Entresto Approved for Heart Failure with Preserved Ejection Fraction
What is heart failure?
Patients who have heart failure do not pump enough blood to meet the body’s blood and oxygen requirements. This impairment can cause a slew of adverse effects such as drowsiness, constant cough, weakness, and more. Heart failure patients usually also have other comorbid health conditions such as diabetes. Those with heart failure demonstrate longer hospital stays and increased frequency of hospital visits. Over 50% of individuals with heart failure will die within 5 years of symptom onset, making it a debilitating and devastating disease.
There are two types of heart failure: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). These two subtypes relate to underlying pathophysiology of the disease and an individual’s left ventricular ejection fraction (LVEF). A normal LVEF will be between 50% and 70%. HFrEF is also known as systolic heart failure and occurs due to hypertrophy of the heart’s left ventricle. This enlargement leads to the heart’s inability to adequately pump blood throughout the circulatory system. HFpEF is different in that the left ventricle has adequate pumping power, however, the heart is too stiff. The heart’s chamber therefore does not fill with enough blood.
What treatments are available for heart failure?
HFrEF and HFpEF are treated differently. HFrEF patients have multiple treatment options available, including angiotensin-converting-enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), beta blockers, aldosterone antagonists, and angiotensin receptor-neprilysin inhibitor (ARNi). HFpEF patients, on the other hand, have no approved treatment options available. Their disease can only be controlled by supportive care and symptom management.
The Approval of Entresto for HFpEF
In February, the FDA approved Entresto for the treatment of patients with HFpEF, making it the only approved therapy for this indication. This approval is based on Novartis’ PARAGON-HF trial, which evaluated patients with LVEF of ≥45%. Unfortunately, this trial narrowly missed achieving its primary endpoint with a P-value of 0.06. Because the study just barely fell short of its endpoint, the FDA hosted a Cardiovascular and Renal Drugs Advisory Committee in December of 2020. This meeting brought together a panel of experts in the field of cardiology and beyond to review the data and the efficacy of Entresto in HFpEF. The FDA’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 12-to-1 in support of the new indication for HFpEF.
After receiving positive feedback from the expert panel, the FDA expanded Entresto’s indication to include decreased risk of cardiovascular death and hospitalization for adult patients with chronic heart failure. This indication is all-encompassing, now including HFpEF in addition to HFrEF. Entresto is now the first and only drug approved for HFpEF, bringing hope to almost 2 million patients with chronic heart failure who previously had no treatment options available. Clinical guidelines and treatment algorithms are expected to be expanded to accompany this ground-breaking approval.
- Heart failure and cardiomyopathies. (n.d.). American College of Cardiology. Retrieved September 27, 2021, from https://www.acc.org/Clinical-Topics/http%3a%2f%2fwww.acc.org%2fClinical-Topics%2fHeart-Failure-and-Cardiomyopathies
- Novartis Entresto® granted expanded indication in chronic heart failure by FDA. (n.d.). Novartis. Retrieved September 27, 2021, from https://www.novartis.com/news/media-releases/novartis-entresto-granted-expanded-indication-chronic-heart-failure-fda