Comparable Results Seen From Investigation of Torsemide vs Furosemide in HF

Mortality outcome differences were insignificant following a comparison of torsemide and furosemide among patients with heart failure who were hospitalized for either de novo disease or worsening chronic disease, according to recent study findings in JAMA on 12-month outcomes between the loop diuretics.

Their findings from the TRANSFORM-HF trial compared the 2 medications. According to the study, “Furosemide is the most common loop diuretic used in heart failure and torsemide has increased bioavailability and a longer half-life than furosemide. However, in light of the lack of an adequately powered clinical outcomes study, there is insufficient evidence to recommend torsemide over furosemide.”

Dosage of the drugs was selected by the investigators—1 mg of torsemide to 2 to 4 mg of furosemide—and patients were randomized 1:1. There were 1431 patients taking torsemide and 1428 taking furosemide, all of whom were hospitalized for heart failure at 60 hospitals within the United States. Follow-up data collection ended in July 2022, with an average 30-month follow-up for death and 12 months for hospitalizations. The primary outcome was all-cause mortality, with “changes in dose and frequency of the randomized therapy after discharge at the discretion of the patient’s usual outpatient clinicians.”

Mean (SD) patient ages were 64.0 (14.0) and 65.0 (14.0) in the torsemide and furosemide cohorts, respectively. Fewer participants were female patients (34.8% and 39.0%) than male patients (65.2% and 61.0%), and most were White ethnicity (58.1% and 58.6%) or Black or African American ethnicity (33.1% and 34.6%).

Rates of study withdrawal were comparable between the torsemide and furosemide groups, at 3.7% and 4.2%, respectively. Overall mortality rates were similar as well, at 26.1% and 26.2%, with an overall risk of death in the furosemide group that was just 2% higher (HR, 1.02; 95% CI, 0.89-1.18). Median follow-up was 17.4 months.

Among the secondary outcomes evaluated in the year following randomization, all-cause mortality/all-cause hospitalization were seen in close to equal amounts of patients in each group: 47.3% of the torsemide group and 49.3% of the furosemide group (HR, 0.92; 95% CI, 0.83-1.02). When just hospitalizations were considered, the rates again trended similar, with 536 participants in the torsemide group having 940 hospitalizations and 577 participants in the furosemide group having 987 hospitalizations (rate ratio, 0.94; 95% CI, 0.84-1.07).

Among the overall study cohort, follow-ups with telephone interviews took place at 30 days and 6 and 12 months after hospital discharge. There was an additional follow-up carried out among the first 1500 study participants, who were broken out into 3 groups:

• 1 to 500 were called every 6 months for 30 months
• 501 to 1000 were called every 6 months for 24 months
• 1001 to 1500 were called every 6 months for 18 months

A subanalysis of outcomes among patients who had heart failure with reduced ejection fraction (<40%) showed that at baseline, 81.5% were on beta-blockers; 67.5% were taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or angiotensin receptor-neprilysin inhibitors, with 25.2% solely taking ARNIs; 44.3% were taking mineralocorticoid receptor antagonists; and 7.8% were on sodium-glucose cotransporter 2 inhibitors.

The most common comorbidity among both groups was diabetes, and 67.4% of the torsemide group and 66.9% of the furosemide group had a history of loop diuretic use before randomization in the present study. Of the 3 loop diuretics considered for this patient characteristic, most (52.7% of the torsemide group and 54.5% of the furosemide group) had a prior history of furosemide use.

The present study authors noted that their findings conflict with those of previous studies—mechanistic studies, observational analyses, and meta-analyses—which showed a survival benefit from torsemide.

“There was no evidence that torsemide’s favorable bioavailability or purported antifibrotic effects translated into improved outcomes for patients recently hospitalized with heart failure,” they wrote. These findings were consistent across age, sex, race, and ethnicity. A potential reason for these results is that one-third of the patients in the overall analysis had recently received their heart failure diagnosis, so their clinical outcomes could have been affected by postbaseline changes in therapy.

Reference

Mentz RJ, Anstrom KJ, Eisenstein EL, et al. Effect of torsemide vs furosemide after discharge on all-cause mortality in patients hospitalized with heart failure: the TRANSFORM-HF randomized clinical trial. JAMA. 2023;329(3):214-223.10.1001/jama.2022.23924