HOW DO ANGIOTENSIN RECEPTOR-NEPRILYSIN INHIBITORS (ARNIs) WORK?

Angiotensin receptor-neprilysin inhibitors (ARNIs) are a new class of drugs used for the treatment of heart failure. Sacubitril/valsartan is the first combined agent to be approved in this new class. Sacubitril is a prodrug, and on activation works as a neprilysin inhibitor. Valsartan is an angiotensin II receptor blocker and works by blocking the renin-angiotensin-aldosterone system (RAAS). It is recommended for use as a replacement for an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker in people with heart failure with reduced ejection fraction.

Neprilysin enzyme is also called neutral endopeptidase and plays a role in the degradation of natriuretic peptides and other vasoactive peptides including bradykinin. Natriuretic peptides are responsible for the removal of sodium from the body. Sacubitril (neprilysin inhibitor) increases the availability of natriuretic peptides (bradykinin) to achieve vasodilation and natriuresis (excretion of sodium) which decreases blood pressure and assists heart failure. Bradykinin is a vasodilator that relaxes and widens the walls of blood vessels.

RAAS is a group of hormones that regulate blood pressure, fluid and electrolyte balance, and systemic vascular pressure. Abnormally active RAAS increases blood pressure. Angiotensin II narrows the blood vessels and triggers the release of a hormone that helps in retaining water in the body, which increases blood pressure. Valsartan blocks the angiotensin receptor and inhibits the effects of RAAS.

ARNIs are used to treat:

• Heart failure with reduced ejection fraction

The most common side effects of ARNIs include:

• Dizziness
• Hypotension (drop in blood pressure)
• Renal failure
• Hyperkalemia (increased potassium level in the blood)
• Fatigue
• Increase serum creatinine
• Decreased hematocrit (decrease in the volume of red blood cells)
• Cough
• Orthostatic hypotension (sudden drop in blood pressure when you stand from a seated or lying down position)
• Allergic reactions
• Impotence

The information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Drug names include:

• Entresto
• Sacubitril/valsartan