Design and rationale of the EMPagliflozin after Aortic Valve Replacement (EMPAVR) study: A randomized clinical trial

INTRODUCTION: Left ventricular (LV) hypertrophy and dysfunction secondary to aortic stenosis (AS) are key components of the disease's underlying pathophysiology. Previous trials suggest that up to 1/3 of patients do not benefit symptomatically after aortic valve replacement (AVR), which could be explained by insufficient LV remodeling. Sodium‒glucose cotransporter-2 (SGLT2) inhibitors are effective in heart failure (HF) and have been shown to improve LV remodeling (change in LV mass). METHODS: The EMPAVR study is an investigator-initiated, randomized, placebo-controlled, and double-blinded trial comparing the effect of empagliflozin to placebo in patients with severe and symptomatic AS undergoing transcatheter aortic valve implantation (TAVI). The primary outcome for the EMPAVR trial is the difference in LV mass indexed to body surface area (measured by cardiac CT) from pre-AVR to 6 months post-AVR. Patients are randomized in a 1:1 ratio to 180 days of treatment. DISCUSSION: To the best of our knowledge, the EMPAVR study is the first placebo-controlled trial investigating the effects of SGLT2 inhibition in patients following TAVI because of AS. The EMPAVR study has the potential to pave the way for treatment of the LV in valvular heart disease and may help patients worldwide and expand our understanding of aortic stenosis. TRIAL REGISTRATION: The EMPAVR study was registered in December 2024 (Clinical Trial Registration number: NCT06171802) before enrollment of the first patient. All patients will provide oral and written informed consent. The EMPAVR study is approved by the Regional Committee on Health Research Ethics and the Danish Medicines Agency.