Cardalis® should be given as part of your standard heart failure therapy as soon as clinical signs (such as exercise intolerance, coughing and/or dyspnoea; ISACHC stage II/beginning of ACVIM stage C) appear*.

* For the home-care treatment of congestive heart failure caused by chronic degenerative valvular disease in dogs (with diuretic support as appropriate).

Reminder:
ISACHC stage II: clinical signs of Heart Failure (HF) are evident at rest or with mild exercise and adversely affect the quality of life. Typical signs of HF include exercise intolerance, cough, dyspnea (tachypnea, mild respiratory distress) and mild to moderate ascites in some cases.
ACVIM stage C: Patients with past or current clinical signs of heart failure associated with structural heart disease (left-sided heart enlargement).

Spironolactone is fat soluble and its absorption is increased by bile, which is produced following feeding. It has been shown that the absorption of spironolactone is 80-90% when administered with food versus 32-49% when given without food. For this reason, CARDALIS® has to be given with the meal (whatever the moment of the meal).

References:
Guyonnet J, Elliott J, Kaltsatos V. A preclinical pharmacokinetic and pharmacodynamic approach to determine a dose of spironolactone for treatment of congestive heart failure in dog. J Vet Pharmacol Ther 2010;33(3):260-267.

Yes, it has been shown that CARDALIS® is well tolerated when combined with pimobendan.

Reference:
Ollivier, E., et al. (2012), Safety of a veterinary product combining spironolactone and benazepril (Cardalis®) in healthy and cardiac dogs, ECVIM Congress Proceedings and Poster.

As angiotensin ll, aldosterone have harmful effects which contribute to the vicious cycle of heart failure. ACE Inhibitors, such as benazepril, prevent the production of angiotensin ll. However, aldosterone levels continue to rise in patients receiving an ACE Inhibitor. Indeed the inhibition of aldosterone provided by ACE inhibitors is only partial because other factors than angiotensin II also stimulate aldosterone production.
Differently from ACE inhibitors, spironolactone, an aldosterone receptor antagonist, takes the place of aldosterone on its receptor and therefore directly blocks the harmful effects of aldosterone.

Cardalis® combining benazepril and spironolactone is the best strategy to achieve comprehensive blockade of the RAASystem.

References :
Ovaert P, Elliott J, Bernay F, et al. J Vet Pharmacol Ther 2010;33(2):109-117.
Jeunesse E, Woehrle F, Schneider M, et al. J Vet Cardiol 2007;9(2):63-68.
Atkins CE, Haggstrom J. J Vet Cardiol 2012;14(1):165-184.
Haggstrom J, Hansson K, Karlberg BE, et al. Am J Vet Res 1996;57(11):1645-1652.
Lantis AC, Atkins CE, DeFrancesco TC, et al. J Vet Intern Med 2010;24(3):672.
Lantis AC, Atkins CE, DeFrancesco TC, et al. Am J Vet Res 2011;72(12):1646-1651.
Sayer MB, Atkins CE, Fujii Y, et al. J Vet Intern Med 2009;23(5):1003-1006.
Oyama MA. J Small Anim Pract 2009;50(Suppl 1):3-11.

In a field study (FILIT study), it has been shown that CARDALIS® as first line treatment* improves clinical findings and quality of life of dogs with Congestive Heart Failure due to Chronic Degenerative Valve Disease by one week as evaluated by both veterinarians and dog owners.
These parameters are then stabilized for at least 3 months.

*(in addition to other therapies if necessary)

Reference: Ollivier, E., Grassi, V. (2012), Concomitant use of the FETCH questionnaire and the veterinary evaluation to assess quality of life of cardiac dogs treated with a veterinary product combining spironolactone and benazepril (Cardalis®), ECVIM Congress Proceedings and Poster.

Heart failure causes activation of the RAASystem and the production of angiotensin ll and aldosterone. Combining benazepril and spironolactone in the same tablet, CARDALIS® allows a comprehensive blockade of the RAASystem.
It has been demonstrated that pimobendan is not able to block RAAS activation which happens during Heart Failure. Thus there is an interest to give CARDALIS® in addition to pimobendan from the first clinical signs of Heart Failure.

References:
Lantis AC, Atkins CE, DeFrancesco TC, et al. Am J Vet Res 2011;72(12):1646-1651.
Sayer MB, Atkins CE, Fujii Y, et al. J Vet Intern Med 2009;23(5):1003-1006.
Oyama MA. J Small Anim Pract 2009;50(Suppl 1):3-11.

As a loop diuretic, furosemide activates the RAASystem and so production of angiotensin II and aldosterone. Angiotensin II and aldosterone have harmful effects including vasoconstriction and cardiovascular re-modelling/ fibrosis. For these reasons, Cardalis should be given when furosemide is prescribed.

References:
Atkins CE, Haggstrom J. J Vet Cardiol 2012;14(1):165-184.
Lantis AC, Atkins CE, DeFrancesco TC, et al. J Vet Intern Med 2010;24(3):672.
Sayer MB, Atkins CE, Fujii Y, et al.J Vet Intern Med 2009;23(5):1003-1006.

A field study assessed the efficacy and safety of benazepril and spironolactone versus benazepril alone in dogs suffering from Congestive Heart Failure due to Chronic Degenerative Valve Disease. This study did not demonstrate a significant difference in the group receiving both actives neither on renal parameters (uremia and creatininemia) nor on kalemia compared to the group receiving only benazepril.*
CARDALIS® administration has no harmful effect on the renal function of cardiac dogs compared to benazepril alone.

References:
Ollivier, E., et al. (2012), Safety of a veterinary product combining spironolactone and benazepril (Cardalis®) in healthy and cardiac dogs, ECVIM Congress Proceedings and Poster.
Cardalis®, EPAR Product Information, 2012 August 28th, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/veterinary/002524/WC500131473.pdf

Yes, there is no contra-indication for this use. However, a regular monitoring of the renal function and kalemia has to be performed as it is normally done by the veterinarian in dogs presenting renal failure.

SPC indicates that: “Regular monitoring of renal function and serum potassium levels is recommended in dogs with renal impairment, as they may have an increased risk of hyperkalaemia during treatment with this product.”

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