Clinical and echocardiographic benefit of Sacubitril/Valsartan in a real-world population with HF with reduced ejection fraction

Abstract

The aim of this study was to evaluate the effects of Sacubitril/Valsartan (S/V) on clinical, laboratory and echocardiographic parameters and outcomes in a real-world population with heart failure with reduced ejection fraction (HFrEF). This was a prospective observational study enrolling patients with HFrEF undergoing treatment with S/V. The primary outcome was the composite of cardiac death and HF rehospitalization at 12 months follow-up; secondary outcomes were all-cause death, cardiac death and the occurrence of rehospitalization for worsening HF. The clinical outcome was compared with a retrospective cohort of 90 HFrEF patients treated with standard medical therapy. The study included 90 patients (66.1 ± 11.7 years) treated with S/V. The adjusted regression analysis showed a significantly lower risk for the primary outcome (HR:0.31; 95%CI, 0.11-0.83; p = 0.019) and for HF rehospitalization (HR:0.27; 95%CI, 0.08-0.94; p = 0.039) in S/V patients as compared to the control group. A significant improvement in NYHA class, left ventricular ejection fraction, left ventricular end systolic volume and systolic pulmonary arterial pressure was observed up to 6 months. S/V did not affect negatively renal function and was associated with a significantly lower dose of furosemide dose prescribed at 6-and 12-month follow-up. In this study, S/V reduced the risk of HF rehospitalization and cardiac death at 1 year in patients with HFrEF. S/V improved NYHA class, echocardiographic parameters and need of furosemide, and preserved renal function.Despite the improvements in clinical management and medical therapy of heart failure (HF), the outcome of patients with HF and reduced ejection fraction (HFrEF) remains poor 1 . If compared to the other HF entities, this category shows distinct demographic characteristics, comorbidities, response to therapy, and a substantially higher risk of mortality secondary to sudden cardiac death (SCD) and rehospitalization for worsening HF 2 . Many HFrEF patients are still undertreated and several drugs, such as beta-blockers and ACE inhibitors (ACEi), are under-dosed. This issue is also related to the incorrect risk evaluation by clinicians, who are likely to consider the absence or paucity of symptoms as an indicator of HF stability 3 . In fact, HFrEF is a progressive disorder that, despite the improvement of patient's clinical status achieved with conventional medications, may be associated with a high risk of adverse events at short and long-term follow-up 4 .Current European guidelines 5 recommend the use Sacubitril/Valsartan (S/V), an angiotensin receptorneprilysin inhibitor (ARNI), in replacement of the renin-angiotensin-aldosterone system (RAAS) inhibition in ambulatory HFrEF patients still symptomatic despite optimal medical therapy (OMT). This recommendation comes from a single randomized study named PARADIGM-HF trial 6 , which showed the superiority of S/V compared to Enalapril in reducing the incidence of cardiovascular death or hospitalizations for HF. Few studies have so far investigat...

Effects of Sacubitril/Valsartan on the Right Ventricular Arterial Coupling in Patients with Heart Failure with Reduced Ejection Fraction

“…In addition to a reduction in the rate of mortality and hospitalisation [ 2 , 3 ], both randomised clinical trials and real-life studies have shown that sacubitril/valsartan induced the “reverse remodelling” of the left ventricle (LV), with a reduction in the ventricular volumes, an increase in the ejection fraction (EF) [ 4 , 5 ], an improvement in the diastolic function [ 6 , 7 ], and a reduction in the degree of functional mitral regurgitation [ 8 ]. In patients with HFrEF, the increased LV filling pressure induces right ventricle (RV) chronic overload, which increases RV afterload and thus leads to RV remodelling, with a reduction in the performance of RV even when it is not directly involved in the development of cardiovascular disease [ 9 , 10 ].…”

Sacubitril/Valsartan: Potential Impact of ARNi “Beyond the Wall” of ACE2 on Treatment and Prognosis of Heart Failure Patients With Coronavirus Disease-19

“…The beneficial effects of S/V in HFrEF were confirmed in recent real-life clinical studies showing a significant reduction of cardiac death and HF rehospitalization, an improvement of echocardiographic parameters, such as left ventricular EF, systolic volume, and systolic pulmonary arterial pressure, of renal function and of quality of life (12)(13)(14). Moreover, S/V treatment can be safely started during hospitalization in daily clinical practice with no evidence of increased risk of hypotension, worsening of renal function and hyperkalaemia (15).…”

Sacubitril/valsartan inhibits obesity-associated diastolic dysfunction through suppression of ventricular-vascular stiffness

“…Sac/val is a first-in-class approved ARNi, that simultaneously provides Ang II type I receptor blockade and NP inhibition. Cardiac protection afforded by sac/val is well recognized with completion of first and second phase clinical trials [37][38][39][40][41]. A Fig.…”