Low-Versus Moderate-Sodium Diet in Patients With Recent Hospitalization for Heart Failure The PROHIBIT (Prevent Adverse Outcomes in Heart Failure by Limiting Sodium) Pilot Study

• Authors: Andreas Kalogeropoulos, Emory University; Lampros Papadimitriou, Stony Brook University; Vasiliki V Georgiopoulou, Emory University; Sandra Dunbar, Emory University; Hal Skopicki, Stony Brook University; Javed Butler, Emory University
• Journal Title: CIRCULATION-HEART FAILURE
• Volume: Volume 13, Number 1
• Publisher: LIPPINCOTT WILLIAMS & WILKINS | 2020-01-01, Pages e006389-e006389
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1161/CIRCHEARTFAILURE.119.006389
• Subjects: Health Sciences, Nursing; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Cardiovascular System & Cardiology; heart failure; hospitalization; quality of life; sodium; dietary; HYPERTONIC SALINE SOLUTION; HIGH-DOSE FUROSEMIDE; EVENT-FREE SURVIVAL; RESTRICTION; DESIGN; INTERVENTIONS; RATIONALE; URINE; outcomes; clinical trials; pilot studies

Abstract

Background: We conducted a pilot study to assess feasibility, on-study retention, trends in natriuretic peptide levels, quality of life, and safety of a 12-week feeding trial with 1500-versus 3000-mg daily sodium meals in high-risk patients with heart failure. Methods: Of 196 patients with recent (≤2 weeks) hospitalization for heart failure, ejection fraction ≤40%, on optimal medical therapy, functionally independent, and able to communicate, 83 (47%) consented to participate. Of these, 27 (age, 6211 years; 22 men; 20 white; ejection fraction, 268%) had 24-hour urine sodium ≥3000 mg and agreed to randomly receive either 1500-mg (N=12) or 3000-mg (N=15) sodium meals. Results: On-study retention at 12 weeks was 77% (82% versus 73%; P=0.53); 6 patients (2 in 1500-mg, 4 in 3000-mg arm) withdrew before study completion. Food satisfaction questionnaires indicated that both diets were well tolerated. Quality of life improved in the 1500-mg arm at 12 weeks but did not change in the 3000-mg arm. Average compliance with meals was 52% (based on urinary sodium) and was not significantly different between arms (42% versus 60%; P=0.25). Study meals reduced 24-hour urinary sodium by 13721 mmol (1500-mg arm) and 8216 mmol (3000-mg arm), both P<0.001; between-arms difference was 55 mmol (95% CI, 3-107; P=0.037). NT-proBNP (N-terminal pro-B-type natriuretic peptide) was not affected. Hospitalizations and low blood pressure events did not differ significantly between arms. Serum creatinine decreased more (by 0.17 mg/dL [95% CI, 0.06-0.28]; P=0.003) in the 1500-mg arm. Creatinine increases >0.5 mg/dL over baseline only occurred in 1 patient in the 3000-mg arm. Conclusions: Even with prepared meals, investigating optimal dietary sodium in heart failure comes with challenges, including need for extensive screening, reluctance to participate, and compliance issues. Because both diets reduced urinary sodium without adverse safety or quality of life signals, a larger trial, with modifications to improve participation and compliance, would be ethical and feasible. Clinical Trial Registration: URL: Https://www.clinicaltrials.gov. Unique identifier: NCT02467296.