Entresto for Heart Failure: Benefits, Side Effects, and More

Heart failure is a common diagnosis, affecting about 6.7 million adults in the United States. This condition happens when some of the heart chambers (ventricles) cannot fill up with blood or contract normally. Heart failure is classified by severity to guide treatment. 

Entresto (sacubitril/valsartan) is a combination medication prescribed to help manage heart failure. It may help individuals maintain a more active lifestyle and support overall heart health.

This article describes Entresto’s action on the body, its benefits, potential side effects, and considerations for use.

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What is Entresto?

Entresto (Sacubitril/valsartan) combines two drugs with different mechanisms of action to better treat heart failure. 

• Sacubitril inhibits neprilysin, an enzyme that breaks down helpful proteins. By reducing neprilysin activity, the body can better support heart function. 
• Valsartan, on the other hand, blocks a chemical called angiotensin II, which can tighten blood vessels and make the heart work harder. Valsartan helps relax blood vessels, lowering blood pressure and reducing the heart's workload. This blood vessel relaxation reduces blood pressure. 

These two medications work together to allow the heart to pump enough blood to meet the body’s oxygen demands. Entresto differs from other heart failure medications in its dual mechanism of action, which may help support heart health and reduce the risk of hospitalization in some patients.

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Indications for Use

Entresto is typically prescribed in patients with heart failure associated with reduced ejection fraction. Ejection fraction is a measurement of how well the ventricles (lower heart chambers) squeeze blood out to the rest of the body. When the ventricles don’t work properly, blood flow is reduced, which may limit the amount of oxygen available to the body.

The choice of heart failure treatment depends on the stage of heart failure, specific patient demographics, and shared decision-making. 

FDA Approval and Clinical Significance

Entresto is FDA-approved for the treatment of heart failure. The PARADIGM-HF study was a landmark clinical trial that studied Entresto's effects on patients with heart failure. The goal was to document how well the combination drug worked better than enalapril (a different heart failure medication) and to see if it could lower the chances of dying from heart problems or hospitalization for heart failure. The study followed patients from 2 to 4.3 years.

• Most patients were around 64 years old, and many had health issues like high blood pressure, past heart attacks, or diabetes. Patients with and without heart failure were included in the study.
• The trial indicated that Entresto may provide added support for heart health compared to enalapril. Patients reported improvements in symptoms and quality of life. 
• Entresto reduced the risk of dying from heart problems by 20% and the chance of being hospitalized for heart failure by 21%. 

Proven Benefits in Heart Failure Patients

Findings from clinical trials have shown that Entresto “combined inhibition of the angiotensin receptor and neprilysin is superior to inhibition of the renin-angiotensin system alone in patients with chronic heart failure.”  

Dosage and How to Take Entresto

The initial dose of Entresto is typically 49mg of sacubitril and 51 mg of valsartan two times a day. Within a couple of weeks, this dose may be increased to 97 mg of sacubitril and 103 mg of valsartan two times a day. 

Entresto is not recommended during pregnancy or breastfeeding, and its safety in children has not been established. Dose adjustment is not typically necessary in mild to moderate kidney impairment. However, more severe cases of kidney disease may require additional dose adjustment. 

Tips for Taking Entresto

• Entresto is usually taken twice a day, but specific dose timing depends on the patient and guidance from their medical provider. 
• The medication is available in pill and sprinkle form. 

Importance of Regular Monitoring

While taking Entresto, blood pressure and kidney function should be closely monitored. Healthcare providers can adjust the dosage or address potential side effects based on these metrics.

Side Effects and Potential Risks

Common side effects of Entresto include:

• Low blood pressure
• High potassium levels (hyperkalemia)
• Cough
• Dizziness
• Renal failure

Serious adverse reactions to Entresto include:

• Angioedema: This medication is contraindicated (not recommended) in patients with a history of angioedema with an ACE inhibitor. 
• Allergic reaction: Patients should not take Entresto if they have a history of hypersensitivity (severe allergy) to either of the medications that make up this drug. 
• Diuretic use: Patients taking high doses of diuretics (blood pressure-lowering medications) are more at risk for hypotension (low blood pressure) when taking Entresto. Dose adjustment may be required if hypotension occurs. 

Contact a healthcare provider or seek emergency care immediately if you experience any severe side effects.

Comparing Entresto with Other Heart Failure Medications

Entresto is similar to other heart failure drugs but differs in outcomes and safety measures. 

Entresto vs. ACE Inhibitors

• Entresto works differently than ACE inhibitors. While ACE inhibitors block certain chemicals to help the heart, Entresto builds on the benefits of ACE inhibitors by blocking neprilysin, which may offer additional support for heart health.
• Clinical trials have shown that Entresto can be more effective than enalapril (an ACE inhibitor) for some patients. 

Entresto vs. ARBs

• Compared to ARBs, Entresto builds on their benefits by blocking neprilysin and angiotensin II, giving extra protection for the heart. However, medication choice depends on the patient and their specific needs. 

Cost and Accessibility Considerations

• Entresto may cost more than generic options, but insurance and patient assistance programs can help make it more affordable.

Frequently Asked Questions About Entresto

How Long Does It Take for Entresto to Work?

Steady levels of Entresto in the blood occur in about three days. It may take several weeks for the medication to take full effect.

Can Entresto Be Taken with Other Heart Medications?

Entresto should not be taken with another ACE inhibitor because of the risk of severe swelling (angioedema). Entresto should not be taken with another angiotensin II receptor blocker or Tekturna. Tell your doctor what medications and supplements you are taking before starting a new treatment. 

What to Do If a Dose is Missed

If you miss a dose of Entresto, take it as soon as possible. If it is almost time for your next dose of the medication, do not take the missed pill; instead, take Entresto at your normal time. 

How Long Should I Stay on Entresto?

Entresto is sometimes taken long-term to support heart health and reduce the risk of heart failure-related hospitalization.

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Key Takeaways

• Entresto combines sacubitril and valsartan to support heart function, help reduce blood pressure, and may reduce the risk of heart failure-related hospitalization.
• Etresto is prescribed for people with heart failure who have reduced ejection fraction, meaning their heart is not pumping as strongly as it should.
• Studies show Entresto works better than some other medicines, like enalapril, in reducing hospital visits and deaths from heart problems. It also improves symptoms and quality of life.
• This medication is usually taken twice a day and comes in pill or sprinkle form. Blood pressure and kidney function should be monitored by a healthcare provider while taking this medicine.
• Common side effects include low blood pressure, dizziness, and high potassium levels. Rare but serious risks include severe swelling (angioedema) and kidney problems.
• To know if Entresto is the right choice for you, discuss your symptoms, other medicines, and treatment goals with your healthcare provider.