TRANSFORM-HF Quality of Life Data Further Informs Diuretic Use in Heart Failure

An analysis of data from the TRANSFORM-HF trial is providing further insight into the comparative effects of furosemide and torsemide in patients hospitalized for heart failure.

Results of the analysis, which used the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and Patient Health Questionnaire-2 (PHQ-2) data to examine effects of both agents on symptoms and quality of life among patients from the landmark trial, suggest there were no significant differences in quality of life measures or symptom improvement over the 12-month period.¹

“My big take home point from transformed is that it clarifies a bit how we should be spending our clinical time when we are thinking about the medical management for our patients with heart failure,” said Stephen Greene, MD, a heart failure cardiologist at Duke University Medical Center, in an interview with HCPLive Cardiology. “Instead of devoting clinical time to thinking about 'Well, hey is torsemide my agent or is furosemide my agent for loop diuretic?', we are better shifting that time spent in thought to actually making sure we, one, prioritize diuretic dosing, and, two, focus on timely optimization of guideline-directed medical therapy.”

Launched in 2018 and presented at the American Heart Association’s (AHA) 2022 Scientific Sessions, TRANSFORM-HF was an open-label, pragmatic trial launched in 2018 with the intent of comparing the effects of torsemide and furosemide in a population of older adults hospitalized with heart failure requiring use of diuretics at 60 sites within the US. A total of 2859 patients underwent randomization in the trial.

Initial results from AHA 2022 indicated all-cause mortality was observed among 374 (17.0 per 100 patient-years) individuals randomized to furosemide and 373 (17.0 per 100 patient-years) individuals randomized to torsemide (Hazard Ratio [HR], 1.02 [95% Confidence Interval [CI], 0.89 to 1.18]; P = .77) at 6 months. Analysis of secondary endpoints indicated all-cause mortality or hospitalization events at 12 months occurred 704 (107.6 per 100 patient-years) times among those randomized to furosemide and 677 (99.2 per 100 patient-years) times among those randomized to torsemide (HR, 0.92 [95% CI, 0.83 to 1.02]; P = .11).²

In the current study, investigators sought to further assess the effects of each agent by comparing quality of life and symptom data recorded within the trial. From the 2859 patients included in the trial, cohorts off 2787 and 2624 patients were identified with baseline KCCQ-CSS and PHQ-2 scores available for analysis. The median baseline scores were 42 (Interquartile range [IQR], 25 to 60) and 2 (IQR, 0 to 3) for KCCQ-CSS and PHQ-2, respectively.¹

Results of the investigators’ analysis suggested there was no significant difference between torsemide and furosemide in change from baseline to 12 months in KCCQ-CSS (adjusted mean difference 0.06 [95% CI, -2.26 to 2.37]; P = .96) or the proportion of patients with PHQ-2 score of 3 or more (15.1% vs 13.2%; P = .34). Further analysis indicated the KCCQ-CSS were similar at the 1-month (adjusted mean difference 1.36 [95% CI, -0.64 to 3.36]; P = .18) and 6-month follow-ups (adjusted mean difference -0.37 [95% CI, -2.52 to 1.78]; P=0.73), with investigators noting this was consistent across subgroups defined by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent prior to hospitalization.¹

With an interest in learning more about the analysis and how it helps further inform use of loop diuretics in people with symptomatic heart failure, our editorial team sat down with Greene at the Metabolic Institute of America’s 7th annual Heart in Diabetes meeting.

Greene reports having received funds for consulting or research grants from Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others. Here is a full list of relevant disclosures.

References:

1. Greene SJ, Velazquez EJ, Anstrom KJ, et al. Effect of Torsemide vs Furosemide on Symptoms and Quality of Life Among Patients Hospitalized for Heart Failure: The TRANSFORM-HF Randomized Clinical Trial [published online ahead of print, 2023 May 22]. Circulation. 2023;10.1161/CIRCULATIONAHA.123.064842. doi:10.1161/CIRCULATIONAHA.123.064842
2. Campbell P. Torsemide provides no benefit over furosemide for mortality, hospitalization in heart failure. HCP Live. November 5, 2022. Accessed June 12, 2023. https://www.hcplive.com/view/torsemide-provides-no-benefit-over-furosemide-for-mortality-hospitalization-in-heart-failure.