Key Points:
- While fluid restriction is a standard recommendation for patients with chronic heart failure (HF), there is limited evidence to support its use.
- The FRESH-UP trial was designed to examine the utility of fluid restriction vs liberal fluid intake in individuals with NYHA II or III chronic HF.
- There was no difference in symptom burden or safety events between the liberal fluid intake and fluid restriction groups, with an increase in thirst distress in the fluid restriction group.
While fluid restriction has been considered a cornerstone of HF symptom management, recent observational evidence has questioned its utility. Most consensus guidelines continue to recommend fluid restriction, and clinical trial evidence directly comparing these two strategies has so far been lacking. In a breaking presentation at the 2025 ACC Scientific Sessions today, Dr. Roland RJ van Kimmenade and his team presented their study: “Liberal Fluid Intake versus Fluid Restriction in Chronic Heart Failure,” or the FRESH-UP study, which was simultaneously published in Nature Medicine.
The FRESH-UP trial (NCT04551729) randomized 504 adults across seven medical centers in the Netherlands with a diagnosis of NYHA II/III chronic HF as per ESC guidelines for at least six months prior to randomization. Relevant exclusion criteria were changes in medical therapy within two weeks of randomization, an admission, PCI, CABG, or device implantation within three months, baseline hyponatremia <130 mmol/L, or an eGFR < 30mL/min/1.73m2. Patients were randomized to liberal fluid intake (ie, no restriction) or fluid restriction of 1.5L a day. The primary outcome was health status at three months as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ-OSS). Secondary outcomes included thirst distress at three months, as measured by the Thirst Distress Scale (TDS-HF), as well as death, all-cause hospitalizations, HF hospitalizations, AKI, and reported fluid intake.
The median age was 69, with 33% women, 98% white individuals, and a mean LVEF of 40%. Prior to randomization, 49% of the liberal fluid intake group and 44% if the fluid restriction group had previously had liberal fluid intake. The average daily Lasix equivalent dose was 40mg a day in each group. There was no significant difference in the primary outcome between the liberal and restrictive strategies at three months (74.0 vs 72.2, p=0.06). On subgroup analyses, a significant p-interaction (p=0.006) was observed for individuals with a median BUN <7.4 mmol/L vs those without, with more benefit conferred with a liberal fluid intake for those with lower BUN. Thirst distress was higher in the fluid restriction group (18.6 vs 16.9, p<0.001), and fluid intake was, as expected, higher in the liberal than the fluid restriction group (1764 vs 1480ml, p<0.001). No differences were observed in death, all-cause or HF hospitalizations, or AKI.
When discussing the clinical implications of the study at the Scientific Sessions, Dr. van Kimmenade stated: “Difference in KCCQ-OS after adjustment for baseline scores after three months was 2.17…in favor of liberal fluid intake, but the primary outcome was not met…The FRESH-UP study questions the benefit of fluid restriction in chronic heart failure.”