Durham, NC—Based on past studies, researchers hoped to prove that torsemide is more effective in reducing mortality in heart failure (HF) patients than the older and more commonly prescribed furosemide. A large, new trial indicated, however, that the two drugs are no different in their ability to improve patient survival.

The open-label, pragmatic randomized trial, Torsemide Comparison with Furosemide for Management of Heart Failure (TRANSFORM-HF), was led by researchers from the Duke Clinical Research Institute in Durham, North Carolina, and supported by the National Institutes of Health.

These drugs are both diuretics, which help with congestion and breathing difficulties caused by fluid buildup in HF patients.

“Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide,” the authors pointed out in an article from the Journal of the American Medical Association. They sought to answer the question of whether torsemide actually leads to decreased mortality compared with furosemide among patients hospitalized for HF.

During the TRANSFORM-HF trial, researchers recruited 2,859 participants hospitalized with HF (regardless of ejection fraction) at 60 hospitals in the United States. Recruitment began in June 2018 and lasted 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. Participants had a median age of 65 years (interquartile range, 56-75), with 36.9% women and 33.9% black.

Of the patients, 1,431 received the loop diuretic strategy of torsemide compared with 1,428 on furosemide. Dosages were selected by the investigators. The focus was on all-cause mortality in a time-to-event analysis. Of the five secondary outcomes, all-cause mortality or all-cause hospitalization and total hospitalizations assessed over 12 months were considered highest in the hierarchy.

Over a median follow-up of 17.4 months, approximately 4% of each group withdrew, and approximately one-fourth of the patients died.

With the remaining participants, the authors hypothesized that torsemide would reduce all-cause mortality by 20% compared with furosemide. The results of the trial suggested otherwise, however. 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).

The researchers pointed out that hospitalizations also were similar: 940 total among 536 participants in the torsemide group and 987 among 577 participants in the furosemide group (rate ratio, 0.94; 95% CI, 0.84-1.07). They added that results were similar across prespecified subgroups, including among patients with reduced, mildly reduced, or preserved ejection fraction.

“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,” the authors wrote. “However, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence.”

“Overall, our study showed that torsemide did not improve survival compared to furosemide in this high-risk population of patients with heart failure, and we also observed similar rates of hospitalization with the two medications,” study coleader Robert J. Mentz, MD, chief of the heart failure section in the Division of Cardiology and associate professor of medicine at Duke University Medical Center in Durham, North Carolina, said in an NIH press release.

“We’re not saying that patients don’t need diuretics. We’re saying that there’s no difference in the survival benefit of these two therapies,” Dr. Mentz noted. “This suggests we should be spending more time focusing on the right diuretic dose for our patients and working to treat patients with therapies that improve clinical outcomes in heart failure.”

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