The management of heart failure with improved ejection fraction remains unresolved, particularly after stabilization. This study aimed to determine whether maintenance with an angiotensin receptor-neprilysin inhibitor (ARNI) was superior to de-escalation to an angiotensin receptor blocker (ARB).

In this open-label, prospective pilot study conducted at the Samsung Medical Center in Seoul, South Korea, 98 patients with heart failure with improved ejection fraction who were stabilized on ARNI were randomized using a block allocation table to either switch to an ARB or continue with an ARNI. The primary outcome was a change in N-terminal pro b-type natriuretic peptide (NT-proBNP) during the follow-up period. The secondary outcomes were defined as: a) NT-proBNP increase, and b) heart failure admission. Additionally, a post-hoc composite outcome was evaluated, defined as the occurrence of any of the following: NT-proBNP increase, heart failure admission, left ventricular ejection fraction reduction, or left ventricular end-diastolic volume increase.

Baseline characteristics did not differ significantly between the de-escalation group (n=49) and the maintenance group (n=49) including NT-proBNP levels (P=.765). During follow-up, NT-proBNP levels remained comparable at 6 and 12 months (P=.642 and P=.964). Secondary outcomes, including the post-hoc composite outcome, did not differ significantly between the groups.

This study demonstrates no significant difference in worsening heart failure indices or clinical outcomes between ARB de-escalation and ARNI maintenance in patients with heart failure with improved ejection fraction and stabilized NT-proBNP levels. These findings suggest the potential for flexible medication management, although further validation is needed.

(ClinicalTrials.gov number: NCT04803175).