Entresto and the Treatment of Heart Failure

Heart failure (HF) is a common pathology that affects over 6 million adults. The lifetime

risk of HF is 1:9 for males and 1:6 for females, and increases greatly in individuals who

have experienced prior myocardial infarction (MI). Thus, treatment and prevention of HF

are a major priority for most health care professionals, yet poor prevention and care are

the most cited reasons for adverse clinical outcomes.

In 2014, the FDA approved the drug Entresto for the management and treatment of HF,

finding that it significantly reduced the risk of death from HF-related conditions by 16-

20% and was particularly effective at reducing the risk of death for HF patients with

reduced left ventricular ejection fraction (LVEF). Entresto is actually a combination of

two drugs: sacubitril, which inhibits the enzyme neprilysin, and valsartan, which is an

angiotensin II receptor antagonist.

How do these drugs work together to reduce the risk of further heart failure and

preserve function? In your response, briefly describe the two signaling pathways that

are affected by the drug, how they are affected, and what the body's overall response to

the drug intervention is. How does this benefit patients with HF?