Delayed Initiation of ARNI and SGLT2i in Heart Failure With Corrected Aetiology (DELAY-HF), Pilot Study

研究药物 / 干预措施

Sacubitril / Valsartan、SGLT-2 inhibitor、Sacubitril / Valsartan、SGLT2 Inhibition

申办方

Kyungsub Song

研究简介（原文）

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.

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