ARNI Medications and Heart Failure in Elderly Parents — A Caregiver's Guide

Your parent's cardiologist just prescribed something called "Entresto" or mentioned switching them to an "ARNI." You have heard of beta-blockers and ACE inhibitors, but ARNI is a new one. You are sitting in the parking lot after the appointment, trying to understand what you just agreed to.

This is a reasonable place to be. ARNI medications are relatively new — Entresto (sacubitril/valsartan) was approved in 2015 and has since become a standard-of-care medication for certain types of heart failure. But "relatively new" in cardiology terms means many caregivers have not encountered it before, and the prescribing conversation in a busy cardiology office does not always leave time for thorough explanation.

Here is what you need to understand.

What ARNI stands for and how it works

ARNI stands for Angiotensin Receptor-Neprilysin Inhibitor. The name reflects the two mechanisms working simultaneously in one pill.

The only approved ARNI medication is sacubitril/valsartan, sold under the brand name Entresto. It combines:

• Valsartan (an ARB — angiotensin receptor blocker), which blocks the effects of angiotensin II, a hormone that causes blood vessels to constrict and promotes fluid retention. ARBs have been used in heart failure and hypertension for decades.
• Sacubitril, a neprilysin inhibitor. Neprilysin is an enzyme that breaks down natriuretic peptides — natural hormones the heart produces to lower blood pressure, reduce fluid retention, and protect the heart from stress. By inhibiting neprilysin, sacubitril allows these protective peptides to remain active longer.

Together, the two components work to reduce the workload on the failing heart: lowering blood pressure, reducing excess fluid, and allowing the heart's own protective mechanisms to function more effectively.

Who is it prescribed for?

Entresto is primarily prescribed for heart failure with reduced ejection fraction (HFrEF), sometimes called "systolic heart failure." In this condition, the heart muscle is weakened and does not pump blood as forcefully as it should. The ejection fraction — the percentage of blood the heart pumps out with each beat — is lower than normal (typically below 40%).

Large clinical trials have shown that in patients with HFrEF, Entresto reduces the risk of cardiovascular death and hospitalization for heart failure more effectively than the standard ACE inhibitor treatment it typically replaces.

It is also increasingly used in some patients with heart failure with preserved ejection fraction (HFpEF), though the evidence is less definitive in that population.

Why your parent may be switching from an ACE inhibitor

If your parent was previously on an ACE inhibitor (lisinopril, enalapril, ramipril) for heart failure and is now being switched to Entresto, this is a deliberate clinical decision. Current heart failure guidelines recommend that patients with HFrEF who can tolerate it should be on an ARNI rather than an ACE inhibitor, because the evidence for benefit is stronger.

This does not mean the ACE inhibitor was wrong before — it was the standard of care. It means cardiology guidelines have evolved and the cardiologist is updating the regimen accordingly.

Important: There must be a washout period of at least 36 hours between stopping an ACE inhibitor and starting Entresto. The reason is angioedema — a dangerous swelling of the face, throat, or airway. When an ARNI is taken alongside an ACE inhibitor (or started too soon after stopping one), the risk of this reaction increases significantly. If the transition is being managed at home rather than in a hospital setting, confirm with the cardiologist exactly when to stop the ACE inhibitor and when to start Entresto.

What caregivers need to watch for

Low blood pressure (hypotension)

Entresto lowers blood pressure through both the valsartan and sacubitril mechanisms. The most common side effect in elderly patients is low blood pressure, which can cause dizziness, lightheadedness, and falls — particularly when standing up from a chair or bed (orthostatic hypotension).

For seniors who are already at fall risk, this is a serious concern. If your parent becomes notably dizzy or has a near-fall after starting Entresto, contact the cardiologist. The dose may need adjustment, or a diuretic dose may need to be reduced to compensate.

Take home blood pressure readings in the first few weeks after starting Entresto. Many cardiologists recommend aiming for blood pressure readings around 110-120/70-80 in heart failure patients — this is lower than typical hypertension targets, so a reading that looks "low" may be acceptable for this condition. Ask the cardiologist what the target range is for your parent specifically.

High potassium (hyperkalemia)

The valsartan component of Entresto, like all ARBs, causes the kidneys to retain potassium. In seniors with reduced kidney function — which is common in heart failure patients — this can lead to elevated potassium levels. Hyperkalemia (high potassium) can cause dangerous cardiac arrhythmias.

Your parent will need regular blood tests to monitor potassium and kidney function, typically within one to two weeks of starting Entresto and then at regular intervals. If your parent uses salt substitutes (many of which contain potassium chloride), this should be disclosed to the cardiologist — it adds to the potassium load.

Signs of high potassium: muscle weakness, fatigue, irregular heartbeat, nausea. Any of these after starting Entresto should prompt a call to the doctor.

Kidney function changes

Because Entresto lowers blood pressure in the vessels supplying the kidneys, creatinine may rise modestly after starting. A small rise is expected and does not automatically mean the drug should be stopped. A significant or rapidly rising creatinine requires medical evaluation.

Angioedema

Though rare when the transition from an ACE inhibitor is managed correctly, angioedema is a serious risk. Symptoms include sudden swelling of the face, lips, tongue, or throat — and in severe cases, it can obstruct breathing. This is a medical emergency requiring immediate 911 contact.

African American patients have a somewhat higher baseline risk of angioedema with these medications and should be monitored more closely in the early period.

Cough

Unlike ACE inhibitors, ARBs (and by extension ARNIs) do not typically cause the persistent dry cough that leads many patients to switch away from ACE inhibitors. If your parent was previously bothered by cough on lisinopril or enalapril, Entresto is less likely to cause this problem.

Managing Entresto alongside other heart failure medications

Entresto is almost always prescribed as part of a combination regimen for heart failure. Most patients are also taking:

• A beta-blocker (metoprolol succinate, carvedilol, bisoprolol) — to slow and strengthen the heartbeat
• A diuretic (furosemide, spironolactone, or eplerenone) — to manage fluid retention
• Sometimes an SGLT2 inhibitor (empagliflozin/Jardiance, dapagliflozin/Farxiga) — a newer addition that reduces fluid and provides additional cardiovascular protection

This is a complex regimen. Each of these medications affects blood pressure and fluid balance. When Entresto is added or doses are adjusted, it can affect how well the other medications work. This is why close follow-up with the cardiologist in the first few weeks is essential — the doses of diuretics and other blood pressure agents often need recalibrating.

Questions to ask the cardiologist

When Entresto is being started, these questions help caregivers manage the transition safely:

• What blood pressure readings should prompt me to call you?
• When does my parent need their first blood test after starting this medication?
• Should we adjust any of the other heart failure medications alongside this change?
• Is there anything in the current medication list that could interact with Entresto?
• What are the signs of angioedema, and what should I do if I see them?

Coordinating a parent's heart failure medications — multiple drugs from multiple specialists, each with its own monitoring requirements — is one of the more demanding aspects of senior caregiving. The Medication Management Kit for Senior Caregivers includes specialist coordination worksheets, a Master Medication Record template, lab tracking forms, and a doctor appointment prep guide to help you manage complex medication regimens with confidence.

Get the Medication Management Kit →