Sacubitril and Valsartan Explained: How Sacomni 100 Works

Sacubitril is a prodrug, meaning it is inactive as swallowed and is converted by the body into its active form. That active form blocks an enzyme called neprilysin.

Neprilysin circulates in the body and breaks down several small peptide hormones, the most important here being the natriuretic peptides released by heart muscle when it is stretched. These peptides are the heart's own distress signal and its own remedy. They tell the kidneys to release sodium and water, they relax blood vessels, and they oppose the hormones that drive scarring and thickening of heart tissue. When neprilysin is blocked, these peptides last longer and act more strongly.

Valsartan is an angiotensin receptor blocker. Angiotensin II is a powerful hormone in the renin angiotensin aldosterone system. It narrows blood vessels, prompts aldosterone release, and encourages the body to retain salt and water. Valsartan sits on the receptor that angiotensin II needs, so the hormone cannot act.

Blocking neprilysin on its own has a drawback. The same enzyme also breaks down angiotensin II, so inhibiting it would leave more angiotensin II in circulation and cancel much of the benefit. That is why a neprilysin inhibitor is never used alone in heart failure.

Pairing it with an angiotensin receptor blocker solves the problem. Sacubitril lifts the helpful peptides while valsartan holds down the harmful hormone. The result is described as an angiotensin receptor neprilysin inhibitor, shortened to ARNI, and it is now a recognised part of heart failure treatment worldwide.

The pairing also explains why an ARNI is never given together with an ACE inhibitor. Both would raise levels of peptides that ACE and neprilysin normally clear, including bradykinin, and that overlap increases the risk of angioedema. A washout gap between the two is standard practice.

Sacomni 100 does not contain two tablets pressed together. The composition describes Sacubitril 49 mg and Valsartan 51 mg as a sodium salt complex, a single crystalline arrangement of both molecules.

There are practical reasons for this design.

This is also why the strength on the pack is expressed as a combined number. Sacomni 100 refers to 49 plus 51 milligrams, and Sacomni 50 refers to 24 plus 26 milligrams.

Within the group of medicines that act on the renin angiotensin aldosterone system, there are three familiar options.

Doctors also use beta blockers, mineralocorticoid receptor antagonists, sodium glucose co transporter inhibitors and diuretics in heart failure. These act through different pathways and are usually combined rather than substituted. Which combination suits a particular patient depends on ejection fraction, blood pressure, kidney function, potassium and tolerance, and that judgement belongs to the treating doctor.

Understanding the molecules explains several instructions that otherwise seem arbitrary.

Because valsartan blocks aldosterone release, potassium tends to rise, which is why potassium supplements and potassium based salt substitutes are restricted and blood tests are repeated. Because both molecules lower blood pressure, dizziness is common early on and standing up slowly helps. Because the medicine changes kidney blood flow, dehydration and anti inflammatory painkillers matter more than they would otherwise.

One detail is useful to know before a blood test. Since sacubitril protects natriuretic peptides, the marker BNP can rise on treatment even when the patient is improving. Doctors therefore prefer NT-proBNP, which is not broken down by neprilysin, when they want to follow heart strain in someone on an ARNI. If a laboratory report confuses you, ask your doctor which marker was measured.

This article is for general information only and is not a substitute for advice from a registered medical practitioner.