Cardiovascular events with esaxerenone versus spironolactone in hypertension

Mineralocorticoid receptor antagonists (MRAs) exhibit distinct pharmacologic profiles, yet their differential clinical relevance remains underexplored. This study assessed cardiovascular prevention with nonsteroidal esaxerenone (ESAX) relative to steroidal spironolactone (SPL) in hypertensive populations. From a nationwide claims database, we identified individuals with hypertension who newly initiated ESAX or SPL. Cardiovascular disease (CVD) was defined as a composite outcome of heart failure, atrial fibrillation, myocardial infarction, or stroke. We compared the incidence between the two groups using propensity score-based overlap weighting. A total of 5,960 individuals were included in the analysis: 3,776 who initiated ESAX and 2,184 SPL. The median (interquartile range) age was 73 (67-79) years, and 2,977 (50%) were men. The median estimated glomerular filtration rate was 66 (56-76) ml/min/1.73 m², and 1,210 (20%) had diabetes mellitus. During a median follow-up of 451 (208-816) days, 1,060 CVD events were observed. In weighted Cox regression, ESAX use was associated with a lower likelihood of developing CVD compared with SPL (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.70-0.91). This finding was mainly attributable to risk reductions in heart failure (HR, 0.80; 95% CI, 0.70-0.92) and atrial fibrillation (HR, 0.63; 95% CI, 0.44-0.91), with associations for myocardial infarction (HR, 0.97; 95% CI, 0.48-1.96) and stroke (HR, 0.88; 95% CI, 0.64-1.19) being non-significant. Our analysis showed a reduced incidence of CVD associated with ESAX, pointing to potential drug-specific differences within the MRA class.