A new analysis published in JAMA Cardiology has found that timely and broad adoption of Entresto (sacubitril/valsartan) by all eligible heart failure patients with reduced ejection fraction (HFrEF) could prevent or postpone more than 28,000 deaths each year in the US alone. This analysis, based on an application of the results of PARADIGM-HF to published heart failure statistics, is the first to quantify the possible impact of Entresto's potential benefit in reducing death.

Heart failure is a chronic condition that contributes to more than 300,000 deaths in the US every year. About half of people with heart failure have HFrEF. This new analysis estimates that as many as 28,484 deaths in HFrEF patients annually could be prevented or postponed with optimal use of Entresto (with sensitivity analyses demonstrating a range of 18,230 to 41,017).

Further, the study suggests that delaying routine use of Entresto in clinical practice could have a substantial negative effect on patients, given the expected risk-benefit profile, as it could result in failure to prevent tens of thousands of deaths. These findings demonstrate the significant survival benefits Entresto could offer to those living with HFrEF, if patients in the group defined by the authors were given access to treatment. The study authors stated that nearly 84% of HFrEF patients - 2.2 million people - may be candidates for treatment with Entresto.

Heart failure is a life-threatening condition and despite available medicines, about half of patients diagnosed with heart failure die within 5 years. According to the study authors, these findings may substantially impact the national health of the HFrEF population, offering significant clinical benefit in preventing or postponing death when applied in clinical practice.

"This analysis demonstrates that Entresto can save the lives of thousands of patients every year if used in all eligible heart failure patients with reduced ejection fraction (HFrEF)," said Vas Narasimhan, global head of development and chief medical officer for Novartis. "Entresto has now independently received a class I recommendation in clinical guidelines and was shown in multiple analysis to be cost effective so physicians and health care systems should feel confident in ensuring rapid and broad use of this breakthrough medicine."

In a separate analysis published in the same issue of JAMA Cardiology, researchers used data from the PARADIGM-HF trial to model the health consequences and cost-effectiveness of Entresto over a 30-year time period. They compared Entresto to the ACE-inhibitor enalapril and found Entresto was associated with more than a year longer average survival time, and that it was cost-effective compared to enalapril when these medications were used with other standard of care therapies. For every 1,000 patients treated with Entresto vs. enalapril, potentially 59.7 HF hospital admissions could be averted per each year alive in the model. In addition, Entresto increased life expectancy at an incremental cost-effectiveness ratio consistent with other high-value widely accepted cardiovascular interventions such as implantable cardioverter defibrillators (ICDs) and cholesterol-lowering statins before they became generic.

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, which accounts for both direct and indirect costs.

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 U.S. 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.