How Entresto Improves Ejection Fraction and Heart Failure Outcomes
Explore the science, uses, effectiveness, and safety of Entresto for improving heart ejection fraction in heart failure patients.
Entresto (sacubitril/valsartan) is a vital medication in the management of heart failure, offering significant improvements in heart ejection fraction, quality of life, and survival for many people living with this condition. This comprehensive article explores how Entresto works, its approved uses, effectiveness in specific populations, safety, and what patients should know about the drug’s impact on heart health.
What Is Entresto and How Does It Work?
Entresto belongs to a group of medicines known as angiotensin receptor-neprilysin inhibitors (ARNIs). It is a combination of two medications:
- Valsartan – an angiotensin receptor blocker (ARB) that reduces blood pressure and helps protect the kidneys
- Sacubitril – a neprilysin inhibitor that causes blood vessels to relax and widen, making it easier for the heart to pump blood
Mechanism of Action:
- Valsartan blocks angiotensin II type-1 receptors, limiting the hormone’s effect, which can otherwise cause blood vessels to constrict and raise blood pressure. This action reduces the workload on the heart and helps prevent further heart and kidney damage.
- Sacubitril inhibits neprilysin, an enzyme that breaks down vasodilating peptides. When neprilysin is blocked, these peptides stay active longer, promoting vasodilation (widening of blood vessels), increased excretion of sodium, and reduced strain on the heart muscle.
This dual action is more effective than using either component alone for many people with heart failure with reduced ejection fraction (HFrEF).
What Heart Conditions Can Entresto Treat?
Entresto is approved to treat heart failure — a condition where the heart cannot pump enough blood and oxygen to meet the body’s needs. While not a cure, Entresto improves symptoms, quality of life, and key measures like ejection fraction, which refers to the percentage of blood the left ventricle pumps out with each contraction.
Indications in Adults
- Heart failure with reduced ejection fraction (HFrEF): Known as systolic heart failure, this condition involves an enlarged, weakened left ventricle that cannot effectively circulate blood. Entresto is often used in place of ACE inhibitors for HFrEF, especially when standard treatments don’t achieve adequate results or aren’t well-tolerated.
Approximately half of all people with heart failure have HFrEF. - Heart failure with preserved ejection fraction (HFpEF): Cleared by the FDA in 2021, Entresto can now be used in adults with HFpEF, where the heart muscle contracts normally but is too stiff to relax and fill properly.
Indications in Children
- Pediatric Use: The FDA has extended Entresto’s use for certain children with symptomatic heart failure, after careful evaluation of clinical studies.
Always consult with a pediatric cardiologist for specific recommendations and dosing.
How Does Entresto Improve Ejection Fraction?
Ejection fraction measures the percentage of blood that leaves your heart each time it contracts. Heart failure often reduces this percentage. Improving ejection fraction is critical, as lower values are linked with worse symptoms and prognosis.
Key Clinical Trials and Evidence
Several large studies have explored Entresto’s impact on heart structure and function:
What others are reading
- PROVE-HF Trial: Showed a median increase in left ventricular ejection fraction (LVEF) from 28.2% to 37.8% at 12 months for people on Entresto, with a significant improvement seen as early as 6 months (mean increase of 5.2%).
This was accompanied by positive changes in cardiac biomarkers and favorable cardiac “reverse remodeling” – a process in which heart chambers return closer to normal size and function. - EVALUATE-HF Trial: Compared Entresto to enalapril (an ACE inhibitor) and found that, while both did not significantly affect aortic stiffness in the study timeframe, Entresto was more effective in improving the structure and function of the left ventricle.
- PARADIGM-HF Trial: Established Entresto as superior to traditional ACE inhibitors in reducing the risk of cardiovascular death and hospitalization from heart failure.
Cardiac Remodeling: Why It Matters
Heart failure triggers adverse remodeling of the heart — the chambers stretch, thicken, or become misshapen, which impairs function. Entresto helps reverse these changes by improving:
- Left ventricular size and shape
- Pumping ability (ejection fraction)
- Levels of key biomarkers, such as NT-proBNP (a protein that rises when the heart is under stress)
Improving remodeling frequently translates to better symptoms, fewer hospitalizations, and longer life.
What Are the Benefits of Entresto for Heart Failure?
- Improved ejection fraction and heart function
- Lower rates of hospitalization for heart failure exacerbation
- Reduction in cardiovascular mortality
- Better quality of life and exercise tolerance
- Potential to reverse or improve cardiac remodeling (the structural damage to the heart)
For most people with HFrEF, Entresto is now considered a first-line or foundational therapy, unless there are contraindications.
Who Should Not Take Entresto?
Entresto may not be advisable for everyone with heart failure. You should not take Entresto if you:
- Have a known allergy to sacubitril, valsartan, or any component of the drug
- Are taking an angiotensin-converting enzyme (ACE) inhibitor (requires a 36-hour washout period before starting Entresto)
- Have a history of angioedema (dangerous swelling) related to ACE inhibitors or ARBs
- Are pregnant or may become pregnant (can harm the unborn baby)
- Have severe liver disease (speak to your doctor about potential risks and alternatives)
Common and Serious Side Effects
Most people tolerate Entresto well, but as with any medication, side effects are possible:
| Common Side Effects | Possible Serious Side Effects |
|---|---|
|
|
Contact your healthcare provider if you notice symptoms like facial swelling, extreme dizziness, unexplained muscle weakness, or changes in urination.
How Does Entresto Compare to Other Heart Failure Medications?
- ACE inhibitors and ARBs remain standard therapies for heart failure, but Entresto’s dual mechanism offers additional benefits and is often preferred for eligible patients.
- Beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors are often used alongside Entresto to further improve outcomes.
Life Extension and Prognosis Improvements
Entresto has been shown to extend life for people with HFrEF. Clinical trials show:
- Lower rates of cardiovascular death compared to standard therapy
- Reduced risk of hospitalization for heart failure flare-ups
Your exact prognosis depends on multiple factors (age, comorbid conditions, cardiac function), but Entresto can play a major role in improving both longevity and quality of life.
Using Entresto with Other Heart Medications
Entresto is typically started in place of an ACE inhibitor or ARB, but is safely combined with several other standard treatments:
- Beta-blockers — lower heart rate and reduce workload
- MRAs (e.g., spironolactone, eplerenone) — further reduce neurohormonal activation
- SGLT2 inhibitors — increasingly used for HFrEF even in people without diabetes
- Diuretics — as needed for controlling fluid overload
Always discuss your medication plan with your healthcare provider, making them aware of all drugs and supplements you take to avoid adverse interactions.
Frequently Asked Questions (FAQs)
How long does it take Entresto to start working?
Entresto reaches peak levels in the blood 30 minutes to 2 hours after a dose. Consistent, therapeutic drug levels stabilize within about 3 days with the recommended twice-daily dosing. Most people begin to notice improvement in symptoms and exercise tolerance in weeks to months, though full cardiac remodeling and gains in ejection fraction may take 6–12 months, as clinical trials have shown.
How much can Entresto increase ejection fraction?
In clinical studies like the PROVE-HF trial, Entresto increased median ejection fraction from approximately 28% to nearly 38% within 12 months of therapy, with a meaningful rise observed as early as 6 months.
What are some ways to improve ejection fraction naturally?
- Eat a heart-healthy diet (low in salt, saturated fat, and processed foods)
- Engage in regular, moderate exercise (such as daily walks, as approved by your doctor)
- Effectively manage stress and mental health
- Avoid smoking and limit alcohol consumption
- Take all medications as prescribed and keep routine appointments
While medications like Entresto are fundamental, these lifestyle adjustments strongly support heart function and may help maximize your ejection fraction over time.
Does Entresto work the same for everyone?
Most people with HFrEF benefit from Entresto, but individual responses vary due to factors like concurrent conditions, how advanced their heart failure is, and their genetic makeup. Nearly all patients will need a personalized approach designed by their cardiologist.
Can children take Entresto?
The FDA approved Entresto for pediatric use in certain cases of symptomatic heart failure. The safety and dosing for children must be carefully considered by pediatric specialists, as studies are more limited than in adults.
Summary
Entresto is a modern, evidence-based therapy that can substantially improve ejection fraction and survival in people with heart failure, especially those with a reduced ejection fraction. Working through a unique combination of valsartan and sacubitril, Entresto not only addresses symptoms but may also repair some of the underlying structural damage caused by heart failure. For many, it is now a cornerstone of heart failure management — but, like all medications, it must be taken under expert supervision with careful monitoring for side effects and interactions. Speak with your cardiologist to determine if Entresto is right for you or your loved one.
References
- https://www.healthline.com/health/heart/entresto-ejection-fraction-improvement
- https://www.novartis.com/news/media-releases/entresto-improved-measures-heart-structure-and-function-hfref-patients-new-novartis-study-additional-data-complement-findings
- https://www.ema.europa.eu/en/news/new-medicine-treat-heart-failure-recommended-approval
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7062818/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC5768868/
- https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044586
- https://www.webmd.com/heart-disease/heart-failure/entresto-heart-failure
- https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1102521/full
Similar Articles
Read full bio of Sneha Tete
