Trial Finds No Benefit with Torsemide Versus Furosemide in Heart Failure

Experts said the results will likely not alter practice and clinicians will likely continue to use torsemide.

Late-breaking results from the TRANSFORM-HF trial were presented at the American Heart Association 2022 Scientific Sessions, showing no apparent benefit.

The TRANSFORM-HF trial examined the loop diuretic torsemide versus furosemide, which is the most commonly used loop diuretic, according to presenter Robert Mentz, MD. Despite the widespread usage of furosemide, some earlier data suggest that torsemide may have advantages thanks to its more consistent oral availability, longer duration of action, anti-aldosterone effects, and anti-fibrotic myocardial effects. Additionally, prior observational studies have suggested potential outcome benefits with torsemide.

In the TRANSFORM-HF trial, the primary objective was to compare treatment strategies with torsemide versus furosemide on long-term clinical outcomes among patients hospitalized with heart failure through a pragmatic trial.

The trial included patients regardless of ejection fraction, as long as there was a long-term plan to use loop diuretics. The primary endpoint was all-cause mortality, with the hypothesis that torsemide would reduce mortality by 20% versus furosemide. Secondary endpoints included a composite with all-cause hospitalization and total hospitalizations.

Enrollment for the trial began in June 2018 and investigators recruited an average of 2 or more patients per month per site before the pandemic. As of January 2022, the trial had enrolled 2800 patients. Follow-up ended July 29, 2022, with 2973 enrolled participants and 2859 randomized 1:1 between the 2 arms.

The participants had well-balanced baseline characteristics, with 37% women and a mean age of 64 years. Approximately 30% had newly diagnosed heart failure and the majority had heart failure with reduced ejection fraction.

Over a median follow-up of 17.4 months, there was a very high event rate in the furosemide arm with 374 events (26.2%). A similar high event rate was seen in the torsemide arm, with 373 events (26.1%), indicating no benefit with torsemide.

Researchers saw similar results with all-cause mortality or hospitalization. Participants in the furosemide arm saw 704 events, compared to 677 events in the torsemide group. Finally, there were 987 hospitalizations in the furosemide arm versus 940 in the torsemide group.

Mentz noted several limitations and future opportunities for the research. First, he said that crossovers between the 2 groups and discontinuation would bias toward neutral results. Second, the dose was left to clinicians’ discretion, which could influence the results. There was also no assessment of other adverse events, such as worsening renal function, electrolyte abnormalities, or non-hospitalization events. Future work should characterize how non-adherence and dose may have affected the findings, Mentz said.

Based on their findings, the investigators concluded that a strategy using torsemide had similar efficacy compared with furosemide for the clinical outcomes of mortality and hospitalization in patients hospitalized with heart failure.

Additionally, Mentz said the pragmatic structure of the trial had significant benefits. The broad eligibility criteria and streamlined study protocol enabled the inclusion of diverse participants, and pragmatic elements lowered traditional barriers. There were also opportunities to enhance patient adherence and engagement at follow-up, and the real-world comparative-effectiveness study results are generalizable to routine clinical practice.

REFERENCE

Mentz R. Comparative Effectiveness of Torsemide Versus Furosemide in Heart Failure. Presented at: American Heart Association 2022 Scientific Sessions. November 5, 2022.