SGLT2 inhibitor with and without ALDosterone AntagonIst for heart failure with preserved ejection fraction: Design paper
Abstract Background Sodium glucose co‐transporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRA) reduce heart failure (HF) events in patients with heart failure and mildly reduced or preserved ejection fraction (HFmr/pEF). The randomized comparison of SGLT2i/MRA combination v...
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Wiley
2025-08-01
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| Series: | ESC Heart Failure |
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| Online Access: | https://doi.org/10.1002/ehf2.15294 |
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| author | João Pedro Ferreira Francisco Vasques‐Nóvoa Francisca Saraiva Ana C. Oliveira Jorge Almeida Ana Beatriz Batista Arsénio Barbosa Ana Filipa Ferreira Cátia Costa Diogo Santos‐Ferreira Fernando Friões Cândida Goncalves João Tiago Guimarães Marta Leite Pedro Marques Joana Mascarenhas Maria Inês Matos Catarina Pereira Pedro Rodrigues Abhinav Sharma Gualter Silva Inês Pereira‐Sousa Carla Sousa Faiez Zannad Joana Pimenta Ricardo Fontes‐Carvalho Adelino Leite‐Moreira |
| author_facet | João Pedro Ferreira Francisco Vasques‐Nóvoa Francisca Saraiva Ana C. Oliveira Jorge Almeida Ana Beatriz Batista Arsénio Barbosa Ana Filipa Ferreira Cátia Costa Diogo Santos‐Ferreira Fernando Friões Cândida Goncalves João Tiago Guimarães Marta Leite Pedro Marques Joana Mascarenhas Maria Inês Matos Catarina Pereira Pedro Rodrigues Abhinav Sharma Gualter Silva Inês Pereira‐Sousa Carla Sousa Faiez Zannad Joana Pimenta Ricardo Fontes‐Carvalho Adelino Leite‐Moreira |
| author_sort | João Pedro Ferreira |
| collection | DOAJ |
| description | Abstract Background Sodium glucose co‐transporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRA) reduce heart failure (HF) events in patients with heart failure and mildly reduced or preserved ejection fraction (HFmr/pEF). The randomized comparison of SGLT2i/MRA combination versus SGLT2i or MRA alone requires further testing in HFmr/pEF. Aims To compare the efficacy (NT‐proBNP change as primary outcome) and safety (potassium, creatinine, and blood pressure changes) of dapagliflozin/spironolactone combination versus dapagliflozin alone (primary comparison) and spironolactone alone (exploratory comparison). Methods SOGALDI‐PEF (SOdium‐Glucose cotransporter 2 inhibitor, ALDosterone AntagonIst, or both for heart failure with preserved ejection fraction; NCT05676684), a proof‐of‐concept investigator‐initiated two‐centre randomized cross‐over trial comparing three arms (dapagliflozin, spironolactone, or both) for three periods of 12 weeks each intercalated by a wash‐out period of 4 weeks. After two independent trials demonstrating efficacy of SGLT2i in HFmr/pEF, a mid‐trial protocol amendment dropped the spironolactone alone sequence and reduced the wash‐out period to 1 week. A sample size of 108 patients was estimated to provide 80% power, at a 0.05 alfa level, to detect a 0.15 LogNT‐proBNP difference between the spironolactone/dapagliflozin combination and dapagliflozin alone sequence. Results SOGALDI‐PEF included 108 patients with a median age of 76 years, 57% women, 42% with atrial fibrillation, 46% with type 2 diabetes, 33% having an eGFR below 60 mL/min/1.73m2, and 93% having an ejection fraction ≥ 50%. The median serum potassium was 4.3 mmol/L, and the median NT‐proBNP was 764 pg/mL. Most patients were treated with renin–angiotensin blockers (68%), beta‐blockers (70%) and loop diuretics (69%). Compared to other HFmr/pEF trials, SOGALDI‐PEF patients were older, were more frequently women, had a high prevalence of atrial fibrillation, and had more often a preserved ejection fraction. Conclusions SOGALDI‐PEF will be the first trial in HFmr/pEF to test the combination of dapagliflozin/spironolactone vs dapagliflozin alone in a randomized manner. SOGALDI‐PEF will provide information on the potential efficacy and safety of concomitant administration of spironolactone with dapagliflozin vs dapagliflozin alone in an elderly population with HFmr/pEF. |
| format | Article |
| id | doaj-art-5a54ebabe54243e587c0ee67909bbc03 |
| institution | Kabale University |
| issn | 2055-5822 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj-art-5a54ebabe54243e587c0ee67909bbc032025-08-20T03:36:08ZengWileyESC Heart Failure2055-58222025-08-011243134314410.1002/ehf2.15294SGLT2 inhibitor with and without ALDosterone AntagonIst for heart failure with preserved ejection fraction: Design paperJoão Pedro Ferreira0Francisco Vasques‐Nóvoa1Francisca Saraiva2Ana C. Oliveira3Jorge Almeida4Ana Beatriz Batista5Arsénio Barbosa6Ana Filipa Ferreira7Cátia Costa8Diogo Santos‐Ferreira9Fernando Friões10Cândida Goncalves11João Tiago Guimarães12Marta Leite13Pedro Marques14Joana Mascarenhas15Maria Inês Matos16Catarina Pereira17Pedro Rodrigues18Abhinav Sharma19Gualter Silva20Inês Pereira‐Sousa21Carla Sousa22Faiez Zannad23Joana Pimenta24Ricardo Fontes‐Carvalho25Adelino Leite‐Moreira26RISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalServiço de Medicina Interna Unidade Local de Saúde São João Porto PortugalRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalServiço de Medicina Interna Unidade Local de Saúde São João Porto PortugalRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalServiço de Cardiologia Unidade Local de Saúde Gaia/Espinho Gaia Vila Nova de Gaia PortugalRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalServiço de Medicina Interna Unidade Local de Saúde São João Porto PortugalRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalServiço de Patologia Clínica Unidade Local de Saúde São João Porto PortugalServiço de Cardiologia Unidade Local de Saúde Gaia/Espinho Gaia Vila Nova de Gaia PortugalRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalServiço de Medicina Interna Unidade Local de Saúde Gaia/Espinho Gaia Vila Nova de Gaia PortugalServiço de Medicina Interna Unidade Local de Saúde Gaia/Espinho Gaia Vila Nova de Gaia PortugalServiço de Medicina Interna Unidade Local de Saúde Gaia/Espinho Gaia Vila Nova de Gaia PortugalServiço de Medicina Interna Unidade Local de Saúde São João Porto PortugalResearch Institute of the McGill University Health Centre, Department of Medicine McGill University Montreal Quebec CanadaServiço de Cardiologia Unidade Local de Saúde Gaia/Espinho Gaia Vila Nova de Gaia PortugalRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalServiço de Cardiologia Unidade Local de Saúde São João Porto PortugalUniversité de Lorraine INSERM, Centre d'Investigations Cliniques 1433, CHRU de Nancy, Inserm 1116 and INI‐CRCT (Cardiovascular and Renal Clinical Trialists) F‐CRIN Network Nancy FranceRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalRISE‐Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina Universidade do Porto Porto PortugalAbstract Background Sodium glucose co‐transporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRA) reduce heart failure (HF) events in patients with heart failure and mildly reduced or preserved ejection fraction (HFmr/pEF). The randomized comparison of SGLT2i/MRA combination versus SGLT2i or MRA alone requires further testing in HFmr/pEF. Aims To compare the efficacy (NT‐proBNP change as primary outcome) and safety (potassium, creatinine, and blood pressure changes) of dapagliflozin/spironolactone combination versus dapagliflozin alone (primary comparison) and spironolactone alone (exploratory comparison). Methods SOGALDI‐PEF (SOdium‐Glucose cotransporter 2 inhibitor, ALDosterone AntagonIst, or both for heart failure with preserved ejection fraction; NCT05676684), a proof‐of‐concept investigator‐initiated two‐centre randomized cross‐over trial comparing three arms (dapagliflozin, spironolactone, or both) for three periods of 12 weeks each intercalated by a wash‐out period of 4 weeks. After two independent trials demonstrating efficacy of SGLT2i in HFmr/pEF, a mid‐trial protocol amendment dropped the spironolactone alone sequence and reduced the wash‐out period to 1 week. A sample size of 108 patients was estimated to provide 80% power, at a 0.05 alfa level, to detect a 0.15 LogNT‐proBNP difference between the spironolactone/dapagliflozin combination and dapagliflozin alone sequence. Results SOGALDI‐PEF included 108 patients with a median age of 76 years, 57% women, 42% with atrial fibrillation, 46% with type 2 diabetes, 33% having an eGFR below 60 mL/min/1.73m2, and 93% having an ejection fraction ≥ 50%. The median serum potassium was 4.3 mmol/L, and the median NT‐proBNP was 764 pg/mL. Most patients were treated with renin–angiotensin blockers (68%), beta‐blockers (70%) and loop diuretics (69%). Compared to other HFmr/pEF trials, SOGALDI‐PEF patients were older, were more frequently women, had a high prevalence of atrial fibrillation, and had more often a preserved ejection fraction. Conclusions SOGALDI‐PEF will be the first trial in HFmr/pEF to test the combination of dapagliflozin/spironolactone vs dapagliflozin alone in a randomized manner. SOGALDI‐PEF will provide information on the potential efficacy and safety of concomitant administration of spironolactone with dapagliflozin vs dapagliflozin alone in an elderly population with HFmr/pEF.https://doi.org/10.1002/ehf2.15294Heart failure and mildly reduced or preserved ejection fractionDapagliflozin/spironolactone/dapagliflozin/spironolactone combinationRandomized cross‐over trial |
| spellingShingle | João Pedro Ferreira Francisco Vasques‐Nóvoa Francisca Saraiva Ana C. Oliveira Jorge Almeida Ana Beatriz Batista Arsénio Barbosa Ana Filipa Ferreira Cátia Costa Diogo Santos‐Ferreira Fernando Friões Cândida Goncalves João Tiago Guimarães Marta Leite Pedro Marques Joana Mascarenhas Maria Inês Matos Catarina Pereira Pedro Rodrigues Abhinav Sharma Gualter Silva Inês Pereira‐Sousa Carla Sousa Faiez Zannad Joana Pimenta Ricardo Fontes‐Carvalho Adelino Leite‐Moreira SGLT2 inhibitor with and without ALDosterone AntagonIst for heart failure with preserved ejection fraction: Design paper ESC Heart Failure Heart failure and mildly reduced or preserved ejection fraction Dapagliflozin/spironolactone/dapagliflozin/spironolactone combination Randomized cross‐over trial |
| title | SGLT2 inhibitor with and without ALDosterone AntagonIst for heart failure with preserved ejection fraction: Design paper |
| title_full | SGLT2 inhibitor with and without ALDosterone AntagonIst for heart failure with preserved ejection fraction: Design paper |
| title_fullStr | SGLT2 inhibitor with and without ALDosterone AntagonIst for heart failure with preserved ejection fraction: Design paper |
| title_full_unstemmed | SGLT2 inhibitor with and without ALDosterone AntagonIst for heart failure with preserved ejection fraction: Design paper |
| title_short | SGLT2 inhibitor with and without ALDosterone AntagonIst for heart failure with preserved ejection fraction: Design paper |
| title_sort | sglt2 inhibitor with and without aldosterone antagonist for heart failure with preserved ejection fraction design paper |
| topic | Heart failure and mildly reduced or preserved ejection fraction Dapagliflozin/spironolactone/dapagliflozin/spironolactone combination Randomized cross‐over trial |
| url | https://doi.org/10.1002/ehf2.15294 |
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