Torsemide not associated with significant difference in all-cause mortality over 12 months compared to furosemide – The TRANSFORM-HF randomized clinical trial

1. In this randomized clinical trial, among 2859 patients, death occurred in 26.1% of patients randomized to torsemide and 26.2% of patients randomized to furosemide over a median follow-up period of 17.4 months, with no significant difference between groups.

2. Rates of hospitalizations in the torsemide and furosemide groups were 37.5% and 40.4%, respectively.

Evidence Rating Level:1 (Excellent)

Study Rundown: Heart failure (HF) is commonly characterized by symptoms of congestion and volume overload that can present as dyspnea and edema. Current guidelines recommend the use of diuretics for the treatment of congestion in symptomatic patients with HF. Furosemide is the most commonly prescribed diuretic for HF, however, recent clinical data suggest potential benefits of torsemide when compared when furosemide. The objective of the TRANSFORM-HF (Torsemide Comparison with Furosemide for Management of Heart Failure) trial was to compare the effectiveness of torsemide with furosemide in patients hospitalized with HF. A total of 2859 participants hospitalized with HF were recruited between 2018 and 2022, with follow-up through 30 months for death and 12 months for hospitalizations. Patients were randomized to receive either torsemide (n=1431) or furosemide (n=1428). The main outcome was all-cause mortality, and secondary outcomes included all-cause hospitalization and total hospitalizations assessed over 12 months. Death occurred in 26.1% of patients in the torsemide group, and 26.2% of patients in the furosemide group. 12 months post-randomization, all-cause mortality or all-cause hospitalization occurred in 47.3% of patients in the torsemide group and 49.3% of patients in the furosemide group. When compared with furosemide, torsemide did not result in a significant difference in all-cause mortality over 12 months.  A major strength of this trial was that over 30% women were recruited for both intervention groups. Interpretation of these findings may be limited, however, due to the loss to follow-up, participant crossover and non-adherence.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

Relevant Reading: Diuretic changes, health care resource utilization, and clinical outcomes for heart failure with reduced ejection fraction: From the change the management of patients with heart failure registry

In-Depth [randomized controlled trial]: This study investigated whether torsemide resulted in decreased mortality compared with furosemide in patients hospitalized for HF. The TRANSFORM-HF trial recruited a total of 2859 patients that were randomized to receive either torsemide (n = 1431) or furosemide (n = 1428). The primary outcome was all-cause mortality, with secondary outcomes including all-cause hospitalization and total hospitalizations assessed over 12 months. Death occurred in 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group (HR, 1.02 [95% CI, 0.89-1.18]; P = .76). 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 (HR, 0.92 [95% CI, 0.83-1.02]). There were 940 total hospitalizations among 536 participants (37.5%) in the torsemide group and 987 total hospitalizations among 577 participants (40.4%) in the furosemide group (rate ratio, 0.94 [95% CI, 0.84 – 1.07]). The post hoc analysis addressed competing risks for all-cause hospitalizations over a 12-month period and determined a hazard ratio of 0.88 (95% CI, 0.78 – 0.99) with torsemide compared with furosemide.

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