Treatment of heart failure using angiotensin receptor neprilysin inhibitor

Heart failure (HF) is characterized by ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, accelerated apoptosis, and genetic mutations. Current guidelines recommend using angiotensin receptor neprilysin inhibitor (ARNI) therapy for HF with reduced and preserved ejection fraction (HFpEF). Recent large-scale randomized clinical trials have confirmed the superiority of sacubitril/valsartan to other conventional drugs to treat HF. Growing evidence has revealed the cardioprotective effects of sacubitril/valsartan on cellular and molecular modulation in cardiac remodeling, although their molecular mode of action in cardiac remodeling is still unknown. An understanding of the molecular mechanism(s) of action of sacubitril/valsartan will therefore be helpful, but future research needs to be done to unravel the proper potential use of the drug in the treatment of HF. A meta-analysis of 16 studies involving 1937 patients found that ARNI was likely to improve left ventricular function by increasing left ventricular ejection fraction (LVEF) (WMD: 2.36, 95% CI: 1.09–3.62), stroke volume (WMD: 16.800, 95% CI: 11.385–22.215), left ventricular short-axis shortening rate (WMD: 2.05, 95% CI: 0.25–3.86), decreasing left ventricular end-diastolic dimension (WMD: −2.48, 95% CI: −3.83 to −1.13), left atrial diameter (WMD: −2.23, 95% CI: −2.83 to −1.63), C-reactive protein level (WMD: −1.40, 95% CI: −2.62 to −0.18), and N-terminal pro-B-type natriuretic peptide level (WMD: −494.92, 95% CI: −641.34 to −348.50). ARNI has a higher total effective rate (RR: 1.15, 95% CI: 1.08–1.21) via the Kansas City cardiomyopathy questionnaire (WMD: 4.13, 95% CI: 3.46–4.81), and 6-Minute Walk Test (WMD: 51.35, 95% CI: 26.99–75.71) compared with ACEI and ARB. In addition, ARNI decreased the readmission rate (RR: 0.54, 95% CI: 0.43–0.68) (all P<.05). There were no significant differences in the adverse outcomes, suggesting that ARNI may be an effective strategy for improving left ventricular function and quality of life, and reducing the readmission rate in patients with HF with mildly reduced ejection fraction.