Hundemer GL, et al. - Here, the physicians examined the risk of incident cardiovascular events in patients with primary aldosteronism treated with mineralocorticoid receptor (MR) antagonists compared with patients with essential hypertension. Among primary aldosteronism, the current practice of MR antagonist therapy was correlated 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 could mitigate this excess risk.

Methods

• A cohort study was performed using patients from a research registry from Brigham and Women's Hospital, Massachusetts General Hospital, and their affiliated partner hospitals.
• Using International Classification of Disease, 9th and 10th Revision codes, the physicians identified patients with primary aldosteronism, who were evaluated between the years 1991-2016 and were at least 18 years of age.
• Patients who underwent surgical adrenalectomy, had a previous cardiovascular event, were not treated with MR antagonists, or had no follow-up visits after study entry, were excluded.
• They identified a population with essential hypertension that was frequency matched by the decade of age at study entry, from the same registry.
• Patient cohort data was extracted and collated into a de-identified database.
• An incident cardiovascular event was the primary outcome, defined as a composite of incident myocardial infarction or coronary revascularization, hospital admission with congestive heart failure, or stroke, which was evaluated using adjusted Cox regression models.
• The individual components of the composite cardiovascular outcome, as well as incident atrial fibrillation, incident diabetes, and death were included as the secondary outcomes.

Results

• From the registry, the physicians identified 602 eligible patients with primary aldosteronism treated with MR antagonists and 41,853 age-matched patients with essential hypertension.
• Throughout the study, the 2 groups of patients had similar cardiovascular risk profiles and blood pressure.
• In patients with primary aldosteronism on MR antagonists, the incidence of cardiovascular events was higher 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).
• Moreover, 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]) were observed in patients with primary aldosteronism.
• The excess risk for cardiovascular events and mortality, compared with essential hypertension, 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).
• On the other hand, patients who were treated with higher MR antagonist doses and had unsuppressed renin (≥1 μg/L per h) had no significant excess risk.