Mineralocorticoid receptor (MR) antagonists are the recommended medical therapy for primary aldosteronism. Whether this recommendation effectively reduces cardiometabolic risk is not well understood. We aimed to investigate the risk of incident cardiovascular events in patients with primary aldosteronism treated with MR antagonists compared with patients with essential hypertension. We identified 602 eligible patients with primary aldosteronism treated with MR antagonists and 41 853 age-matched patients with essential hypertension from the registry. The two groups of patients had comparable cardiovascular risk profiles and blood pressure throughout the study. The incidence of cardiovascular events was higher in patients with primary aldosteronism on MR antagonists than in patients with essential hypertension (56·3 [95% CI 48·8–64·7] vs 26·6 [26·1–27·2] events per 1000 person-years, adjusted hazard ratio 1·91 [95% CI 1·63–2·25]; adjusted 10-year cumulative incidence difference 14·1 [95% CI 10·1–18·0] excess events per 100 people). Patients with primary aldosteronism also had higher adjusted risks for incident mortality (hazard ratio [HR] 1·34 [95% CI 1·06–1·71]), diabetes (1·26 [1·01–1·57]), and atrial fibrillation (1·93 [1·54–2·42]). Compared with essential hypertension, the excess risk for cardiovascular events and mortality was limited to patients with primary aldosteronism whose renin activity remained suppressed (<1 μg/L per h) on MR antagonists (adjusted HR [2·83 [95% CI 2·11–3·80], and 1·79 [1·14–2·80], respectively) whereas patients who were treated with higher MR antagonist doses and had unsuppressed renin (≥1 μg/L per h) had no significant excess risk. The current practice of MR antagonist therapy in primary aldosteronism is associated with significantly higher risk for incident cardiometabolic events and death, independent of blood pressure control, than for patients with essential hypertension. Titration of MR antagonist therapy to raise renin might mitigate this excess risk.
