In patients with primary aldosteronism (PA), long-term cardiovascular and mortality outcomes after adrenalectomy vs mineralocorticoid receptor antagonist (MRA) have not been compared yet. We aim to compare the clinical outcomes of these patients after treatment.

A systematic review and meta-analysis was conducted by searching PubMed, Cochrane library, and Embase from no start date restriction to 18 December 2021. Our composite primary outcomes were long-term all-cause mortality and/or major adverse cardiovascular events (MACE), including coronary artery disease (CAD), stroke, arrhythmia, and congestive heart failure. We adopted the random-effects model and performed subgroup analyses, meta-regression, and trial sequential analysis (TSA).

A total of 9 studies with 8473 adult patients with PA (≥18 years) were enrolled. A lower incidence of composite primary outcomes was observed in the adrenalectomy group (odds ratio (OR): 0.46 (95% CI: 0.38-0.56), P < 0.001). We found a lower incidence of all-cause mortality (OR: 0.33 (95% CI: 0.15-0.73), P = 0.006) and MACE (OR: 0.55, (95% CI: 0.40-0.74), P = 0.0001) in the adrenalectomy group. The incidence of CAD (OR: 0.33 (95% CI: 0.15-0.75), P = 0.008), arrhythmias (OR: 0.46 (95% CI: 0.27-0.81), P = 0.007), and congestive heart failure (OR: 0.52 (95% CI: 0.33-0.81), P = 0.004) was also lower in adrenalectomy group. The metaregression showed patient's age may attenuate the benefits of adrenalectomy on composite primary outcomes (coefficient: 1.084 (95% CI: 1.005-1.169), P = 0.036). TSA demonstrated that the accrued sample size and effect size were sufficiently large to draw a solid conclusion, and the advantage of adrenalectomy over MRA was constant with the chronological sequence.

In conclusion, adrenalectomy could be preferred over MRA for patients with PA in reducing the risk of all-cause mortality and/or MACE and should be considered as the treatment of choice. That patients with PA could get less benefit from adrenalectomy as they age warrants further investigation.