Entresto® in Dogs — A Practical Guide to Patient Selection, Dosing, Side Effects, and Monitoring

Entresto® in Dogs — A Practical Guide to Patient Selection, Dosing, Side Effects, and Monitoring

By Christina Bové, DVM, MS, DACVIM (Cardiology)

“A promising medication becomes clinically useful only when we understand which patients may benefit, how to dose it safely, and what we need to monitor along the way.”

In Parts 1 and 2, we looked at why sacubitril/valsartan (Entresto®) is generating interest in veterinary cardiology, how it works, and what the canine studies actually show.

Now comes the practical question:

How do we actually use Entresto in dogs?

The answer is still evolving. Sacubitril/valsartan is not FDA-approved for dogs, so its use in veterinary patients is extra-label. We do not have a veterinary label establishing an approved canine indication, dose, or monitoring protocol. Instead, current use is based on the limited published canine studies, emerging clinical experience, and individual patient assessment.

That makes it particularly important to distinguish between what has been studied, what is emerging as practical clinical use, and what we still don't know.

A Practical Change: Generic Sacubitril/Valsartan Is Now Available

Cost has historically been one of the practical barriers to using Entresto in veterinary patients, particularly for larger dogs requiring multiple tablets twice daily.

That landscape has changed.

The FDA approved the first generic sacubitril/valsartan tablets in May 2024 but only became available in U.S. pharmacies in July 2025. The generic tablets have the same 24/26-mg, 49/51-mg, and 97/103-mg strengths as brand-name Entresto. The FDA notes that generic drugs must demonstrate bioequivalence and meet the same quality and manufacturing standards as their brand-name counterparts.

The availability of generic sacubitril/valsartan has the potential to make chronic treatment considerably more practical for veterinary patients than it was when only the branded product was available.

For simplicity, I'll continue to refer to Entresto throughout this article, but the discussion applies to sacubitril/valsartan generally.

Which Dogs Might Be Candidates?

This is probably the biggest question—and right now, there isn't one answer that applies to every stage of MMVD.

Stage B2: Promising, But Still Investigational

Stage B2 may ultimately be one of the most interesting places for sacubitril/valsartan in MMVD—but it is also where we need to be especially careful about separating biologic promise from proven clinical benefit.

Pimobendan remains the evidence-based cornerstone of Stage B2 therapy. The question isn't whether Entresto should replace pimobendan. It is whether adding sacubitril/valsartan to pimobendan could provide additional benefit, particularly in dogs with more advanced or progressive Stage B2 disease.

The Newhard study provides the strongest published evidence we currently have in this population. Thirteen dogs with Stage B2 MMVD were enrolled, and importantly, all were already receiving pimobendan. Seven dogs received sacubitril/valsartan and six received placebo for 30 days. Dogs receiving sacubitril/valsartan had significantly less increase in urinary aldosterone-to-creatinine ratio than dogs receiving placebo, suggesting meaningful modulation of the RAAS even before CHF develops.

What the study did not show was whether those neurohormonal effects translate into something clinically meaningful. It was small and short-term and was not designed to determine whether Entresto delays the onset of CHF, improves quality of life, or prolongs survival.

That distinction is important. In Stage B2, our goal isn't simply to improve a biomarker—we want to keep the dog out of heart failure for as long as possible.

There is, however, growing clinical interest in using sacubitril/valsartan in selected dogs with more advanced Stage B2 disease. Recent guidance from veterinary cardiologists at the University of Illinois specifically includes advanced Stage B2 dogs at risk of heart failure among the patients in whom sacubitril/valsartan may be considered. This reflects an important evolution in how I think about this drug: while Entresto is not routine Stage B2 therapy, its potential role may not need to wait until a dog has already developed CHF.

In practice, the patient that interests me most is the late or progressive Stage B2 dog—a dog already receiving pimobendan but demonstrating substantial or progressive cardiac enlargement and appearing to move closer to CHF. In that patient, adding sacubitril/valsartan may be reasonable to consider on an individualized, extra-label basis, with a clear discussion that clinical practice is currently ahead of outcome data.

I would not routinely add Entresto simply because a dog meets Stage B2 criteria. Patient selection matters, and blood pressure, renal function, electrolytes, hydration status, concurrent medications, and the trajectory of the dog's cardiac enlargement all factor into that decision.

For now, I think the Stage B2 evidence can be summarized simply:

We have evidence that sacubitril/valsartan has biologic activity when added to pimobendan. We do not yet have evidence that it delays CHF.

And that leaves what may be one of the most important unanswered questions for this drug:

If pimobendan already delays the onset of CHF, could adding sacubitril/valsartan in dogs with advanced or progressive Stage B2 disease keep them out of heart failure even longer?

That is the Stage B2 trial I would most like to see.

Stage C: Where It Becomes More Clinically Interesting

Once CHF has developed, I think the rationale for sacubitril/valsartan becomes stronger.

These dogs have substantial neurohormonal activation and are typically receiving multimodal therapy directed at different components of heart failure. Sacubitril/valsartan is particularly interesting because it adds a different mechanism to that multimodal approach—simultaneously enhancing the natriuretic peptide system through neprilysin inhibition and blocking angiotensin II signaling through AT1-receptor antagonism.

The Saengklub study is particularly useful here. Twenty-one dogs with Stage C MMVD received either sacubitril/valsartan at approximately 20 mg/kg q12h or ramipril, while both groups continued pimobendan and furosemide. After four weeks, dogs receiving sacubitril/valsartan demonstrated greater reductions in several echocardiographic measures of cardiac size.

These findings are intriguing because they suggest that adding sacubitril/valsartan to an established CHF regimen may have favorable effects on cardiac remodeling. However, this was a small, short-term study, and echocardiographic improvement is a surrogate endpoint. We still don't know whether these changes translate into fewer recurrent CHF episodes, improved quality of life, slower disease progression, or longer survival.

For me, Stage C is a reasonable population in which to consider Entresto as an adjunctive therapy, particularly when additional neurohormonal modulation may be beneficial. The goal is to build on a multimodal heart-failure strategy by targeting another important pathway involved in disease progression.

Stage D: Perhaps the Most Compelling Current Population

I find the current evidence particularly interesting in dogs with advanced or refractory CHF.

In Carlson and Stern's 2026 retrospective study, 50 dogs with CHF secondary to MMVD received chronic sacubitril/valsartan. Of the 45 dogs included in the survival analysis, 28 had Stage D disease, making this particularly relevant to the type of advanced heart-failure patient in whom we are often looking for additional therapeutic options.

These dogs represent a very different clinical population from the relatively controlled patients enrolled in many prospective studies. Dogs with Stage D MMVD may already require high-dose furosemide or torsemide, pimobendan, spironolactone, and other medications to maintain control of CHF. Despite that complexity, chronic sacubitril/valsartan was generally well tolerated in the Carlson cohort.

This is where I find the concept of adding Entresto particularly compelling. In refractory CHF, we are often trying to control a disease in which multiple maladaptive pathways remain active despite comprehensive therapy. Adding neprilysin inhibition together with angiotensin-receptor blockade gives us another way to address that neurohormonal burden.

But these are also the patients in whom I am most cautious.

Dogs with Stage D disease may already have azotemia, high diuretic requirements, borderline hydration, lower systemic blood pressure, or electrolyte abnormalities. Introducing another medication that affects vascular tone, renal hemodynamics, and RAAS signaling requires thoughtful patient selection.

So while Stage D may currently be one of the most compelling populations in which to consider Entresto, it is also the population in which starting conservatively, knowing the baseline blood pressure and renal values, and monitoring closely after initiation become especially important.

For me, the appeal of sacubitril/valsartan across Stage C and D is its ability to add another complementary mechanism to an increasingly sophisticated multimodal approach to canine heart failure.

How Much Entresto Do We Give?

This can become confusing quickly because Entresto was developed for people, and the tablet labels list the amount of each individual component.

The available tablet strengths are:

For the veterinary dosing discussed here, it is important to think about the combined sacubitril + valsartan amount.

So a 24/26-mg tablet provides 50 mg total sacubitril/valsartan, while a 49/51-mg tablet provides 100 mg total.

What Doses Have Actually Been Used in Dogs?

The published canine studies give us a useful starting point.

In the Newhard Stage B2 study, the target dose was approximately 20 mg/kg q12h.

In the Saengklub Stage C study, dogs received 20 mg/kg q12h.

And in the Carlson and Stern Stage C/D cohort, the mean chronic dose was 18.1 ± 5.4 mg/kg q12h.

Recent practical veterinary guidance from the University of Illinois discusses a target range of approximately 15–30 mg/kg q12h, with a lower starting dose around 10 mg/kg q12h and subsequent titration based on the individual patient.

A practical way to remember it:

Start around 10 mg/kg q12h → assess tolerance → titrate toward approximately 15–30 mg/kg q12h as appropriate.

Published canine studies have commonly used approximately 20 mg/kg q12h.

I don't feel that every dog needs to start at the study dose.

In many of the patients in whom I'm most interested in Entresto, I specifically don't want to start aggressively.

Why Start Lower?

The typical MMVD patient is not necessarily the idealized clinical-trial patient.

Many are older and already receiving several cardiovascular medications. A Stage C or D dog may be receiving substantial loop-diuretic doses, spironolactone, pimobendan, and potentially other medications. Renal values may already be mildly elevated, and systemic blood pressure may leave less room for additional vasodilation.

For me, there is little advantage to immediately reaching a target dose if I compromise renal function or blood pressure in the process.

My approach is:

Start conservatively → assess tolerance → titrate the patient.

A stable dog with normal renal function, normal electrolytes, and robust blood pressure is very different from an elderly Stage D dog receiving high dose torsemide with slowly progressive azotemia.

The dose should reflect that.

Translating the Dose Into Actual Tablets

Many of the MMVD patients I treat fall in the 5–15 kg range, although MMVD certainly occurs in larger dogs.

If I am aiming for a conservative starting dose of approximately 10 mg/kg q12h, some easy reference points are:

These are starting-dose examples, not rigid dosing recommendations.

An easy shortcut is:

5 kg → 50 mg
10 kg → 100 mg
20 kg → 200 mg

≈ 10 mg/kg q12h

Dogs that fall between convenient tablet sizes may require individualized dosing. This becomes particularly relevant in small dogs, where a single tablet change can represent a substantial change in mg/kg dose.

What Do I Do With the ACE Inhibitor?

This is probably the single most important drug-interaction point:

Do NOT administer Entresto concurrently with an ACE inhibitor.

Sacubitril inhibits neprilysin, while ACE inhibition also reduces bradykinin degradation. Concurrent administration can increase bradykinin accumulation and the potential for adverse effects.

Human labeling requires a minimum 36-hour washout when transitioning between an ACE inhibitor and Entresto. Current University of Illinois veterinary guidance recommends approximately 48 hours in dogs.

For practical canine use, I favor the more conservative veterinary recommendation:

Stop the ACE inhibitor → wait approximately 48 hours → start Entresto.

I would not overlap enalapril or benazepril with sacubitril/valsartan.

And remember that valsartan already provides RAAS blockade through angiotensin II receptor antagonism. The goal isn't to stack an ACE inhibitor on top of an ARNI.

What About Spironolactone?

Spironolactone is a little different. I don't automatically discontinue spironolactone when starting Entresto. The two medications act at different points within the neurohormonal pathways involved in heart failure: valsartan blocks angiotensin II at the AT1 receptor, while spironolactone blocks the downstream effects of aldosterone at the mineralocorticoid receptor.

That combination may be clinically useful, but it also makes monitoring potassium and renal function particularly important. Hydration status and blood pressure should also be considered, especially in dogs receiving higher doses of loop diuretics.

In a stable patient with acceptable renal function, potassium, hydration, and blood pressure, I may continue spironolactone when adding Entresto. However, I would be much more cautious in a dog with hyperkalemia, progressive azotemia, dehydration, or hypotension, and would monitor those patients more closely after starting or titrating sacubitril/valsartan.

Importantly, we don't yet have robust prospective canine data specifically evaluating the combination of sacubitril/valsartan and spironolactone, so this remains an area where individualized patient assessment and monitoring are especially important.

What About Pimobendan?

I continue it.

Pimobendan remains part of the treatment plan when I add Entresto. In fact, the available canine studies have largely evaluated sacubitril/valsartan within pimobendan-based therapy, which is how I think about using it clinically.

In the Newhard Stage B2 study, all dogs were already receiving pimobendan and continued it throughout the study. In the Saengklub Stage C study, both groups continued pimobendan and furosemide while sacubitril/valsartan or ramipril was added.

Practically, this means I don't make changes to pimobendan simply because I am starting Entresto. I continue the dose appropriate for that dog's stage and clinical status and consider sacubitril/valsartan an additional component of the overall treatment plan.

This is also helpful when starting a new medication in a dog with CHF: whenever possible, I prefer not to change multiple medications simultaneously. Keeping pimobendan and the rest of a stable regimen consistent makes it easier to assess the dog's response and tolerance after Entresto is introduced.

What If the Dog Is Already Azotemic?

Azotemia is one of the most common reasons to hesitate when considering Entresto—and reasonably so. Many dogs with Stage C or D MMVD are older, receiving chronic loop diuretics, and may already have some degree of cardiorenal compromise or underlying CKD.

But I don't think the decision should come down to:

“Is the creatinine elevated: yes or no?”

I am much more interested in the trend and the clinical context.

Is the azotemia mild and stable, or is it progressing? Is the dog appropriately hydrated? What is the blood pressure? What is the potassium? How much furosemide or torsemide is required to maintain control of CHF? Is the dog also receiving spironolactone? Is there pre-existing CKD? Have the diuretic dose or other cardiac medications recently changed?

Most importantly, what has this dog's renal function been doing over time?

A dog with mild, stable azotemia, adequate blood pressure, normal potassium, good hydration, and controlled CHF is very different from a dog with progressively increasing renal values, dehydration, hypotension, or hyperkalemia.

How I Approach Dosing in an Azotemic Dog

The Carlson and Stern study provides particularly useful practical information here because pre-existing azotemia did not automatically exclude dogs from treatment—it changed how sacubitril/valsartan was introduced and titrated.

In their protocol, dogs with a BUN >40 mg/dL and/or creatinine >1.8 mg/dL were started more conservatively at approximately 5–10 mg/kg q12h. They could still be titrated toward 15–30 mg/kg q12h if tolerated based on serum biochemistry, but titration was slower, with approximately 4–8 weeks between dose increases. By comparison, nonazotemic dogs were generally titrated at 2–4-week intervals.

Current University of Illinois guidance takes a similarly conservative approach, although it does not provide a separate dosing protocol specifically for azotemic dogs. Their general approach is to start around 10 mg/kg q12h and gradually titrate toward a practical target of 20–30 mg/kg q12h, with the dose individualized according to patient size, renal function, and tolerance.

I would not interpret Carlson's BUN >40 mg/dL or creatinine >1.8 mg/dL values as absolute contraindication thresholds. Those were the criteria used in their clinical protocol to identify dogs that warranted more conservative dosing and slower titration, rather than validated cutoffs defining which dogs can or cannot receive Entresto.

For me, the practical takeaway is:

Pre-existing azotemia may change how I start and titrate Entresto without necessarily eliminating it as an option.

What Happened to Renal Values in the Carlson Study?

The renal data are also interesting because the response was not uniformly negative.

At the time Entresto was prescribed, 19 of 50 dogs (38%) had a BUN >40 mg/dL, creatinine >1.8 mg/dL, or both. At the first reevaluation 7–14 days later, 8 of those 19 dogs had increases in BUN, creatinine, or both—but another 8 had decreases. Across the entire cohort, 13 dogs had clinically meaningful decreases in BUN, creatinine, or both after starting sacubitril/valsartan.

I would not interpret those improvements as evidence that Entresto is renoprotective. Renal values in dogs with CHF are influenced by multiple factors, including hydration, renal perfusion, diuretic requirements, concurrent medication changes, underlying CKD, and progression of heart failure.

There was also an important adverse event: one dog developed progressive, clinically meaningful azotemia attributed to sacubitril/valsartan that required discontinuation of the medication and renal supportive therapy. Overall, however, the drug was continued in 96% of dogs in the cohort.

Current Illinois guidance likewise identifies worsening renal function as a potential concern, particularly in dogs with pre-existing renal disease or dehydration, and recommends reassessing renal values and electrolytes within 1–2 weeks after initiation or a dose adjustment.

My Practical Approach

So I don't use a single BUN or creatinine value to decide whether a dog can receive Entresto. I want to know whether the dog's cardiorenal status is stable enough to introduce another medication and whether I can monitor the response appropriately.

Mild, stable azotemia does not automatically rule Entresto out. Progressive azotemia, dehydration, hypotension, or hyperkalemia makes me considerably more cautious.

In an azotemic patient, I am more likely to start toward the lower end of the dosing range—approximately 5–10 mg/kg q12h—recheck renal values, electrolytes, hydration, and blood pressure early, and titrate more slowly if the patient remains clinically and biochemically stable. Carlson's protocol used 4–8-week intervals between dose increases in these dogs, and I think that provides a useful framework rather than feeling obligated to rapidly reach a target dose.

Ultimately, the goal isn't to normalize a single BUN or creatinine value. It's to maintain the best possible balance between controlling heart failure, maintaining adequate perfusion, and preserving renal function in the individual patient.

When Blood Pressure Changes the Plan

Because sacubitril/valsartan can lower systemic blood pressure, I want a baseline blood pressure before starting therapy, particularly in dogs with advanced CHF, high diuretic requirements, or other factors that may reduce hemodynamic reserve. Current veterinary guidance also recommends monitoring blood pressure during therapy.

There is no established Entresto-specific blood-pressure cutoff in dogs, so I interpret the measurement in the context of the patient and its previous blood-pressure trend. An SBP below approximately 90 mmHg represents true systemic hypotension and would make me very cautious about starting or continuing to titrate therapy, particularly if accompanied by weakness, lethargy, collapse, poor perfusion, dehydration, or worsening renal function.

At less dramatic reductions in blood pressure, clinical context matters. A bright, hydrated, asymptomatic dog with an SBP of 110 mmHg is very different from a weak or dehydrated dog with the same measurement.

The blood-pressure number matters, but so does the dog attached to it.

If blood pressure decreases meaningfully after starting or increasing Entresto, I reassess hydration, diuretic requirements, renal function, and the rest of the cardiac medication plan before deciding whether the Entresto dose needs to be reduced.

What Do I Check Before Starting?

Before starting Entresto, I want a reasonably current picture of the patient's renal, electrolyte, and hemodynamic status.

At minimum, I assess:

• Blood pressure

• BUN and creatinine

• Electrolytes, particularly potassium

• Hydration status

• Current furosemide or torsemide dose

• Concurrent cardiac medications

• Current CHF control and disease stage

• Recent renal and diuretic trends

• Whether the dog is currently receiving an ACE inhibitor

I'm not trying to create an elaborate new Entresto workup.

I simply want to know where the patient is starting so I can recognize a meaningful change after therapy begins.

When Do I Recheck?

For a stable patient, I generally recheck renal values, electrolytes, and blood pressure within approximately 1–2 weeks of starting Entresto. I repeat that monitoring after a meaningful dose increase. This is also the interval recommended in current Illinois veterinary guidance.

I may recheck sooner in a higher-risk patient, particularly a dog with pre-existing azotemia, lower blood pressure, dehydration risk, high diuretic requirements, hyperkalemia, or multiple medications affecting the RAAS.

One important distinction is that rechecking and titrating are not the same thing.

I may check renal values after 1–2 weeks and decide everything looks good—but still leave an azotemic dog at the same dose longer before increasing it. As discussed above, Carlson and Stern used a slower titration strategy in dogs with pre-existing azotemia.

So my approach is:

Recheck early. Titrate gradually.

I also don't think every Entresto recheck requires an echocardiogram. Early monitoring is primarily about tolerance and safety—blood pressure, renal function, electrolytes, hydration, and how the dog is doing clinically. Echocardiography and thoracic imaging remain guided by the underlying MMVD and CHF rather than by the medication itself.

What Adverse Effects Am I Watching For?

The Carlson and Stern study is reassuring from a tolerability standpoint. Among 50 dogs with CHF receiving chronic sacubitril/valsartan, only 3 dogs (6%) had adverse events attributed to the medication.

Two dogs developed gastrointestinal adverse effects, and one developed progressive clinically meaningful azotemia requiring discontinuation and renal supportive care.

That is encouraging, particularly because this was not a population of young, otherwise healthy dogs. These were dogs with established CHF, including Stage D disease, receiving multiple cardiac medications. The mean sacubitril/valsartan dose in the cohort was 18.1 ± 5.4 mg/kg q12h.

Based on the available canine data and the pharmacology of the drug, the main problems I monitor for are:

• Worsening renal function or azotemia

• Hypotension

• Hyperkalemia

• Gastrointestinal intolerance

It is worth making one distinction clear: hypotension and hyperkalemia were not the adverse events reported in the Carlson cohort. They remain important potential complications to monitor for, particularly in dogs receiving other medications that affect the RAAS. Illinois specifically lists hypotension, renal dysfunction, hyperkalemia, and gastrointestinal signs among the potential adverse effects clinicians should monitor.

I also tell owners to contact me if they notice a meaningful change after starting or increasing the medication—particularly weakness, marked lethargy, collapse, decreased appetite, vomiting, or diarrhea. Those clinical signs may be the first indication that the treatment plan needs to be reassessed.

When Would I Reduce the Dose or Stop It?

I don't make that decision based on one laboratory value in isolation.

I'm more concerned about a consistent trend or a clinical change suggesting that the patient isn't tolerating therapy.

That might include progressive azotemia, clinically important hypotension, hyperkalemia, dehydration, persistent gastrointestinal signs, weakness or collapse, or deterioration that develops after starting or increasing Entresto.

But in a dog with advanced CHF receiving multiple medications, the answer isn't always simply:

“The creatinine increased, so stop Entresto.”

I want to know why the patient changed.

Was the loop diuretic recently increased? Is the dog dehydrated? Has appetite or water intake decreased? Is underlying CKD progressing? Is blood pressure lower? Were several medications changed simultaneously? Has CHF improved enough that the diuretic requirement may actually be lower?

This is especially important because renal responses to sacubitril/valsartan are not necessarily predictable from a single baseline value. Experimental canine work also demonstrates that ARNI therapy can have complex effects on renal hemodynamics rather than simply reducing renal perfusion. In healthy dogs receiving 20 mg/kg q12h, renal plasma flow increased and GFR ultimately increased despite a decrease in systolic blood pressure. That finding should not be extrapolated to mean Entresto improves renal function in dogs with CHF or CKD, but it reinforces why the cardiorenal response needs to be interpreted in context.

There are also experimental canine cardiorenal-syndrome data showing improvements in some renal injury biomarkers with sacubitril/valsartan, although again these are mechanistic experimental data rather than clinical evidence in naturally occurring MMVD.

For me, the practical principle remains:

Treat the patient—not a single laboratory value.

My Practical Entresto Checklist

When I'm considering sacubitril/valsartan in a dog with MMVD, my framework is fairly simple:

1. Know why you're adding it.
Advanced or progressive Stage B2? Stage C CHF? Refractory Stage D disease? The evidence and treatment goals are different at each stage.

2. Review the current medications.
Know exactly what the dog is receiving, including diuretics, spironolactone, pimobendan, and any RAAS-modulating medications. If the dog is receiving an ACE inhibitor, discontinue it and allow the appropriate washout before starting sacubitril/valsartan.

3. Know your baseline.
Blood pressure, renal values, potassium, hydration, diuretic requirements, and recent trends.

4. Choose the starting dose for the patient.
Approximately 10 mg/kg q12h is a reasonable practical starting point for many dogs. In an azotemic or otherwise higher-risk patient, 5–10 mg/kg q12h may be more appropriate based on the Carlson experience. Illinois likewise generally begins around 10 mg/kg q12h and individualizes dosing according to renal function, size, and tolerance.

5. Recheck early.
Generally within 1–2 weeks, and sooner when the patient's baseline risk warrants it.

6. Titrate the patient.
Published canine MMVD studies have commonly evaluated approximately 20 mg/kg q12h, while current Illinois guidance describes a practical range of 15–30 mg/kg q12h and generally targets 20–30 mg/kg q12h when tolerated.

But there is no reason to force every dog to a particular dose.

The target is the dose the individual patient tolerates—not simply the number at the end of a dosing range.

My Perspective as a Cardiologist

What I find most encouraging about the newer Entresto data isn't simply the reported survival time.

It's that sacubitril/valsartan appears clinically usable in the type of dogs we actually see with advanced MMVD—older dogs receiving multiple cardiac medications, often with substantial diuretic requirements and sometimes with renal concerns.

Carlson and Stern's study is particularly useful from that perspective. Their cohort included 50 dogs with established CHF, including a substantial number with Stage D disease, receiving sacubitril/valsartan chronically at a mean dose of 18.1 ± 5.4 mg/kg q12h. Only 3 of 50 dogs had adverse events attributed to the medication.

The reported survival times are certainly intriguing, but I think the more defensible takeaway from a retrospective study without a contemporary control group is feasibility and tolerability. We cannot conclude that sacubitril/valsartan caused the longer survival reported in the cohort.

What we can say is that it was successfully incorporated into complex heart-failure regimens in many dogs with advanced MMVD.

That matters.

My practical approach is therefore relatively simple:

Start conservatively. Know the blood pressure and renal function before you start. Recheck early. Then titrate the patient—not the textbook dose.

I'm equally interested in what we may eventually learn about Stage B2. Newhard demonstrated measurable neurohormonal activity when sacubitril/valsartan was added to pimobendan in dogs with Stage B2 MMVD, without significant differences in systolic arterial pressure, renal biochemical parameters, or electrolytes over the short 30-day study.

Current Illinois guidance has gone a step further clinically and includes advanced Stage B2 dogs at risk of heart failure among the patients in whom sacubitril/valsartan may reasonably be considered.

But the question I really want answered is:

Could adding sacubitril/valsartan to pimobendan in advanced Stage B2 disease keep dogs out of CHF longer?

That's the study I would most like to see.

The Bottom Line

Sacubitril/valsartan remains extra-label in dogs, and there are still important unanswered questions.

For Stage B2, we have evidence of biologic activity but no evidence yet that adding it delays CHF.

For Stage C, short-term data suggest favorable changes in cardiac remodeling.

For Stage C and D CHF, newer retrospective data suggest that chronic therapy is feasible and generally well tolerated, including in dogs with advanced disease. Carlson's survival findings are intriguing, but prospective controlled studies are needed before we can attribute an outcome benefit to Entresto.

For now, I view sacubitril/valsartan as an emerging adjunct within an individualized, multimodal approach to MMVD and CHF.

Choose the patient carefully. Start conservatively. Don't overlap with an ACE inhibitor. Establish a baseline. Recheck early. Then titrate based on the individual dog.

We still need prospective trials to determine whether Entresto delays CHF in Stage B2 and improves meaningful clinical outcomes once CHF has developed.

But I think we've reached an exciting point: the question is becoming less about whether sacubitril/valsartan has a role in canine cardiology and more about which patients are most likely to benefit and where it will ultimately fit in MMVD therapy.

References

1. Newhard DK, Jung S, Winter RL, Duran SH. A prospective, randomized, double-blind, placebo-controlled pilot study of sacubitril/valsartan (Entresto) in dogs with cardiomegaly secondary to myxomatous mitral valve disease. J Vet Intern Med. 2018;32(5):1555–1563. doi:10.1111/jvim.15240.

2. Saengklub N, Pirintr P, Nampimoon T, Kijtawornrat A, Chaiyabutr N. Short-term effects of sacubitril/valsartan on echocardiographic parameters in dogs with symptomatic myxomatous mitral valve disease. Front Vet Sci. 2021;8:700230. doi:10.3389/fvets.2021.700230.

3. Carlson JA, Stern JA. Long-term sacubitril/valsartan is well tolerated in dogs with heart failure and myxomatous mitral valve disease and suggests excellent survival benefits. Am J Vet Res. 2026;87(8):ajvr.26.02.0048. doi:10.2460/ajvr.26.02.0048. PMID: 41985537.

4. Kadotani S. Beyond the Guidelines: Sacubitril/Valsartan (Entresto®) in Managing Cardiac Disease. University of Illinois College of Veterinary Medicine. Published June 30, 2026.

5. U.S. Food and Drug Administration. 2024 First Generic Drug Approvals: Sacubitril and Valsartan Tablets. First generic approvals May 28, 2024. The FDA lists three first-generic approvals and the 24/26-mg, 49/51-mg, and 97/103-mg strengths.

6. Acierno MJ, Brown S, Coleman AE, et al. ACVIM consensus statement: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med. 2018;32(6):1803–1822. doi:10.1111/jvim.15331.