuire Sanjiv J. Shah Kavita Sharma Guillermo Umpierrez Mikhail N. Kosiborod Baseline kidney function and the effects of dapagliflozin on health status in heart failure in DEFINE‐HF and PRESERVED‐HF ESC Heart Failure dapagliflozin ejection fraction health status heart failure renal function |
| title | Baseline kidney function and the effects of dapagliflozin on health status in heart failure in DEFINE‐HF and PRESERVED‐HF |
| title_full | Baseline kidney function and the effects of dapagliflozin on health status in heart failure in DEFINE‐HF and PRESERVED‐HF |
| title_fullStr | Baseline kidney function and the effects of dapagliflozin on health status in heart failure in DEFINE‐HF and PRESERVED‐HF |
| title_full_unstemmed | Baseline kidney function and the effects of dapagliflozin on health status in heart failure in DEFINE‐HF and PRESERVED‐HF |
| title_short | Baseline kidney function and the effects of dapagliflozin on health status in heart failure in DEFINE‐HF and PRESERVED‐HF |
| title_sort | baseline kidney function and the effects of dapagliflozin on health status in heart failure in define hf and preserved hf |
| topic | dapagliflozin ejection fraction health status heart failure renal function |
| url | https://doi.org/10.1002/ehf2.15184 |
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