New FDA Indication Opens Up Use of Sacubitril/Valsartan in HFpEF

The US Food and Drug Administration has granted an expanded indication to sacubitril/valsartan (Entresto) that would allow for use of the therapy in at least some patients with heart failure and preserved ejection fraction (HFpEF), drugmaker Novartis announced Tuesday.

Before the change, the label stated that the angiotensin receptor-neprilysin inhibitor (ARNI) was indicated for reducing the risk of CV death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction. The new label removes the mention of reduced ejection fraction and includes the following note: “Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal.” The fuller prescribing information also mentions that “LVEF is a variable measure, so use clinical judgment in deciding whom to treat.”

This is the first time, Novartis points out in a press release, that there is a heart failure treatment with an indication that includes patients with either reduced LVEF (HFrEF) or HFpEF.

The FDA’s decision is based on the results of the PARAGON-HF trial, released in full in September 2019. The trial, which included patients with guideline-defined HFpEF, narrowly missed its primary endpoint, a composite of heart failure hospitalization or CV death. It appeared, however, that sacubitril/valsartan reduced risk in patients with an LVEF at the lower end of the range included in the study (45% to 57%).

Novartis said that of the more than 6 million people in the United States who have chronic heart failure, about 5 million “may be appropriate” for treatment with the ARNI by virtue of having either a reduced LVEF or one that is “below normal” but not low enough to be considered reduced.

“We can now offer a treatment to a wider range of patients who have an LVEF below normal,” Scott Solomon, MD (Brigham and Women’s Hospital, Boston, MA), co-chair of the PARAGON-HF executive committee, said in the press release.

In Europe, sacubitril/valsartan remains indicated for adult patients with symptomatic chronic HF and a reduced ejection fraction.