Ferreira João Pedro, Vasques-Nóvoa Francisco, Saraiva Francisca, Oliveira Ana C, Almeida Jorge, Batista Ana Beatriz, Barbosa Arsénio, Ferreira Ana Filipa, Costa Cátia, Santos-Ferreira Diogo, Friões Fernando, Goncalves Cândida, Guimarães João Tiago, Leite Marta, Marques Pedro, Mascarenhas Joana, Matos Maria Inês, Pereira Catarina, Rodrigues Pedro, Sharma Abhinav, Silva Gualter, Pereira-Sousa Inês, Sousa Carla, Zannad Faiez, Pimenta Joana, Fontes-Carvalho Ricardo, Leite-Moreira Adelino
RISE-Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Université 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, France.
ESC Heart Fail. 2025 Aug;12(4):3134-3144. doi: 10.1002/ehf2.15294. Epub 2025 May 19.
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.
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).
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.
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/1.73m, 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.
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.
钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）和盐皮质激素受体拮抗剂（MRA）可减少射血分数轻度降低或保留的心力衰竭（HFmr/pEF）患者的心力衰竭事件。SGLT2i/MRA联合用药与单独使用SGLT2i或MRA的随机对照比较，在HFmr/pEF患者中还需要进一步试验验证。
比较达格列净/螺内酯联合用药与单独使用达格列净（主要比较）和单独使用螺内酯（探索性比较）的疗效（以NT-proBNP变化作为主要结局）和安全性（血钾、肌酐和血压变化）。
SOGALDI-PEF（钠-葡萄糖协同转运蛋白2抑制剂、醛固酮拮抗剂或两者联合用于射血分数保留的心力衰竭；NCT05676684），一项由研究者发起的概念验证性双中心随机交叉试验，比较三个治疗组（达格列净、螺内酯或两者联合），每组治疗12周，期间穿插4周的洗脱期。在两项独立试验证明SGLT2i对HFmr/pEF有效后，试验中期方案修订取消了单独使用螺内酯的序列，并将洗脱期缩短至1周。估计样本量为108例患者，在α水平为0.05时，检验效能为80%，以检测螺内酯/达格列净联合用药组与单独使用达格列净组之间0.15的LogNT-proBNP差异。
SOGALDI-PEF纳入了108例患者，中位年龄76岁，57%为女性，42%患有心房颤动，46%患有2型糖尿病，33%的估算肾小球滤过率（eGFR）低于60 mL/min/1.73m²，93%的射血分数≥50%。血清钾中位数为4.3 mmol/L，NT-proBNP中位数为764 pg/mL。大多数患者接受肾素-血管紧张素阻滞剂（68%）、β受体阻滞剂（70%）和襻利尿剂（69%）治疗。与其他HFmr/pEF试验相比，SOGALDI-PEF患者年龄更大，女性更常见，心房颤动患病率高，射血分数保留的情况更常见。
SOGALDI-PEF将是第一项在HFmr/pEF患者中以随机方式测试达格列净/螺内酯联合用药与单独使用达格列净疗效对比的试验。SOGALDI-PEF将提供关于在HFmr/pEF老年人群中，螺内酯与达格列净联合用药对比单独使用达格列净的潜在疗效和安全性的信息。
