Sacubitril/valsartan in cardiovascular disease: evidence to date and place in therapy

Abstract

Cardiovascular (CV) disease is a major cause of morbidity and mortality in the developing and the developed world. Mortality from CV disease had plateaued in the recent years raising concerning alarms about the sustained efficacy of available preventive and treatment options. Heart failure (HF) is among the major contributors to the CV-related health care burden, a persisting concern despite the use of clinically proven guideline-directed therapies. A requirement for more efficient medical therapies coupled with recent advances in bio-innovation led to the creation of sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), which demonstrated substantial CV benefit when compared with the standard of care, enalapril, in patients with HF and reduced ejection fraction. Further investigations of this novel combination ARNI at the tissue level shed light into the anti-remodeling and cardioprotective effects of sacubitril/valsartan, while clinical studies in the phenotypes of HF with preserved ejection fraction, hypertension and subsets, coronary outcomes, postmyocardial infarction, and renal disease suggested that this combination could be beneficial across a wide spectrum of CV disease. Sacubitril/valsartan is a much-needed therapeutic advance in the avenue of CV disease.

Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure

“…The PIONEER-HF study (comparison of sacubitril/valsartan versus enalapril on effect on nt-pro-bnp in patients stabilized from an acute heart failure episode), which showed that treatment with sacubitril/valsartan produced a significantly greater reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels than enalapril without increasing the rates of major adverse events in patients hospitalized with acute decompensated heart failure (Velazquez et al, 2019), may help in overcoming the clinical inertia (Jarcho, 2019). The angiotensin receptor–neprilysin inhibitor (ARNI) has shown considerable cardiovascular benefit and absolute risk reduction compared with the standard-of-care treatment in the PARADIGM (Yandrapalli et al, 2018) and PIONEER-HF (Morrow et al, 2019; Velazquez et al, 2019) trials. The composite endpoint, which was explored as part of a prespecified exploratory analysis, consisted of death, rehospitalization for heart failure (hospital stay >24 hours), requirement for a left ventricular assist device insertion, or listing for a cardiac transplantation.…”

The Effects of Resveratrol in Patients with Cardiovascular Disease and Heart Failure: A Narrative Review

“…Various HF treatments exist and have shown success in reducing HF-associated mortality, such as implantable cardioverter defibrillators, heart transplant surgery, and numerous medications including ones that target the sympathetic nervous system (β-adrenergic receptor blockers), the renin-angiotensin aldosterone system (angiotensin converting enzyme inhibitors and angiotensin II receptor blockers) [ 14 ], and the pacemaker current of the sinoatrial cells (ivabradine) [ 15 ]. Furthermore, medications focusing on dual inhibition of the renin-angiotensin aldosterone system (RAAS) as well as neprilysin blockade [ 16 ] (angiotensin receptor-neprilysin inhibitor) have been shown to cause a significantly greater reduction in CV-related death, HF hospitalizations, and all-cause mortality compared to only RAAS blockade [ 17 ]. However, mortality rates following diagnosis of HF remain high [ 18 ].…”

Neprilysin: A Potential Therapeutic Target of Arterial Hypertension?

“…Having as a goal to be considered a therapeutic option, the combination sacubitril/valsartan has been studied in a variety of clinical trials [ 71 , 72 ]. Moreover, beneficial effects over renal function have been observed, specifically in diabetic patients with HF and a maximum blockage of RAAS, as demonstrated by Parcker et al .…”

“…In order to assess the effectivity of this drug combination in HF, the phenotypes of heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) have been considered (Table 1 ) [ 71 ]. PARAMOUNT-HF study was the first to provide clinical data about Sacubitril/Valsartan in patients with preserved (45% or more) left ventricular ejection fraction (LVEF) and also with high serum levels of NT-proBNP, with their primary objective to compare the efficacy and security of an angiotensin receptor-neprilysin inhibitor against an ARB (Valsartan) [ 75 ], noticing a reduction in serum concentrations of this marker in the group of dual therapy, and also showing a similar profile of side effects, independent of their antihypertensive actions [ 76 ].…”