Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial

• Published in: Nature medicine Vol. 29; no. 10; pp. 2625 - 2632
• Main Authors: ter Maaten, Jozine M., Beldhuis, Iris E., van der Meer, Peter, Krikken, Jan A., Postmus, Douwe, Coster, Jenifer E., Nieuwland, Wybe, van Veldhuisen, Dirk J., Voors, Adriaan A., Damman, Kevin
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2023; Nature Publishing Group
• Subjects: 692/308/409; 692/699/75/230; Algorithms; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer Research; Congestive heart failure; Customization; Diuretics; Heart failure; Infectious Diseases; Metabolic Diseases; Molecular Medicine; Mortality; Neurosciences; Patients; Sodium; Therapy
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-023-02532-z

Measurement of natriuresis has been suggested as a reliable, easily obtainable biomarker for assessment of the response to diuretic treatment in patients with acute heart failure (AHF). Here, to assess whether natriuresis-guided diuretic therapy in patients with AHF improves natriuresis and clinical outcomes, we conducted the pragmatic, open-label Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure trial, in which 310 patients (45% female) with AHF requiring treatment with intravenous loop diuretics were randomly assigned to natriuresis-guided therapy or standard of care (SOC). In the natriuresis-guided arm, natriuresis was determined at set timepoints, prompting treatment intensification if spot urinary sodium levels were <70 mmol l −1 . The dual primary endpoints were 24 h urinary sodium excretion and a combined endpoint of time to all-cause mortality or adjudicated heart failure rehospitalization at 180 days. The first primary endpoint was met, as natriuresis in the natriuresis-guided and SOC arms was 409 ± 178 mmol arm versus 345 ± 202 mmol, respectively ( P  = 0.0061). However, there were no significant differences between the two arms for the combined endpoint of time to all-cause mortality or first heart failure rehospitalization, which occurred in 46 (31%) and 50 (31%) of patients in the natriuresis-guided and SOC arms, respectively (hazard ratio 0.92 [95% confidence interval 0.62–1.38], P  = 0.6980). These findings suggest that natriuresis-guided therapy could be a first step towards personalized treatment of AHF. ClinicalTrials.gov registration: NCT04606927 . In patients with acute heart failure, personalized dosing of a diuretic led to treatment intensification in the majority of patients and improved natriuresis, but had no effects on time to all-cause mortality or heart failure rehospitalization.