Spironolactone and coronary atherosclerotic plaque modulation: insights from a serial coronary computed tomography angiography cohort study

Abstract While preclinical evidence suggests spironolactone inhibits atherosclerosis, clinical data remain inconclusive. This serial coronary computed tomography angiography (CCTA) cohort study evaluated the association between spironolactone and coronary atherosclerotic plaque progression. Among 3,632 patients with serial CCTA scans (median interscan interval: 3.5 years), 349 received spironolactone and 3,283 did not. After 1:4 propensity score matching (344 spironolactone users vs. 1,376 non-users), Cox regression analyses revealed no significant reduction in plaque progression with spironolactone. For maximal stenosis severity (MAX), the hazard ratio (HR) was 0.94 (95% CI: 0.76–1.16, p = 0.566); for segment involvement score (SIS), HR was 1.05 (95% CI: 0.88–1.26, p = 0.560); and for segment stenosis score (SSS), HR was 1.07 (95% CI: 0.91–1.26, p = 0.434). Event rates for all endpoints were comparable between groups. These findings suggest that spironolactone lacks a clinically significant anti-atherosclerotic effect in modulating coronary plaque progression, underscoring the need for further investigation into its mechanistic role and therapeutic utility in cardiovascular disease.