Objectives

To determine whether torsemide results in decreased mortality compared with furosemide among individuals hospitalized for heart failure.

Background

Heart failure is a major and growing public health problem worldwide. Many patients with heart failure experience symptoms of congestion and volume overload including dyspnea and edema. The majority of patients with symptomatic heart failure are prescribed loop diuretics for the treatment of congestion. Guidelines indicate that the use of diuretics is a cornerstone of a successful approach to the treatment of congestion in heart failure.

Furosemide is the most commonly used loop diuretic for heart failure. However, preclinical and clinical data suggest potential benefits of torsemide compared with furosemide. Torsemide has increased bioavailability and a longer half-life than furosemide. Torsemide may also have beneficial effects on myocardial fibrosis, aldosterone production, sympathetic activation, ventricular remodeling, and natriuretic peptides. Several small studies of torsemide vs furosemide and meta-analyses suggest a decrease in morbidity and potentially mortality with torsemide compared with furosemide. However, in light of the lack of an adequately powered clinical outcomes study, there is insufficient evidence to recommend torsemide over furosemide. TRANSFORM-HF was initiated to compare the effect of torsemide with furosemide in individuals hospitalized with heart failure.

Participants

Eligible participants were hospitalized for heart failure and could have either de novo heart failure or worsening of chronic heart failure. Participants had either a left ventricular ejection fraction of 40% or less within 24 months or an elevated natriuretic peptide level during the index hospitalization as measured by the local laboratory. Participants needed to have a plan for daily outpatient oral loop diuretic with anticipated long-term use. Exclusion criteria included individuals with end-stage kidney disease requiring dialysis or a history of heart transplant or left ventricular assist device.

A total of 2859 eligible individuals were randomized with 1431 randomized to receive torsemide and 1428 randomized to receive furosemide.

Design

The TRANSFORM-HF study was an open-label, pragmatic, randomized, multi-center clinical trial of individuals hospitalized with heart failure regardless of ejection fraction.

Participants were recruited during hospitalization with heart failure, at the discretion of the healthcare provider. Prior to hospital discharge, participants were randomly assigned in a 1:1 ratio to a treatment strategy of torsemide or furosemide. Dose and frequency of the randomized therapy during hospitalization and at discharge were determined by the treating clinician with the following conversion provided as a guide: 1 mg of torsemide to 2 to 4 mg of oral furosemide. Changes in dose and frequency of the randomized therapy after discharge were at the discretion of the participant’s usual outpatient clinicians. Participants received medication as per routine care with the open-label study medication prescription. Participants had 30-day, 6-month and 12-month follow-up phone contacts for assessments of vital status, interval hospitalizations, adherence, and quality of life. Subsets of participants enrolled early in the study had additional phone contacts beyond 12 months, up to 30 months, at six-month intervals, to document vital status.

The primary objective was to compare the treatment strategy of torsemide versus furosemide on clinical outcomes over 12 months in individuals with heart failure who were hospitalized. The secondary objectives of this study examined the effect of torsemide versus furosemide for the following endpoints: all-cause mortality or all-cause hospitalization over 12 months, total hospitalizations over 12 months, all-cause mortality or all-cause hospitalization over 30 days, health-related quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) over 12 months, and symptoms of depression as measured by the Patient Health Questionnaire-2 (PHQ-2) over 12 months.

Conclusions

Among participants discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months.

Mentz RJ, Anstrom KJ, Eisenstein EL, et al. Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial. JAMA. 2023;329(3):214-223. doi:10.1001/jama.2022.23924

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