ARNI vs ACEI: What’s the Real Difference?

If you’ve been told you need a pill to protect your heart, you’ve probably heard the terms ARNI and ACEI tossed around. Both belong to the same family of drugs that relax blood vessels, but they aren’t interchangeable. Knowing how each works, what they’re best at, and where they can cause trouble will help you and your doctor pick the right one.

How ACE Inhibitors Work

ACEI stands for Angiotensin‑Converting Enzyme Inhibitor. The drug blocks an enzyme that turns angiotensin I into angiotensin II, a hormone that narrows arteries and raises blood pressure. With less angiotensin II, arteries stay wider, blood pressure drops, and the heart doesn’t have to work as hard. Classic ACEI drugs include lisinopril, enalapril, and ramipril.

How ARNI Works and Why It’s Different

ARNI stands for Angiotensin Receptor‑Neprilysin Inhibitor. It’s actually a two‑in‑one combo: a low‑dose ARB (like valsartan) that blocks the angiotensin II receptor, plus a neprilysin inhibitor (sacubitril) that boosts natriuretic peptides. Those peptides help the kidneys get rid of extra sodium, relax vessels, and protect heart cells. The result is a double‑action formula that often lowers blood pressure more than an ACEI alone.

When it comes to heart failure with reduced ejection fraction (HFrEF), large trials such as PARADIGM‑HF showed that sacubitril/valsartan (the brand name Entresto) cut cardiovascular death and hospitalizations by about 20 % compared with enalapril. That’s a big win for patients who can tolerate the combo.

Side‑effect profiles also diverge. ACEI users often complain of a dry cough because the drug increases bradykinin levels. About 5‑10 % of patients stop ACEI because of that cough. ARNI reduces the cough risk but can raise the chance of low blood pressure, especially when you start on a high dose. Both groups can develop high potassium or kidney function changes, so regular labs are a must.

Cost is another practical factor. Generic ACEI pills have been cheap for years, while ARNI is still brand‑only in many markets and can cost several times more. Insurance plans may require a step‑therapy rule, meaning you have to try an ACEI first before they approve an ARNI.

Choosing the right drug also depends on other health conditions. If you have a history of angio‑edema, an ACEI is off the table; an ARNI is also risky because it contains an ARB, so doctors often switch to a pure ARB instead. For patients with chronic kidney disease, both classes need careful dose adjustments, but ARNI may offer extra kidney protection in some cases.

In practice, many clinicians start patients on an ACEI or ARB, watch their lab results, and then consider switching to an ARNI if the heart failure is still progressing or if blood pressure needs extra control. The switch is usually done by stopping the ACEI for 36 hours to avoid a rare but serious reaction called angio‑edema.

Bottom line: ACEI is a solid, affordable first‑line choice for high blood pressure and early heart failure. ARNI shines when you need stronger heart‑failure protection and can handle the higher price and monitoring requirements. Talk with your doctor about your specific heart health, kidney function, and budget to decide which path fits you best.