Novartis announced that Entresto (sacubitril/valsartan) has been given a Class I recommendation, the strongest endorsement, in updated clinical practice guidelines simultaneously released by the American College of Cardiology (ACC), the American Heart Association (AHA) and the Heart Failure Society of America (HFSA) in the US, and the European Society of Cardiology in the EU.

In the US Entresto is now a standard therapy for heart failure with reduced ejection fraction (HFrEF) as an alternative to an ACE inhibitor or an angiotensin II receptor blocker, given together with a beta blocker and an aldosterone antagonist. In addition, the guidelines call for doctors to switch HFrEF patients with mild to moderate symptoms from ACEs or ARBs to Entresto.

"These strong, swift and broad recommendations by US cardiology organizations, redefine the standard of care for how reduced ejection fraction heart failure is treated," said Vas Narasimhan, global head of development and chief medical officer for Novartis. "We know patients with heart failure suffer reduced quality of life and remain at high risk of hospitalization or death, and these new guidelines are a strong call to action to ensure patients receive the most effective therapies."

In the EU, the ESC HF guidelines recommend doctors switch HFrEF patients meeting the PARADIGM-HF criteria to Entresto from an ACE or ARB. Both guideline committees considered evidence from PARADIGM-HF, the largest heart failure trial ever, which showed Entresto significantly reduced deaths from cardiovascular causes and heart failure hospitalizations in patients with HFrEF.

Heart failure is a debilitating and life-threatening condition, which impacts over 60 million people worldwide. It is the leading cause of hospitalization in people over the age of 65. About half of people with heart failure have HFrEF. Reduced ejection fraction means the heart does not contract with enough force, so less blood is pumped out. Heart failure presents a major and growing health-economic burden that currently costs the world economy $108 billion every year.

Novartis has established the largest global clinical program in the heart failure disease area across the pharma industry to date, FortiHFy, comprising over 40 active or planned clinical studies designed to generate an array of additional data on symptom reduction, efficacy, quality of life benefits and real world evidence with Entresto, as well as to extend understanding of heart failure.

Entresto is a twice-a-day medicine that reduces the strain on the failing heart. It does this by enhancing the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the harmful effects of the overactive renin-angiotensin-aldosterone system (RAAS). Other heart failure medicines only block the harmful effects of the overactive RAAS. Entresto contains the neprilysin inhibitor sacubitril and the angiotensin receptor blocker (ARB) valsartan.

In Europe, Entresto is indicated in adult patients for treatment of symptomatic chronic heart failure with reduced ejection fraction. In the US. Entresto is indicated for the treatment of heart failure (NYHA class II-IV) in patients with systolic dysfunction. It has been shown to reduce the rate of cardiovascular death and heart failure hospitalization compared to enalapril, and also to reduce the rate of all-cause mortality compared to enalapril. Entresto is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other angiotensin receptor blocker (ARB). Approved indications may vary depending upon the individual country.

PARADIGM-HF was a randomized, double-blind, phase III study evaluating the efficacy and safety profile of Entresto versus enalapril (a widely studied ACE inhibitor) in 8,442 patients with HFrEF. The baseline characteristics showed the patients enrolled were typical HFrEF patients with NYHA Class II-IV heart failure. PARADIGM-HF was specifically designed to see if LCZ696 could decrease CV mortality by at least 15% vs. enalapril. Patients received LCZ696 or enalapril in addition to current best treatment regimen. The primary endpoint was a composite of time to first occurrence of either cardiovascular death or heart failure hospitalization, and is the largest heart failure study ever done.