Entresto is a medication combining two active pharmaceutical ingredients, sacubitril and valsartan. It was originally developed for human patients with chronic heart failure, demonstrating significant benefits by managing the complex neurohormonal processes driving heart disease progression. Veterinary cardiologists are now exploring its use as an advanced therapeutic option for dogs suffering from specific cardiac conditions. This article explains why Entresto is used in canines, how its unique dual mechanism functions, the practicalities of dosing and administration, and the potential safety considerations involved.
Canine Heart Disease and Treatment Rationale
The primary condition for which Entresto is considered in dogs is myxomatous mitral valve disease (MMVD), the most common cause of heart failure in canines. MMVD involves progressive degeneration and thickening of the mitral valve leaflets, preventing them from closing completely. This causes mitral regurgitation, reducing the heart’s pumping efficiency and overloading the left chambers.
As the disease advances, the heart activates powerful neurohormonal systems, notably the Renin-Angiotensin-Aldosterone System (RAAS). Chronic RAAS activation causes blood vessel constriction, fluid retention, and harmful cardiac remodeling, leading to congestive heart failure (CHF). CHF is characterized by fluid accumulation, typically in the lungs, causing clinical signs like coughing and difficulty breathing.
Traditional treatments often suppress the RAAS using drugs like Angiotensin-Converting Enzyme (ACE) inhibitors. However, ACE inhibitors do not fully block the system’s detrimental effects, and the disease often progresses. Entresto provides a comprehensive, dual-action mechanism that blocks harmful vasoconstriction while enhancing the body’s natural protective systems. This approach aims to manage the long-term strain on the heart and delay disease progression.
How Entresto Works: The Dual-Action Approach
Entresto is classified as an Angiotensin Receptor-Neprilysin Inhibitor (ARNI), reflecting the two distinct actions of its component drugs: valsartan and sacubitril.
Valsartan is an Angiotensin Receptor Blocker (ARB) that directly inhibits Angiotensin II, a potent RAAS hormone. Angiotensin II constricts blood vessels and signals the kidneys to retain sodium and water, increasing blood pressure and the heart’s workload. By blocking the Angiotensin II type 1 (AT1) receptor, valsartan prevents these harmful effects, resulting in vasodilation that lowers blood pressure and reduces resistance against the heart.
Sacubitril, the second component, works by inhibiting the enzyme neprilysin. Neprilysin breaks down beneficial substances, particularly natriuretic peptides (NPs). These NPs, such as B-type natriuretic peptide (BNP), are released by the heart in response to muscle stretch and naturally counter the effects of the RAAS.
Blocking neprilysin prevents the degradation of these peptides, leading to their sustained presence in the bloodstream. The increased natriuretic peptides promote diuresis (removal of excess fluid) and natriuresis (excretion of sodium). This dual mechanism—valsartan suppressing the RAAS and sacubitril enhancing the protective NP system—reduces fluid overload and minimizes long-term strain on the canine heart.
Dosing, Administration, and Veterinary Oversight
Entresto is not a commercially approved veterinary drug, so its administration is strictly regulated by a veterinarian. The medication is given orally, typically twice daily, and consistent timing is important to maintain steady drug levels in the bloodstream. Because human Entresto tablets are fixed-dose, veterinary pharmacists often compound the medication into customized capsules or a suspension to achieve the precise weight-based dosage required for dogs.
Standardized veterinary dosing guidelines are still developing. Clinical studies have explored a dosage of 20 mg/kg every 12 hours, but many cardiologists recommend starting lower, typically 5 to 10 mg/kg twice daily. The dose is gradually increased based on the dog’s tolerance and response, and owners must follow the veterinarian’s instructions precisely and never attempt to adjust the dose without consultation.
Before starting treatment, the dog undergoes thorough diagnostics, including a complete blood panel, chest X-rays, and an echocardiogram, to establish baseline values and confirm the diagnosis. Ongoing and frequent veterinary monitoring is required, especially during the initial phase of treatment.
Monitoring focuses on blood pressure measurements and specific blood tests for kidney function, such as Blood Urea Nitrogen (BUN) and creatinine. Electrolyte levels, particularly potassium, must also be monitored, as the drug’s actions can affect these values.
Potential Side Effects and Safety Considerations
Limited veterinary studies suggest Entresto is generally well tolerated in dogs, but owners should be aware of potential adverse reactions, often extrapolated from human experience. Common effects are mild and may include gastrointestinal upset (vomiting or diarrhea) and general lethargy or weakness. These symptoms can sometimes be managed by adjusting the medication timing or the dog’s feeding schedule.
More serious concerns relate to the drug’s effects on the circulatory and renal systems. Since valsartan lowers blood pressure, excessive reduction (hypotension) can occur, potentially causing extreme weakness or collapse. The drug’s influence on the RAAS can also lead to a temporary increase in kidney values (azotemia) or high potassium levels (hyperkalemia).
A significant safety consideration is the interaction with ACE inhibitors, which are standard in canine heart failure therapy. Entresto should not be administered concurrently with an ACE inhibitor, requiring a washout period when transitioning between the two classes.
This is due to the theoretical risk of angioedema, a severe swelling of the face and throat, known in humans when these drugs are combined. Owners must immediately contact their veterinarian if they observe signs of severe adverse reactions, such as profound weakness, facial swelling, or significant changes in appetite.