Why Entresto Is a Winner for Heart Failure


Two new analyses have further cemented Entresto's place in heart failure therapy.

Novartis’s heart failure (HF) drug, sacubitril/valsartan (Entresto), was approved by the FDA last year to reduce the risk of cardiovascular (CV) death and hospitalization in patients with chronic HF (NYHA class II-IV) and reduced ejection fraction (EF).1 Although it was deemed a promising treatment for HF at the time, physicians were slow to prescribe it.2

The tide started to turn when the American College of Cardiology (ACC)/American Heart Association (AHA) released a 2016 guideline update focused on new pharmacological therapies for heart failure. In the guideline, Entresto received a class I recommendation for patients with chronic symptomatic HF with a reduced EF (NYHA class II or III) who tolerate an angiotensin converting enzyme inhibitor or angiotensin receptor blocker to further reduce morbidity and mortality. In other words, Entresto is now considered the cornerstone of treatment for HF patients with reduced EF.

About a month after the guideline’s release, 2 new analyses further cemented Entresto’s place in HF therapy.3,4

The first analysis quantified the projected gains in deaths prevented or postponed with comprehensive implementation of Entresto therapy in patients with HF and reduced EF. Eligibility was based on the population of patients with HF covered under current Entresto product labeling, while the magnitude of mortality reduction was determined by the PARADIGM-HF trial. The number needed to treat (NNT), standardized to 12 months, was used to calculate the number of potential lives saved per year with Entresto therapy.3

The total US prevalence of HF is 5.7 million cases, and about half of these patients have a left ventricular EF of <40%. However, some patients may not be candidates for Entresto because of disease state severity or contraindications/intolerance.

The analysis determined that about 2.2 million patients are candidates for Entresto. The NNT to prevent 1 death was calculated as 80.3, and the number of deaths that could potentially be prevented each year with optimal implementation of Entresto therapy is 28,484. Multiple-way sensitivity analyses using the analysis-of-extremes method yields the range of deaths potentially avoided from a lower limit of 18,230 to an upper limit of 41,017.3

The authors of the first analysis concluded that a substantial number of deaths could potentially be prevented by optimal implementation of Entresto, supporting the need for comprehensive implementation efforts.3

The second analysis compared the cost effectiveness of Entresto with that of enalapril in patients with HF and reduced EF. A HF disease simulation was developed for the US population using data derived from the PARADIGM-HF trial, which compared enalapril 10 mg twice-daily with sacubitril 97 mg/valsartan 103 mg twice-daily. A population was simulated with equivalent characteristics as the trial population and then modeled to evaluate the costs and health consequences for the duration of the trial and beyond for up to 30 years.4

The model follows a standard structure of HF where each month, a patient has a risk of either surviving without further complication, becoming hospitalized, or dying. The mean age of the population was 63.8 years.4

Costs included both medication costs and the downstream costs of hospitalizations that occurred in each group of simulated patients. The monthly cost for Entresto was $375, compared with $0.96 for enalapril. The mean cost of HF hospitalizations was $18,158 compared with $10,467 for non-HF hospitalizations.4

The simulation also projected the lifetime discounted HF-related health care costs and quality-adjusted life-years (QALYs) accrued under the 2 treatment options. Incremental cost-effectiveness ratios (ICERs) were calculated per conventional cost-effectiveness analysis guidelines.4

The results showed that there would be 220 fewer hospital admissions per 1000 patients with HF treated with Entresto compared with enalapril over 30 years. The incremental costs and QALYs gained with Entresto treatment were estimated at $35,512 and 0.78, respectively, compared with enalapril. This equated to an ICER of $45,017 per QALY for the base-case.4

The ACC/AHA and World Health Organization consider an ICER per QALY of <$50,000 to be a “very good value,” and Entresto compared well with other accepted CV therapies when they were first adopted or approved. The study authors concluded that Entresto is more cost effective than enalapril.4


1. Entresto [package insert]. East Hanover, New Jersey: Novartis Pharmaceuticals Corp; August 2015.

2. Roland D. Novartis heart-failure pill hits hurdles with doctors. Wall Street Journal. wsj.com/articles/novartis-heart-failure-pill-falls-short-of-sales-expectations-1458155650. Published March 16, 2016.

3. Fonarow GC, Hernandez AF, Solomon SD, et al. Potential mortality reduction with optimal implementation of angiotensin receptor neprilysin inhibitor therapy in heart failure. JAMA Cardiol. Published online June 22, 2016.

4. Gaziano TA, Fonarow GC, Claggett B, et al. Cost-effectiveness analysis of sacubitril/valsartan vs enalapril in patients with heart failure and reduced ejection fraction. JAMA Cardiol. Published online June 22, 2016.

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