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. 2025 Jan;13(1):14-27.
doi: 10.1016/j.jchf.2024.09.017.

Diuretic Potentiation Strategies in Acute Heart Failure

Tariq Jamal Siddiqi  1 , Milton Packer  2 , Justin A Ezekowitz  3 , Gregg C Fonarow  4 , Stephen J Greene  5 , Michelle Kittleson  6 , Muhammad Shahzeb Khan  7 , Robert J Mentz  5 , Jeffrey Testani  8 , Adriaan A Voors  9 , Javed Butler  10
Affiliations

Diuretic Potentiation Strategies in Acute Heart Failure

Tariq Jamal Siddiqi et al. JACC Heart Fail. 2025 Jan.

Abstract

Several trials have evaluated diuretic-based strategies to improve symptoms and outcomes in patients with acute heart failure (AHF). The authors sought to summarize the effect of different combination strategies on symptoms, physical signs, physiological variables, and outcomes in patients with AHF. Twelve trials were identified that assessed the addition of thiazide diuretics, sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, vasopressin receptor antagonists, carbonic anhydrase inhibitors, or loop diuretic intensification to conventional therapy for AHF. The trials evaluated short-term markers of congestion and symptoms, and none were powered for clinical outcomes. Short-term responses (such as relief from dyspnea, physical signs of congestion, and weight change) varied greatly across studies; all diuretic strategies were accompanied by short-term increases in serum creatinine and did not demonstrate benefits on mortality or recurrent heart failure events. The available evidence suggests that intensification of loop diuretic agents produces relief of physical signs of decongestion, but the importance of different strategies for short-term decongestion strategy for health status and long-term outcomes has not been established.

Keywords: acute heart failure; clinical trials; diuretic agents.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Packer has received consulting fees from 89bio, Abbvie, Altimmune, Amgen, Ardelyx, AstraZeneca, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Lilly, Moderna, Novartis, Reata, Regeneron, Relypsa, and Salamandra, and is a Trial Executive Committee member of the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance. Dr Ezekowitz has received research grants from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, eko.ai, US2.ai, Merck, Novartis, Otsuka, Sanofi, and Servier, and consulting fees from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Merck, Novartis, Otsuka, Sanofi, and Servier. Dr Fonarow has served as a consultant for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Eli Lilly, Johnson and Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Otsuka, Pfizer, and Sanofi; has served on advisory boards or as a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Eli Lilly, Lexicon, Merck, Novo Nordisk, Otsuka, Roche Diagnostics, Sanofi, scPharmaceuticals, Tricog Health, and Urovant Pharmaceuticals; and has received speaker fees from Bayer, Boehringer Ingelheim, Cytokinetics, Lexicon, and Roche Diagnostics. Dr Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Dr Testani has received fees from 3ive labs, Bayer, Bristol-Myers Squibb, AstraZeneca, Novartis, Cardionomic, MagentaMed, Reprieve, Fire1, W.L. Gore and Associates, Sanofi, Sequana Medical, Otsuka, Abbott, Merck, Windtree Therapeutics, Lexicon Pharmaceuticals, Precardia, Relypsa, Regeneron, Becton Dickinson, Edwards Lifesciences, and Lilly, and holds a patent for treatment of diuretic resistance issued to Yale and Corvidia Therapeutics, a patent for methods for measuring renalase issued to Yale, and a patent for treatment of diuretic resistance pending with Reprieve. Dr Voors has received research support and/or has been a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Myokardia, Novo Nordisk, Novartis, and Roche Diagnostics. Dr Butler has received payment or honoraria for lectures, presentations, Speakers Bureau, manuscript writing, or educational events from Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, AstraZeneca, Bayer, BerlinCures, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sanofi, Sequana Medical, Occlutech, and Vifor, and is a Trial Executive Committee member of Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance. All other authors have no relationships relevant to the contents of this paper to disclose.

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