Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure
Authors: Mentz Robert J. , Anstrom Kevin J. , Eisenstein Eric L. , Sapp Shelly , Greene Stephen J. , Morgan Shelby , Testani Jeffrey M. , Harrington Amanda H. , Sachdev Vandana , Ketema Fassil , Kim Dong-Yun , Desvigne-Nickens Patrice , Pitt Bertram , Velazquez Eric J. ,   TRANSFORM-HF Investigators, Adams Kirkwood F. , Bhatt Kunal , DeWald Tracy , Axsom Kelly M. , Murthy Sandhya , Rich Jonathan D. , Testani Jeffrey , Smith Bryan A. , Vader Justin M. , McCulloch Michael D. , Skopicki Hal A. , Psotka Mitchell A. , Heroux Alain L. , Lala-Trindade Anuradha , Stevens Gerin R. , Tang WH Wilson , Lev Yair A. , William Preethi , Eberly Arthur L. , Gottleib Stephen S. , Haught W. Herbert , Grafton Gillian F. , Larned Joshua M. , Tejwani Lokesh K. , Mody Freny V. , Krim Selim R. , Robinson Monique T. , Fang James C. , Adler Alexander A. , Bell Adrian C. , Banerjee Dipanjan , Ruiz Duque Ernesto A. , Mizyed Ahmad M. , Rommel John J. , Arhinful Justice S. , Goyal Parag , Hall Michael E. , Hummel Scott L. , Shetty Sanjay , Haas Donald C. , Vilaro Juan R. , Alexy Tamas , Herre John M. , Clark John M. , Ambrosy Andrew P. , Gaglianello Nunzio A. , Ramasubbu Kumudha , Meadows Judith L. , Tabtabai Sara R. , Sherwood Melody , Hasni Syed , D'Urso Michael , Muneer Basharat , Dunlap Stephanie H. , Davis William , Friedman Dennis , Guglin Maya , Ferguson Andrew D. , Abbate Antonio , Smart Frank 
Published: January 2023

Importance

Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide.

Objective

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

Design, Setting, and Participants

TRANSFORM-HF was an open-label, pragmatic randomized trial that recruited 2859 participants hospitalized with heart failure (regardless of ejection fraction) at 60 hospitals in the United States. Recruitment occurred from June 2018 through March 2022, with follow-up through 30 months for death and 12 months for hospitalizations. The final date for follow-up data collection was July 2022.

Interventions

Loop diuretic strategy of torsemide (n = 1431) or furosemide (n = 1428) with investigator-selected dosage.

Main Outcomes and Measures

The primary outcome was all-cause mortality in a time-to-event analysis. There were 5 secondary outcomes with all-cause mortality or all-cause hospitalization and total hospitalizations assessed over 12 months being highest in the hierarchy. The prespecified primary hypothesis was that torsemide would reduce all-cause mortality by 20% compared with furosemide.

Results

TRANSFORM-HF randomized 2859 participants with a median age of 65 years (IQR, 56-75), 36.9% were women, and 33.9% were Black. Over a median follow-up of 17.4 months, a total of 113 patients (53 [3.7%] in the torsemide group and 60 [4.2%] in the furosemide group) withdrew consent from the trial prior to completion. Death occurred in 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group (hazard ratio, 1.02 [95% CI, 0.89-1.18]). Over 12 months following randomization, all-cause mortality or all-cause hospitalization occurred in 677 patients (47.3%) in the torsemide group and 704 patients (49.3%) in the furosemide group (hazard ratio, 0.92 [95% CI, 0.83-1.02]). There were 940 total hospitalizations among 536 participants in the torsemide group and 987 total hospitalizations among 577 participants in the furosemide group (rate ratio, 0.94 [95% CI, 0.84-1.07]). Results were similar across prespecified subgroups, including among patients with reduced, mildly reduced, or preserved ejection fraction.

Conclusions and Relevance

Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months. However, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence.

Trial Registration

ClinicalTrials.gov Identifier: NCT03296813