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Torasemide Recommendations

Grade

MMVD (Stage D)

Recommendations by ACVIM Stage

We recommend following ACVIM and similar consensus guidelines for disease staging and the use of ACEi in canine heart failure.

ACVIM MMVD (Stage D) 

Stage D patients have heart failure refractory to stage C treatment protocols. Few clinical trials have addressed drug efficacy and safety in this patient population. 


Pimobendan is administered at 0.25 – 0.3 mg/kg PO every 12 hours, potentially a third daily dose, in addition to some or all of the following medicines.


  • Pimobendan: 0.25 – 0.3 mg/kg PO every 12 hours, potentially a third daily dose. 

  • Furosemide:  6- 8 mg/kg/day in divided doses. However, Torasemide is substituted when patients are no longer considered adequately responsive to Furosemide.

  • Torsemide  0.1-0.2 mg/kg, q12-24h, replaces previous Furosemide dosing with subsequent upward titration (Torsemide is commenced at 5%-10% of the last Furosemide dose in mg/kg). Any initial dose depends on each patient's previous and existing diuretic needs. 

  • Spironolactone: 2 mg/kg PO every 12 to 24 hours (Keene et al., 2019).

  • Benazepril: 0.5 mg/kg PO, q12-24h

Additional Medications and Procedures

These are clinician and patient-specific. Examples include cavitary centesis (abdominal paracentesis, thoracentesis), which may be required to relieve respiratory distress or discomfort. We refer clinicians to current ACVIM MMVD recommendations. 

Subsequent Dosing

  • Dosing Interval: The daily dose is often divided and administered in two equal portions 12 hours apart. 

  • Dose Adjustments: Titrate +/-  0.1 mg/kg PO, q12-24h in response to monitoring patient needs. 

  • Maintenance: The maintenance dose is individually determined through appropriate patient monitoring and associated dose titration. Most patients require <0.3 mg/kg, PO, q12-24h, but doses as high as 0.6mg/kg, PO q 24h appear well tolerated. 

  • Overdose: Clinical studies have not assessed doses greater than 0.8 mg/kg/day, which are associated with an increased risk of dehydration, electrolyte imbalance, renal insufficiency, anorexia, weight loss and cardiovascular collapse.

Therapeutics

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Sole Use

  • Furosemide Replacement: Torasemide is the preferred diuretic in cases of myxomatous mitral valve disease (MMVD) stages C and D, which are no longer responsive to furosemide (Hori et al., 2007). Therefore, in standard medical protocols, its use replaces Furosemide. Concurrent use of multiple-loop diuretics is contraindicated (CEVA Animal Health, 2019; Vetoquinol, 2015). 

Multi-Modal Use

  • ACVIM Consensus Guidelines: Because Torasemide is generally deployed in the late stages of MMVD (Stages C and D), it is usually used multimodally alongside additional medicines  (e.g., Pimobendan, ACE inhibitors, digoxin). Combined with other cardiac treatments, any dosing regimen requires monitoring and modification to balance patient response to therapy (Keene et al., 2019; Vetoquinol, 2015).

  • Acute Crisis: Dogs presenting in acute crisis (pulmonary oedema, pleural effusion and ascites) require emergency treatment with injectable drugs before commencing oral diuretic therapy (Keene et al., 2019).

Efficacy Profile

  • Potency: Torsemide is 10 to 20 times more potent as a loop diuretic than Furosemide. 

  • Bioavailability: It has higher bioavailability and a longer duration of action than Furosemide, with reduced comparative calciuresis and kaliuresis. 

  • Azotaemia: Elevations in BUN and creatinine are seen. Long-term outcomes do not show that azotaemic qualities have detrimental patient effects. 

Treatment Goals

  • Symptom Control: Relieving and managing pulmonary oedema, pleural effusion and ascites.

  • QOL: Improved quality of life of patients with MMVD. 

  • Survival Time: Extended survival times = quality-adjusted life years (QALYs)

Treatment Endpoints

  • Torasemide therapy is seldom withdrawn until patients experience death or euthanasia. 

Therapeutic Monitoring

One (UK/EU) SPC (Vetoquinol, 2015) states that Renal function, hydration status and serum electrolytes status should be monitored (Serum electrolytes, BUN, creatinine, SDMA +/- glucose if diabetic):


  • When treatment with Torasemide is commenced

  • 24-48h post Torasemide commencement

  • 24-48h post Torasemide dose adjustment

  • If adverse events occur.


Additionally, patients will benefit from regular physical assessments covering. Heart rate and quality, respiratory rate and effort (resting and sleeping), blood pressure, signs associated with oedema, thirst, urine output and weight.

Evidence

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1 Species-Specific Evidence Review

  1. Besche, B., Blondel, T., Guillot, E., Garelli-Paar, C., Oyama, M.A., 2020. Efficacy of oral torasemide in dogs with degenerative mitral valve disease and new onset congestive heart failure: The CARPODIEM study. J Vet Intern Med 34, 1746–1758. https://doi.org/10.1111/jvim.15864

  2. Chetboul, V., Pouchelon, J.-L., Menard, J., Blanc, J., Desquilbet, L., Petit, A., Rougier, S., Lucats, L., Woehrle, F., Investigators,  the T. study, 2017. Short-Term Efficacy and Safety of Torasemide and Furosemide in 366 Dogs with Degenerative Mitral Valve Disease: The TEST Study. Journal of Veterinary Internal Medicine 31, 1629–1642. https://doi.org/10.1111/jvim.14841

  3. Hori, Y., Takusagawa, F., Ikadai, H., Uechi, M., Hoshi, F., Higuchi, S., 2007. Effects of oral administration of furosemide and torsemide in healthy dogs. Am J Vet Res 68, 1058–1063. https://doi.org/10.2460/ajvr.68.10.1058

  4. Hosseini, F., Mahmoudi Filabadi, Z., Hill, P.B., Hosseininejad, M., 2023. Evaluation of the short-term echocardiographic effects of two loop diuretics, furosemide and torsemide, in a group of dogs. Veterinary Medicine and Science 9, 1508–1512. https://doi.org/10.1002/vms3.1129

  5. Keene, B.W., Atkins, C.E., Bonagura, J.D., Fox, P.R., Häggström, J., Fuentes, V.L., Oyama, M.A., Rush, J.E., Stepien, R., Uechi, M., 2019. ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. J Vet Intern Med 33, 1127–1140. https://doi.org/10.1111/jvim.15488

  6. Peddle, G.D., Singletary, G.E., Reynolds, C.A., Trafny, D.J., Machen, M.C., Oyama, M.A., 2012. Effect of torsemide and furosemide on clinical, laboratory, radiographic and quality of life variables in dogs with heart failure secondary to mitral valve disease. Journal of Veterinary Cardiology, The Mitral Valve 14, 253–259. https://doi.org/10.1016/j.jvc.2012.01.003

  7. Potter, B.M., Ames, M.K., Hess, A., Poglitsch, M., 2019. Comparison between the effects of torsemide and furosemide on the renin-angiotensin-aldosterone system of normal dogs. Journal of Veterinary Cardiology 26, 51–62. https://doi.org/10.1016/j.jvc.2019.11.003

  8. Sogame, Y., Okano, K., Hayashi, K., Uchida, T., Tsuda, Y., 1996. Urinary excretion profile of torasemide and its diuretic action in dogs. J Pharm Pharmacol 48, 375–379. https://doi.org/10.1111/j.2042-7158.1996.tb05936.x

  9. Uechi, M., Matsuoka, M., Kuwajima, E., Kaneko, T., Yamashita, K., Fukushima, U., Ishikawa, Y., 2003. The effects of the loop diuretics furosemide and torasemide on diuresis in dogs and cats. J Vet Med Sci 65, 1057–1061. https://doi.org/10.1292/jvms.65.1057

2 Condition-Specific Evidence Review

  1. Besche, B., Blondel, T., Guillot, E., Garelli-Paar, C., Oyama, M.A., 2020. Efficacy of oral torasemide in dogs with degenerative mitral valve disease and new onset congestive heart failure: The CARPODIEM study. J Vet Intern Med 34, 1746–1758. https://doi.org/10.1111/jvim.15864

  2. Chetboul, V., Pouchelon, J.-L., Menard, J., Blanc, J., Desquilbet, L., Petit, A., Rougier, S., Lucats, L., Woehrle, F., Investigators,  the T. study, 2017. Short-Term Efficacy and Safety of Torasemide and Furosemide in 366 Dogs with Degenerative Mitral Valve Disease: The TEST Study. Journal of Veterinary Internal Medicine 31, 1629–1642. https://doi.org/10.1111/jvim.14841

  3. Keene, B.W., Atkins, C.E., Bonagura, J.D., Fox, P.R., Häggström, J., Fuentes, V.L., Oyama, M.A., Rush, J.E., Stepien, R., Uechi, M., 2019. ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. J Vet Intern Med 33, 1127–1140. https://doi.org/10.1111/jvim.15488

  4. Peddle, G.D., Singletary, G.E., Reynolds, C.A., Trafny, D.J., Machen, M.C., Oyama, M.A., 2012. Effect of torsemide and furosemide on clinical, laboratory, radiographic and quality of life variables in dogs with heart failure secondary to mitral valve disease. Journal of Veterinary Cardiology, The Mitral Valve 14, 253–259. https://doi.org/10.1016/j.jvc.2012.01.003

3 Substance-Specific Evidence Review

  1. Bikdeli, B., Strait, K.M., Dharmarajan, K., Partovian, C., Coca, S.G., Kim, N., Li, S.-X., Testani, J.M., Khan, U., Krumholz, H.M., 2013. Dominance of furosemide for loop diuretic therapy in heart failure: time to revisit the alternatives? J Am Coll Cardiol 61, 1549–1550. https://doi.org/10.1016/j.jacc.2012.12.043

  2. Cosín, J., Díez, J., Investigators,  on behalf of the T., 2002. Torasemide in chronic heart failure: results of the TORIC study. European Journal of Heart Failure 4, 507–513. https://doi.org/10.1016/S1388-9842(02)00122-8

  3. Ghys, A., Denef, J., Delarge, J., Georges, A., 1985. Renal effects of the high ceiling diuretic torasemide in rats and dogs. Arzneimittelforschung 35, 1527–1531.

  4. Mentz, R.J., Hasselblad, V., DeVore, A.D., Metra, M., Voors, A.A., Armstrong, P.W., Ezekowitz, J.A., Tang, W.H.W., Schulte, P.J., Anstrom, K.J., Hernandez, A.F., Velazquez, E.J., O’Connor, C.M., 2016. Torsemide versus Furosemide in Patients with Acute Heart Failure (From the ASCEND-HF Trial). Am J Cardiol 117, 404–411. https://doi.org/10.1016/j.amjcard.2015.10.059

  5. Müller, K., Gamba, G., Jaquet, F., Hess, B., 2003. Torasemide vs. furosemide in primary care patients with chronic heart failure NYHA II to IV--efficacy and quality of life. Eur J Heart Fail 5, 793–801. https://doi.org/10.1016/s1388-9842(03)00150-8

  6. Vargo, D.L., Kramer, W.G., Black, P.K., Smith, W.B., Serpas, T., Brater, D.C., 1995. Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide and furosemide in patients with congestive heart failure. Clinical Pharmacology & Therapeutics 57, 601–609. https://doi.org/10.1016/0009-9236(95)90222-8

4 Efficacy Review

  1. Besche, B., Blondel, T., Guillot, E., Garelli-Paar, C., Oyama, M.A., 2020. Efficacy of oral torasemide in dogs with degenerative mitral valve disease and new onset congestive heart failure: The CARPODIEM study. J Vet Intern Med 34, 1746–1758. https://doi.org/10.1111/jvim.15864

  2. Chetboul, V., Pouchelon, J.-L., Menard, J., Blanc, J., Desquilbet, L., Petit, A., Rougier, S., Lucats, L., Woehrle, F., Investigators,  the T. study, 2017. Short-Term Efficacy and Safety of Torasemide and Furosemide in 366 Dogs with Degenerative Mitral Valve Disease: The TEST Study. Journal of Veterinary Internal Medicine 31, 1629–1642. https://doi.org/10.1111/jvim.14841

  3. Hosseini, F., Mahmoudi Filabadi, Z., Hill, P.B., Hosseininejad, M., 2023. Evaluation of the short-term echocardiographic effects of two loop diuretics, furosemide and torsemide, in a group of dogs. Veterinary Medicine and Science 9, 1508–1512. https://doi.org/10.1002/vms3.1129

  4. Peddle, G.D., Singletary, G.E., Reynolds, C.A., Trafny, D.J., Machen, M.C., Oyama, M.A., 2012. Effect of torsemide and furosemide on clinical, laboratory, radiographic and quality of life variables in dogs with heart failure secondary to mitral valve disease. Journal of Veterinary Cardiology, The Mitral Valve 14, 253–259. https://doi.org/10.1016/j.jvc.2012.01.003

Supplementary Information 1 | UK SPC Links

  1. CEVA Animal Health, S., 2019. Isemid | European Medicines Agency [WWW Document]. URL https://www.ema.europa.eu/en/medicines/veterinary/EPAR/isemid (accessed 12.7.23).

  2. Vetoquinol, S., 2015. UpCard | European Medicines Agency [WWW Document]. URL https://www.ema.europa.eu/en/medicines/veterinary/EPAR/upcard (accessed 12.6.23).

Supplementary Information 2 | QALYs

  1. Cohen, J., Neumann, P., Wong, J., 2018. A Call for Open-Source Cost-Effectiveness Analysis. Annals of internal medicine 168. https://doi.org/10.7326/L17-0695

  2. Neumann, P., Anderson, J., Panzer, A., Pope, E.,  D’Cruz, B., Kim, D., Cohen, J., 2018. Comparing the cost-per-QALYs  gained and cost-per-DALYs averted literatures. Gates open research 2. https://doi.org/10.12688/gatesopenres.12786.2

  3. Neumann, P., Cohen, J., 2018. QALYs in 2018-Advantages and Concerns. JAMA 319. https://doi.org/10.1001/jama.2018.6072

  4. Neumann, P., Thorat, T., Zhong, Y., Anderson,  J., Salem, M., Sandberg, E., Saret, C., Wilkinson, C., Cohen, J., 2016. A  Systematic Review of Cost-Effectiveness Studies Reporting Cost-per-DALY  Averted. PloS one 11. https://doi.org/10.1371/journal.pone.0168512

  5. Neumann, P.J., Kim, D.D., 2023. Cost-effectiveness Thresholds Used by Study Authors, 1990-2021. JAMA 329, 1312–1314. https://doi.org/10.1001/jama.2023.1792

  6. P Neumann, Cohen, J., 2015. Measuring the Value of Prescription Drugs. The New England journal of medicine 373. https://doi.org/10.1056/NEJMp1512009

Supplementary Information 3 | 1317822

  • Some material recommended by the [Primer] author, was taken from SPCs or extrapolated from veterinary and pharmacology texts, or is the authors opinion.

Monograph Details

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Evidence Development

Evidence Search and Search Engines

  1. Stuart McArthur B Vet Med MRCVS

Evidence Analysis and Zotero database

  1. Stuart McArthur B Vet Med MRCVS

Monograph Development

Primary Monograph Author(s)

  1. Stuart McArthur B Vet Med MRCVS

Primary Monograph Editor(s)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Consensus Development

Suitability Workgroup (A-Z)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Safety Workgroup (A-Z)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Posology Workgroup (A-Z)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Efficacy Workgroup (A-Z)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Monograph Quality Workgroup (A-Z)

  1. John Doe MRCVS 

  2. Jane Doe DVM

Review Date(s) 

  • Last Review Date: 18.01.24

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