Torsemide Provides No Benefit Over Furosemide for Mortality, Hospitalization in Heart Failure

Robert Mentz, MD

To the disappointment of many in the heart failure community, the results of the TRANSFORM-HF trial indicate torsemide did not provide mortality and hospitalization rates relative to furosemide in patients with heart failure.

Funded by the National Heart, Lung, and Blood Institute and presented at the American Heart Association (AHA) 2022 Scientific Sessions, results of the open-label trial indicate there was no meaningful difference in effectiveness for mortality and hospitalization endpoints between a loop diuretic strategy using torsemide or furosemide in patients with heart failure.

“We were disappointed at first because we hoped that there would be a significant clinical difference between these two medicines based on prior studies and clinical experience. While we did not see better outcomes with torsemide, these results help inform our ability to take better care of people living with heart failure,” said Robert J. Mentz, MD, an associate professor of medicine, an associate professor of population health sciences at Duke University School of Medicine, and a chief of the heart failure section at Duke Clinical Research Institute (DCRI), in a statement from the AHA.

Launched in 2018, the Torsemide Comparison with Furosemide for Management of Heart Failure (TRANSFORM-HF) study was as an open-label, pragmatic trial conducted with the intent of comparing the aforementioned loop diuretics in a population of older US adults with heart failure requiring use of diuretics. With this in mind, Mentz and a team of colleagues from the DCRI, Yale School of Medicine, and the NHLBI designed the trial to randomize hospitalized patients with heart failure, regardless of ejection fraction, from 60 US sites in a 1:1 ratio to either torsemide or furosemide.

A total of 2973 consented to take part in the study and 2859 were randomized, with 1431 randomized to torsemide and 1428 randomized to furosemide. The primary outcome of interest for the trial was all-cause mortality. The trial also included multiple secondary endpoints, including total hospitalizations a composite of all-cause mortality and all-cause hospitalizations. Investigators noted a centralized follow-up procedure was implemented for the trial, with follow-up conducted through the DCRI Call Center at 30 days, 6 months, and 12 months after hospital discharge.

Investigators highlighted the diversity achieved within the study’s patient population, with more than one-third of participants being women, one-third being Black adults, and the median age for all participants was 65 years. Additionally, investigators pointed out the population represents a broad range of severity of heart failure and included both newly diagnosed and worsening heart failure.

Over a follow-up period lasting a median of 17.9 months, all-cause mortality was observed among 374 (17.0 per 100 patient-years) individuals randomized to furosemide and 373 (17.0 per 100 patient-years) individuals randomized to torsemide (HR, 1.02 [95% CI, 0.89-1.18]; P=.77) at 6 months. Analysis of secondary endpoints indicated all-cause mortality or hospitalization events at 12 months occurred 704 (107.6 per 100 patient-years) times among those randomized to furosemide and 677 (99.2 per 100 patient-years ) tunes among those randomized to torsemide (HR, 0.92 [95% CI, 0.83-1.02]; P=.11). When assessing total hospitalizations, hospitalization events occurred 987 times among 577 individuals randomized to furosemide and occurred 940 times among 36 individuals randomized to torsemide (RR, 0.94 [95% CI, 0.84-1.07]).

During his presentation at AHA 22, Mentz noted multiple limitations for clinicians to consider when interpreting the results of the TRANSFORM-HF trial, but also pointed out the future opportunities for further examination on the topic born out of the trial.

“Now that we have an answer in this debate, we encourage healthcare professionals to redirect time in a more patient-focused way. Rather than focus on one loop diuretic versus the other, we can focus efforts on making sure the appropriate dose of the loop diuretic is prescribed and re-double our efforts on the therapies that improve outcomes for our patients,” Mentz added.

This study, “Comparative Effectiveness of Torsemide versus Furosemide in Heart Failure: Primary Results of the TRANSFORM-HF Trial,” was presented at AHA 22.