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Randomized Controlled Trial
. 2024 Mar;17(3):e011246.
doi: 10.1161/CIRCHEARTFAILURE.123.011246. Epub 2024 Mar 4.

Torsemide Versus Furosemide After Discharge in Patients Hospitalized With Heart Failure Across the Spectrum of Ejection Fraction: Findings From TRANSFORM-HF

Chris J Kapelios  1 , Stephen J Greene  2   3 , Robert J Mentz  2   3 , Uchechukwu Ikeaba  2 , Daniel Wojdyla  2 , Kevin J Anstrom  4 , Eric L Eisenstein  2 , Bertram Pitt  5 , Eric J Velazquez  6 , James C Fang  2 ; TRANSFORM-HF Investigators
Affiliations
Randomized Controlled Trial

Torsemide Versus Furosemide After Discharge in Patients Hospitalized With Heart Failure Across the Spectrum of Ejection Fraction: Findings From TRANSFORM-HF

Chris J Kapelios et al. Circ Heart Fail. 2024 Mar.

Abstract

Background: The TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) found no significant difference in all-cause mortality or hospitalization among patients randomized to a strategy of torsemide versus furosemide following a heart failure (HF) hospitalization. However, outcomes and responses to some therapies differ by left ventricular ejection fraction (LVEF). Thus, we sought to explore the effect of torsemide versus furosemide by baseline LVEF and to assess outcomes across LVEF groups.

Methods: We compared baseline patient characteristics and randomized treatment effects for various end points in TRANSFORM-HF stratified by LVEF: HF with reduced LVEF, ≤40% versus HF with mildly reduced LVEF, 41% to 49% versus HF with preserved LVEF, ≥50%. We also evaluated associations between LVEF and clinical outcomes. Study end points were all-cause mortality or hospitalization at 30 days and 12 months, total hospitalizations at 12 months, and change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score.

Results: Overall, 2635 patients (median 64 years, 36% female, 34% Black) had LVEF data. Compared with HF with reduced LVEF, patients with HF with mildly reduced LVEF and HF with preserved LVEF had a higher prevalence of comorbidities. After adjusting for covariates, there was no significant difference in risk of clinical outcomes across the LVEF groups (adjusted hazard ratio for 12-month all-cause mortality, 0.91 [95% CI, 0.59-1.39] for HF with mildly reduced LVEF versus HF with reduced LVEF and 0.91 [95% CI, 0.70-1.17] for HF with preserved LVEF versus HF with reduced LVEF; P=0.73). In addition, there was no significant difference between torsemide and furosemide (1) for mortality and hospitalization outcomes, irrespective of LVEF group and (2) in changes in Kansas City Cardiomyopathy Questionnaire clinical summary score in any LVEF subgroup.

Conclusions: Despite baseline demographic and clinical differences between LVEF cohorts in TRANSFORM-HF, there were no significant differences in the clinical end points with torsemide versus furosemide across the LVEF spectrum. There was a substantial risk for all-cause mortality and subsequent hospitalization independent of baseline LVEF.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296813.

Keywords: diuretics; hospitalization; mortality; quality of life.

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Conflict of interest statement

Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, the American Heart Association (929502), the National Heart, Lung, and Blood Institute, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards for Amgen, AstraZeneca, Boehringer Ingelheim/Lilly, Bristol Myers Squibb, Cytokinetics, Roche Diagnostics, and Sanofi; serves as a consultant for Amgen, Bayer, Bristol Myers Squibb, Boehringer Ingelheim/Lilly, CSL Vifor, Merck, PharmaIN, Roche Diagnostics, Sanofi, Tricog Health, Urovant Pharmaceuticals; and has received speaker fees from Boehringer Ingelheim, Cytokinetics, and Roche Diagnostics. Dr Anstrom has received research support from Merck, Bayer, Pfizer, National Institutes of Health, and the Patient-Centered Outcomes Research Institute. Dr Mentz receives research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. All other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Forest plot depicting hazard ratios (HR)/rate ratio (RR) assessing relative risk of all clinical endpoints across the 3 left ventricular ejection fraction groups
Figure 2.
Figure 2.. Unadjusted hazard for the all-cause mortality at 12 months (upper), all-cause mortality and/or all-cause hospitalization at 12 months (middle) and all-cause hospitalization at 12 months (lower) across the left ventricular ejection fraction (LVEF) stratified by sex.
Restricted cubic spline of (4-spline knot) spline of LVEF on the x axis and the result of Cox regression model expressed as hazard ratios (95% CI) on the y axis. Line represents the point estimate for the HR and the shaded region the 95% confidence intervals. The bars on the lower panel represent distribution of patients across LVEF.
Figure 3.
Figure 3.
Forest plot depicting hazard ratios (HR)/rate ratio (RR) of the treatment effect for all endpoints across the 3 left ventricular ejection fraction groups
Figure 4.
Figure 4.. Hazard for the study clinical outcomes with torsemide vs furosemide across the left ventricular ejection fraction (LVEF) spectrum.
Restricted cubic spline of (4-spline knot) spline of LVEF on the x axis and the result of Cox regression model expressed as hazard ratios (95% CI) on the y axis. All-cause mortality at 12 months (top left), all-cause mortality and/or all-cause hospitalization at 12 months (top right), all-cause mortality at 30 days (bottom left) and all-cause hospitalization at 12 months (bottom right). Line represents the point estimate for the HR and the shaded region the 95% confidence intervals.
See this image and copyright information in PMC

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