The Consumer’s Guide to Angiotensin-Receptor Neprilysin Inhibitors (ARNIs) for Heart Failure
Learn more about a new first-in-class medication for people with heart failure.
M ore than 6 million adults in the United States have heart failure. Of these, about half have diastolic heart failure and the other half have systolic heart failure.
In February 2021, the U.S. Food and Drug Administration (FDA) approved a new class of medications called angiotensin receptor–neprilysin inhibitors (ARNI) for people with certain types of diastolic heart failure — the first time a treatment was approved for this condition. ARNIs have also been approved to treat systolic heart failure since 2015.
If you’ve been diagnosed with heart failure but haven’t found a treatment that has helped ease your symptoms, you may want to ask your doctor about ARNIs. Use this guide to learn more about this medication, including whether you may be a candidate.
How ARNIs Work
7 Essential Facts About ARNIs for Heart Failure
1. There is one ARNI that has been approved by the FDA to treat 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.
2. ARNIs can treat both diastolic and systolic 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.
3. ARNIs come in tablet and liquid form.
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.
4. ARNIs reduce your risk of hospitalization and cardiovascular death.
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.
5. ARNIs can help improve the structure of your heart.
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.
6. You can switch to an ARNI from an ACE inhibitor or angiotensin II receptor blocker (ARB), or start taking an ARNI first.
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.
7. ARNIs are usually well tolerated but can have side effects.
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.
Should I Take an ARNI for Heart Failure?
If you’ve been diagnosed with heart failure with reduced (40 percent or lower) or preserved ejection fraction, you may be a candidate for an ARNI.
You may also benefit from an ARNI if you’re currently taking another heart failure medication but aren’t getting the results you’d like or are bothered by the side effects — for instance, if you’re taking an ACE inhibitor and coughing a lot.
Some people aren’t candidates for the medication, though. This includes people who are pregnant, planning on becoming pregnant, or breastfeeding, because this type of drug can be toxic to fetuses and babies.
Because these drugs can lower blood pressure levels, people with very low blood pressure due to kidney disease, liver disease, or other conditions may not be able to take an ARNI. You also shouldn’t take it if you’re allergic to any of its ingredients or you’ve experienced angioedema while taking an ACE inhibitor or ARB. If you’re taking an ACE inhibitor and want to switch, you’ll need a three-day washout period before starting the ARNI. Lastly, people with diabetes who are taking aliskiren should avoid ARNIs.
4 FAQs About ARNIs
Next Steps: Making the Decision to Take an ARNI for Heart Failure
- Are you satisfied with your current heart failure treatment?
- Has your current medication improved your symptoms as much as you’d hoped?
- Are you coughing a lot when taking an ACE inhibitor or having other bothersome side effects from your medication?
- How much has heart failure affected your quality of life?
- How often do you have to cancel or end activities early because of your condition?
- Have you tried other treatments for heart failure?
- Do you think I can gain better control of my heart failure?
- What medications do you recommend for heart failure, and why?
- Am I a good candidate for an ARNI?
- What results can I expect from an ARNI?
- What side effects should I be aware of?
- Are there contraindications I should know about?
- How will this medication affect my kidneys?
- Will I have to get follow-up blood work after I start this medication?
- What other things can I do to help treat my heart failure?