Impact of in-hospital initiation of angiotensin receptor-neprilysin inhibition on left ventricular reverse remodeling in acute heart failure: an insight from PREMIER trial

Background In the PREMIER study, early initiation of sacubitril/valsartan (Sac/Val) led to a greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels over 8 weeks compared to renin-angiotensin system (RAS) inhibitors in stabilized patients after acute heart failure (AHF) hospitalization. However, the effect of this treatment on echocardiographic parameters remains unknown. Purpose In this post-hoc sub-study of the PREMIER trial, we sought to evaluate the treatment effects of Sac/Val on left ventricular (LV) reverse remodeling in stabilized patients after AHF. Methods The PREMIER study was a physician-initiated, multicenter, prospective, randomized, open-label trial enrolling stabilized Japanese inpatients after AHF. This sub-study compared the changes from baseline echocardiographic parameters at 8 weeks between patients treated with Sac/Val and RAS inhibitors. Results Among the full analysis set of the PREMIER study, this analysis included 206 patients (mean age 73 years; 64 females [31.1%]), who had echocardiographic data (Figure 1). The Sac/Val group (n=94) significantly improved LV functional and morphological parameters at 8 weeks (Figure 2). Compared with the control group (n=112), preload-dependent parameters improved significantly, including LV end-diastolic volume index (mean: −5.1 mL/m²; 95% CI: −10.2 to −0.04; p = 0.047) and tricuspid regurgitation peak velocity (mean: −0.17 m/s; 95% CI: −0.31 to −0.03; p = 0.016). In a subgroup analysis stratified by left ventricular ejection fraction (LVEF), the reverse remodeling effect was primarily observed in patients with LVEF < 40%. Conclusions Early Sac/Val initiation after AHF hospitalization significantly improved LV function and morphology, particularly in patients with LVEF < 40%, supporting its role in LV reverse remodeling.