Effects of Henagliflozin on Cardiac Structure in Patients with Heart Failure with Preserved Ejection Fraction Undergoing Dialysis: The HELD-HF Randomized Controlled Trial

Background: Among patients undergoing dialysis, heart failure with preserved ejection fraction (HFpEF) is frequently observed and associated with increased mortality. This study assessed the safety and efficacy of long-term treatment with henagliflozin, a SGLT2 inhibitor, in improving cardiac structure in dialysis patients with HFpEF. Methods: In this randomized, double-blind, placebo-controlled trial (ChiCTR2300073169), patients undergoing haemodialysis or peritoneal dialysis with HFpEF (left ventricular ejection fraction ≥50%) were randomized (1:1) to receive henagliflozin 5 mg once daily or matching placebo, in addition to their usual therapy for 24 weeks.The primary outcome was the between-group difference in change in left ventricular mass index (LVMI) from baseline to week 24, as measured by echocardiography. Secondary outcomes were the changes in left atrial volume index (LAVI), E/e’, e’, N-terminal pro-brain natriuretic peptide (NT-proBNP) after 24 weeks of treatment. Adverse events were recorded until 28 weeks after enrollment. Efficacy analyses were conducted according to the full analysis set. Results: From September 2023 to February 2024, 112 patients were randomized. From baseline to week 24, the mean change in LVMI was –3.38 ± 12.00 g/m2 in the henagliflozin group and 2.08 ± 12.25 g/m2 in the placebo group, with a between-group difference of -5.38 g/m2(95%CI, -10.12 to -0.64 g/m2; p=0.026) (table 1). Sensitivity analysis using last observation carried forward imputation and per protocol populations showed similar results, supporting a significant reduction in LVMI with henagliflozin versus placebo. No differences were observed between the two groups in secondary efficacy outcomes, including LAVI, E/e’, e’, and NT-proBNP. The incidence of adverse events was similar between the two groups (35.7% in the henagliflozin group and 32.1% in the placebo group). Conclusion: Henagliflozin significantly reduced LVMI compared with placebo in patients with HFpEF on dialysis and was safe over 24 weeks of treatment.