Fluid Restriction in Heart Failure vs. Liberal Fluid Uptake - FRESH-UP

Mar 30, 2025
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Author/Summarized by Author:
Bria J Rice, MD
Summary Reviewer:
Fred M. Kusumoto, MD, FACC; Barry Borlaug, MD, FACC
Trial Sponsor:
Dutch Heart Foundation and Radboud UMC/Maastricht UMC Interuniversity
Date Presented:
03/30/2025
Date Published:
03/30/2025
Date Updated:
03/30/2025
Original Posted Date:
03/30/2025
References

Contribution To Literature:

The FRESH-UP study demonstrated that for patients with chronic heart failure (HF), liberal fluid intake did not result in a significant difference in health status vs. fluid restriction up to 1500 mL per day, and lowered perceived thirst distress.

Description:

The goal of the trial was to assess the safety and effect of lifestyle advice of a liberal vs. a restrictive fluid regimen in patients with chronic HF in an outpatient setting.

Study Design

Patients at seven sites in the Netherlands were randomly assigned in a 1:1 ratio to standardized lifestyle advice of either liberal fluid intake with no restriction (n=254) or fluid restriction up to 1500 mL per day (n=250) for a 3-month period.

  • Total number of enrollees: 504
  • Duration of follow-up: 3 months
  • Mean patient age: 69.2 years
  • Percentage female: 32.7%

Inclusion criteria:

  • Age ≥18 years
  • Patients treated for chronic HF for >6 months prior to randomization
  • NYHA class II or III HF symptoms
  • Any left ventricular ejection fraction was acceptable

Exclusion criteria:

  • HF hospitalization within 3 months prior to randomization
  • Coronary intervention or implantation of a pacemaker device within 3 months of randomization
  • Changes in medical HF therapy within 14 days prior to randomization
  • GFR <30 mL/min/1.73 m2
  • Hyponatremia

Principal Findings:

The primary outcome, the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OSS), was 74.0 in the liberal fluid intake group vs. 72.2 in the fluid restriction group at 3 months. After adjusting for baseline scores, the mean difference between groups was 2.17 (95% CI, -0.06 to 4.39, p=0.06), which did not reach statistical significance. 

Secondary outcomes:

Patients in the liberal fluid intake arm had lower perceived thirst distress at 3 months per the Thirst Distress Scale for patients with HF [TDS-HF]: 16.9 vs. 18.6. The mean difference after adjustment of baseline scores was -2.29 [95% CI, -1.09 to 3.49, p<0.001]). 

There were no statistically significant differences in safety endpoints between the liberal vs. restricted fluid intake arms:

  • Death: 1 vs. 2 patients
  • All-cause hospitalization: 20 vs. 15 patients
  • HF hospitalization: 4 vs. 4 patients
  • IV loop diuretic usage: 5 vs. 7 patients
  • Acute kidney injury: 3 vs. 4 patients

However, the overall number of clinical safety events was low, limiting the statistical power to detect meaningful differences between groups. This is likely due to modest sample size and short duration of follow-up.  

Behavioral Impact and Demographics:

Advice regarding fluid intake impacted patient behavior, with patients in the liberal fluid group reporting significantly higher fluid consumption than those in the restricted group: 1,764 vs. 1,483, p<0.001. Notably, only 34% of patients in the liberal arm drank >2000 mL per day; and the population was primarily male and Caucasian and of European descent. Thus, results may have reduced generalizability to patients consuming >3000 mL/day, women, and other racial groups. 

Interpretation:

Fluid restriction is often recommended for HF patients to prevent congestion. However, evidence on the benefit and safety of this advice has been unclear. The FRESH-UP late-breaking, randomized, controlled trial demonstrates that for patients with chronic, symptomatic (NYHA II-III) HF, strict fluid restriction does not enhance health status, as assessed by the KCCQ-OSS. In fact, observational data suggest that fluid restriction in this population may increase thirst distress without reducing all-cause mortality, hospitalization, acute kidney injury, or the need for HF medication escalation.

The results of FRESH-UP suggest that liberal fluid intake is safe in patients with chronic HF and may improve their well-being. Furthermore, it challenges providers to reconsider widespread fluid restrictions for all patients with HF and consider a more individualized approach. Future research investigating the effects of fluid intake on patients with more advanced HF is needed. 

References:

Herrmann JJ, Brunner-La Rocca HP, Baltussen LE, et al. Liberal Fluid Intake Versus Fluid Restriction in Chronic Heart Failure: A Randomized Clinical Trial. Nat Med 2025;Mar 30:[Epub ahead of print].

Presented by Dr. Roland van Kimmenade at the American College of Cardiology Annual Scientific Session (ACC.25), Chicago, IL, March 30, 2025.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: ACC25, ACC Annual Scientific Session, Heart Failure


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