Withdrawal of Spironolactone for Heart Failure With Improved Ejection Fraction: An Open-Label, Pilot, Randomized Controlled Trial (With-HF Trial).

Background and objectives: The optimal strategy for the maintenance or discontinuation of evidence-based medication is unclear in heart failure (HF) patients with improved left ventricular ejection fraction (LVEF). We tested the feasibility and safety of withdrawing mineralocorticoid receptor antagonists (MRAs) in this population.

Methods: This is an open-label, prospective, randomized controlled pilot trial including HF patients whose LVEF improved from ≤35% to ≥50% after guideline-directed medical therapy. While testing withdrawal of MRA, other medications were maintained. The primary endpoint was the proportion of patients showing deteriorations in LVEF by ≥10% at 6-month follow-up. The secondary endpoints were numerical changes in echocardiographic parameters, changes in blood natriuretic peptide levels, and adverse clinical events relevant to HF.

Results: We randomly assigned 62 HF patients with improved LVEF to the withdrawal or continuation groups. Two (6.7%) patients in the withdrawal group and one (3.2%) patient in the continuation group showed deterioration in LVEF by ≥10% at 6 months; one of the 2 patients in the withdrawal group who showed a decline in LVEF had LVEF of less than 50% at follow-up. Re-initiation of MRA did not occur in any patients. Compared with baseline, echocardiographic parameters, including LV end-diastolic volume index, global longitudinal strain, and natriuretic peptides, were similar at follow-up in both groups.

Conclusions: MRA withdrawal was associated with a low risk of significant deterioration of cardiac function in HF patients with improved LVEF of ≥50%. MRA withdrawal may be feasible and safe in this population.

Trial registration: ClinicalTrials.gov Identifier: NCT04367051.