STEPping down diuretic therapy with semaglutide in obesity-related heart failure with preserved ejection fraction: decongestion or disease modification?

• Published in: European heart journal Vol. 45; no. 35; pp. 3270 - 3273
• Main Authors: Ostrominski, John W, Chatur, Safia, Vaduganathan, Muthiah
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 14.09.2024
• Subjects: Diuretics - administration & dosage; Diuretics - therapeutic use; Glucagon-Like Peptides - administration & dosage; Glucagon-Like Peptides - therapeutic use; Heart Failure - drug therapy; Humans; Obesity - complications; Stroke Volume - drug effects; Stroke Volume - physiology
• ISSN: 0195-668X; 1522-9645; 1522-9645
• DOI: 10.1093/eurheartj/ehae410

Graphical Abstract Graphical Abstract *Hazard ratio reflects reported treatment effects of spironolactone vs. placebo on outpatient loop diuretic intensification (either new introduction or dose escalation). Discontinuations were not evaluated. The median loop diuretic dose in each trial was 40 mg furosemide equivalents per day. Although between-trial comparisons should be cautiously interpreted (only the STEP-HFpEF Program explicitly targeted obesity-related HFmrEF/HFpEF), loop diuretic therapy initiations and discontinuations appear greater with once-weekly semaglutide (2.4 mg) compared with SGLT2i and ARNI. These findings are broadly consistent with between-trial treatment effects on loop diuretic dose escalations and reductions, supporting a decongestive effect of semaglutide in obesity-related HFmrEF/HFpEF, potentially as part of a broader disease-modifying role. Abbreviations: ARNI = angiotensin receptor–neprilysin inhibitor; BMI = body mass index; DELIVER = Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure; EMPEROR-Preserved = Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction; GLP-1RA = glucagon-like peptide-1 receptor agonist; HFmrEF = heart failure with mildly reduced ejection fraction; HFpEF = heart failure with preserved ejection fraction; MRA = mineralocorticoid receptor antagonist; PARAGON-HF = Prospective Comparison of ARNI with ARB [angiotensin -receptor blockers] Global Outcomes in HF with Preserved Ejection Fraction; STEP-HFpEF = Semaglutide Treatment Effect in People with Obesity and HFpEF; SGLT2i = sodium–glucose co-transporter 2 inhibitor; TOPCAT = Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist.