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ABSTRACT Aim Methods and results Conclusions The TRANSFORM‐HF trial demonstrated no significant outcome differences between torsemide and furosemide following hospitalization for heart failure (HF), but may have been impacted by non‐adherence to the randomized diuretic. The current study sought to determine the treatment effect of torsemide versus furosemide using an on‐treatment analysis inclusive of all randomized patients except those confirmed non‐adherent to study diuretic.TRANSFORM‐HF was an open‐label, pragmatic randomized trial of 2859 patients hospitalized for HF from June 2018 through March 2022. Patients were randomized to a loop diuretic strategy of torsemide versus furosemide with investigator‐selected dosage. This post‐hoc on‐treatment analysis included all patients alive with either known or unknown diuretic status, and excluded patients confirmed to be non‐adherent to study diuretic. This modified on‐treatment definition was applied separately at time of hospital discharge and 30‐day follow‐up. All‐cause mortality and hospitalization outcomes were assessed over 12 months. Overall, 2570 (89.9%) and 2374 (83.0%) patients were included in on‐treatment analyses at discharge and 30‐day follow‐up, respectively. There was no significant difference in all‐cause mortality between torsemide and furosemide in patients on‐treatment at discharge (17.5% vs. 17.8%; hazard ratio [HR] 1.01 [95% confidence interval [CI] 0.83–1.22], p = 0.96) and at 30‐day follow‐up (14.5% vs. 15.0%; HR 1.02 [95% CI 0.81–1.27], p = 0.90). All‐cause mortality or all‐cause hospitalization was similar between torsemide and furosemide in patients who were on‐treatment at discharge (58.3% vs. 61.3%; HR 0.92 [95% CI 0.82–1.03]) and 30‐day follow‐up (60.9% vs. 64.4%; HR 0.93 [95% CI 0.82–1.05]). In patients who were on‐treatment at 30‐day follow‐up, there were 677 total hospitalizations in the torsemide group and 686 total hospitalizations in the furosemide group (rate ratio 0.99 [95% CI 0.86–1.14], p = 0.87).In TRANSFORM‐HF, a post‐hoc on‐treatment analysis did not meaningfully differ from the original trial results. Among those deemed compliant with the assigned diuretic, there remained no significant difference in mortality or hospitalization after HF hospitalization with a strategy of torsemide versus furosemide.Clinical Trail Registration: ClinicalTrials.gov Identifier: NCT03296813. [ABSTRACT FROM AUTHOR]

Background: Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As prespecified secondary end points, the TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF. Methods: TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomly assigned in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on prespecified secondary end points, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; assessed as adjusted mean difference in change from baseline; range, 0–100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (range, 0–6; score ≥3 supporting evaluation for depression) over 12 months. Results: Baseline data were available for 2787 (97.5%) patients for KCCQ-CSS and 2624 (91.8%) patients for Patient Health Questionnaire-2. Median (interquartile range) baseline KCCQ-CSS was 42 (27–60) in the torsemide group and 40 (24–59) in the furosemide group. At 12 months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference, 0.06 [95% CI, –2.26 to 2.37]; P =0.96) or the proportion of patients with Patient Health Questionnaire-2 score ≥3 (15.1% versus 13.2%: P =0.34). Results for KCCQ-CSS were similar at 1 month (adjusted mean difference, 1.36 [95% CI, –0.64 to 3.36]; P =0.18) and 6-month follow-up (adjusted mean difference, –0.37 [95% CI, –2.52 to 1.78]; P =0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent before hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization. Conclusions: Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, previous loop diuretic use, and baseline health status. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296813. [ABSTRACT FROM AUTHOR]