Focused Treatment of Heart Failure with Reduced Ejection Fraction Using Sacubitril/Valsartan

Abstract

The clinical syndrome of heart failure (HF) can be described as the reduced capacity of the heart to deliver blood throughout the body. To compensate for inadequate tissue perfusion, the renin–angiotensin aldosterone system (RAAS) and the sympathetic nervous system (SNS) become activated, resulting in increased blood pressure, heart rate, and blood volume. Consequent activation of the natriuretic peptide system (NPS) typically balances these effects; however, the NPS is unable to sustain compensation for excessive neurohormonal activation over time. Until recently, mortality benefits have been provided to patients with HF only by therapies that target the RAAS and SNS, including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, and beta-blockers. Sacubitril/valsartan, the first-in-class angiotensin receptor/neprilysin inhibitor (ARNI), targets both the NPS and RAAS to further improve clinical outcomes. This review discusses the focused management of patients with HF with reduced ejection fraction (HFrEF) and suggests changes to current management paradigms. From this assessment, the evidence supports favoring sacubitril/valsartan over ACEIs or ARBs, and this therapy should be used in conjunction with beta-blockers to further decrease morbidity and mortality in patients with HFrEF.

Sacubitril/Valsartan in Management of Heart Failure: A Review of Safety, Efficacy and Cost-Effectiveness

“…Heart failure is a complex clinical syndrome resulting from various pathophysiological dysfunctions [2]. Normal cardiac functioning is regulated by a balanced relationship between myocardial contractility and the volume of blood circulated throughout the body [3]. In HF due to systolic dysfunction, there is a depressed myocardial contractility which corresponds to reduced cardiac output (CO) [3].…”

“…Decreased CO further leads to a decrease in mean arterial pressure (MAP) and therefore decreased tissue perfusion [3].…”

“…There are several compensatory mechanisms in HF that maintain adequate tissue perfusion, MAP, and CO during left ventricular failure. Three important compensatory mechanism regulating progression of HF are; Frank-Starling mechanism, neurohormonal activation, and ventricular remodeling [3].…”

“…Clinically, cardiac dysfunction caused by HF is classified into systolic HF and diastolic HF [3]. Systolic HF or HF with reduced ejection fraction (HFrEF) is due to depressed myocardial contractility therefore, resulting in left ventricular ejection fraction (LVEF) ≤ 40%.…”

“…Systolic HF or HF with reduced ejection fraction (HFrEF) is due to depressed myocardial contractility therefore, resulting in left ventricular ejection fraction (LVEF) ≤ 40%. Whereas, diastolic HF or HF with preserved ejection fraction (HFpEF) is due to reduced ventricular relaxation and filling hence, have LVEF ≥ 50% [3].…”