FDA Approves Entresto for Systolic Heart Failure

Intended to reduce risk of cardiovascular death and heart failure-related hospitalization, the FDA has approved Entresto.

The US Food and Drug Administration (FDA) has approved an oral fixed-dose combination

of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker (ARB) valsartan (Entresto, Novartis) for patients with heart failure and reduced ejection fraction.

The approval was based on findings from PARADIGM-HF, a double-blind clinical trial that involved 8442 patients with class II-IV heart failure and reduced ejection fraction. Trial participants were randomly assigned to either Entresto 200 mg (sacubitril 97 mg/valsartan 103 mg) twice daily or the angiotensin-converting enzyme (ACE) inhibitor enalapril (10 mg) twice daily. PARADIGM-HF was stopped early based on patient outcomes on a prespecified interim analysis that showed lower cardiovascular mortality in the Entresto group.

At median 27-month follow-up significantly fewer patients in the Entresto group had reached the primary endpoint – composite of first hospitalization for worsening heart failure or cardiovascular death – than the enalapril group (21.8% vs 26.5%).

Patients in the Entresto group also experienced reduced risk for first hospitalization for worsening heart failure (12.8% vs 15.6%), reduced risk of death from cardiovascular causes (13.3% vs 16.5%) and lower all-cause mortality (17% vs 19.8%). 

The most common adverse effects were hypotension (14% of patients) and hyperkalemia, as well as cough (11.3%) and elevated serum creatinine (3.3%). Angiodema occurred in 0.5% of patients in the Entresto group compared with 0.2% in the enalapril group. These percentages remained significantly lower and side effects occurred less frequently in Entresto patients than in patients on enalapril.

“Entresto should be considered for use instead of an ACE inhibitor or ARB for first-line treatment of reduced ejection fraction heart failure,” Mark Abramowicz, MD, and colleagues wrote in JAMA.

Disclosure: Novartis provided funding for the PARADIGM-HF trial.


  1. Abramowicz M, Zuccotti G, Pflomm J-M (Eds.).  Sacubitril/Valsartan (Entresto) for Heart Failure. JAMA. 2015;314(7):722-723.