Appeal type: Medical necessity
Decision: Overturned

Cardiomyopathy
Pharmacy/Prescription Drugs

The patient is a male with a history of hypertension. He was diagnosed with nonischemic cardiomyopathy with New York Heart Association Functional Class II symptoms and a left ventricular ejection fraction of 41% by cardiac magnetic resonance imaging (MRI). He was prescribed carvedilol and Entresto, with improvement in his symptoms and functional capacity. Entresto was discontinued for insurance reasons. His symptoms have recurred, and his functional capacity has declined. The subject under review is the medical necessity of Entresto.

The health plan's determination is overturned.

This patient with a nonsischemic cardiomyopathy and New York Heart Association Functional Class II symptoms was prescribed Entresto, with improvement in his symptoms and functional capacity. Prior to therapy initiation, his left ventricular ejection fraction (LVEF) by cardiac MRI was 41%. In the pivotal PARADIGM trial, 8442 patients with class II, III, or IV heart failure and a left ventricular ejection fraction of 40% or less were randomly assigned to receive Entresto versus enalapril. Entresto proved to be superior to enalapril in reducing the risks of death and of hospitalization for heart failure. It is Food and Drug Administration (FDA)-indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. Per the American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) Focused Update on New Pharmacological Therapy for Heart Failure, "In patients with chronic symptomatic heart failure with reduced ejection fraction New York Heart Association (NYHA) class II or III who tolerate an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB), replacement by an angiotensin receptor-neprilysin inhibitor (ARNI) is recommended to further reduce morbidity and mortality. "This patient's left ventricular ejection fraction (LVEF) of 41% was one percentage point higher than the 40% or less used as an initial cutoff in the PARADIGM trial. However, there is no clinically meaningful difference between an LVEF of 40% and one of 41%. In addition, there are limitations to the measurements of LVEF with MRI, as with other methods. Cardiac MRI requires multiple breath holds, and image quality may be poor in patients who cannot hold their breath. If the level of inspiration is different during the acquisition of different levels, segments of the left ventricle (LV) may not be imaged while other segments may be imaged twice. This may lead to variability in calculated volumes and LVEF. Reproducibility studies have shown that MRI-calculated LVEF can vary up to five percentage points. Thus, it is quite possible that, were this patient to have undergone a second study, his LVEF might have been as low as 36%. Moreover, neither the FDA indication for Entresto nor the ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure, specify an absolute cutoff above which Entresto is not recommended. An LVEF of 41% represents a substantially reduced ejection fraction; normal is 55% or greater. Finally, this patient had symptomatic improvement with Entresto, which he took until recently when it was discontinued for insurance reasons. His symptoms worsened when the drug was discontinued. For these reasons, Entresto is medically necessary in this instance.