Furosemide resists newer, more potent loop diuretic during HF hospitalization

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CHICAGO — The choice between furosemide and torsemide did not matter for longer-term clinical outcomes for hospitalized patients with heart failure, according to the TRANSFORM-HF comparative efficacy trial.

The incidence of all-cause mortality was just over 26% over a median follow-up of 17.4 months, the same 17.0 per 100 patient-years, for those randomly assigned to one either of loop diuretics during their hospital stay (HR 1.02, 95% CI 0.89-1.18), reported Robert Mentz, MD, of Duke University Medical Center in Durham , North Carolina, at the annual meeting of the American Heart Association (AHA).

No difference between the groups was observed in terms of total subsequent hospitalizations (37.5% with torsemide versus 40.4% with furosemide, RR 0.94, 95% CI 0.84-1.07 ) or deaths and hospitalizations combined, i.e. (47.3% versus 49.3%, RR 0.92, 95% CI 0.83-1.02).

“We were initially disappointed because we expected there would be a clinically meaningful difference between these two drugs based on previous studies and clinical experience. Although we did not see better results with torsemide, these results help us better care for people living with heart failure,” Mentz said in a press release.

“Now that we have an answer in this debate, we encourage healthcare professionals to redirect time in a more patient-centered way. Rather than focusing on one loop diuretic over the other , we can focus our efforts on ensuring the correct dose of the loop diuretic is prescribed and redouble our efforts on therapies that improve outcomes for our patients,” he said.

Furosemide has historically been the most commonly used loop diuretic for volume management in heart failure. It remains preferred due to its familiarity and low cost in clinical practice. Torsemide, a newer but still relatively inexpensive agent, is thought to work better due to more consistent oral bioavailability, longer duration of action, and other mechanistic effects – but it hasn’t. been proven to be clinically more effective.

AHA session discussant Biykem Bozkurt, MD, PhD, of Baylor College of Medicine in Houston, said TRANSFORM-HF investigators may have been overly optimistic in trying to show a torsemide survival advantage when , in recent trials, most heart failure drugs are combined. with a reduction in cardiovascular deaths and hospitalizations for heart failure in particular.

Additionally, the Mentz group included the group of historically difficult-to-treat individuals with preserved ejection fraction, and the overall cohort was subjected to increasing medical therapy directed by background guidelines during the study. , noted Bozkurt.

As such, she concluded, “TRANSFORM is unlikely to change practice. Clinicians are likely to continue to use torsemide at their discretion, particularly when better bioavailability and diuretic potency are desired, particularly in patients with heart failure with diuretic resistance, significant congestion, and chronic kidney disease.”

The trial was conducted at 60 US sites and began recruiting in 2018.

Mentz and colleagues had 2,859 people (mean age 65, less than 40% female, 33% black) randomized to receive one of the two loop diuretics under study. The proportion of newly diagnosed heart failure was 30%.

Mentz emphasized the pragmatic nature of the trial, which had broad eligibility criteria and a streamlined study protocol integrated into routine care. There were no in-person study visits, and instead investigators relied on telephone follow-up and national death records.

Prior to admission, 67% of participants were taking a loop diuretic, primarily furosemide, with a total daily dose of 66 mg furosemide equivalent. The total daily dose increased to approximately 80 mg furosemide equivalent at discharge, after local clinicians had the opportunity to decide the diuretic dosage for each patient.

As TRANSFORM-HF was conducted in an open label, it is possible that a bias led to change of drug during the study. Crossover and discontinuation of diuretics have occurred in furosemide and torsemide users.

Nevertheless, Mentz reported that the main findings persisted in the in-treatment analysis of people who took their assigned medications at discharge and 30 days.

As the trial was conducted during the pandemic, the all-cause results may also have been affected by COVID-19. Additionally, the trial did not assess decongestion or adverse events such as deterioration of kidney function, electrolyte abnormalities, or out-of-hospital events.

Disclosures

TRANSFORM-HF was supported by the National Heart, Lung and Blood Institute.

Mentz disclosed relationships with Abbott, Boehringer Ingelheim/Lilly, Cytokinetics, Amgen, AstraZeneca, Bayer, InnoLife, Merck, Novartis, Sanofi/Lexicon, Vifor, GlaxoSmithKline, American Reagent, Medtronic, Zoll and Windtree.

Bozkurt disclosed relationships with Bristol Myers Squibb, scPharmaceuticals, Baxter Health Care, Sanofi Aventis Pharmaceuticals, Relypsa, Respicardia, Abbot Vascular and Liva Nova.

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