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Pimobendan Recommendations

Grade

MMVD

We recommend following ACVIM consensus guidelines for disease staging and the use of  pimobendan in canine heart failure. Recommendations below are given by disease stage:

Stage A

Monitor Only

  • No treatment is recommended. Patients should be assessed and regularly staged using ACVIM consensus-derived protocols (Keene et al., 2019). Avoid pimobendan use as unwanted hemodynamic responses may occur (SPC data). 

Stage B1  

Monitor Only

  • No treatment is recommended where ACVIM B2 diagnostic criteria are not met. Patients should be assessed and regularly staged using ACVIM consensus-derived protocols (Keene et al., 2019). Avoid pimobendan use as unwanted hemodynamic responses may occur (SPC data). 

Stage B2

Home-based Stage B2 MMVD Treatment

Pimobendan is commenced Once ACVIM stage B2 diagnostic criteria have been met


  • Pimobendan: 0.25-0.3 mg/kg, PO, q12h (Boswood et al., 2016; Hansson et al., 2002). Pimobendan is recommended in all cases where ACVIM B2 criteria have been met and is usually initiated at 0.25-0.3 mg/kg, PO, q12h.

  • Benazepril: 0.25 mg (range 0.25-0.5) mg/kg, PO q12-24h.  Recommendations on use are equivocal. 50% of ACVIM consensus panellists recommended ACEi treatment if the LA diameter had increased on successive monitoring examinations or was deemed significantly enlarged on initial examination.

  • Additional Medications: No other pharmacologic treatments for Stage B are recommended

Stage C

Initial Hospital Stabilisation Stage C MMVD

Acute Stage C MMVD cases may require hospital admission for appropriate care. Acute hospital-based patient stabilisation is beyond the scope of this Benazeptil monograph, but combinations of the following medications and procedures are often employed in a suitable nursing environment.


  • Bolus Furosemide: 2-5 mg/kg IV, loading dose. Repeat every 1 to 2 hours until the respiratory rate and respiratory character improve.  Then, 1-2 mg/kg IV/IM q6-8h is used for maintenance.  A maximum daily dose of 12 mg/kg has been advised (DeFrancesco, 2013; Keene et al., 2019).

  • CRI Furosemide: 0.66-1 mg/kg/h after an IV bolus of 2-5 mg/kg as above (Ohad, et al. 2018).

  • Oxygen: Where possible, provide an oxygen chamber with minimal patient restraint, in preference to a mask or flow by. 

  • Dobutamine CRI: 2.5-10 μg/kg/min may improve the left ventricular function in patients who fail to respond adequately to diuretics.

  • Sodium Nitroprusside CRI:  1 to 15 μg/kg/min for up to 48 h may stabilise life-threatening, poorly responsive pulmonary oedema (Sabbah et al., 1993).

  • Nitroglycerin (Glyceryl Trinitrate): 0.25–1.0 cm of a 2% transdermal ointment q 8–24 h for 1–2 d

  • Anxiolytic: Typically an opiate ( e.g. methadone, butorphanol or Buprenorphine) or a neuroleptic combination.

  • Additional medication 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.

Home-based Stage C MMVD Treatment

Once an acute patient is adequately stabilised, oral Pimobendan therapy is initiated. Benazepril is administered in addition to Pimobendan with various additional medications, such as Furosemide, Torasemide, and Spironolactone, helping to stabilise the patient.


  • Furosemide: 2 mg/kg, PO, q6-12h, up to 8 mg/kg daily.

  • Pimobendan: 0.25 – 0.3 mg/kg PO every 8-12 hours. Some AVCIM consensus panellists propose a third daily dose as patients near end-stage disease.

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

  • Benazepril is administered at 0.5 mg/kg PO, q24h (or 0.25 mg/kg PO, q12h).

Stage D

Any Stage D Patient

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. Pimobendan is administered orally twice daily, with or without food. Some experts advise a third treatment in refractory stage D patients (Keene et al., 2019). 

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

  • Furosemide:  6- 8 mg/kg/day in divided doses, or Torasemide is substituted where 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).

  • Benazepril: 0.5 mg/kg PO, q12-24h

  • Additional medication 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.

Ongoing Treatment

  • ACVIM Consensus Guidelines: Our experts recommend following ACVIM consensus guidelines for staging and managing MMVD. All initial dosing regimens require appropriate monitoring and modification to balance the treatment response (Keene et al., 2019).

  • The duration of chronic Pimobendan treatment is unlimited and usually lifelong until death or euthanasia (Keene et al., 2019).

Additional Medications

  • ACVIM Consensus Guidelines:  Pimobendan is deployed in ACVIM Stages B2. C and D of MMVD. It is generally used alongside additional medicines, e.g., Benazepril, Furosemide, Torasemide and Spironolactone.

Patient Preparation

  • ACVIM MMVD Staging: Patients should be staged and assessed using ACVIM consensus-derived protocols. 

  • Baseline Values: Baseline values for therapeutic monitoring should be recorded for comparison during subsequent monitoring sessions. (Keene et al., 2019).

Therapeutic Monitoring

  • Electrolyte Monitoring: Measure serum creatinine and electrolyte concentrations 3-14 days after beginning an ACEI (Keene et al., 2019).

  • Respiratory Rate Monitoring: Most stable, well-controlled CHF patients at home have mean SRR and RRR <30 breaths/min (Keene et al., 2019; Porciello et al., 2016). 

  • ACVIM MMVD Staging: Patients should be regularly staged and assessed using ACVIM consensus-derived protocols (Keene et al., 2019).

  • Physical Assessments: MMVD Patients benefit from regular physical assessments. Typically, they include heart rate and quality, respiratory rate and effort (resting and sleeping), blood pressure, signs associated with oedema, thirst, urine output, and weight.


Therapeutics

​

About Pimobendan and MMVD 

Pimobendan, an inodilator with positive inotropic and vasodilatory effects, is indicated in all ACVIM MMVD Stages B2 cases and above. Substantial evidence supports beneficial use (Apple et al., 2016; Boswood et al., 2016; Häggström et al., 2013a, 2013b, 2008; Iwanuk et al., 2019a, 2019b; Lombard et al., 2006).

MMVD Suitability by ACVIM Stage

Pimobendan is indicated in all cases of ACVIM MMVD Stages B2 and above, and substantial evidence supports its beneficial use.

Stage A and B1

Unsuitable: No specific medical protocol is recommended for treating ACVIM stage A and B1 heart failure. 


  • Pimobendan is not advised (Häggström et al., 2008; King et al., 2018; Keene et al., 2019). 

Stage B2

Suitable: Pimobendan is recommended as the first-line response in managing chronic ACVIM stage B2 canine heart failure (Häggström et al., 2008; King et al., 2018; Keene et al., 2019). 


  • Some experts use benazepril for adjuvant treatment of Pimobendan in chronic Stage B1 heart failure with significant left chamber remodelling (Keene et al., 2019).

Stage C

Suitable: Pimobendan/Frusemide protocols are recommended for the management of stabilised  ACVIM stage C canine heart failure (Häggström et al., 2008; King et al., 2018; Keene et al., 2019). 


  • Additional medicines such as Benazepril, Spironolactone and hospital stabilising medications may be deployed case-by-case (Keene et al., 2019). 

Stage D

Suitable: Pimobendan/Torasemide protocols are recommended as a salvage response in  ACVIM stage D canine heart failure. Hypochloremia is a helpful marker for stage D (Adin et al., 2020). These cases are refractory to standard stage C Pimobendan/Frusemide protocols (Häggström et al., 2008; King et al., 2018; Keene et al., 2019). 


  • Additional medicines such as Benazepril, Spironolactone and hospital stabilising medications may be deployed case-by-case (Keene et al., 2019). 

  • Where Torasemide is unavailable, frequent high doses of Furosemide are still administered (≤6 mg/kg/day). 

  • Euthanasia should be recommended in cases where a suitable quality of life is not possible through the available therapeutic options. 

Treatment Goals

To maintain patient comfort at each stage of MMVD and prolong the length, quality of life, and rate of stage progression of MMVD patients at each ACVIM stage.


  • Organ Level: The objective of Pimobendan administration is to improve cardiac function in canine patients with MMVD and to slow, halt or reverse the progression and stage of MMVD.

  • Patient Level: The treatment objective is to increase the quality and quantity of survival time (QALYs) for patients with MMVD and to slow, halt or reverse the progression and stage of MMVD.

  • Client Level:  The goal of treatment is to offer value-for-money QALYs to clients with dogs experiencing MMVD.


Overall assessment of improved quality of life of patients with MMVD receiving Pimobendan currently relies upon a subjective, case-by-case judgement; however, there is a clear case for a future focus on the cost and quantity of beneficial quality-adjusted life years (QALYs) achieved through systematic review of specific Pimobendan protocols for all MMVD stages (Cohen et al., 2018; Neumann et al., 2018, 2016; Neumann and Cohen, 2018; Neumann and Kim, 2023; P Neumann and Cohen, 2015).

Treatment End Point

  • The duration of Pimobendan treatment is unlimited in canine MMVD cases where there is a benefit, so it is usually lifelong, i.e. until death or euthanasia (Keene et al., 2019). 

Alternative Products

  • No recommendations can be made at this time. We refer clinicians to current ACVIM CHF/MMVD recommendations for cats and dogs.

Alternative Protocols

  • No recommendations can be made at this time. We refer clinicians to current ACVIM CHF/MMVD recommendations for cats and dogs.

Related Monographs

Evidence

​

1 Species-Specific Evidence Review 

  1. Adin, D., Kurtz, K., Atkins, C., Papich, M.G., Vaden, S., 2020. Role of electrolyte concentrations and renin-angiotensin-aldosterone activation in the staging of canine heart disease. J Vet Intern Med 34, 53–64. https://doi.org/10.1111/jvim.15662

  2. Ames, M.K., Atkins, C.E., Lantis, A.C., Werre, S.R., 2013. Effect of furosemide and high-dosage pimobendan administration on the renin-angiotensin-aldosterone system in dogs. Am J Vet Res 74, 1084–1090. https://doi.org/10.2460/ajvr.74.8.1084

  3. Apple, S., Menciotti, G., Braz-Ruivo, L., Crosara, S., Häggström, J., Borgarelli, M., 2016. Effects of pimobendan on myocardial perfusion and pulmonary transit time in dogs with myxomatous mitral valve disease: a pilot study. Australian Veterinary Journal 94, 324–328. https://doi.org/10.1111/avj.12480

  4. Atkinson, K.J., Fine, D.M., Thombs, L.A., Gorelick, J.J., Durham, H.E., 2009. Evaluation of pimobendan and N-terminal probrain natriuretic peptide in the treatment of pulmonary hypertension secondary to degenerative mitral valve disease in dogs. J Vet Intern Med 23, 1190–1196. https://doi.org/10.1111/j.1939-1676.2009.0390.x

  5. Boswood, A., Häggström, J., Gordon, S.G., Wess, G., Stepien, R.L., Oyama, M.A., Keene, B.W., Bonagura, J., MacDonald, K.A., Patteson, M., Smith, S., Fox, P.R., Sanderson, K., Woolley, R., Szatmári, V., Menaut, P., Church, W.M., O’Sullivan, M.L., Jaudon, J.-P., Kresken, J.-G., Rush, J., Barrett, K.A., Rosenthal, S.L., Saunders, A.B., Ljungvall, I., Deinert, M., Bomassi, E., Estrada, A.H., Fernandez Del Palacio, M.J., Moise, N.S., Abbott, J.A., Fujii, Y., Spier, A., Luethy, M.W., Santilli, R.A., Uechi, M., Tidholm, A., Watson, P., 2016. Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial. J Vet Intern Med 30, 1765–1779. https://doi.org/10.1111/jvim.14586

  6. Chetboul, V., Lefebvre, H.P., Sampedrano, C.C., Gouni, V., Saponaro, V., Serres, F., Concordet, D., Nicolle, A.P., Pouchelon, J.-L., 2007. Comparative adverse cardiac effects of pimobendan and benazepril monotherapy in dogs with mild degenerative mitral valve disease: a prospective, controlled, blinded, and randomized study. J Vet Intern Med 21, 742–753. https://doi.org/10.1892/0891-6640(2007)21[742:caceop]2.0.co;2

  7. DeFrancesco, T.C., 2013. Management of Cardiac Emergencies in Small Animals. Veterinary Clinics of North America: Small Animal Practice 43, 817–842. https://doi.org/10.1016/j.cvsm.2013.03.012

  8. Ferasin, L., Marcora, S., 2007. A pilot study to assess the feasibility of a submaximal exercise test to measure individual response to cardiac medication in dogs with acquired heart failure. Vet Res Commun 31, 725–737. https://doi.org/10.1007/s11259-007-3566-7

  9. Häggström, J., Boswood, A., O’Grady, M., Jöns, O., Smith, S., Swift, S., Borgarelli, M., Gavaghan, B., Kresken, J.-G., Patteson, M., Åblad, B., Bussadori, C.M., Glaus, T., Kovačević, A., Rapp, M., Santilli, R.A., Tidholm, A., Eriksson, A., Belanger, M.C., Deinert, M., Little, C.J.L., Kvart, C., French, A., Rønn-Landbo, M., Wess, G., Eggertsdottir, A., Lynne O’Sullivan, M., Schneider, M., Lombard, C.W., Dukes-McEwan, J., Willis, R., Louvet, A., DiFruscia, R., 2013a. Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study. J Vet Intern Med 27, 1441–1451. https://doi.org/10.1111/jvim.12181

  10. Häggström, J., Boswood, A., O’Grady, M., Jöns, O., Smith, S., Swift, S., Borgarelli, M., Gavaghan, B., Kresken, J.-G., Patteson, M., Ablad, B., Bussadori, C.M., Glaus, T., Kovacević, A., Rapp, M., Santilli, R.A., Tidholm, A., Eriksson, A., Belanger, M.C., Deinert, M., Little, C.J.L., Kvart, C., French, A., Rønn-Landbo, M., Wess, G., Eggertsdottir, A.V., O’Sullivan, M.L., Schneider, M., Lombard, C.W., Dukes-McEwan, J., Willis, R., Louvet, A., DiFruscia, R., 2008. Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: the QUEST study. J Vet Intern Med 22, 1124–1135. https://doi.org/10.1111/j.1939-1676.2008.0150.x

  11. Häggström, J., Lord, P.F., Höglund, K., Ljungvall, I., Jöns, O., Kvart, C., Hansson, K., 2013b. Short-term hemodynamic and neuroendocrine effects of pimobendan and benazapril in dogs with myxomatous mitral valve disease and congestive heart failure. J Vet Intern Med 27, 1452–1462. https://doi.org/10.1111/jvim.12217

  12. Hamabe, L., Kawamura, K., Kim, S.-M., Yoshiyuki, R., Fukayama, T., Shimizu, M., Fukushima, R., Tanaka, R., 2014. Comparative evaluation of calcium-sensitizing agents, pimobendan and SCH00013, on the myocardial function of canine pacing-induced model of heart failure. J Pharmacol Sci 124, 386–393. https://doi.org/10.1254/jphs.13196fp

  13. Hezzell, M.J., Block, C.L., Laughlin, D.S., Oyama, M.A., 2018. Effect of prespecified therapy escalation on plasma NT-proBNP concentrations in dogs with stable congestive heart failure due to myxomatous mitral valve disease. J Vet Intern Med 32, 1509–1516. https://doi.org/10.1111/jvim.15228

  14. Ichihara, K., Abiko, Y., 1991. The effect of pimobendan on myocardial mechanical function and metabolism in dogs: comparison with dobutamine. J Pharm Pharmacol 43, 583–588. https://doi.org/10.1111/j.2042-7158.1991.tb03541.x

  15. Iwanuk, N., Nolte, I., Wall, L., Sehn, M., Raue, J., Pilgram, A., Rumstedt, K., Bach, J.-P., 2019a. Effect of Pimobendan on NT-proBNP and c troponin I before and after a submaximal exercise test in dogs with preclinical mitral valve disease without cardiomegaly - a randomised, double-blinded trial. BMC Vet Res 15, 237. https://doi.org/10.1186/s12917-019-1980-z

  16. Iwanuk, N., Wall, L., Nolte, I., Raue, J., Rumstedt, K., Pilgram, A., Sehn, M., Rohn, K., Bach, J.-P., 2019b. Effect of pimobendan on physical fitness, lactate and echocardiographic parameters in dogs with preclinical mitral valve disease without cardiomegaly. PLoS One 14, e0223164. https://doi.org/10.1371/journal.pone.0223164

  17. Kanno, N., Kuse, H., Kawasaki, M., Hara, A., Kano, R., Sasaki, Y., 2007. Effects of pimobendan for mitral valve regurgitation in dogs. J Vet Med Sci 69, 373–377. https://doi.org/10.1292/jvms.69.373

  18. 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

  19. Lombard, C.W., Jöns, O., Bussadori, C.M., 2006. Clinical efficacy of pimobendan versus benazepril for the treatment of acquired atrioventricular valvular disease in dogs. J Am Anim Hosp Assoc 42, 249–261. https://doi.org/10.5326/0420249

  20. Mattin, M.J., Brodbelt, D.C., Church, D.B., Boswood, A., 2019. Factors associated with disease progression in dogs with presumed preclinical degenerative mitral valve disease attending primary care veterinary practices in the United Kingdom. J Vet Intern Med 33, 445–454. https://doi.org/10.1111/jvim.15390

  21. Yata, M., Kooistra, H.S., Beijerink, N.J., 2019. Cardiorenal and endocrine effects of synthetic canine BNP1-32 in dogs with compensated congestive heart failure caused by myxomatous mitral valve disease. J Vet Intern Med 33, 462–470. https://doi.org/10.1111/jvim.15416

2 Condition-Specific Evidence Review

  1. Adin, D., Kurtz, K., Atkins, C., Papich, M.G., Vaden, S., 2020. Role of electrolyte concentrations and renin-angiotensin-aldosterone activation in the staging of canine heart disease. J Vet Intern Med 34, 53–64. https://doi.org/10.1111/jvim.15662

  2. Ames, M.K., Atkins, C.E., Lantis, A.C., Werre, S.R., 2013. Effect of furosemide and high-dosage pimobendan administration on the renin-angiotensin-aldosterone system in dogs. Am J Vet Res 74, 1084–1090. https://doi.org/10.2460/ajvr.74.8.1084

  3. Atkinson, K.J., Fine, D.M., Thombs, L.A., Gorelick, J.J., Durham, H.E., 2009. Evaluation of pimobendan and N-terminal probrain natriuretic peptide in the treatment of pulmonary hypertension secondary to degenerative mitral valve disease in dogs. J Vet Intern Med 23, 1190–1196. https://doi.org/10.1111/j.1939-1676.2009.0390.x

  4. Boswood, A., Häggström, J., Gordon, S.G., Wess, G., Stepien, R.L., Oyama, M.A., Keene, B.W., Bonagura, J., MacDonald, K.A., Patteson, M., Smith, S., Fox, P.R., Sanderson, K., Woolley, R., Szatmári, V., Menaut, P., Church, W.M., O’Sullivan, M.L., Jaudon, J.-P., Kresken, J.-G., Rush, J., Barrett, K.A., Rosenthal, S.L., Saunders, A.B., Ljungvall, I., Deinert, M., Bomassi, E., Estrada, A.H., Fernandez Del Palacio, M.J., Moise, N.S., Abbott, J.A., Fujii, Y., Spier, A., Luethy, M.W., Santilli, R.A., Uechi, M., Tidholm, A., Watson, P., 2016. Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial. J Vet Intern Med 30, 1765–1779. https://doi.org/10.1111/jvim.14586

  5. Chetboul, V., Lefebvre, H.P., Sampedrano, C.C., Gouni, V., Saponaro, V., Serres, F., Concordet, D., Nicolle, A.P., Pouchelon, J.-L., 2007. Comparative adverse cardiac effects of pimobendan and benazepril monotherapy in dogs with mild degenerative mitral valve disease: a prospective, controlled, blinded, and randomized study. J Vet Intern Med 21, 742–753. https://doi.org/10.1892/0891-6640(2007)21[742:caceop]2.0.co;2

  6. Ferasin, L., Marcora, S., 2007. A pilot study to assess the feasibility of a submaximal exercise test to measure individual response to cardiac medication in dogs with acquired heart failure. Vet Res Commun 31, 725–737. https://doi.org/10.1007/s11259-007-3566-7

  7. Häggström, J., Boswood, A., O’Grady, M., Jöns, O., Smith, S., Swift, S., Borgarelli, M., Gavaghan, B., Kresken, J.-G., Patteson, M., Åblad, B., Bussadori, C.M., Glaus, T., Kovačević, A., Rapp, M., Santilli, R.A., Tidholm, A., Eriksson, A., Belanger, M.C., Deinert, M., Little, C.J.L., Kvart, C., French, A., Rønn-Landbo, M., Wess, G., Eggertsdottir, A., Lynne O’Sullivan, M., Schneider, M., Lombard, C.W., Dukes-McEwan, J., Willis, R., Louvet, A., DiFruscia, R., 2013a. Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study. J Vet Intern Med 27, 1441–1451. https://doi.org/10.1111/jvim.12181

  8. Häggström, J., Boswood, A., O’Grady, M., Jöns, O., Smith, S., Swift, S., Borgarelli, M., Gavaghan, B., Kresken, J.-G., Patteson, M., Ablad, B., Bussadori, C.M., Glaus, T., Kovacević, A., Rapp, M., Santilli, R.A., Tidholm, A., Eriksson, A., Belanger, M.C., Deinert, M., Little, C.J.L., Kvart, C., French, A., Rønn-Landbo, M., Wess, G., Eggertsdottir, A.V., O’Sullivan, M.L., Schneider, M., Lombard, C.W., Dukes-McEwan, J., Willis, R., Louvet, A., DiFruscia, R., 2008. Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: the QUEST study. J Vet Intern Med 22, 1124–1135. https://doi.org/10.1111/j.1939-1676.2008.0150.x

  9. Häggström, J., Lord, P.F., Höglund, K., Ljungvall, I., Jöns, O., Kvart, C., Hansson, K., 2013b. Short-term hemodynamic and neuroendocrine effects of pimobendan and benazapril in dogs with myxomatous mitral valve disease and congestive heart failure. J Vet Intern Med 27, 1452–1462. https://doi.org/10.1111/jvim.12217

  10. Hansson, K., Häggström, J., Kvart, C., Lord, P., 2002. Left Atrial to Aortic Root Indices Using Two-Dimensional and M-Mode Echocardiography in Cavalier King Charles Spaniels with and Without Left Atrial Enlargement. Veterinary Radiology & Ultrasound 43, 568–575. https://doi.org/10.1111/j.1740-8261.2002.tb01051.x

  11. Hezzell, M.J., Block, C.L., Laughlin, D.S., Oyama, M.A., 2018. Effect of prespecified therapy escalation on plasma NT-proBNP concentrations in dogs with stable congestive heart failure due to myxomatous mitral valve disease. J Vet Intern Med 32, 1509–1516. https://doi.org/10.1111/jvim.15228

  12. Iwanuk, N., Nolte, I., Wall, L., Sehn, M., Raue, J., Pilgram, A., Rumstedt, K., Bach, J.-P., 2019a. Effect of Pimobendan on NT-proBNP and c troponin I before and after a submaximal exercise test in dogs with preclinical mitral valve disease without cardiomegaly - a randomised, double-blinded trial. BMC Vet Res 15, 237. https://doi.org/10.1186/s12917-019-1980-z

  13. Iwanuk, N., Wall, L., Nolte, I., Raue, J., Rumstedt, K., Pilgram, A., Sehn, M., Rohn, K., Bach, J.-P., 2019b. Effect of pimobendan on physical fitness, lactate and echocardiographic parameters in dogs with preclinical mitral valve disease without cardiomegaly. PLoS One 14, e0223164. https://doi.org/10.1371/journal.pone.0223164

  14. Kanno, N., Kuse, H., Kawasaki, M., Hara, A., Kano, R., Sasaki, Y., 2007. Effects of pimobendan for mitral valve regurgitation in dogs. J Vet Med Sci 69, 373–377. https://doi.org/10.1292/jvms.69.373

  15. 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

  16. Lombard, C.W., Jöns, O., Bussadori, C.M., 2006. Clinical efficacy of pimobendan versus benazepril for the treatment of acquired atrioventricular valvular disease in dogs. J Am Anim Hosp Assoc 42, 249–261. https://doi.org/10.5326/0420249

  17. Mattin, M.J., Brodbelt, D.C., Church, D.B., Boswood, A., 2019. Factors associated with disease progression in dogs with presumed preclinical degenerative mitral valve disease attending primary care veterinary practices in the United Kingdom. J Vet Intern Med 33, 445–454. https://doi.org/10.1111/jvim.15390

  18. Porciello, F., Rishniw, M., Ljungvall, I., Ferasin, L., Haggstrom, J., Ohad, D.G., 2016. Sleeping and resting respiratory rates in dogs and cats with medically-controlled left-sided congestive heart failure. The Veterinary Journal 207, 164–168. https://doi.org/10.1016/j.tvjl.2015.08.017

  19. Sabbah, H.N., Levine, T.B., Gheorghiade, M., Kono, T., Goldstein, S., 1993. Hemodynamic response of a canine model of chronic heart failure to intravenous dobutamine, nitroprusside, enalaprilat, and digoxin. Cardiovasc Drugs Ther 7, 349–356. https://doi.org/10.1007/BF00880158

  20. Yata, M., Kooistra, H.S., Beijerink, N.J., 2019. Cardiorenal and endocrine effects of synthetic canine BNP1-32 in dogs with compensated congestive heart failure caused by myxomatous mitral valve disease. J Vet Intern Med 33, 462–470. https://doi.org/10.1111/jvim.15416

3 Substance-Specific Evidence Review 

  1. Ames, M.K., Atkins, C.E., Lantis, A.C., Werre, S.R., 2013. Effect of furosemide and high-dosage pimobendan administration on the renin-angiotensin-aldosterone system in dogs. Am J Vet Res 74, 1084–1090. https://doi.org/10.2460/ajvr.74.8.1084

  2. Apple, S., Menciotti, G., Braz-Ruivo, L., Crosara, S., Häggström, J., Borgarelli, M., 2016. Effects of pimobendan on myocardial perfusion and pulmonary transit time in dogs with myxomatous mitral valve disease: a pilot study. Australian Veterinary Journal 94, 324–328. https://doi.org/10.1111/avj.12480

  3. Atkinson, K.J., Fine, D.M., Thombs, L.A., Gorelick, J.J., Durham, H.E., 2009. Evaluation of pimobendan and N-terminal probrain natriuretic peptide in the treatment of pulmonary hypertension secondary to degenerative mitral valve disease in dogs. J Vet Intern Med 23, 1190–1196. https://doi.org/10.1111/j.1939-1676.2009.0390.x

  4. Bell, E.T., Devi, J.L., Chiu, S., Zahra, P., Whittem, T., 2016. The pharmacokinetics of pimobendan enantiomers after oral and intravenous administration of racemate pimobendan formulations in healthy dogs. J Vet Pharmacol Ther 39, 54–61. https://doi.org/10.1111/jvp.12235

  5. Boswood, A., Häggström, J., Gordon, S.G., Wess, G., Stepien, R.L., Oyama, M.A., Keene, B.W., Bonagura, J., MacDonald, K.A., Patteson, M., Smith, S., Fox, P.R., Sanderson, K., Woolley, R., Szatmári, V., Menaut, P., Church, W.M., O’Sullivan, M.L., Jaudon, J.-P., Kresken, J.-G., Rush, J., Barrett, K.A., Rosenthal, S.L., Saunders, A.B., Ljungvall, I., Deinert, M., Bomassi, E., Estrada, A.H., Fernandez Del Palacio, M.J., Moise, N.S., Abbott, J.A., Fujii, Y., Spier, A., Luethy, M.W., Santilli, R.A., Uechi, M., Tidholm, A., Watson, P., 2016. Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial. J Vet Intern Med 30, 1765–1779. https://doi.org/10.1111/jvim.14586

  6. Chetboul, V., Lefebvre, H.P., Sampedrano, C.C., Gouni, V., Saponaro, V., Serres, F., Concordet, D., Nicolle, A.P., Pouchelon, J.-L., 2007. Comparative adverse cardiac effects of pimobendan and benazepril monotherapy in dogs with mild degenerative mitral valve disease: a prospective, controlled, blinded, and randomized study. J Vet Intern Med 21, 742–753. https://doi.org/10.1892/0891-6640(2007)21[742:caceop]2.0.co;2

  7. Fujino, K., Sperelakis, N., Solaro, R.J., 1988. Sensitization of dog and guinea pig heart myofilaments to Ca2+ activation and the inotropic effect of pimobendan: comparison with milrinone. Circ Res 63, 911–922. https://doi.org/10.1161/01.res.63.5.911

  8. Fukutomi, T., Satoh, K., Ogoshi, S., Ichihara, K., 2000. Effects of pimobendan and EGIS 9377, cardiotonic agents, and OG-VI, a nucleoside-nucleotide mixture, administered during reperfusion after ischemia on stunned myocardium in dogs. Coron Artery Dis 11, 83–90. https://doi.org/10.1097/00019501-200002000-00014

  9. Fusellier, M., Desfontis, J.-C., Le Roux, A., Madec, S., Gautier, F., Thuleau, A., Gogny, M., 2008. Effect of short-term treatment with meloxicam and pimobendan on the renal function in healthy beagle dogs. J Vet Pharmacol Ther 31, 150–155. https://doi.org/10.1111/j.1365-2885.2007.00934.x

  10. Goto, Y., Hata, K., 1997. Mechanoenergetic effect of pimobendan in failing dog hearts. Heart Vessels Suppl 12, 103–105.

  11. Hamabe, L., Kawamura, K., Kim, S.-M., Yoshiyuki, R., Fukayama, T., Shimizu, M., Fukushima, R., Tanaka, R., 2014. Comparative evaluation of calcium-sensitizing agents, pimobendan and SCH00013, on the myocardial function of canine pacing-induced model of heart failure. J Pharmacol Sci 124, 386–393. https://doi.org/10.1254/jphs.13196fp

  12. Hata, K., Goto, Y., Futaki, S., Ohgoshi, Y., Yaku, H., Kawaguchi, O., Takasago, T., Saeki, A., Taylor, T.W., Nishioka, T., 1992. Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with dobutamine. Circulation 86, 1291–1301. https://doi.org/10.1161/01.cir.86.4.1291

  13. Helms, S.R., Fox, S., Mixon, W., Vail, J., 2012. Compounded pimobendan for canine chronic degenerative mitral valve disease and pulmonary hypertension. Int J Pharm Compd 16, 34–41.

  14. Ichihara, K., Abiko, Y., 1991. The effect of pimobendan on myocardial mechanical function and metabolism in dogs: comparison with dobutamine. J Pharm Pharmacol 43, 583–588. https://doi.org/10.1111/j.2042-7158.1991.tb03541.x

  15. Iwanuk, N., Nolte, I., Wall, L., Sehn, M., Raue, J., Pilgram, A., Rumstedt, K., Bach, J.-P., 2019a. Effect of Pimobendan on NT-proBNP and c troponin I before and after a submaximal exercise test in dogs with preclinical mitral valve disease without cardiomegaly - a randomised, double-blinded trial. BMC Vet Res 15, 237. https://doi.org/10.1186/s12917-019-1980-z

  16. Iwanuk, N., Wall, L., Nolte, I., Raue, J., Rumstedt, K., Pilgram, A., Sehn, M., Rohn, K., Bach, J.-P., 2019b. Effect of pimobendan on physical fitness, lactate and echocardiographic parameters in dogs with preclinical mitral valve disease without cardiomegaly. PLoS One 14, e0223164. https://doi.org/10.1371/journal.pone.0223164

  17. Kanno, N., Kuse, H., Kawasaki, M., Hara, A., Kano, R., Sasaki, Y., 2007. Effects of pimobendan for mitral valve regurgitation in dogs. J Vet Med Sci 69, 373–377. https://doi.org/10.1292/jvms.69.373

  18. Lombard, C.W., Jöns, O., Bussadori, C.M., 2006. Clinical efficacy of pimobendan versus benazepril for the treatment of acquired atrioventricular valvular disease in dogs. J Am Anim Hosp Assoc 42, 249–261. https://doi.org/10.5326/0420249

  19. O’Grady, M.R., Minors, S.L., O’Sullivan, M.L., Horne, R., 2008. Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy. J Vet Intern Med 22, 897–904. https://doi.org/10.1111/j.1939-1676.2008.0116.x

  20. Pagel, P.S., Hettrick, D.A., Warltier, D.C., 1996. Comparison of the effects of levosimendan, pimobendan, and milrinone on canine left ventricular-arterial coupling and mechanical efficiency. Basic Res Cardiol 91, 296–307. https://doi.org/10.1007/BF00789302

  21. Sayer, M.B., Atkins, C.E., Fujii, Y., Adams, A.K., DeFrancesco, T.C., Keene, B.W., 2009. Acute effect of pimobendan and furosemide on the circulating renin-angiotensin-aldosterone system in healthy dogs. J Vet Intern Med 23, 1003–1006. https://doi.org/10.1111/j.1939-1676.2009.0367.x

  22. Schneider, P., Güttner, J., Eckenfels, A., Heinzel, G., von Nicolai, H., Trieb, G., Lehmann, H., 1997. Comparative cardiac toxicity of the i.v. administered benzimidazole pyridazinon derivative Pimobendan and its enantiomers in female Beagle dogs. Exp Toxicol Pathol 49, 217–224. https://doi.org/10.1016/s0940-2993(97)80013-9

  23. Shipley, E.A., Hogan, D.F., Fiakpui, N.N., Magee, A.N., Green, H.W., Sederquist, K.A., 2013. In vitro effect of pimobendan on platelet aggregation in dogs. Am J Vet Res 74, 403–407. https://doi.org/10.2460/ajvr.74.3.403

  24. Summerfield, N. j., Boswood, A., O’Grady, M. r., Gordon, S. g., Dukes-McEwan, J., Oyama, M. a., Smith, S., Patteson, M., French, A. t., Culshaw, G. j., Braz-Ruivo, L., Estrada, A., O’Sullivan, M. l., Loureiro, J., Willis, R., Watson, P., 2012. Efficacy of Pimobendan in the Prevention of Congestive Heart Failure or Sudden Death in Doberman Pinschers with Preclinical Dilated Cardiomyopathy (The PROTECT Study). Journal of Veterinary Internal Medicine 26, 1337–1349. https://doi.org/10.1111/j.1939-1676.2012.01026.x

  25. Suzuki, S., Fukushima, R., Ishikawa, T., Hamabe, L., Aytemiz, D., Huai-Che, H., Nakao, S., Machida, N., Tanaka, R., 2011. The Effect of Pimobendan on Left Atrial Pressure in Dogs with Mitral Valve Regurgitation. Journal of Veterinary Internal Medicine 25, 1328–1333. https://doi.org/10.1111/j.1939-1676.2011.00800.x

  26. Takahashi, R., Endoh, M., 2001. Increase in myofibrillar Ca2+ sensitivity induced by UD-CG 212 Cl, an active metabolite of pimobendan, in canine ventricular myocardium. J Cardiovasc Pharmacol 37, 209–218. https://doi.org/10.1097/00005344-200102000-00008

  27. Takahashi, R., Shimazaki, Y., Endoh, M., 2001. Decrease in Ca(2+)-sensitizing effect of UD-CG 212 Cl, a metabolite of pimobendan, under acidotic condition in canine ventricular myocardium. J Pharmacol Exp Ther 298, 1060–1066.

  28. Tjostheim, S.S., Kellihan, H.B., Grint, K.A., Stepien, R.L., 2019. Effect of sildenafil and pimobendan on intracardiac heartworm infections in four dogs. J Vet Cardiol 23, 96–103. https://doi.org/10.1016/j.jvc.2019.02.001

  29. Tokuriki, T., Miyagawa, Y., Takemura, N., 2015. Overdose Ingestion of Pimobendan in a Dog. 動物の循環器 48, 21–28. https://doi.org/10.11276/jsvc.48.21

  30. van Meel, J.C., Entzeroth, M., Redemann, N., Haigh, R.M., 1995. Effects of pimobendan and its metabolite on myofibrillar calcium responsiveness and ATPase activity in the presence of inorganic phosphate. Arzneimittelforschung 45, 136–141.

  31. Yata, M., McLachlan, A.J., Foster, D.J.R., Page, S.W., Beijerink, N.J., 2016. Pharmacokinetics and cardiovascular effects following a single oral administration of a nonaqueous pimobendan solution in healthy dogs. J Vet Pharmacol Ther 39, 45–53. https://doi.org/10.1111/jvp.12243

4 Efficacy Evidence Review

  1. Apple, S., Menciotti, G., Braz-Ruivo, L., Crosara, S., Häggström, J., Borgarelli, M., 2016. Effects of pimobendan on myocardial perfusion and pulmonary transit time in dogs with myxomatous mitral valve disease: a pilot study. Australian Veterinary Journal 94, 324–328. https://doi.org/10.1111/avj.12480

  2. Boswood, A., Häggström, J., Gordon, S.G., Wess, G., Stepien, R.L., Oyama, M.A., Keene, B.W., Bonagura, J., MacDonald, K.A., Patteson, M., Smith, S., Fox, P.R., Sanderson, K., Woolley, R., Szatmári, V., Menaut, P., Church, W.M., O’Sullivan, M.L., Jaudon, J.-P., Kresken, J.-G., Rush, J., Barrett, K.A., Rosenthal, S.L., Saunders, A.B., Ljungvall, I., Deinert, M., Bomassi, E., Estrada, A.H., Fernandez Del Palacio, M.J., Moise, N.S., Abbott, J.A., Fujii, Y., Spier, A., Luethy, M.W., Santilli, R.A., Uechi, M., Tidholm, A., Watson, P., 2016. Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial. J Vet Intern Med 30, 1765–1779. https://doi.org/10.1111/jvim.14586

  3. Häggström, J., Boswood, A., O’Grady, M., Jöns, O., Smith, S., Swift, S., Borgarelli, M., Gavaghan, B., Kresken, J.-G., Patteson, M., Åblad, B., Bussadori, C.M., Glaus, T., Kovačević, A., Rapp, M., Santilli, R.A., Tidholm, A., Eriksson, A., Belanger, M.C., Deinert, M., Little, C.J.L., Kvart, C., French, A., Rønn-Landbo, M., Wess, G., Eggertsdottir, A., Lynne O’Sullivan, M., Schneider, M., Lombard, C.W., Dukes-McEwan, J., Willis, R., Louvet, A., DiFruscia, R., 2013a. Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study. J Vet Intern Med 27, 1441–1451. https://doi.org/10.1111/jvim.12181

  4. Häggström, J., Boswood, A., O’Grady, M., Jöns, O., Smith, S., Swift, S., Borgarelli, M., Gavaghan, B., Kresken, J.-G., Patteson, M., Ablad, B., Bussadori, C.M., Glaus, T., Kovacević, A., Rapp, M., Santilli, R.A., Tidholm, A., Eriksson, A., Belanger, M.C., Deinert, M., Little, C.J.L., Kvart, C., French, A., Rønn-Landbo, M., Wess, G., Eggertsdottir, A.V., O’Sullivan, M.L., Schneider, M., Lombard, C.W., Dukes-McEwan, J., Willis, R., Louvet, A., DiFruscia, R., 2008. Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: the QUEST study. J Vet Intern Med 22, 1124–1135. https://doi.org/10.1111/j.1939-1676.2008.0150.x

  5. Häggström, J., Lord, P.F., Höglund, K., Ljungvall, I., Jöns, O., Kvart, C., Hansson, K., 2013b. Short-term hemodynamic and neuroendocrine effects of pimobendan and benazapril in dogs with myxomatous mitral valve disease and congestive heart failure. J Vet Intern Med 27, 1452–1462. https://doi.org/10.1111/jvim.12217

  6. Iwanuk, N., Nolte, I., Wall, L., Sehn, M., Raue, J., Pilgram, A., Rumstedt, K., Bach, J.-P., 2019a. Effect of Pimobendan on NT-proBNP and c troponin I before and after a submaximal exercise test in dogs with preclinical mitral valve disease without cardiomegaly - a randomised, double-blinded trial. BMC Vet Res 15, 237. https://doi.org/10.1186/s12917-019-1980-z

  7. Iwanuk, N., Wall, L., Nolte, I., Raue, J., Rumstedt, K., Pilgram, A., Sehn, M., Rohn, K., Bach, J.-P., 2019b. Effect of pimobendan on physical fitness, lactate and echocardiographic parameters in dogs with preclinical mitral valve disease without cardiomegaly. PLoS One 14, e0223164. https://doi.org/10.1371/journal.pone.0223164

  8. Lombard, C.W., Jöns, O., Bussadori, C.M., 2006. Clinical efficacy of pimobendan versus benazepril for the treatment of acquired atrioventricular valvular disease in dogs. J Am Anim Hosp Assoc 42, 249–261. https://doi.org/10.5326/0420249

Supplementary Information 

5.1 UK SPC Links

  1. Cardisan 1.25 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A013008 (accessed 12.22.23).

  2. Cardisan 2.5 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A013007 (accessed 12.22.23).

  3. Cardisan 5 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A013009 (accessed 12.22.23).

  4. Cardisan 10 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A013010 (accessed 12.22.23).

  5. Cardisan 15 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A013011 (accessed 12.22.23).

  6. Cardisure Flavoured 1.25 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A011500 (accessed 12.22.23).

  7. Cardisure flavoured 2.5 mg Tablets For dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008038 (accessed 12.22.23).

  8. Cardisure Flavoured 5 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008039 (accessed 12.22.23).

  9. Fortekor Plus 5mg/10mg Tablets [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009422 (accessed 12.22.23).

  10. Pimocard 1.25 mg Flavoured Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008358 (accessed 12.22.23).

  11. Pimocard 2.5 mg Flavoured Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008359 (accessed 12.22.23).

  12. Pimocard 10 mg Flavoured Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008361 (accessed 12.22.23).

  13. Pimotab 1.25 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010358 (accessed 12.22.23).

  14. Pimotab 2.5 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010359 (accessed 12.22.23).

  15. Pimotab 5 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010360 (accessed 12.22.23).

  16. Pimotab 10 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010361 (accessed 12.22.23).

  17. Pimotab 15 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010362 (accessed 12.22.23).

  18. Vetmedin 0.75 mg/ml Solution for Injection for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008883 (accessed 12.22.23).

  19. Vetmedin Chew 1.25 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009246 (accessed 12.22.23).

  20. Vetmedin Chew 2.5 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009247 (accessed 12.22.23).

  21. Vetmedin Chew 5 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009248 (accessed 12.22.23).

  22. Vetmedin Chew 10 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009249 (accessed 12.22.23).

  23. Zelys 1.25 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009706 (accessed 12.22.23).

  24. Zelys 5 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009707 (accessed 12.22.23).

5.2 Additional Material Consulted

  1. Booth, D., 2011. Small Animal Clinical Pharmacology and Therapeutics - 2nd Edition [WWW Document]. URL https://shop.elsevier.com/books/small-animal-clinical-pharmacology-and-therapeutics/boothe/978-0-7216-0555-5 (accessed 1.24.24).

  2. Maddison, G., 2008. Small Animal Clinical Pharmacology E-Book: 2nd edition | Edited by Jill E. Maddison | ISBN: 9780702037252 [WWW Document]. Elsevier Asia Bookstore. URL https://www.asia.elsevierhealth.com/small-animal-clinical-pharmacology-e-book-9780702037252.html (accessed 1.23.24).

  3. Plumb, 2024. Pimobendan [WWW Document]. URL https://app.plumbs.com/drug/GRsXwRfMyEPROD?source=search&searchQuery=pimobend (accessed 1.24.24).

  4. PubChem, 2024. Pimobendan [WWW Document]. URL https://pubchem.ncbi.nlm.nih.gov/compound/4823 (accessed 2.25.24).

  5. WHO, 2024. Pimobendan WHOCC - ATCvet Index [WWW Document]. URL https://www.whocc.no/atcvet/atcvet_index/ (accessed 2.25.24).

5.4 Expert Opinion

  • McArthur, S. (2024) Extrapolating pharmacological properties in man and veterinary species. Additional material in collating the data displayed is expert opinion derived from clinical experience or reputable texts.

 5.5 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

Monograph Details

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