Safety of esaxerenone (CS-3150) and its impacts on blood pressure and renal function: A systematic review and meta-analysis.

Background: The safety and efficacy of esaxerenone (ESAX), a novel nonsteroidal mineralocorticoid receptor antagonist, remain insufficiently explored in systematic reviews and meta-analyses (SR/MA). This SR/MA aimed to investigate the safety and effects of ESAX on blood pressure (BP) and renal function.

Methods: Multiple databases and registers were systematically searched to identify randomized controlled trials and real-world studies evaluating the safety and efficacy of ESAX in various conditions. The primary outcome was the risk of adverse events (AEs); secondary outcomes included its effects on BP and renal parameters.

Results: This SR/MA included 22 studies (N = 4699); 6 studies (5 randomized controlled trials and one retrospective study; n = 3211) with comparator groups were meta-analyzed. While more subjects on ESAX, especially at higher doses, experienced drug-related AEs (risk ratio [RR] 1.77) and discontinued due to these AEs (RR 6.75) compared to placebo, the number of subjects with any or serious AEs and drug-related serious AEs was similar between the 2 groups. Higher doses of ESAX were associated with increased risks of rising serum potassium levels (RR 3.30) and drug discontinuation related to these increases (RR 5.71) compared to the placebo. ESAX and active comparators exhibited comparable AEs except for a higher risk (RR 2.87) of increasing serum potassium levels with ESAX. ESAX led to larger decreases in estimated glomerular filtration rate and urine albumin-creatinine ratio than placebo. ESAX was more effective than placebo and active comparators in lowering office systolic and diastolic BP. ESAX 5 mg showed greater 24-hour average ambulatory BP reductions compared to the active comparators.

Conclusion: ESAX appears reasonably safe, with a modest risk of hyperkalemia and worsening of renal function, and modest efficacy in the treatment of hypertension and albuminuria.