Effects and Safety of Henagliflozin on Cardiac Structure in Dialysis Patients with Heart Failure with Preserved Ejection Fraction

Background Few effective drug treatments exist for dialysis patients with heart failure with preserved ejection fraction (HFpEF). This study aimed to evaluate the effects of henagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on cardiac structure, and its safety in such population. Methods In this multicenter, randomized, double-blind, placebo-controlled trial, dialysis patients with HFpEF were randomly assigned (1:1) to receive henagliflozin or placebo for 24 weeks. All enrolled participants received conventional therapy. The primary outcome was the change in left ventricular mass index (LVMI) from baseline to week 24. The secondary outcomes were the changes in left atrial volume index (LAVI), E/e’, e’, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and safety. Efficacy was assessed in the intention-to-treat population. Safety was assessed in the as-treated population. Analysis of covariance was used to assess treatment effects. Results A total of 112 participants were randomly assigned to the henagliflozin group (n=56) and the placebo group (n=56). Of these, 60 participants were on hemodialysis and 52 were on peritoneal dialysis. From baseline to week 24, henagliflozin resulted in a greater reduction inleast-squares mean (±SE) change in LVMI than placebo (-3.27±1.71 g/m 2 versus 2.01±1.69 g/m 2 ), with a between-group difference of -5.27 g/m 2 (95% confidence interval [CI], -10.02 to -0.53 g/m 2 ; P =0.03). In the prespecified subgroup by dialysis modality, the between-group difference in LVMI change from baseline to week 24 was -6.86 g/m 2 (95% CI, -14.02 to 0.29 g/m 2 ) among participants on peritoneal dialysis and -3.91 g/m 2 (95% CI, -10.45 to 2.63 g/m 2 ) among participants on hemodialysis. No between-group differences in secondary outcomes were observed. The incidence of adverse events was similar between the henagliflozin and placebo groups (36% vs. 34%). Conclusions Henagliflozin was associated with a greater reduction in LVMI at week 24 compared with placebo and was tolerable in dialysis patients with HFpEF. Larger studies are needed to confirm the LVMI-lowering effect of henagliflozin.