STEPwise De-escalation and Optimizing Withdrawal of ARNI and SGLT2i in Normalized Heart Failure (STEP-DOWN HF Trial)
This is a multicenter, randomized, open-label pilot study to evaluate whether stepwise withdrawal of two heart failure medications-angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitor (SGLT2i)-is safe in patients with Heart Failure with improved Ejection Fraction (HFimpEF) whose underlying structural cause (valvular heart disease or ischemic cardiomyopathy) has been completely corrected by surgery or intervention. Eighty adult patients (40 per arm) whose left ventricular ejection fraction (LVEF) has recovered to 50% or higher and whose NT-proBNP is ≤ 250 ng/L will be randomized 1:1 to either (1) stepwise withdrawal of ARNI followed by SGLT2i over one month under close echocardiographic monitoring, or (2) continuation of their current guideline-directed medical therapy. The primary outcome is the change in LVEF at 12 months, with non-inferiority of the withdrawal strategy declared if the LVEF decline is within 5 percentage points of the continuation arm. Secondary outcomes include cardiovascular death, heart failure hospitalization, NT-proBNP, quality of life (KCCQ-12), 6-minute walk distance, and adverse events. Results from this pilot will inform the design and sample size of a subsequent definitive non-inferiority trial and may provide initial evidence to guide deprescribing decisions in clinical practice.
• Adults aged 19 years or older
• Prior left ventricular ejection fraction (LVEF) ≤40% before surgery or intervention, with recovery to ≥50% (normalized range) at the time of enrollment
• N-terminal pro-B-type natriuretic peptide (NT-proBNP) \<250 ng/L
• Complete correction of a reversible underlying cause of heart failure: surgical or transcatheter correction of valvular heart disease (mitral regurgitation, aortic stenosis, aortic regurgitation), or percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for ischemic cardiomyopathy
• Currently receiving both ARNI and SGLT2i for at least 3 months at enrollment (MRA and/or beta-blocker may also be used)
• Clinically stable outpatient with no heart failure-related hospitalization within the prior 6 months
• Able to provide written informed consent