Sacubitril: What It Is, How It Works, and What You Need to Know

When it comes to treating sacubitril, a medication used to improve survival and reduce hospital stays in people with chronic heart failure. Also known as the active component in Entresto, it works by blocking harmful stress pathways in the heart while boosting natural protective hormones. Unlike older heart failure drugs that just slow things down, sacubitril actually helps the heart repair itself—something doctors didn’t think was possible just a decade ago.

Sacubitril doesn’t work alone. It’s always paired with valsartan, an ARB (angiotensin receptor blocker) that helps relax blood vessels and lower pressure, forming the combination drug Entresto. Together, they target two major problems in heart failure: too much stress hormone activity and not enough natural heart-protective signals. This combo has been shown in large clinical trials to cut hospital visits by nearly 20% and lower death risk compared to older standards like enalapril. It’s not a cure, but it’s one of the few heart failure drugs that actually changes the disease’s path.

People who take sacubitril usually have moderate to severe heart failure with reduced ejection fraction—that means the heart isn’t pumping hard enough. It’s not for everyone. If you’ve had swelling from ACE inhibitors in the past, or if you’re pregnant, it’s off the table. Your doctor will check your kidney function and potassium levels before starting you on it. It’s also not a first-line drug for mild cases—you need to have tried other meds first.

What makes sacubitril different from other heart drugs is how it acts on the body’s own systems. It stops neprilysin, an enzyme that breaks down beneficial peptides like natriuretic hormones. Those hormones help your body get rid of salt and water, relax blood vessels, and reduce heart strain. By protecting them, sacubitril gives your heart a natural boost. That’s why it’s called an ARNI—angiotensin receptor-neprilysin inhibitor. You won’t find this mechanism in beta-blockers, diuretics, or even ACE inhibitors.

Some patients report dizziness or low blood pressure at first, especially if they’re also on other heart meds. But those side effects usually settle in a few weeks. The real win? People who stick with it report feeling less tired, less short of breath, and more able to walk, climb stairs, or play with grandkids without stopping. It’s not magic—but it’s close.

If you’ve been on heart failure meds for a while and still feel worn out, sacubitril might be worth asking about. It’s not cheap, but generic versions are starting to appear, and many Canadian pharmacies offer it at deep discounts. You’ll find real patient stories below about how switching to Entresto changed their daily lives—and how others managed the transition from older drugs like lisinopril or carvedilol. You’ll also see how it stacks up against newer options like vericiguat or omecamtiv mecarbil, and what to watch for if you’re thinking about switching.