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In talking to healthcare leaders about drug utilization, I’ve fielded many questions concerning the application of clinical evidence to specific drugs and drug categories. I address one popular topic below.

DEAR LUMERE: I’m a pharmacy clinical coordinator, and my hospital’s cardiologists are clamoring for Entresto (sacubitril/valsartan) to treat patients with chronic heart failure. They point to strong efficacy data and last year’s updated American College of Cardiology/American Heart Association guidelines that recommend it over ACE inhibitors and ARBs. Should we add Entresto to our inpatient formulary? – UNCLEAR ABOUT ENTRESTO

DEAR UNCLEAR ABOUT ENTRESTO: Let’s look at your question from three angles:

  • Patient safety: Switching from an angiotensin-converting enzyme (ACE) inhibitor to Entresto requires a 36-hour washout period to eliminate the risk of angioedema. Therefore, patients who were previously on therapy cannot start Entresto immediately upon admission.
  • Cost effectiveness: Entresto can cost two orders of magnitude more than ACE inhibitors and angiotensin receptor blockers (ARBs). While some studies have shown that Entresto meets commonly accepted incremental cost-effectiveness thresholds over a patient’s lifetime, the short-term incremental cost-effectiveness is much harder to justify.12
  • Limited patient population: Entresto is appropriate only for approximately 40% of patients with heart failure.3 It was not widely adopted in its first year and last year fell $30M short of a projected $200M in global sales.

Given these factors, patients should not be starting Entresto in the inpatient setting, and it doesn’t make sense for most hospitals to carry it on their shelves.

Lumere’s online Pharmacy Solutions apply the power of evidence to help health systems optimize costs and improve patient care. To learn more, email



This Article is provided “AS IS”, with all faults and without any warranty of any kind; any and all warranties are expressly disclaimed. No information in this Article is, or should be construed as medical advice, a guarantee of any product safety or any endorsement of any product or service; use of this Article is at your own risk. Lumere shall not be liable, in any way, for any use of this Article or decisions made and/or actions taken based upon the contents herein. Discussion of experimental uses of drugs as described in this Article is for informational purposes only, and is not to be interpreted as an endorsement or encouragement of off-label use of any product.

1 Cost-Effectiveness of Sacubitril-Valsartan in Patients with Heart Failure with Reduced Ejection Fraction. Sandhu AT, Ollendorf DA, Chapman RH, Pearson SD, Heidenreich PA, Annals of Internal Medicine, (8/2016)

2 Cost-Effectiveness of Sacubitril-Valsartan Combination Therapy Compared with Enalapril for the Treatment of Heart Failure With Reduced Ejection Fraction. King JB, Shah RU, Bress AP, Nelson RE, Bellows BK, JACC: Heart Failure, (5/2016)

3 Potential Mortality Reduction with Optimal Implementation of Angiotensin Receptor Neprilysin Inhibitor Therapy in Heart Failure. Fonarow GC, Hernandez AF, Solomon SD, Yancy CW, JAMA Cardiology, (09/2016)