A New Drug to Pump up the Weak Heart

What Is Heart And Its Function?

The heart will act as a muscular pump that supplies oxygenated (oxygen-rich blood) blood to all parts of the body. The deoxygenated blood (blood with less oxygen) will enter the right side of the heart, which is sent to the lungs for oxygenation. The oxygen-rich blood from the lungs will enter the left side of the heart and get distributed all over the body through an artery called the aorta.

A complex electrical condition system present in the heart wall will initiate and distribute the electrical impulses evenly to allow the heart to beat. The valves present in the heart will prevent the backflow of blood. Each part of the heart will work together to maintain average blood circulation in the body. When one or more of these parts are dysfunctional, the heart becomes weak.

What Is A Weak Heart?

All heart diseases together are referred to as a weak heart. But, this will not precisely describe the type of heart disease, severity, and symptoms associated with it. Some heart diseases are more dangerous than others, but eventually, all heart diseases are life-threatening.

A weak heart means that the heart cannot function properly and adequately. Since the heart's function is to supply blood to all parts of the body, the body parts may not receive adequate blood rich in oxygen and nutrients when it becomes weak. The heart can become weak by the following factors:

• Abnormal heart muscle.

• Insufficient blood supply to the heart.

• Death of a portion of the heart.

• Irregular heart rate and rhythm.

• Enlarged heart.

• Failing heart.

• Defective heart valves.

• Congenital heart disease.

The Common Medications Used For Heart Failure Are:

• ACE inhibitors.

• Diuretics.

• Sacubitril Valsartan.

• Digoxin.

• Hydralazine with nitrate.

• Angiotensin-2 receptor blockers (ARBs).

• Beta-blockers.

• Mineralocorticoid receptor antagonists.

• Ivabradine.

What Is The New Drug Used To Pump Up The Weak Heart?

There is a lot of buzzing in the heart physicians community and heart patients about the new drug for heart failure. This new drug Sacubitril is the first of the neprilysin inhibitors class of drugs. In a large trial involving 8500 heart patients, it was found to be better in saving lives and decreasing the incidence of hospital admissions due to disease exacerbation (heart failure hospitalization) than the class of drugs which are currently the cornerstone of heart failure therapy, the ACE-inhibitors (angiotensin-converting enzyme). The new drug is expected to replace the latter for good. The drug is launched as a combination drug consisting of Valsartan and Sacubitril and is available in the name Entresto. It is currently available in North America and Europe. The combination drug has already gained a high recommendation in most of the major heart failure guidelines in the world.

What Are The Indications For Entresto?

Indicated in a patient with heart failure with the following symptoms:

• To reduce the risk of death and hospitalization in people with long-lasting heart failure.

• To treat heart failure in children from1 to less than 18 years old.

• A left ventricular ejection fraction (LVEF) is less than or equal to 40%.

• For people with the maximum tolerated dose of a beta-blocker (unless contraindicated or unable to tolerate) for the treatment of heart failure, Entresto can be given.

• For people who are stabilized on an angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) and if it is contraindicated or if the patient cannot tolerate it, Entresto can be given. But, it should not be co-administered with an ACEI or an ARB.

What Should You Avoid Before Taking Entresto?

• Get up slowly and steady yourself and avoid getting up too fast to prevent a fall.

• Do not take potassium supplements or salt substitutes when you are on Entresto unless recommended by your doctor.

• Avoid drinking alcohol.

What Should You Tell Your Physician Before Taking Entresto?

• Kidney or liver problems.

• Diabetes.

• If you are taking a low salt diet.

• If you are dehydrated.

• Pregnant or plan to become pregnant.

• Breastfeeding or plan to breastfeed.

• History of hereditary angioedema.

What Are The Dosing Regimen For Entresto?

Initial dose: Sacubitril 49 mg-Valsartan 51 mg to be taken twice a day orally.

Maintenance dose: Sacubitril 97 mg-Valsartan 103 mg to be taken twice a day orally.

How To Take The Drug Entresto?

• Take the drug Entresto exactly as prescribed by the healthcare provider.

• Follow the instructions provided on the prescription label before usage.

• The drug should not be taken in larger or smaller amounts or for more than recommended.

• Entresto can be taken with or without food.

• Take medicine at the same time each day.

• Sacubitril and valsartan doses are prescribed based on the child's weight. Therefore if the child gains or loses weight, the dosing has to be changed.

• If a person cannot swallow a full tablet, oral suspension (liquid) can be given. Inform the physician or the pharmacist if you cannot swallow the tablet.

• Shake the oral suspension (liquid) before use.

• Use the dosing syringe or a medicine dose-measuring device to measure the dose.

• The physician should regularly monitor blood pressure and kidney function.

• Store the tablet at room temperature and throw away any oral suspension if not used within 15 days once mixed. Do not refrigerate the oral suspension.

What Are the Side Effects Of Entresto?

Although it is a good breakthrough, it comes with its own set of adverse effects. But, almost all of them are less in frequency than ACE-inhibitors. The most common side effects with Entresto (which may affect more than 1 in 10 people) are high blood potassium levels, low blood pressure, and reduced kidney function. A potentially severe side effect, angioedema (a rapid swelling of deeper skin tissues and the tissues around the throat, causing breathing difficulty), can occur uncommonly (affecting fewer than 1 in 100 people). There is also an unanswered question of a theoretical possibility that the drug increases the chances of dementia. However, not even one case was reported in the large trial of this drug. This will probably get answered in the subsequent trials.

• Hypotension.

• Hyperkalemia.

• Cough.

• Dizziness.

• Orthostasis.

• Falls.

Rare side effects of Entresto:

• Angioedema.

• Hypersensitivity reactions like rash, pruritus, and anaphylaxis.

What Are The Warnings And Precautions Of Entresto?

• Discontinue the drug as soon as possible when pregnancy is detected.

• This drug can affect the renin-angiotensin system and cause oligohydramnios, resulting in fetal injury or death.

• It can harm the fetus when administered to a pregnant woman during the second and third trimesters of pregnancy can reduce the fetal renal function and increase fetal and neonatal morbidity and death.

• It should not be administered in patients with hereditary angioedema. Discontinue the drug immediately once signs and symptoms of angioedema are observed. In such cases, provide appropriate therapy, and monitor for patent airway.

Call your physicians if you have any symptoms like:

• Light-headed feeling.

• Extreme tiredness.

• Slow heart rate, muscle weakness, weak pulse, or tingly feeling (due to high potassium).

• Little or no urinating, painful urination, swelling in your feet or ankles, feeling tired, or shortness of breath (due to kidney problems).

What Are The Contraindications For Entresto?

• Hypersensitivity to any drug.

• History of angioedema to previous ACE inhibitor or ARB therapy.

• Administration of neprilysin inhibitors (for example, sacubitril) with ACE inhibitors can increase the angioedema risk. So do not administer ACE inhibitors within 36 hours of changing to or from Sacubitril/Valsartan.

• Entresto should not be used with Aliskiren in patients with diabetes.

• It should not be used in patients with volume depletion or salt depletion or those taking diuretics because it can lower the blood pressure in these patients and worsen the condition.

Missed Dose:

Try to take the missed dose as soon as you remember, or skip the missed dose if it is already time for the next scheduled dose. Do not double the medicine to compensate for the missed dose.

Overdose:

In the case of overdose, seek emergency medical attention.

Storage:

Oral suspension:

• Store in less than 25ºC for up to 15 days and do not refrigerate.

• Shake well before each use.

Tablets:

• To be stored at controlled room temperature (25ºC).

• Protect it from moisture.

• Store in the original package takes out only if required.

Conclusion:

Whether introducing this drug is a major breakthrough or a minor advancement will be decided by its performance in the years to come. We will just have to wait and see.