Entresto (Sacubitril/Valsartan): First-in-Class Angiotensin Receptor Neprilysin Inhibitor FDA Approved for Patients with Heart Failure. (2015)

Heart failure affects an estimated 5.7 million patients aged ≥20 years in the United States, according to the 2009–2012 National Health and Nutrition Examination Survey.1 Approximately 870,000 new cases of heart failure occur annually. Heart failure is projected to affect more than 8 million individuals aged ≥18 years in the United States by 2030, representing a 46% increase from 2012.1 The incidence of heart failure is substantially higher in the elderly population, approaching 10 of 1000 people aged ≥65 years.1

Heart failure is a life-threatening condition that occurs when the heart cannot pump enough blood and oxygen to meet the body's needs.2 Approximately 50% of patients with heart failure die within 5 years of diagnosis.3 In fact, heart failure was a contributing cause of death in 1 of 9 deaths in 2009.3 The common causes of heart failure include coronary artery disease, diabetes, obesity, and hypertension.2 The lifetime risk for heart failure in people with blood pressure >90 mm Hg is twice that of those with blood pressure <140 mm Hg/90 mm Hg.1

The symptoms of heart failure include dyspnea, fatigue and weakness, edema, persistent cough, rapid or irregular heartbeat, and anginal pain.2,4 Heart failure is generally categorized into 4 classes (class I-IV) based on symptom severity, as delineated in the New York Heart Association (NYHA) functional classification system (Table 1).



Table 1

NYHA Functional Classification of Heart Disease Severity



Ejection fraction is a key measurement in assessing the heart's ability to pump out blood and in diagnosing and monitoring heart failure.5 A substantial number of patients with heart failure have a normal ejection fraction. A preserved ejection fraction (ie, diastolic heart failure) indicates that the heart muscle contracts normally, but the ventricles do not relax as they should; a reduced ejection fraction (ie, systolic heart failure) indicates that the heart muscle does not contract effectively and less oxygen-rich blood is pumped out to the body.5

In addition to its high mortality rate and considerable impact on an individual's overall health and daily life, heart failure is associated with serious complications, including kidney damage or failure, heart valve problems, heart rhythm problems, and liver damage.2

Overall, the societal and economic burden of heart failure is staggering.6 In the United States, heart failure accounted for $31 billion in total annual costs in 2012.7 Of this total, approximately $21 billion was attributed to direct medical costs and nearly $10 billion to indirect costs (eg, lost productivity from morbidity and premature mortality); hospitalizations accounted for an estimated 80% of the direct costs attributed to heart failure.7 In fact, heart failure is the leading cause of hospitalizations in patients aged ≥65 years.8,9 Furthermore, the total direct medical cost of heart failure is projected to increase from $21 billion in 2012 to $70 billion by 2030.7 Heart failure also expends more Medicare dollars than any other diagnosis.6

The early diagnosis and treatment of heart failure are essential to improving patients’ quality and duration of life.3 Nonpharmacologic approaches to treating heart failure include behavioral and dietary changes, physical activity, and daily symptom tracking.3 Heart failure prevention involves managing conditions that lead to this condition, including coronary artery disease, hypertension, diabetes, and obesity. In some cases, surgery is used to treat an underlying cause of heart failure.2

Pharmacologic treatments for heart failure typically comprise a combination of drugs depending on the symptoms.2 Until recently, these drugs included renin-angiotensin system inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, in addition to beta-blockers, diuretics, aldosterone antagonists, inotropes, and digoxin.2