Entresto’s Mechanism of Action Explained

Entresto is a significant advancement in the management of chronic heart failure. It offers a unique approach to addressing physiological changes in this condition. It provides a new option for individuals with heart failure, aiming to improve their well-being and long-term outlook. Entresto is a prescription drug designed to treat certain types of heart failure, and its effectiveness can vary based on an individual’s medical history and diagnosis.

Understanding Heart Failure

Chronic heart failure is a medical condition where the heart muscle struggles to pump enough blood to meet the body’s demands. This inefficiency can lead to blood backing up, causing fluid to accumulate in various parts of the body, such as the lungs and legs. Fluid accumulation in the lungs can cause shortness of breath, and swelling in the legs and feet is also common.

When the heart cannot supply adequate blood flow, organs and tissues may not receive enough oxygen, leading to symptoms like fatigue and reduced ability to exercise. The body attempts to compensate for this reduced pumping ability by activating certain systems, but over time, these compensatory mechanisms can actually worsen the condition. This chronic strain can lead to further volume overload and increased heart rate, deteriorating the heart’s function.

The Dual Action of Entresto

Entresto is a medication because it combines two active components: sacubitril and valsartan. This combination works through a dual mechanism, targeting two pathways involved in heart failure progression. The medication is categorized as an angiotensin receptor neprilysin inhibitor (ARNI).

Sacubitril acts as a neprilysin inhibitor. Neprilysin is an enzyme naturally present that breaks down beneficial substances called natriuretic peptides (NPs). These peptides, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), play a protective role in the cardiovascular system by promoting the excretion of sodium and water, widening blood vessels, and reducing stress on the heart. By inhibiting neprilysin, sacubitril increases the levels of these natriuretic peptides, allowing them to exert their beneficial effects. This leads to increased sodium and fluid removal from the body, which helps to ease the workload on the heart.

Valsartan is an angiotensin receptor blocker (ARB). It works by blocking the effects of a hormone called angiotensin II. Angiotensin II is a substance that causes blood vessels to narrow, promotes the retention of salt and water by the kidneys, and contributes to the remodeling of the heart muscle. Valsartan prevents angiotensin II from exerting these effects. This action helps blood vessels relax, reduces fluid retention, and decreases the strain on the heart.

The combined effect of sacubitril and valsartan is synergistic, providing a more comprehensive therapeutic approach than either component alone. While sacubitril enhances the body’s natural protective systems by increasing natriuretic peptides, valsartan directly counteracts the harmful effects of the renin-angiotensin-aldosterone system (RAAS), which is often overactive in heart failure. This dual action helps to restore a more favorable balance of neurohormones in the body, improving heart function and reducing cardiac workload.

Benefits of Entresto’s Action

The dual mechanism of Entresto provides clinical benefits for patients with chronic heart failure. A significant outcome is a reduction in hospitalizations due to heart failure. Clinical trials have shown that Entresto can reduce the risk of heart failure hospitalizations compared to standard treatments.

Beyond reducing hospital admissions, Entresto has been shown to improve symptoms associated with heart failure. Patients may experience less shortness of breath and fatigue, leading to an enhanced quality of life. The medication also contributes to increased survival rates compared to other therapies. These benefits extend to patients with severe heart failure symptoms and are consistent regardless of other background therapies.