Liberal fluid intake vs fluid restriction in chronic heart failure, Semaglutide in MASH and First Line Treatment of Pulmonary Sarcoidosis with Prednisone or Methotrexate

Aug 11, 2025

Should fluid restriction truly be recommended in chronic heart failure?

Liberal fluid intake versus fluid restriction in chronic heart failure: a randomized clinical trial (FRESH-UP)

Herrmann JJ et al. Nature Medicine (March 2025)

Bottom Line: This multicenter open-label trial evaluated the effects of fluid restriction vs liberation in outpatients with chronic heart failure over a period of 3 months. A total of 504 participants were randomized to receive advice for liberal fluid intake or fluid restriction (up to 1,500 ml per day). The primary outcome was health status measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score. The score was 74.0 in the liberal group and 72.2 in the restriction group, with a mean difference of 2.17 (95% CI -0.06 to 4.39; P = 0.06), indicating that the primary outcome was not met. Thirst distress was higher in the fluid restriction group, and no safety differences were noted. The study questions the benefit of fluid restriction in this patient population.

LINK TO THE ROUNDS TABLE PODCAST

LINK TO ARTICLE (FRESH-UP)


Semaglutide for MASH!

Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis (ESSENCE)

Sanyal AJ et al. NEJM (April 2025)

Bottom line: This ongoing phase 3, multicenter, randomized, double-blind, placebo-controlled trial assigned 1197 patients with biopsy-defined metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis stage 2 or 3 to receive either semaglutide 2.4 mg once-weekly or placebo for 240 weeks. The primary outcomes evaluated at this interim analysis (week 72, 800 patients) included resolution of steatohepatitis and reduction in liver fibrosis. Results showed 62.9% of the semaglutide group achieved resolution of steatohepatitis compared to 34.3% in the placebo group (estimated difference, 28.7 percentage points; 95% confidence interval [CI], 21.1 to 36.2; P<0.001). 36.8% of the semaglutide group had a reduction in liver fibrosis versus 22.4% in the placebo group (estimated difference, 14.4 percentage points; 95% CI, 7.5 to 21.3; P<0.001). Gastrointestinal adverse events were more common in the semaglutide group. This interim analysis indicates the efficacy of Semaglutide in improving liver histology.

LINK TO THE ROUNDS TABLE PODCAST

LINK TO ARTICLE (ESSENCE)


Should Methotrexate be first-line for sarcoidosis?

First-Line Treatment of Pulmonary Sarcoidosis with Prednisone or Methotrexate (PREDMETH)

Kahlmann V et al. NEJM (May 2025)

Bottom Line: This multicenter, open-label, noninferiority trial evaluated the efficacy and safety of methotrexate compared to prednisone in treating pulmonary sarcoidosis in 138 patients who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive either methotrexate or prednisone. The primary outcome was the mean change in the percentage of predicted forced vital capacity from baseline to week 24. The noninferiority margin for the primary end point was 5 percentage points. Results showed methotrexate at 6.11 percentage points (95% CI, 3.72 to 8.50) and prednisone at 6.75 percentage points (95% CI, 4.50 to 8.99). Methotrexate was noninferior to prednisone with regard to the primary end point, with an adjusted between-group difference of −1.17 percentage points (95% CI, −4.27 to 1.93). Both treatments had a similar adverse event profile, with distinct common side effects for each.

LINK TO ARTICLE (PREDMETH)


Trial Files Issue #2025-17