Our pharmacologic toolbox for managing congestive heart failure (CHF) in dogs continues to evolve. One newer medication that practitioners may encounter is sacubitril/valsartan (Entresto). In human medicine, Entresto has become an important therapy in heart failure management and is now beginning to gain attention in veterinary cardiology as well.
Sacubitril/valsartan combines two active components:
- Sacubitril — a neprilysin inhibitor
- Valsartan — an angiotensin receptor blocker (ARB)
Valsartan provides blockade of the renin-angiotensin-aldosterone system (RAAS), while sacubitril increases circulating natriuretic peptides by inhibiting neprilysin-mediated breakdown. This results in beneficial effects, including vasodilation, natriuresis, and reduced maladaptive neurohormonal activation. In human medicine, this combination has been shown to reduce mortality and hospitalization rates in patients with heart failure.
In dogs, sacubitril/valsartan is considered an adjunctive therapy and is not intended to replace standard CHF medications such as pimobendan, diuretics, or ACE inhibitors/ARB therapy without cardiology guidance. Current veterinary experience remains limited compared to human medicine. However, early studies and clinical experience suggest that it is well tolerated, and some dogs may benefit from ARNI (angiotensin receptor-neprilysin inhibitor) therapy.
Reasonable candidates for consideration may include:
- Dogs with myxomatous mitral valve disease (MMVD)
- Dogs with dilated cardiomyopathy (DCM)
- Patients with persistent or recurrent CHF despite standard therapy
- Cases where additional RAAS suppression or afterload reduction may be beneficial (e.g., advanced stage B2 dogs at risk of heart failure)
At the University of Illinois, we typically initiate sacubitril/valsartan after evaluating renal values, electrolytes, blood pressure, and staging of heart disease. Dosing is started conservatively and up-titrated gradually, based on patient response and tolerance.
Practical canine target dose is 15-30 mg/kg PO q12 (combined sacubitril + valsartan). We generally start around 10 mg/kg q12 with a target dose of 20-30 mg/kg q12, depending on patient size, renal function, and tolerance.
A washout period of approximately 48 hours is recommended when transitioning patients from an ACE inhibitor due to the risk of excessive RAAS blockade and hypotension.
Potential Side Effects and Monitoring Considerations
Practitioners should be aware of several potential adverse effects associated with sacubitril/valsartan therapy:
- Hypotension
Due to vasodilation and RAAS blockade, systemic blood pressure may decrease. Clinical signs can include weakness, lethargy, collapse, or decreased appetite. - Azotemia / Renal Dysfunction
Similar to ACE inhibitors and ARBs, decreases in renal perfusion may lead to worsening kidney values, particularly in patients with pre-existing renal disease or dehydration. - Electrolyte Abnormalities
Hyperkalemia may occur, especially when combined with other RAAS-suppressive medications such as spironolactone or ACE inhibitors. - Gastrointestinal Signs
Vomiting, diarrhea, hyporexia, or general gastrointestinal upset may occur in some patients.
We recommend:
- Blood pressure monitoring
- Renal value and electrolyte recheck within 1 to 2 weeks after initiation or dose adjustment
- Continued monitoring for changes in appetite, activity level, respiratory status, and hydration
While additional studies are still needed in veterinary medicine, sacubitril/valsartan represents an emerging option that may provide benefit in carefully selected canine heart failure patients. As with any newer therapy, patient selection, monitoring, and individualized treatment planning remain critical.
If you are considering sacubitril/valsartan for a patient and would like to discuss whether the medication may be appropriate, please feel free to contact our cardiology service for consultation.
Find links to all the hospital service consultation forms at: go.illinois.edu/consultationforms
By Saki Kadotani, DVM, MS, DACVIM (Cardiology)
Feature image of Dr. Kadotani by Fred Zwicky
