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. 2025 Jan 1;36(1):99-107.
doi: 10.1681/ASN.0000000000000481. Epub 2024 Aug 28.

Mechanistic Differences between Torsemide and Furosemide

Veena S Rao  1 , Zachary L Cox  2   3 , Juan B Ivey-Miranda  1   4 , Daniel Neville  1 , Natasha Balkcom  1 , Julieta Moreno-Villagomez  1   5 , Daniela Ramos-Mastache  5 , Christopher Maulion  1 , Lavanya Bellumkonda  1 , W H Wilson Tang  6 , Sean P Collins  7 , Eric J Velazquez  1 , Robert J Mentz  8 , F Perry Wilson  1   9 , Jeffrey M Turner  10 , Christopher S Wilcox  11 , David H Ellison  12 , James C Fang  13 , Jeffrey M Testani  1
Affiliations

Mechanistic Differences between Torsemide and Furosemide

Veena S Rao et al. J Am Soc Nephrol. .

Abstract

Key Points:

  1. Oral torsemide was not superior to furosemide in measures of renal tubular delivery or duration of action.

  2. A dose equivalence of approximately 40 mg oral furosemide:10 mg oral torsemide resulted in similar natriuresis.

  3. The two-fold higher doses of torsemide did not improve fluid status due to the kidney’s compensation.

Background: Torsemide is proposed to have clinically important pharmacokinetic and pharmacodynamic advantages over furosemide. However, clinical outcomes did not differ in the Torsemide Comparison with Furosemide for Management of Heart Failure (TRANSFORM) randomized trial.

Methods: We conducted a multicenter mechanistic substudy of patients with heart failure randomized to oral furosemide or torsemide (TRANSFORM-Mechanism trial). At baseline and 30 days, participants underwent detailed assessments of pharmacokinetic and pharmacodynamic parameters.

Results: The TRANSFORM-Mechanism trial enrolled 88 participants. Kidney bioavailability, or the proportion of dose delivered to the tubular site of action, was significantly less with torsemide compared with furosemide (median, 17.1% [interquartile range, 12.3%–23.5%] versus 24.8% [16.6%–34.1%], P < 0.001). Furosemide had a longer duration of kidney drug delivery and natriuresis (P ≤ 0.004 for both). Prescribed doses of furosemide and torsemide in the TRANSFORM-Mechanism trial were similar to the TRANSFORM trial, with clinicians on average using a 2:1 dose equivalence conversion between drugs. However, these doses resulted in a substantially greater natriuresis with torsemide (P < 0.001). A dose equivalence of approximately 4:1 resulted in similar natriuresis. Higher diuretic doses in the torsemide group resulted in mild perturbations in kidney function and significant increases in renin, aldosterone, and norepinephrine (P < 0.05 for all). Plasma volume (P = 0.52) and body weight (P = 0.89) did not improve with torsemide versus furosemide.

Conclusions: We observed no meaningful pharmacokinetic/pharmacodynamic advantages for torsemide versus furosemide. The greater natriuresis from higher diuretic doses in the torsemide group was offset by greater neurohormonal activation and kidney dysfunction.

Clinical Trial registry name and registration number:: TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure (TRANSFORM-HF), NCT03296813; Torsemide Comparison With Furosemide for Management of Patients With Stable Heart Failure (TFO), NCT05093621.

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Conflict of interest statement

Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/JSN/E835.

References

    1. Heidenreich PA Bozkurt B Aguilar D, et al. . 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263–e421. doi:10.1016/j.jacc.2021.12.012 - DOI - PubMed
    1. Felker GM, Ellison DH, Mullens W, Cox ZL, Testani JM. Diuretic therapy for patients with heart failure: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75(10):1178–1195. doi:10.1016/j.jacc.2019.12.059 - DOI - PubMed
    1. Greene SJ Velazquez EJ Anstrom KJ, et al. . Pragmatic design of randomized clinical trials for heart failure: rationale and design of the TRANSFORM-HF trial. JACC Heart Fail. 2021;9(5):325–335. doi:10.1016/j.jchf.2021.01.013 - DOI - PMC - PubMed
    1. 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. doi:10.1001/jama.2022.23924 - DOI - PMC - PubMed
    1. Vargo DL, Kramer WG, Black PK, Smith WB, Serpas T, Brater DC. Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide and furosemide in patients with congestive heart failure. Clin Pharmacol Ther. 1995;57(6):601–609. doi:10.1016/0009-9236(95)90222-8 - DOI - PubMed

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