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Aims: The effect of uric acid (UA)-lowering therapy with xanthine oxidoreductase (XOR) inhibitors on the development of cardiovascular disease requires further investigation. This study aimed to evaluate the long-term effects of febuxostat on arterial stiffness, focusing on liver function., Methods: The PRIZE study involved random assignment of patients with asymptomatic hyperuricemia to receive either add-on febuxostat treatment (febuxostat group) or non-pharmacological treatment (control group). Of the 514 participants, 23 and 14 patients in the febuxostat and control groups, respectively, underwent assessment of arterial stiffness using the cardio-ankle vascular index (CAVI). The participants in each group were further grouped on the basis of their baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels (above or below the media value or 30 U/L). The primary endpoint was the change in the CAVI from baseline to 12 and 24 months., Results: Overall, no significant differences were found between the control and febuxostat groups in the least-squares mean estimates of changes in CAVI at 24 months (mean between-group difference, -0.41 [95% CI, -1.05 to 0.23]; p=0.204). However, there were significant differences in participants with higher baseline ALT or AST levels above 30 U/L at 24 months (mean between-group difference, -1.12 [95% CI, -2.23 to -0.01]; p=0.048 for ALT ≥ 30 U/L and -1.08 [95% CI, -2.13 to -0.03]; p=0.044 for AST ≥ 30 U/L)., Conclusions: Two-year treatment with febuxostat demonstrated a beneficial effect on CAVI in patients with hyperuricemia and liver dysfunction.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes., Methods: A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values., Results: In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was - 1.07 (95% confidence interval [CI] - 1.29 to - 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight., Conclusions: In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo. Trial registration jRCTs031180120., (© 2024. The Author(s).)