Natriuresis as marker for personalized diuretic therapy in patients with acute HF

ESC Congress 2023 In the pragmatic PUSH-AHF trial, natriuresis-guided diuretic therapy was safe and improved natriuresis and diuresis in patients with acute HF compared with standard of care, without affecting 180-day clinical outcomes.

Presented at the ESC Congress 2023 by: Jozine ter Maaten, MD, PhD - Groningen, the Netherlands

Introduction and methods

The standard treatment of acute HF (AHF) with loop diuretics is not sufficient for a large number of patients. Based on loop diuretics’ ability to promote urinary sodium excretion (natriuresis), the researchers hypothesized natriuresis is a potential marker to guide diuretic therapy and improve treatment of these patients.

The PUSH-AHF (Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure) trial was a single-center, pragmatic, open-label RCT in which 310 AHF patients who required intravenous (IV) loop diuretic therapy were randomized to natriuresis-guided diuretic therapy or standard of care. In the natriuresis-guided therapy group, spot urine sodium levels were assessed at set time points until 36 hours after initiation of IV loop diuretic therapy. In this treatment group, decongestive therapy was adjusted in patients with an insufficient response based on a prespecified treatment algorithm (spot urinary sodium <70 mmol/L).

The 2 coprimary endpoints were: (1) 24-hour natriuresis; and (2) a composite outcome of time to all-cause mortality or adjudicated HF rehospitalization at 180 days. Statistical significance was set at P<0.025.

Main results

• Mean (± SD) 24-hour natriuresis was improved in patients assigned to natriuresis-guided diuretic therapy compared with those receiving standard of care (409 ± 178 vs. 345 ± 202 mmol urinary sodium/24 h; P=0.0061).
• However, there was no significant difference between the natriuresis-guided therapy and standard-of-care groups in the other coprimary endpoint of 180-day all-cause mortality or HF rehospitalization (31% vs. 31%; HR: 0.92; 95%CI: 0.62–1.38; P=0.6980).
• The natriuresis-guided therapy group did show a significantly lower incidence of in-hospital mortality compared with the standard-of-care group (2 vs. 14 deaths). However, this was not a prespecified endpoint.
• The beneficial effect of natriuresis-guided therapy was also observed for 48-hour natriuresis (P=0.0241), 24-hour diuresis (P=0.0053), and 48-hour diuresis (P=0.0139).
• The active treatment was not associated with electrolyte or renal function disturbances.

Conclusion

This pragmatic trial showed that natriuresis-guided diuretic therapy was safe and improved natriuresis and diuresis in AHF patients compared with standard of care, without affecting 180-day clinical outcomes. The researchers conclude “natriuresis-guided diuretic therapy is a first personalized approach in treating patients with AHF.”

- Our reporting is based on the information provided at the ESC Congress –

The results of this study were simultaneously published in Nature Medicine.