Comparing adrenalectomy and mineralocorticoid receptor antagonists in primary aldosteronism: a systematic review and meta-analysis of cardiac outcomes

Abstract Background Primary aldosteronism (PA) is the leading potentially curable cause of secondary hypertension and is strongly associated with adverse cardiovascular outcomes, particularly left ventricular hypertrophy (LVH) and myocardial remodeling. Purpose Although both adrenalectomy and medical therapy with mineralocorticoid receptor antagonists (MRAs) are established treatments, their long-term comparative effects on cardiac structure and function remain debated. Methods A systematic search of MEDLINE and Embase was conducted for studies published up to November 2024. Prospective and retrospective clinical trials with a minimum follow-up of 6 months were included if they reported changes in LVM and other predefined remodeling cardiac outcomes in PA patients undergoing adrenalectomy or medical therapy. Data extraction was performed independently by two reviewers and analyzed using random effects and fixed-effect models. Risk-of-bias assessments were conducted using standardized tools. The primary outcome was the percentage reduction in LVM. Secondary outcomes included changes in LVH relative ratio (RR), left ventricular remodeling indices, and systolic and diastolic function parameters. Results Seventeen studies (n = 1,696 patients; 49% adrenalectomy, 51% MRA therapy) were included. Patients undergoing adrenalectomy exhibited a significantly greater reduction in indexed LVM (mean difference: –3.5%; 95% CI: –4.9% to –2.2%; P 0.0001) compared to medical therapy. Adrenalectomy was also associated with a 32% reduction in RR (95% CI: 41% to 23%; P = 0.03), whereas medical therapy achieved a 19% reduction (95% CI: 28% to 9%; P = 0.38). Meta-regression analysis identified shorter hypertension duration as a key predictor of greater LVM regression following adrenalectomy, whereas high sodium intake attenuated the beneficial effects of MRAs on cardiac remodeling. Systolic function, as assessed by left ventricular ejection fraction, showed a slight but significant improvement after adrenalectomy, while global longitudinal strain remained unchanged across treatment groups. Conclusions Adrenalectomy achieves superior long-term regression of LVM and more effective reversal of LVH compared to MRAs in patients with PA. These findings reinforce current clinical guidelines that advocate adrenalectomy as the preferred first-line treatment for unilateral PA, given its ability to directly eliminate aldosterone excess at its source. Future research should focus on the comparative efficacy of adrenalectomy versus emerging nonsteroidal MRAs and aldosterone synthase inhibitors in attenuating aldosterone-induced cardiac remodeling, refining personalized therapeutic strategies, and optimizing long-term cardiovascular outcomes in patients with PA.