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Benazepril

Grade

MMVD (All Stages)

See through space

Recommendations by ACVIM Stage

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

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).

Stage B2 - Home-Based Treatment

Once the ACVIM stage B2 diagnostic criteria have been met, Pimobendan is commenced. 50% of ACVIM consensus panellists recommend additional ACEi treatment if the LA diameter has increased on successive monitoring examinations or is deemed significantly enlarged on initial examination.


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

  • Benazepril: 0.25 mg (range 0.25-0.5) mg/kg, PO q12-24h. Benazepril is recommended if the LA diameter has increased on successive monitoring examinations or if it is deemed significantly enlarged on the initial examination.

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

Stage C - Initial Hospital Stabilisation

Acute Stage C MMVD cases usually 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.

Stage C Home-Based 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: 0.5 mg/kg PO, q24h (or 0.25 mg/kg PO, q12h).

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. Benazepril is administered at 0.5 mg/kg PO, q12-24h, in addition to some or all of:


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

  • 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).

  • 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.

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).

  • Dosing Changes: This depends upon signs and CHF staging, and we recommend alignment with ACVIM consensus recommendations. Typically, the Benazepril dose may be increased to a minimum dose of 0.5 mg/kg PO, q 24h (range 0.5-1.0), with changes to the other multimodal protocol comments as necessary (Keene et al., 2019).

  • Dosing Frequency: Benazepril is administered orally once or twice daily, with or without food (Keene et al., 2019). Twice daily dose frequency is proposed to optimise the cardioprotective benefit of ACEIs (Ward et al., 2021).

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., Furosemide, Pimobendan, 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

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About Benazepril and MMVD

Benazepril demonstrated promise as a sole agent treatment of CHF, many cases of which are MMVD. Survival time was 2.7 times longer in a benazepril-treated group (428 days)  compared with a placebo group (BENCH (BENazepril in Canine Heart disease) Study Group, 1999). However, insufficient evidence suggests that dogs with asymptomatic mitral valve disease will live longer if treated with benazepril (Brennan and Stavisky, 2015).


Pimobendan plus conventional therapy prolongs the time to sudden death, euthanasia for cardiac reasons, or treatment failure in dogs with CHF caused by MMVD compared with benazepril plus conventional therapy (Häggström et al., 2013). Therefore, benazepril is no longer considered a first-line MMVD agent (Keene et al., 2019).


The potential benefit of adding Benazepril to Pimobendan-based therapy remains unclear, with some experts favouring its use whilst others suggesting no additional benefit (Rishniw, 2020).

MMVD Suitability by ACVIM Stage

Whilst an ACEi such as Benazepril is included in most ACVIM protocols for MMVD stage B2 and above, conclusive evidence supporting its benefit is limited.

Stage A and B1

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

Stage B2

  • 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). Benazepril is recommended as an adjuvant treatment in support of Pimobendan in chronic Stage B1 heart failure with significant left chamber remodelling (Keene et al., 2019).

Stage C

  • Benazepril is recommended for adjuvant treatment in support of Frusemide/Pimobendan protocols for managing chronic Stage C heart failure (Keene et al., 2019). Additional medicines such as Spironolactone and hospital stabilising medications may be deployed case-by-case.

Stage D

  • Benazepril is recommended for adjuvant treatment of Torasemide/Pimobendan protocols for managing chronic Stage D heart failure (Keene et al., 2019). Additional medicines such as Spironolactone and hospital stabilising medications may be deployed case-by-case.

Benazepril Treatment Goals

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

Assessing any improved quality of life of patients with MMVD receiving Benazepril 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 specific Benazepril protocols.


  • Organ Level: Benazepril administration aims 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 for patients with MMVD and to slow, halt or reverse the disease progression.

  • Client Level: The goal of treatment is to offer clients with dogs experiencing MMVD a value-for-money increase in beneficial quality-adjusted life years (QALYs) .

Benazepril Treatment End Point

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

Related Monographs

Evidence

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1 Species-Specific Evidence Review 

  1. BENCH (BENazepril in Canine Heart disease) Study Group, 1999. The effect of benazepril on survival times and clinical signs of dogs with congestive heart failure: Results of a multicenter, prospective, randomized, double-blinded, placebo-controlled, long-term clinical trial. J Vet Cardiol 1, 7–18. https://doi.org/10.1016/S1760-2734(06)70025-X

  2. Brennan, M., Stavisky, J., 2015. Benazepril in dogs with asymptomatic mitral valve disease. Veterinary Record 177, 392–392. https://doi.org/10.1136/vr.h4110

  3. Coffman, M., Guillot, E., Blondel, T., Garelli-Paar, C., Feng, S., Heartsill, S., Atkins, C.E., 2021. Clinical efficacy of a benazepril and spironolactone combination in dogs with congestive heart failure due to myxomatous mitral valve disease: The BEnazepril Spironolactone STudy (BESST). J Vet Intern Med 35, 1673–1687. https://doi.org/10.1111/jvim.16155

  4. 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. Journal of Veterinary Internal Medicine 27, 1441–1451. https://doi.org/10.1111/jvim.12181

  5. 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

  6. 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

  7. 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

  8. King, J.N., Hirakawa, A., Sonobe, J., Otaki, H., Sakakibara, N., Seewald, W., Forster, S., 2018. Evaluation of a fixed-dose combination of benazepril and pimobendan in dogs with congestive heart failure: a randomized non-inferiority clinical trial. J Vet Sci 19, 117–128. https://doi.org/10.4142/jvs.2018.19.1.117

  9. Kittleson, M., Rishniw, M., Pion, P., Kass, P., 2009. Effect of benazepril on survival and cardiac events in dogs with asymptomatic mitral valve disease: A retrospective study of 141 cases. J Vet Intern Med 23, 953–954; author reply 955-956. https://doi.org/10.1111/j.1939-1676.2009.0361.x

  10. O’Grady, M.R., O’Sullivan, M.L., Minors, S.L., Horne, R., 2009. Efficacy of benazepril hydrochloride to delay the progression of occult dilated cardiomyopathy in Doberman Pinschers. J Vet Intern Med 23, 977–983. https://doi.org/10.1111/j.1939-1676.2009.0346.x

  11. Suzuki, S., Fukushima, R., Ishikawa, T., Yamamoto, Y., Hamabe, L., Kim, S., Yoshiyuki, R., Machida, N., Tanaka, R., 2012. Comparative effects of amlodipine and benazepril on Left Atrial Pressure in Dogs with experimentally-induced Mitral Valve Regurgitation. BMC Vet Res 8, 166. https://doi.org/10.1186/1746-6148-8-166

  12. Ward, J.L., Chou, Y.-Y., Yuan, L., Dorman, K.S., Mochel, J.P., 2021. Retrospective evaluation of a dose-dependent effect of angiotensin-converting enzyme inhibitors on long-term outcome in dogs with cardiac disease. J Vet Intern Med 35, 2102–2111. https://doi.org/10.1111/jvim.16236

2 Condition-Specific Evidence Review

  1. BENCH (BENazepril in Canine Heart disease) Study Group, 1999. The effect of benazepril on survival times and clinical signs of dogs with congestive heart failure: Results of a multicenter, prospective, randomized, double-blinded, placebo-controlled, long-term clinical trial. J Vet Cardiol 1, 7–18. https://doi.org/10.1016/S1760-2734(06)70025-X

  2. Coffman, M., Guillot, E., Blondel, T., Garelli-Paar, C., Feng, S., Heartsill, S., Atkins, C.E., 2021. Clinical efficacy of a benazepril and spironolactone combination in dogs with congestive heart failure due to myxomatous mitral valve disease: The BEnazepril Spironolactone STudy (BESST). J Vet Intern Med 35, 1673–1687. https://doi.org/10.1111/jvim.16155

  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., 2013. 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. Journal of Veterinary Internal Medicine 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. 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. 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

  7. Suzuki, S., Fukushima, R., Ishikawa, T., Yamamoto, Y., Hamabe, L., Kim, S., Yoshiyuki, R., Machida, N., Tanaka, R., 2012. Comparative effects of amlodipine and benazepril on Left Atrial Pressure in Dogs with experimentally-induced Mitral Valve Regurgitation. BMC Vet Res 8, 166. https://doi.org/10.1186/1746-6148-8-166

  8. Ward, J.L., Chou, Y.-Y., Yuan, L., Dorman, K.S., Mochel, J.P., 2021. Retrospective evaluation of a dose-dependent effect of angiotensin-converting enzyme inhibitors on long-term outcome in dogs with cardiac disease. J Vet Intern Med 35, 2102–2111. https://doi.org/10.1111/jvim.16236

3 Substance-Specific Evidence Review

  1. Adin, D., Atkins, C., Wallace, G., Klein, A., 2021. Effect of spironolactone and benazepril on furosemide‐induced diuresis and renin‐angiotensin‐aldosterone system activation in normal dogs. J Vet Intern Med 35, 1245–1254. https://doi.org/10.1111/jvim.16097

  2. BENCH (BENazepril in Canine Heart disease) Study Group, 1999. The effect of benazepril on survival times and clinical signs of dogs with congestive heart failure: Results of a multicenter, prospective, randomized, double-blinded, placebo-controlled, long-term clinical trial. J Vet Cardiol 1, 7–18. https://doi.org/10.1016/S1760-2734(06)70025-X

  3. Coffman, M., Guillot, E., Blondel, T., Garelli-Paar, C., Feng, S., Heartsill, S., Atkins, C.E., 2021. Clinical efficacy of a benazepril and spironolactone combination in dogs with congestive heart failure due to myxomatous mitral valve disease: The BEnazepril Spironolactone STudy (BESST). J Vet Intern Med 35, 1673–1687. https://doi.org/10.1111/jvim.16155

  4. 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., 2013. 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. Journal of Veterinary Internal Medicine 27, 1441–1451. https://doi.org/10.1111/jvim.12181

  5. 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

  6. Regulski, M., Regulska, K., Stanisz, B.J., Murias, M., Gieremek, P., Wzgarda, A., Niznik, B., 2015. Chemistry and pharmacology of Angiotensin-converting enzyme inhibitors. Curr Pharm Des 21, 1764–1775. https://doi.org/10.2174/1381612820666141112160013

  7. Suzuki, S., Fukushima, R., Ishikawa, T., Yamamoto, Y., Hamabe, L., Kim, S., Yoshiyuki, R., Machida, N., Tanaka, R., 2012. Comparative effects of amlodipine and benazepril on Left Atrial Pressure in Dogs with experimentally-induced Mitral Valve Regurgitation. BMC Vet Res 8, 166. https://doi.org/10.1186/1746-6148-8-166

  8. Toutain, P.L., Lefèbvre, H.P., 2004. Pharmacokinetics and pharmacokinetic/pharmacodynamic relationships for angiotensin-converting enzyme inhibitors. Journal of Veterinary Pharmacology and Therapeutics 27, 515–525. https://doi.org/10.1111/j.1365-2885.2004.00601.x

  9. Ward, J.L., Chou, Y.-Y., Yuan, L., Dorman, K.S., Mochel, J.P., 2021. Retrospective evaluation of a dose-dependent effect of angiotensin-converting enzyme inhibitors on long-term outcome in dogs with cardiac disease. J Vet Intern Med 35, 2102–2111. https://doi.org/10.1111/jvim.16236

4 Efficacy Evidence Review

  1. BENCH (BENazepril in Canine Heart disease) Study Group, 1999. The effect of benazepril on survival times and clinical signs of dogs with congestive heart failure: Results of a multicenter, prospective, randomized, double-blinded, placebo-controlled, long-term clinical trial. J Vet Cardiol 1, 7–18. https://doi.org/10.1016/S1760-2734(06)70025-X

  2. Brennan, M., Stavisky, J., 2015. Benazepril in dogs with asymptomatic mitral valve disease. Veterinary Record 177, 392–392. https://doi.org/10.1136/vr.h4110

  3. Coffman, M., Guillot, E., Blondel, T., Garelli-Paar, C., Feng, S., Heartsill, S., Atkins, C.E., 2021. Clinical efficacy of a benazepril and spironolactone combination in dogs with congestive heart failure due to myxomatous mitral valve disease: The BEnazepril Spironolactone STudy (BESST). J Vet Intern Med 35, 1673–1687. https://doi.org/10.1111/jvim.16155

  4. 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. Journal of Veterinary Internal Medicine 27, 1441–1451. https://doi.org/10.1111/jvim.12181

  5. 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

  6. 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

  7. King, J.N., Hirakawa, A., Sonobe, J., Otaki, H., Sakakibara, N., Seewald, W., Forster, S., 2018. Evaluation of a fixed-dose combination of benazepril and pimobendan in dogs with congestive heart failure: a randomized non-inferiority clinical trial. J Vet Sci 19, 117–128. https://doi.org/10.4142/jvs.2018.19.1.117

  8. Kittleson, M., Rishniw, M., Pion, P., Kass, P., 2009. Effect of benazepril on survival and cardiac events in dogs with asymptomatic mitral valve disease: A retrospective study of 141 cases. J Vet Intern Med 23, 953–954; author reply 955-956. https://doi.org/10.1111/j.1939-1676.2009.0361.x

  9. O’Grady, M.R., O’Sullivan, M.L., Minors, S.L., Horne, R., 2009. Efficacy of benazepril hydrochloride to delay the progression of occult dilated cardiomyopathy in Doberman Pinschers. J Vet Intern Med 23, 977–983. https://doi.org/10.1111/j.1939-1676.2009.0346.x

  10. Suzuki, S., Fukushima, R., Ishikawa, T., Yamamoto, Y., Hamabe, L., Kim, S., Yoshiyuki, R., Machida, N., Tanaka, R., 2012. Comparative effects of amlodipine and benazepril on Left Atrial Pressure in Dogs with experimentally-induced Mitral Valve Regurgitation. BMC Vet Res 8, 166. https://doi.org/10.1186/1746-6148-8-166

  11. Ward, J.L., Chou, Y.-Y., Yuan, L., Dorman, K.S., Mochel, J.P., 2021. Retrospective evaluation of a dose-dependent effect of angiotensin-converting enzyme inhibitors on long-term outcome in dogs with cardiac disease. J Vet Intern Med 35, 2102–2111. https://doi.org/10.1111/jvim.16236

Supplementary Information 

1 UK SPC Links

  1. Arixil Vet 5 mg Film-coated Tablet for Dogs and Cats [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009988 (accessed 1.1.24).

  2. Arixil Vet 20 mg Film-coated Tablet for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009989 (accessed 1.1.24).

  3. Banacep Vet 5 mg Film-coated Tablet for Dogs and Cats [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A006998 (accessed 1.1.24).

  4. Banacep Vet 20 mg Film-coated Tablet for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008086 (accessed 1.1.24).

  5. Benazecare Flavour 5 mg Tablets for Dogs and Cats [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A006679 (accessed 1.1.24).

  6. Benazecare Flavour 20 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A006680 (accessed 1.1.24).

  7. BenazeVet 2.5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010811 (accessed 1.1.24).

  8. BenazeVet 5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010803 (accessed 1.1.24).

  9. BenazeVet 20 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010804 (accessed 1.1.24).

  10. Benefortin Flavour 2.5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008272 (accessed 1.1.24).

  11. Benefortin Flavour 5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008273 (accessed 1.1.24).

  12. Benefortin Flavour 20 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008274 (accessed 1.1.24).

  13. Cardalis 2.5 mg/20 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008282 (accessed 1.1.24a).

  14. Cardalis 2.5 mg/20 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008282 (accessed 1.1.24b).

  15. Cardalis 5 mg/40 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008569 (accessed 1.1.24).

  16. Cardalis 10 mg/80 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008570 (accessed 1.1.24).

  17. Fortekor 2.5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A005871 (accessed 1.1.24).

  18. Fortekor Flavour 5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A007625 (accessed 1.1.24).

  19. Fortekor Flavour 20 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A007630 (accessed 1.1.24).

  20. Fortekor Plus 5mg/10mg Tablets [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009422 (accessed 1.1.24).

  21. Kelapril 5 mg, Film-coated Tablets for Dogs and Cats [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008293 (accessed 1.1.24).

  22. Kelapril 20 mg, Film-coated Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008294 (accessed 1.1.24).

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. Benazepril [WWW Document]. URL https://app.plumbs.com/drug/PGVZkcnorQPROD?source=search&searchQuery=benaze (accessed 1.24.24).

3 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

4 Expert Opinion

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

Monograph Details

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