Authors state that the observed reverse cardiac remodelling may provide a mechanistic explanation for the effects of sacubitril-valsartan in patients with HFrEF.
A separately reported study found that treatment of heart failure with reduced ejection fraction with sacubitril-valsartan, compared with enalapril, did not significantly reduce central aortic stiffness.
A related commentary discusses these two papers. It states that there has been an evidence gap in the data assessing how Angiotensin Receptor–Neprilysin Inhibition (ARNI) improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF), and that the data from these studies may substantially advance current understanding. These data strongly suggest that ARNI therapy can promote cardiac reverse remodelling in patients with HFrEF. Although neither investigation assessed this question as its primary end point, and one study was observational in nature, the replication of the reduction in left ventricular volumes and left atrial volumes in these reports, as well as the large, progressive increase in left ventricular ejection fraction in PROVE-HF, are important. As with β-blockers and ACE inhibitors, it thus appears that the benefits of ARNI therapy on clinical outcomes in patients with HFrEF are mediated, at least in part, by their favourable effects on the adverse cardiac remodelling that characterizes this condition.