Enthusiasm Dries Up for Fluid Restriction in Heart Failure

 For people with heart failure (HF), the long-presumed benefits of fluid restriction did not pan out in the FRESH-UP randomized trial.

Patients showed similar changes in their Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Scores 3 months into the trial whether they had been allowed liberal fluid intake or told to restrict fluids to no more than 1.5 L (6.3 cups) per day, according to Roland R.J. van Kimmenade, MD, PhD, of Maastricht University Medical Centre in the Netherlands.

The adjusted between-group difference in improvement was 2.17 points favoring liberal fluid intake (95% CI -0.06 to 4.39) -- a result not meeting expectations for a statistically significant finding but leaning enough in one direction that "we have no reason to assume that fluid restriction would be better" for chronic HF, van Kimmenade said during a press conference at the American College of Cardiology (ACC)opens in a new tab or window annual meeting.

He said that the FRESH-UP trial had been conceived in response to HF patients unhappy with the advice they were getting to restrict their fluid intake. Imagine, he said, having to constantly track how much you've drank and deciding "Should I have a cup of coffee with my spouse in the morning or wait and have a cup of tea with my friend in the afternoon?"

As such, fluid allowance is part of the growing concerns about quality of life in HF, van Kimmenade said.

It's not just about whether patients live or die anymore -- there are so many treatments improving mortality now that the focus needs to shift to quality of life, agreed Shelley Hall, MD, of Baylor University Medical Center in Dallas, in discussing FRESH-UP at the press conference.

"Let's be a little kinder to our patients and ourselves. We don't have to be so harsh pounding fluid restriction [on our patients]," Hall said. "One of the nice things about this for us old-timers is it validates our raised eyebrows when the [limit was raised] from 2 L to 1,500 mL ... 2 L is fine."

Normal fluid intake depends on sex and age. In a National Health and Nutrition Examination Survey from 2009-2012, men in the general population drank on average 3.46 L (14.6 cups) daily, while women drank 2.75 L (11.6 cups) a day.

In FRESH-UP, reported fluid intakes ended up being around 1.76 L with the liberal group and 1.48 L with the restrictive group (P<0.001).

Several secondary outcomes did significantly favor the liberal fluids group:

• Less thirst distress per the Thirst Distress Scale for patients with HF: 16.9 points with liberal fluids vs 18.6 with restrictive fluids (P<0.001)
• Improved KCCQ-Clinical Summary Score: 75.9 vs 74.5 (P=0.032)
• Better KCCQ-Total Summary Score: 78.5 vs 77.2 (P=0.020)

FRESH-UP is currently in press in Nature Medicine, according to van Kimmenade.

For their open-label randomized trial, the investigators recruited adults diagnosed with chronic HF with New York Heart Association class II/III symptoms. From 2021 to 2024, selected participants were randomized to liberal fluid intake (n=254) or fluid restriction (n=250).

The study population was around age 69 on average and around 67% were men. Nearly 98% were white. Mean left ventricular ejection fraction was 40%; about half of the cohort had reduced ejection fraction, the remainder split between mildly reduced and preserved ejection fraction. Additionally, 22% had diabetes, and the mean eGFR was around 62 ml/min/1.73 m².

Before study entry, participants had been on liberal fluid intake in 48.8% and 44.4% between the liberal and restricted fluid groups, respectively. Across participants in general, the vast majority were on renin-angiotensin-aldosterone system inhibitors and beta-blockers; around 60% were on SGLT2 inhibitors.

Over follow-up, investigators found no between-group differences in safety outcomes like mortality, hospitalization, IV loop diuretics usage, and acute kidney injury.

FRESH-UP excluded people who had recent changes in HF medical therapy and those with HF hospitalization or revascularization or cardiac device implant within 3 months prior to randomization. Also excluded were those with hyponatremia and those with severe kidney failure.

Disclosures

FRESH-UP was supported by crowdfunding in collaboration with the Dutch Heart Foundation, and with additional support from Radboud University Medical Centre and Maastricht University Medical Centre.

van Kimmenade had no disclosures.

Hall reported consultant fees/honoraria from Abbott Laboratories, CareDx, CVRx, EvaHeart, and Natera.

Primary Source

American College of Cardiology

Source Reference: opens in a new tab or windowvan Kimmenade RRJ, et al "Liberal fluid intake versus fluid restriction in chronic heart failure: the FRESH-UP study" ACC 2025.

https://www.medpagetoday.com/meetingcoverage/acc/114887