STEPwise De-escalation and Optimizing Withdrawal of ARNI and SGLT2i in Normalized Heart Failure

Summary

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.

Conditions

• Heart Failure With Reduced Ejection Fraction
• Heart Failure
• Ventricular Dysfunction, Left

Interventions

DRUG

Stepwise Withdrawal of ARNI and SGLT2i

Sequential discontinuation of angiotensin receptor-neprilysin inhibitor (ARNI; e.g., sacubitril/valsartan) and sodium-glucose cotransporter-2 inhibitor (SGLT2i; e.g., dapagliflozin or empagliflozin). ARNI is discontinued first; after a 1-month observation with echocardiographic and biomarker assessment, SGLT2i is discontinued if no signs of deterioration are observed. Concomitant MRA and beta-blocker therapy is continued.

DRUG

Continued Guideline-Directed Medical Therapy

Continuation of currently prescribed ARNI and SGLT2i, together with any concomitant MRA and beta-blocker, at the doses being received at enrollment, per current guideline-directed medical therapy.

Sponsors & Collaborators

• Seoul National University Bundang Hospital

  collaborator OTHER

• Ajou University School of Medicine

  collaborator OTHER

• Korea University Anam Hospital

  collaborator OTHER

• Pusan National University Yangsan Hospital

  collaborator OTHER

• Kyungsub Song

  lead OTHER

Principal Investigators

• Hyung Gon Je, Professor · Seoul National University Bundang Hospital

• Su Jin Park, Professor · Ajou University School of Medicine

• Jun Ho Lee, Professor · Korea University Anam Hospital

• Younju Rhee, Professor · Pusan National University Yangsan Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

19 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-30

Primary Completion

2029-06-30

Completion

2029-12-30

Countries

• South Korea

Study Locations