Determining Cost-Effectiveness of Sacubitril/Valsartan in Heart Failure, with Ankeet Bhatt, MD, MBA

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Ankeet Bhatt, MD, MBA provides additional perspective on a recent study examining the cost-effectiveness and health impact of sacubitril/valsartan use at different thresholds of ejection fraction.

A new study leveraging data from a pair of phase 3 trials provides an overview of the cost-effectiveness of sacubitril/valsartan relative to renin-angiotensin system inhibitors (RASis) in patients with heart failure.

Stratifying patients by ejection fraction, results of the investigators' cost-effectiveness modeling provided incremental cost-effectiveness ratios (ICERs) indicating treatment with sacubitril/valsartan was associated with high economic value for patients with ejection fractions of 50% or less and at least intermediate value at ejection fractions of 60% or less.

“These findings may have implications for coverage decisions and value assessments in contemporary clinical practice guidelines,” wrote investigators.

After its initial approval in patients with heart failure with reduced ejection fraction (HFrEF) in 2014, it was more than a half-decade before the FDA would grant approval for a label expansion indicating the agent for use in patients with heart failure with preserved ejection fraction (HFpEF) in 2021. Although historic, the language of the approval, which endorsed the agent for use in those with left ventricular ejection fractions (LVEF) below normal, prompted discussion around the ideal patient population, given previous signals from clinical trials indicating increased efficacy at reduced ejection fractions.

Led by Ankeet Bhatt, MD, MBA, of Kaiser Permanente, the current study was launched with the intent of providing further clarity on the economic- and health-related impact of sacubitril/valsartan use at different thresholds of ejection fraction. For the purpose of analysis, a 5-state Markov model was used to assess the cost-effectiveness of sacubitril-valsartan in treating heart failure. The model considered various factors such as mortality risk reductions, hospitalization rates, quality of life, medication costs, and patient ejection fraction, with the base case analysis focusing on ejection fractions of 60% or less. These models were applied to an ejection fraction distribution of patients from the Get With the Guidelines-Heart Failure Registry.

In total, 13,264 patients were identified for inclusion in the analysis. Among those with ejection reactions of 60% or less, use of sacubitril/valsartan was projected to add 0.53 quality-adjusted life-years an incremental cost of $40,892 relative to RASi, which yielded an ICER of $76,852 per quality-adjusted life-year. In their probabilistic sensitivity analyses, results indicated 95% of the values of the ICER occurred between $71,516 and $82,970 per quality-adjusted life-year.

At an ejection fraction of 60% or less, investigators determined use of sacubitril/valsartan would be at least of intermediate economic value relative to RASis at a cost of $10,242 or less per year. Further analysis suggested it would be of high economic value at a cost of $3673 or less per year, and cost-saving at a cost of $338 or less per year. Investigators pointed out the ICERs for sacubitril/valsartan relative to RASi were $67,331, $59,614, and $56 786 per quality-adjusted life-years at ejection fractions of 55% or less, 50% or less, and 45% or less, respectively.

As part of on-site coverage of the Heart Failure Society of America 2023 Annual Scientific Meeting, the editorial team of HCPLive Cardiology sat down with Bhatt to learn more about this study and the importance of the findings. That conversation is the subject of the following video.


  1. Bhatt AS, Vaduganathan M, Claggett BL, et al. Health and Economic Evaluation of Sacubitril-Valsartan for Heart Failure Management. JAMA Cardiol. Published online September 27, 2023. doi:10.1001/jamacardio.2023.3216
  2. Campbell P. FDA expands label for Sacubitril/Valsartan (entresto) to include some HFPEF patients. HCP Live. February 16, 2023. Accessed October 10, 2023.