Cardiac Drugs for Treatment of Canine Heart Failure

Degenerative mitral valve disease (DMVD) and dilated cardiomyopathy (DCM) are common cardiac diseases in adult dogs. Both diseases can lead to heart failure and loss of quality and quantity of life.

Various cardiac drugs prolong survival and many others help alleviate clinical signs.

DiureticsIndicationsDiuretics are a mainstay of therapy in dogs with congestive heart failure (CHF) due to DMVD or DCM.

AdministrationBolus injections of furosemide (2–4 mg/kg Q 2 H) are used in dogs withrespiratory distress secondary to acute heart failure until respiratory rate and effort begin to improve.

Alternatively, furosemide can be given as a constant rate infusion. Purported advantages of furosemide infusion over intermittent boluses include enhanced natriuresis and diuresis and less urinary potassium loss. I recommend using 0.66 to 1 mg/kg/H, monitoring respiratory rate every hour.

Once acute heart failure is resolved, chronic oral therapy with furosemide (1–2 mg/kg Q 12 H) is initiated. Asdisease progresses, many dogs require escalating doses of furosemide to suppress signs of congestion and total doses of 6 to 8 mg/kg Q 24 H are not uncommon.

ConsiderationsIn experimental studies, dogs have rapidly become resistant to chronic furosemide. In clinical patients, high doses of furosemide are often associated with diminishing polyuria and polydipsia and recurrent episodes of heart failure. In these cases, additional diuretics (hydrochlorothiazide or a hydrochlorothiazide–spironolactone combination, 0.5–1 mg/kg Q 24–48 H) help restore diuretic response. In most cases, the additional diuretics are added to the existing furosemide regimen.

In dogs with advanced disease, and particularly in cases of right heart failure, bioavailability of oral medications is likely reduced. Daily subcutaneous injections of furosemide can be used in place of oral administration and are often associated with restoration of copious diuresis.

MonitoringIn all instances of diuretic use, renal function should be closely monitored.

ACE InhibitorsIndicationsSevere heart disease is generally associated with activation of the reninangiotensin–aldosterone system (RAAS), which promotes fluid retention, vasoconstriction, and myocardial and vascular remodeling. Use of ACE inhibitors in dogs with CHF is associated with improved quality of life and survival; however, data in support of this statement are less robust for dogs with DCM than for dogs with DMVD. When diuretics such as furosemide are administered, the reduction of plasma volume further stimulates RAAS activity and coadministration with an ACE inhibitor is generally recommended.

AdministrationThere are a variety of ACE inhibitors available, including enalapril, benazepril, ramapril, and lisinopril (Table). Differences are relatively minor, mainly involving route of metabolism/excretion and lipophilicity. From a clinical standpoint, many cardiologists consider them to be interchangeable. In the United States, the two most commonly used ACE inhibitors are enalapril and benazepril; both are associated with clinical benefit in dogs with signs of heart failure.

ConsiderationsIn dogs with DMVD, the use of ACE inhibitors in those without clinical signs remains controversial. Two well-designed studies offer slightly different perspectives: One study in Cavalier King Charles spaniels with mild–moderate DMVD clearly indicated that enalapril did not delay onset of CHF. Another study involving dogs of many different breeds and more advanced DMVD also failed to show benefit with respect to the study’s primary endpoint; however, analysis of several secondary endpoints suggested that dogs that received enalapril avoided heart failure longer than dogs that did not.

In my opinion, if ACE inhibitors delay heart failure in dogs with DMVD that show no clinical signs, the effect is inconsistent from individual to individual, relatively small, and unlikely to dramatically change progression of disease. In dogs with severe heart enlargement and at high risk for CHF, I prefer to use an ACE inhibitor in tandem with low-dose diuretic therapy (furosemide, 1 mg/kg Q 24 H), as this more likely reduces plasma volume, intracardiac pressure, and risk of CHF than using an ACE inhibitor alone.

In human patients with asymptomatic DCM, early use of ACE inhibitors is widely recommended. In veterinary medicine, large-scale trials are lacking; however, a small study indicated that ACE inhibitors delayed onset of heart failure in Doberman pinschers with DCM. Thus, in dogs with DCM, I recommend use of ACE inhibitors prior to onset of clinical signs.

MonitoringAdverse effects of ACE inhibitor treatment are relatively rare, but clinically significant renal dysfunction can occur. Less commonly, systemic hypotension or electrolyte imbalances are encountered. Renal function should be evaluated both before and after initiation of ACE inhibitors and at3- to 6-month intervals thereafter.

PimobendanIndicationsBoth DMVD and DCM are associated with progressive loss of myocardial contractility. Poor contractility is much easier to detect in dogs with DCM as opposed to DMVD, where the presence of a large degree of mitral regurgitation often confounds routine echocardiographic evaluation of contractility.

Pimobendan is a positive inotrope and increases contractility through a mechanism different from that of traditional inotropes such as digoxin—the advantage of which is increased contractility without significant increases in myocardial oxygen demand. Pimobendan also relaxes vascular smooth muscle and elicits modest arterial vasodilation; this dual “inodilating” action is unique. Pimobendan improves survival and quality of life in dogs with DMVD, and very likely does the same in dogs with DCM.

AdministrationThe recommended dose is 0.5 mg/kg per day, divided into 2 doses that do not necessarily need to be equal.

ConsiderationsThe benefits of pimobendan have been substantiated in dogs showing clinical signs associated with heart disease due to DMVD and DCM; treatment with this agent is recommended only if clinical signs are evident. Thus, in the majority of instances, pimobendan is prescribed only if and when dogs experience congestive heart failure and its attendant clinical manifestations (eg, cough, dyspnea, tachypnea).

Less commonly, dogs with exercise intolerance or syncope are also candidates for treatment. Currently, no evidence exists for the use of pimobendan in dogs with DMVD or DCM prior to the onset of clinical signs.MonitoringPimobendan is generally well tolerated in dogs and no specific monitoring recommendations accompany its use.

SpironolactoneIndicationsSpironolactone is a relatively weak potassium-sparing diuretic, and its potency prevents its use as the sole diuretic agent in dogs with CHF. The value of spironolactone most likely lies in its action as a specific aldosterone antagonist. Aldosterone is a part of the aforementioned RAAS and promotes fluid retention and vascular and myocardial remodeling. Interestingly, in both humans and dogs with heart disease, aldosterone can be elevated despite the use of ACE inhibitors. Suppression of this “aldosterone escape” by spironolactone is associated with reduced morbidity and improved survival in dogs with DMVD.

AdministrationIn dogs with signs of heart failure, spironolactone (1–2 mg/kg Q 12 H) is recommended in addition to furosemide, ACE inhibitors, and pimobendan. In Europe, where spironolactone is specifically approved for use in dogs with DMVD, the recommended dose is 2 mg/kg Q 24 H. In the United States, many cardiologists use a lower dose of spironolactone (0.5–1 mg/kg day) or spironolactone coupled with a thiazide diuretic such as hydrochlorothiazide.

MonitoringAdverse effects can include hyperkalemia (especially in the face of concurrent ACE inhibitor) and azotemia, and routine renal and electrolyte monitoring is recommended. 

Beta-BlockersIndicationsSympathetic tone is chronically elevated in dogs with DMVD and DCM and is thought to contribute to disease progression. In humans, plasma norepinephrine is a powerful predictor of morbidity and mortality. However, routine use of beta-blockers in veterinary medicine is hindered by lack of well-controlled clinical trials and risk for adverse events when initiating therapy, especially in dogs with advanced disease. In humans, beta-blockade is recommended in virtually all instances of reduced contractility, such as occurs in DCM. Thus, administration of beta-blockers is advocated by many cardiologists in dogs with DCM.

AdminstrationBecause of the risk for acute slowing of heart rate and decreases in contractility, treatment with beta-blockers must be performed with caution. Typically, the dose is up-titrated over 4 to 6 weeks with close monitoring of heart rate, respiratory effort, and blood pressure. Titration is best tolerated in dogs with relatively early DCM.

ConsiderationsIn dogs with DMVD, the use of beta-blockers is controversial and no consensus recommendations can be made.

MonitoringPractitioners who use beta-blockers must be prepared to monitor dogs closely and to deal with acute decompensation should it occur. Consultation with a cardiologist is recommended.

Take NoteDrug doses listed in this article are guidelines for the “typical” dog with heart failure. They may need to be adjusted based on the patient’s severity of signs, renal function, concurrent disease, and response to initial treatment. When prescribing medications to dogs with congestive heart failure due to DMVD or DCM, there is broad consensus that combination therapy with furosemide, an ACE inhibitor, and pimobendan is beneficial.

CARDIAC DRUGS FOR TREATMENT OF CANINE HEART FAILURE • Mark A. Oyama

Suggested ReadingBeta-blockade in the management of systolic dysfunction. In Abbott JA (ed): Vet Clin North Am Small Anim Pract 34:1157-1170, 2004.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. Haggstrom J, Boswood A, O’Grady M, et al. J Vet Intern Med 22:1124-1135, 2008.Effects of enalapril maleate on survival of dogs with naturally acquired heart failure. The long-term investigation of veterinary enalapril (LIVE) study group. Ettinger SJ, Benitz AM, Ericsson GF, et al. JAVMA 213:1573-1577, 1998.Efficacy of enalapril for prevention of congestive heart failure in dogs with myxomatous valve disease and asymptomatic mitral regurgitation. Kvart C, Haggstrom J, Pedersen HD, et al. J Vet Intern Med 16:80-88, 2002.Pathophysiology and therapy of heart failure. Strickland KN. In Tilley LP, Smith FWK, Oyama, MA, Sleeper MM (eds): Manual of Canine and Feline Cardiology, 4th ed—St. Louis: Saunders Elsevier, 2008.Results of the veterinary enalapril trial to prove reduction in onset of heart failure in dogs chronically treated with enalapril alone for compensated, naturally occurring mitral valve insufficiency. Atkins CE, Keene BW, Brown WA, et al. JAVMA 231:1061-1069, 2007.