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Sacubitril/valsartan (Entresto) became the first drug to get a broad heart failure indication that reaches into the normal ejection fraction range for prevention of cardiovascular death and hospitalization, Novartis .

FDA granted the drug an expanded indication "to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal."

An advisory committee weighing approval in December voted unanimously in favor of expanding the angiotensin receptor–neprilysin inhibitor's indication beyond that in heart failure with reduced ejection fraction (HFrEF) based on the PARAGON-HF trial.

While that trial missed its primary endpoint in reducing heart failure hospitalization and cardiovascular death compared with valsartan alone in people with an ejection fraction of 45% or higher, it was a narrow miss overall and significant in the subgroup with an ejection fraction at or below the median of 57%.

The sticking point was how to define which patients with heart failure with preserved ejection fraction (HFpEF) on the lower end of the normal range for whom the drug should be approved.

In the end, the FDA left it up to clinicians to decide.

"This approval is a significant advancement, providing a treatment to many patients who were not eligible for treatment before because their ejection fraction was above the region we normally considered reduced. Until now, treatment for these patients was largely empiric," said Scott Solomon, MD, of Harvard Medical School and Brigham and Women's Hospital, and a leader of the PARAGON-HF trial, in a . "We can now offer a treatment to a wider range of patients who have an LVEF below normal."

After so many drugs have floundered for HFpEF, the advisory panel seemed eager to see the unmet need addressed.

However, as Mary Norine Walsh, MD, of St. Vincent Heart Center in Indianapolis and a past president of the American College of Cardiology, had noted at the time the PARAGON-HF trial results were presented, affordability and insurance struggles may lie ahead.

"In the U.S., the cost is often prohibitive and several pharmacy benefits managers are refusing coverage for this medication for patients with HFrEF. I would expect an even tougher battle if a patient has HFpEF," she told 番茄社区.

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