Results of a large clinical trial counter previous findings of benefit with torsemide.

Several small studies have suggested that the loop diuretic torsemide produces better outcomes than the more commonly used furosemide in patients with heart failure. However, the two agents have never been directly compared in a major clinical trial despite potentially important differences in their bioavailability and other properties. Now, investigators for the TRANSFORM-HF trial (NCT03296813. opens in new tab) report similar 1-year outcomes with use of torsemide versus furosemide in this setting.

In this open-label, pragmatic, multicenter trial, 2859 participants hospitalized for heart failure were randomized to receive torsemide or furosemide. Recruited patients had treatment plans indicating anticipated long-term use of a loop diuretic. The primary outcome was all-cause mortality in a time-to-event analysis. A key secondary outcome was all-cause mortality or all-cause hospitalization assessed over 12 months. Results included the following:

• 12-month death rates of 26.1% in the torsemide group and 26.2% in the furosemide group
• Death or hospitalization in 47.3% and 49.3%, respectively
• A 7% crossover rate from torsemide to furosemide and a 3.8% crossover rate the other way

The authors noted that loss to follow-up and participant crossover and nonadherence were key limitations.

Comment

This study provides evidence that there is little to choose between furosemide and torsemide. As a pragmatic trial, it had broad entry criteria and included people with a range of ejection fractions, which may be good for generalizability, although an editorialist notes challenges in assessing whether there were important differences in subgroups. Also, the trial enrolled fewer patients than planned, reducing the power of subgroup analyses. Nevertheless, it is a solid counterweight to the small and observational studies that noted an immense benefit with torsemide.