By Rebecca Malakoff, DVM, DACVIM (Cardiology)
Loop diuretics have been a mainstay of treatment for congestive heart failure (CHF) for decades, with furosemide the most commonly used drug for veterinary patients. Dogs and cats receiving treatment for CHF often require progressively increasing doses of diuretics to manage their disease, both because of progression of their underlying disease, and due to the development of diuretic resistance. Well-described in human patients, diuretic resistance occurs due to numerous factors including nephron hypertrophy, poor oral bioavailability, poor renal perfusion, and activation of the renin-angiotensin-aldosterone system.
Torsemide is a loop diuretic and a chloride-channel blocker, shown to have a greater bioavailability, longer half-life, and longer duration of action than furosemide in human patients. In addition, torsemide has aldosterone antagonist properties, which may lead to blunting of diuretic resistance and has antifibrotic effects on the myocardium. The TORIC study (Torasemide in Congestive Heart Failure)1 demonstrated superior performance of torsemide in human patients, when compared to furosemide and other diuretics, in lowering total mortality and cardiac mortality as well as reducing hospital readmission rate. In fact, a 2009 review of loop diuretics recommended that torsemide be considered a first-line therapy in humans with heart failure, based on the more favorable pharmacokinetics, efficacy, and safety compared to furosemide.2
Torsemide has been increasingly studied and used in our veterinary patients as well. The basic pharmacokinetic and pharmacodynamic properties have been determined. It has been shown that torsemide at 1/10th the dose of furosemide produces equivalent diuresis in dogs, and that torsemide’s duration of action is approximately twice that of furosemide (12 h vs. 5-6 h).3 A case series of 3 dogs with advanced heart failure described successful use of torsemide to achieve apparent long-term resolution of CHF in patients previously suffering frequent relapses (suspected due to diuretic resistance) on furosemide.4 A 2012 study demonstrated that torsemide was well tolerated and is equivalent to furosemide at controlling clinical signs of CHF in dogs in the short term (double-blinded, randomized, crossover design with total of 14 days in the study period).5 Torsemide use in cats is under investigation as well, and two studies (presented at recent veterinary forums)6,7 retrospectively evaluated cats receiving torsemide yielding similar results. Torsemide was generally well tolerated in these cats with heart failure and a high diuretic requirement, although increased azotemia and decreased potassium were noted in both groups of cats at the first recheck, with a proportion of cats in both series requiring reduced torsemide dosing during chronic use due to azotemia. Increased risk of azotemia may be a concern in our canine patients as well.
Thus far, most use of torsemide in U.S. veterinary patients has been to replace furosemide for patients on moderate to high furosemide doses (roughly 4-8 mg/kg/day). The pharmaceutical company Vetoquinol announced the European release of UpCard® (torasemide) in 2015. The company markets this as a once daily medication (licensed for dogs), and the 2017 TEST study results (Short-Term Efficacy and Safety of Torasemide and Furosemide in 366 Dogs with Degenerative Mitral Valve Disease) demonstrated that torsemide (once daily) was non-inferior to furosemide (twice daily) as part of standard CHF therapy over 3 months.8 It seems likely, therefore, that our European colleagues may be among the first to try torsemide as a first-line diuretic in their veterinary CHF patients rather than as a replacement for furosemide.
- Cosin J, Diez J, TORIC investigators. Torasemide in chronic heart failure: results of the TORIC study. Eur J Heart Fail 2002:4:507-513.
- Wargo KA, Banta WM. A comprehensive review of the loop diuretics: should furosemide be first line? Ann Pharmacother 2009;43:1836-1847.
- Uechi M, Matsuoka M, Kuwajima E, et al. The effects of the loop diuretics furosemide and torasemide on diuresis in dogs and cats. J Vet Med Sci 2003;10:1057-1061.
- Oyama M, Peddle G, Reynolds C, et al. Use of the loop diuretic torsemide in three dogs with advanced heart failure. J Vet Cardiol 2011;13:287-292.
- Peddle G, Singletary G, Reynolds C, et al. Effect of torsemide and furosemide on clinical, laboratory, radiographic and quality of life variables in dogs with heart failure secondary to mitral valve disease. J Vet Cardiol 2012;14:253-259.
- Mcdonald R. Use of torasemide in cats for congestive heart failure. Proceedings: ECVIM-CA Congress, 2016.
- Giatis I, Nguyenba T, Oyama M, et al. Use of torsemide in 17 cats with advanced congestive heart failure. Proceedings: ACVIM 2014.
- Chetboul V, Pouchelon J-L, Menard J, et al. Short-term efficacy and safety of torasemide and furosemide in 366 dogs with degenerative mitral valve disease: the TEST study. J Vet Intern Med 2017;31(6):1629-1642.