The Consumer’s Guide to Angiotensin-Receptor Neprilysin Inhibitors (ARNIs) for Heart Failure

Sacubitril/valsartan, sold under the brand name Entresto, is the first and only ARNI drug approved so far by the FDA to treat people with heart failure.

ARNIs can treat heart failure with reduced ejection fraction (HFrEF, also referred to as systolic heart failure), which occurs when the heart’s left ventricle (a heart chamber) doesn’t contract efficiently, causing less blood to be pumped throughout the body. With a reduced ejection fraction, the heart pumps out no more than 40 percent of the blood in the heart with each contraction. Under normal circumstances, the heart pumps out at least 50 percent of the blood.

ARNIs can also treat heart failure with preserved ejection fraction (HFpEF, also referred to as diastolic heart failure). This means that the heart is pumping out at least 50 percent of the blood, but the heart muscles have stiffened, causing the heart to hold less blood.

Entresto comes in tablet form, in three doses:

• 24/26 milligrams (mg) of sacubitril/valsartan
• 49/51 mg of sacubitril/valsartan
• 97/103 mg of sacubitril/valsartan

Usually, people start out on a dose of 24/26 mg of sacubitril/valsartan, taken twice a day. The dose is gradually increased to the goal dose of 97/103 mg twice a day.

If you have trouble swallowing tablets, your doctor can prescribe a liquid form of the medication in the same dose.

According to a review published in 2019 in Heart Failure Reviews, people who took ARNIs were 20 percent less likely to die of heart-related complications or be hospitalized for heart problems compared with people who took an angiotensin-converting enzyme (ACE) inhibitor.

If you have heart failure, the left ventricle of the heart can become enlarged, which makes it harder to pump blood throughout the body.

ARNIs “can help the heart go back to a normal size and function,” says Preethi Pirlamarla, MD, an advanced heart failure cardiologist at Mount Sinai Hospital in New York City. When the heart returns to normal size and function, the left ventricle can pump blood more effectively. In fact, one study published in JAMA in 2019 found that when people took an ARNI medication for a year, their left ventricle ejection fraction — the marker of how well the heart is pumping out blood — increased from 28 to 38 percent.

You can start taking ARNI drugs as a first-line treatment or switch to one if you haven’t seen any improvements with an ACE inhibitor or ARB. That said, some doctors may want to prescribe valsartan as a stand-alone medication to make sure you can tolerate it, says Maria Mountis, DO, a cardiologist in the division of cardiology, section of heart failure and transplantation, at Cleveland Clinic.

If you’re currently taking an ACE inhibitor and want to change to an ARNI, you’ll need to stop taking the ACE inhibitor at least 36 hours before making the switch.

The most common side effects of ARNIs include low blood pressure, high potassium levels (hyperkalemia), mild kidney dysfunction, cough, and dizziness. These side effects usually disappear in about two weeks. If they don’t, your doctor may lower your dose.

Some people may also experience angioedema — swelling that can occur underneath the skin in many areas of the body, including your face, throat, arms, and legs — a rare but sometimes serious side effect of ARNIs. The condition is more common in Black people as well as people who’ve had angioedema in the past. If you do develop angioedema, you may experience trouble breathing, so seek emergency help right away.