A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted the termination of a trial (BEACON study) [63,64]; however, a multicenter phase 2 RDBPCT in Japan enrolled 124 patients with CKD (stage G3 and G4) and T2D without identified risk factors for fluid overload, such as a baseline brain natriuretic peptide (BNP) count >200 pg/mL and prior history of heart failure (TSUBAKI study) [65]. This evidence concerns the gene NPPB and heart failure.