Sacubitril/Valsartan: A Novel Approach in the Treatment of Heart Failure with Reduced Ejection Fraction

Abstract

Heart failure is a condition in which the heart is unable to supply blood throughout the body. Heart failure [HF] is one of the main healthcare burdens in the world and is more lethal than most cancers. 50% of patients suffering with heart failure die within first 5 years of diagnosis, and 90% die within 10 years. Dyspnea [shortness of breath], Paroxysmal nocturnal dyspnea, edema, and fatigue are common symptoms. Coronary artery disease remains the leading cause of HF.

Many drugs are approved and used in practice for management of this condition, including beta blockers, diuretics, aldosterone antagonists, angiotensin converting enzyme inhibitors [ACEIs], and angiotensin receptor blockers [ARBs]. The FDA approved a drug in 2015 with the brand name Entresto  — sacubitril/valsartan or LCZ696, an angiotensin receptor neprilysin inhibitor [ARNI] — for use in patients with heart failure with reduced ejection fraction [HFrEF] as a replacement to ACEIs and ARBs. The drug works through angiotensin receptor blockage via valsartan as well as neprilysin inhibition with sacubitril. This represents a new milestone in managing heart failure patients and provides a new hope for HF patients.

This was the largest-ever trial conducted for any drug in management of heart failure. The study clearly showed that sacubitril and valsartan complex can significantly reduce mortality and HF hopsitalizations ultimately helping patients stay away from hospitals.

Following the outcomes of PARADIGM-HF, the drug got a fast track approval from various regulators for HFrEF. The trial was intended to last for 36 months, but at 27 month follow-up, the results were extremely overwhelming in both the primary and secondary endpoints, therefore it was thought to be unfair to carry on further with the trial. Also, all patients in the comparator [ACEI] arm were shifted to this new drug [sacubitril/valsartan] so they could also benefit from the great advantages of this new class.