From Molecules to Markets

n July 7, 2015, sacubitril/valsartan became the first angiotensin receptorneprilysin inhibitor approved by the US Food and Drug Administration for use among patients with symptomatic heart failure with reduced ejection fraction (HFrEF).This expedited approval was based on the results of the PARA-DIGM-HF trial (Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure) that showed that among patients with New York Heart Association class II-IV heart failure and ejection fraction ≤40%, treatment with sacubitril/valsartan rather than 10 mg twice daily of enalapril produced a 17.7% reduction in the composite end point of cardiovascular mortality and hospitalizations for heart failure.The study demonstrated a remarkable 19.4% reduction in death from cardiovascular causes and 17.9% reduction in heart failure hospitalizations among patients receiving sacubitril/valsartan compared with those receiving enalapril.1 Sacubitril/valsartan is the first new-in-class medication to demonstrate a mortality benefit in patients with HFrEF since the early 2000s. 2 In this issue of Circulation: Heart Failure, Sangaralingham et al 3 describe the early experience with sacubitril/valsartan among patients enrolled in private or Medicare Advantage insurance plans.Although slow uptake is par for the course for a firstin-class drug, this study reveals a disappointingly low prescription rate of sacubitril/ valsartan among patients with HFrEF in the first 18 months after approval, and a high discontinuation rate among patients who initiate the drug.This disconnect between strong clinical data and low real-world uptake warrants further exploration.Sangaralingham et al analyzed the OptumLabs database, a large collection of medical and pharmaceutical claims data, to evaluate prescription practices, drug costs, and medication use in individuals with HFrEF.In their cohort of 102 247 individuals with HFrEF (identified by International Classification of Diseases, Ninth Revision, codes), only 2244 (2.2%) filled a prescription for sacubitril/valsartan between July 2015 and Dec 2016.Among patients who initiated sacubitril/valsartan, 59.1% remained on the medication after 6 months.They show that persistence on sacubitril/valsartan was associated with previous use of an angiotensin-converting enzyme inhibitor (ACE-I)/angiotensin II receptor blocker (ARB) and initiation on the highest dose of sacubitril/valsartan.Although these estimates are imprecise because of limitations of the underlying data (eg, the absence of New York Heart Association class or ejection fraction in the data set impedes accurate indentification of patients eligible for therapy), they are consistent with the low prescription rates of sacubitril/valsartan observed in the Get-With-the-Guidelines-Heart Failure registry.4 The overall message is an important one: we have on our hands a drug that has the potential to improve quality of life and survival among patients with symptomatic HFrEF, and the vast majority of patients are not receiving it.