New Drug to Prevent Heart Failure

In the event of a myocardial infarction or another related episode concerning one’s cardiovascular health, it is common for an angiotensin converting enzyme inhibitor to be prescribed in addition to a beta adrenergic blocker, and a diuretic or aldosterone antagonist. In place of an ACE inhibitor an angiotensin II receptor blocker (ARB) may be prescribed. However, a new class of drug is being studied that may become an additional team player in the fight against cardiovascular disease.

Sacubitril is a prodrug which is converted to LBQ657 by esterases in the body. This metabolite is a neprilysin inhibitor. Neprilysin is an endopeptidase that can degrade peptides that are responsible for regulating actions in the blood vessels. This can lead to vasoconstriction and increased sodium retention. Thus, sacubitril would work to reduce vasoconstriction and sodium retention.

So far the formulation of this drug has been only in a form coupled with valsartan; it has not been administered as the single drug, sacubitril. It was administered to 8,400 patients with symptomatic heart failure and a left ventricle ejection of 40% or lower. The patients involved had been treated with an ACE inhibitor and a beta adrenergic blocker for at least 4 weeks. Many of the patients were also taking a diuretic. The rate of cardiovascular deaths for those taking sacubitril was 13.3% which was considered significantly lower than that of those taking the ACE inhibitor, enalapril, which was 16.5%.

Thus there is reason to believe that sacubitril, and other drugs from this class of neprilysin inhibitors, may account for a new model of first line drug therapy in the treatment of cardiovascular disease.


Hussar D, Abdelsayed M. Sacubitril/valsartan, ivabradine hydrochloride, alirocumab, and evolocumab. Journ Am Pharm Assoc. 2015; 55(6): 674-78.

J Am Pharm Assoc. 2016; 55(6): 674-678

2 thoughts on “New Drug to Prevent Heart Failure”

  1. I found this article really interesting as I never really considered creating a new drug for a disease that we already have drugs for. With heart disease being one of the deadliest killers in the United States, it only seems fitting that we continue to do everything we can to help cure this disease. Not only is this a new drug that has not yet been used, but it is also in its own class that we have never utilized. I believe that if this drug has success not only will it successfully reach the market but it may lead to the development of many other drugs that would use a similar mechanism and thus be in the same class. I also thought that it was interesting that this drug results in fewer cardiac related deaths when compared to the standard medications that we see frequently.

  2. Earlier in development of this combination medication for heart failure, sacubitril was combined with enalapril. The incidence of adverse events, particularly drug-induced angioedema was quite high and led to the change to an ARB, valsartan.

    Have you seen the news articles and opinion pieces on the direct-to-consumer advertising TV ad with valsartan/sacubitril (Entresto(R))? Thinking is that it is over the top!

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