Sacubitril/Valsartan Misses in Preserved-EF Heart Failure: Top-Line PARAGON-HF

July 30, 2019

Treatment with sacubitril/valsartan (Entresto, Novartis) in patients with heart failure and preserved ejection fraction (HFpEF) failed to show a significant benefit for the primary clinical end point in the large, randomized PARAGON-HF trial, the company has announced.

"The trial narrowly missed statistical significance for its composite primary end point of reducing cardiovascular death and total heart failure hospitalizations. Safety and tolerability were consistent with previously reported sacubitril/valsartan data," said the Novartis statement.

A positive primary outcome for sacubitril/valsartan in the trial might have been a game changer for cardiology, as there are no current medical therapies approved specifically for HFpEF. Secondary findings from the TOPCAT trial have influenced some to favor spironolactone for patients with the syndrome, but renin-angiotensin-system (RAS) inhibitors in general have not been successful.

PARAGON-HF randomly assigned 4822 patients with HFpEF, defined in the trial as heart failure with an ejection fraction of at least 45% and in NYHA class 2 to 4 to receive either sacubitril/valsartan or the angiotensin-receptor blocker (ARB) valsartan for up to 57 months.

The trial's full primary results are slated for presentation at the upcoming European Society of Cardiology scientific sessions, Novartis said. Its statement also hints at favorable secondary findings in PARAGON-HF: "The totality of evidence from the trial suggests that treatment with sacubitril/valsartan may result in clinically important benefits in HFpEF."

Sacubitril/valsartan is classified as an angiotensin-receptor/neprilysin inhibitor (ARNI), a composite molecule that, once administered, releases two drugs, one of which is valsartan.

The drug is currently approved and guideline-recommended for patients with heart failure with reduced ejection fraction (HFrEF).

Novartis provides update on Phase III PARAGON-HF trial in heart failure patients with preserved ejection fraction (HFpEF). Released July 29, 2019.

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