Sacubitril is a medication used in cardiovascular care to address specific heart conditions. It represents an advancement in managing these cardiac issues.
The Neprilysin Inhibitor Class
Neprilysin is an enzyme that breaks down various peptides, including natriuretic peptides, bradykinin, and adrenomedullin. These beneficial peptides contribute to functions such as vasodilation, which widens blood vessels, and natriuresis, promoting the excretion of sodium and water. By degrading these helpful substances, neprilysin can counteract their positive effects on cardiovascular health.
Inhibiting neprilysin increases the levels of these beneficial peptides, enhancing their positive effects on the cardiovascular system. However, neprilysin also breaks down angiotensin II, a hormone harmful to the heart and blood vessels. Blocking neprilysin alone can lead to an undesirable increase in angiotensin II levels, which would negate some therapeutic benefits.
How Sacubitril Works
Sacubitril, a prodrug, is converted into its active form, LBQ657, after administration. LBQ657 inhibits the enzyme neprilysin, preventing the breakdown of natriuretic peptides such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). This allows them to remain active longer, promoting vasodilation, reducing blood volume, and increasing the excretion of sodium and water through the kidneys.
Sacubitril is always given in combination with valsartan, an angiotensin receptor blocker (ARB). This combination forms an Angiotensin Receptor-Neprilysin Inhibitor (ARNI). Valsartan works by blocking the effects of angiotensin II, a hormone that can lead to vasoconstriction, increased blood pressure, and adverse cardiac remodeling. The dual action of sacubitril and valsartan is synergistic; while sacubitril enhances the beneficial natriuretic peptide system, valsartan simultaneously counteracts the potentially harmful effects of increased angiotensin II that might result from neprilysin inhibition alone. This combined approach offers a comprehensive strategy to manage specific cardiovascular conditions, by both promoting protective mechanisms and blocking detrimental pathways.
Sacubitril’s Impact on Heart Health
Sacubitril, when combined with valsartan as an ARNI, has transformed the treatment of chronic heart failure with reduced ejection fraction (HFrEF). This medication improves patient outcomes by addressing the underlying mechanisms of heart failure. Clinical trials have shown that sacubitril/valsartan can reduce the risk of cardiovascular death and hospitalization for heart failure.
Patients receiving this combination therapy experience a reduction in hospitalizations for heart failure, with some studies showing a risk reduction of approximately 21% for hospitalization. The medication also contributes to improved symptoms and overall quality of life for individuals living with heart failure. Furthermore, sacubitril/valsartan has demonstrated a reduction in all-cause mortality, making it a significant advancement in cardiovascular medicine. Its ability to reduce the risk of cardiovascular death by about 20% compared to traditional therapies highlights its profound impact on patient survival.