No survival advantage for either torsemide or furosemide in HF: TRANSFORM-HF

HF regardless of EF

The trial enrolled patients hospitalized with worsening or new-onset HF with a plan for long-term loop diuretic therapy who had either an EF of 40% or lower or, regardless of EF, elevated natriuretic peptide levels when hospitalized.

Of the 2,859 participants, whose mean age was about 65 years, about 36% were women and 34% African American. Overall, 1,428 were assigned to receive furosemide as their initial oral diuretic and 1,431 patients were assigned to the torsemide-first strategy.

The rate of death from any cause in both groups was 17 per 100 patient-years at a median of 17.4 months. The hazard ratio for torsemide vs. furosemide was 1.02 (95% confidence interval, 0.89-1.18; P = .77).

The corresponding HR at 12 months for all-cause death or hospitalization was 0.92 (95% CI, 0.83-1.02;  P = .11). The relative risk for any hospitalization was 0.94 (95% CI, 0.84-1.07).

Pragmatic design: Other implications

Dosing was left to clinician discretion in the open-label study, as was whether patients maintained their assigned drug or switched over to the other agent. Indeed, 5.4% of patients crossed over to the other loop diuretic, and 2.8% went off loop diuretics entirely between in-hospital randomization and discharge, Dr. Mentz reported. By day 30, 6.7% had crossed over, and 7% had stopped taking loop diuretics.

The diuretic crossovers and discontinuations, Dr. Mentz said, likely biased the trial’s outcomes, such that the two strategies performed about equally well. Efforts were made, however, to at least partially overcome that limitation.

“We put measures in place to support adherence – sending letters to their primary doctors, giving them a wallet card so they would know which therapy they were on, having conversations about the importance of trying to stay on the randomized therapy,” Dr. Mentz said in an interview. Still, some clinicians saw differences between the two agents that prompted them, at some point, to switch patients from one loop diuretic to the other.

But interestingly, Dr. Mentz reported, the two strategies did not significantly differ in all-cause mortality or the composite of all-cause mortality or hospitalization in analysis by intention to treat.

Dr. Mentz discloses receiving honoraria from AstraZeneca, Bayer/Merck, Boehringer Ingelheim/Lilly, Cytokinetics, Pharmacosmos, Respicardia, Windtree Therapeutics, and Zoll; and research grants from American Regent and Novartis. Dr. Bozkurt discloses receiving honoraria from AstraZeneca, Baxter Health Care, and Sanofi Aventis and having other relationships with Renovacor, Respicardia, Abbott Vascular, Liva Nova, Vifor, and Cardurion. Dr. Yancy discloses a modest relationship with Abbott.

A version of this article first appeared on Medscape.com.