The study also identified similar 12-month outcomes between torsemide and furosemide regardless of heart failure (HF) type.
Among individuals discharged following hospitalization for heart failure (HF), newly developed or de novo HF demonstrated superior clinical and patient-reported results compared with worsening HF (WHF). Additionally, regardless of HF type, there were no notable variations in 12-month clinical or patient-reported outcomes between torsemide and furosemide.
These findings are based on a subanalysis of the Torsemide Comparison With Furosemide for Management of Heart Failure (TRANSFORM-HF) randomized clinical trial published in JAMA Cardiology.
The substudy included 2858 patients with a documented ejection fraction who participated in the TRANSFORM-HF trial, which was conducted between June 2018 and March 2022. The current patient cohort had a mean (SD) age of 64.5 (14) years, and more than 60% were male. Of this group, 838 patients (29.3%) had de novo HF, and 2020 patients (70.7%) had WHF. Aside from the varying ratios of patients with each HF type, the de novo HF group also had a mean age 6 years younger than that of the WHF group, a higher glomerular filtration rate, lower levels of natriuretic peptides, and were generally discharged on lower doses of loop diuretic.
The study assessed all-cause mortality and hospitalization outcomes for a 12-month period and measured changes from the initial state in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS).
The main finding was that de novo HF was associated with lower all-cause mortality at 12 months, occurring in 65 (9.1%) of patients with newly developed HF compared with 408 (25.4%) of patients with WHF (adjusted HR [aHR], 0.50; 95% CI, 0.38-0.66; P < .001). Patients with de novo HF also experienced a reduced incidence of all-cause first rehospitalization at 12 months, as well as greater improvement from baseline in KCCQ-CSS at 12 months, with a median (IQR) score of 29.94 (27.35-32.54) compared with 23.68 (21.62-25.74) for patients with WHF. The adjusted estimated difference in means was 6.26 (95% CI, 3.72-8.81; P < .001).
Looking at the difference between the 2 drugs, the researchers found no significant difference in mortality between torsemide and furosemide in either patients group. For the de novo group, the number of events per 100 patient-years was 27 (7.4%) for torsemide and 38 (10.9%) for furosemide (aHR, 0.70; 95% CI, 0.40-1.14; P = .15). For the WHF group, these rates were 212 (26.8%) for torsemide and 196 (24.0%) for furosemide (aHR, 1.08; 95% CI, 0.89-1.32; P = .42; P for interaction = .10). The study also did not demonstrate any significant differences in hospitalization, first all-cause hospitalization, or total hospitalization at 12 months between the drugs in either de novo HF or WHF.
The study also revealed generally low (2.8%) rate of discontinuation of diuretics at discharge, with no significant differences between de novo HF and WHF cases. However, patients with de novo HF exhibited a consistent increase in loop diuretic discontinuation at month 1 (6.5%), month 6 (9.1%), and month 12 (12.9%).
Although there was a nominally significant decrease in mortality observed at the 12-month mark among the torsemide group in patients with de novo HF and an ejection fraction of 40% or less—with a significant interaction P value of 0.03—the infrequent occurrence of events in these patients and the absence of a similar pattern in other clinical endpoints suggest that this isolated finding is likely due to chance and, as a result, lacks clinical significance.
The authors acknowledged that factors like sample size, crossover rates, and discontinuation of diuretics during the follow-up period could potentially affect the results. Additionally, despite making statistical adjustments, there remains the possibility of residual or unmeasured confounding influencing the study outcomes.
Krim SR, Anand S, Greene SJ, et al. Torsemide vs furosemide among patients with new-onset vs worsening chronic heart failure: a substu dy of the TRANSFORM-HF randomized clinical trial. JAMA Cardiol. Published online November 13, 2023. doi:10.1001/jamacardio.2023.4776