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Does Entresto improve ejection fraction?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on April 13, 2023.

Official answer


Entresto has been shown to increase left ventricular ejection fraction (LVEF) in the PROVE-HF trial.

The PROVE-HF trial was a Phase IV prospective study of 794 patients with heart failure with reduced ejection fraction (HFrEF).

  • The study looked at how the use of Entresto (sacubitril/valsartan) and changes in a biomarker known as NT-proBNP affected improvements in measures of heart function. High levels of NT-proBNP means your heart may not be pumping as much blood as your body needs.
  • In this study, significant improvements were seen in left ventricular ejection fraction (LVEF).
    • At 12 months, the LVEF increased from a median of 28.2% to 37.8% (difference, 9.4% [95% CI, 8.8 to 9.9%]).
    • A significant 5.2% increase in LVEF was also seen as early as 6 months (5.2%, 95% CI, 4.8% to 5.6%).
    • Importantly, 25% of patients experienced an absolute LVEF increase of more than 13%.
  • Significant improvements in other parameters, such as left ventricular volumes and left atrial volume were also seen.
  • Overall, results from the PROVE-HF trial show significant improvements in measures of cardiac structure and function at six months and one year in HFrEF patients.

What is a normal ejection fraction?

Ejection fraction (EF) is a term that describes how well your heart chambers (the left or right ventricles) can pump blood. The left ventricle is responsible for most of your heart's main pumping action. When your left ventricle is weak or diseased, a lower amount of blood is pumped out when it contracts (squeezes from a heart beat).

Ejection fraction is most commonly measured using an echocardiogram (echo), a painless outline of your heart’s movements using an ultrasound machine.

A normal ejection fraction ranges from 55% to 70%. For example, if your left ventricle ejection fraction (LVEF) is 60%, that means that 60% of the amount of blood in the left ventricle is pumped out with each contraction of your heart. Patients with heart failure typically have ejection fractions of 40% or less.

What happens in heart failure?

Heart failure, also called congestive heart failure, occurs when your heart cannot pump blood properly. This leads to a back-up of blood in the heart as well as kidney problems. Less oxygen-rich blood is pumped out to the body.

Fluid retention (swelling) can occur in your body’s tissues, like the legs (extremities) or lungs. When this happens in the lungs, it becomes harder to breath. Heart failure with reduced ejection fraction, often abbreviated HFrEF, is also known as systolic heart failure.

The level of heart failure you have is often classified based on the New York Heart Association (NYHA) classification:

  • Class I heart failure - no symptoms
  • Class II heart failure - everyday activities can be performed without difficulty but may become fatigued or short of breath with exertion
  • Class III heart failure - trouble completing everyday activities
  • Class IV heart failure - short of breath even at rest.

How is Entresto used?

Entresto (sacubitril/valsartan), from Novartis, is used for the treatment of patients with heart failure and reduced ejection fraction (HFrEF) to lower the risk of cardiovascular death and hospitalization for heart failure. Entresto relaxes blood vessels, improves blood flow, and reduces stress on the heart.

  • Entresto is a combination medication that contains the neprilysin inhibitor sacubitril and the angiotensin receptor blocker (ARB) valsartan.
  • It helps to improve your heart's ability to pump blood to the body. Entresto is usually given together with other heart medications or in place of an ACE inhibitor or other ARB.
  • The most common side effects with Entresto include low blood pressure, high potassium, cough, dizziness, and kidney problems.

When did the FDA approve Entresto?

Entresto was first approved by the FDA in 2015.

  • The PARADIGM-HF trial was a 2014 Phase III pivotal study that led to Entresto’s approval. This study, conducted in over 8,000 patients, showed that Entresto lowered the risk of cardiovascular death or hospitalization for worsening heart failure by 20% after more than two years.
  • Specifically, these outcomes were lowered from 26.5% in patients taking the ACE inhibitor enalapril to 21.8% when compared to Entresto.
  • Most patients were also receiving currently approved heart failure treatments, including beta-blockers, diuretics, and mineralocorticoid antagonists.
  • In 2016, the American College of Cardiology, the American Heart Association and the Heart Failure Society of America updated their treatment guidelines to include Entresto as a Class 1 recommendation based on the PARADIGM-HF trial.

Key Points

  • Entresto has been shown to increase left ventricular ejection fraction (LVEF), the volume of blood that your left ventricle pumps out of your heart when it contracts. This helps to supply more blood and oxygen to your body.
  • Entresto is recommended in heart treatment guidelines to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
  • Entresto, an oral tablet, is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB.

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