Clinical trials

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.

In patients with heart failure due to a reversible underlying cause-such as valvular heart disease or coronary artery disease-surgical or procedural correction of the underlying lesion (valve repair/replacement, TAVI, PCI, or CABG) frequently leads to spontaneous recovery of cardiac function, even without neurohormonal modulators. In this clinical setting, a substantial proportion of patients may not require the full set of guideline-directed medical therapies routinely prescribed for chronic HFrEF. The purpose of this study is to determine whether ARNI (angiotensin receptor-neprilysin inhibitor) and SGLT2 inhibitors are truly necessary in patients whose left ventricular function recovers spontaneously after treatment of a correctable cause of heart failure. The DELAY-HF trial (DELayed initiation of ARNI and SGLT2i in heart failure with corrected aetiologY) is a multicentre, randomised, open-label pilot trial with blinded end-point assessment (PROBE design) evaluating the safety and feasibility of a delayed-initiation strategy of ARNI and SGLT2i, compared with immediate initiation, in patients with heart failure whose underlying cause has been completely corrected by surgical or procedural intervention. A total of 80 patients (40 per arm) will be enrolled at four centres in South Korea. Adults with a preoperative left ventricular ejection fraction (LVEF) ≤40% who have undergone successful correction of a reversible cause of heart failure-either revascularization (PCI or CABG) for ischemic cardiomyopathy or valvular surgery (including TAVI) for left-sided valvular heart disease causing volume overload-will be randomized 1:1 to (1) delayed initiation, in which ARNI/SGLT2i are withheld for 6 months and started only in patients whose LVEF remains ≤40% at the 6-month assessment, versus (2) immediate guideline-directed medical therapy (GDMT) including ARNI/SGLT2i started shortly after the corrective procedure. All patients are followed for 12 months. The primary outcome is the absolute change in LVEF from baseline to 12 months. The between-group difference (delayed minus immediate) will be reported as a point estimate with a two-sided 95% confidence interval and evaluated against a pre-specified decision criterion (lower confidence limit above -5 percentage points). As a pilot trial, DELAY-HF is not powered for a confirmatory non-inferiority test; it aims to estimate the standard deviation of the primary outcome, recruitment and dropout rates, the rescue-therapy rate and safety data needed to design a subsequent confirmatory trial. Key secondary outcomes include cardiovascular and all-cause mortality, heart failure hospitalisation, additional echocardiographic indices, NT-proBNP, KCCQ-12 score, 6-minute walk distance, feasibility metrics, and a cost-effectiveness analysis. By comparing these two strategies, this pilot trial will provide preliminary estimates of the incremental contribution of ARNI and SGLT2i-to further LVEF recovery and to clinical outcomes-in patients who have already demonstrated spontaneous improvement in cardiac function after correction of the underlying cause, and will inform the design of a subsequent confirmatory trial addressing whether these agents are truly necessary in this population.