Comparative efficacy and safety of aldosterone synthase inhibitors in hypertension: a Bayesian network meta-analysis of randomised controlled rials.

introductionResistant hypertension remains a clinical challenge, often linked to elevated aldosterone levels not fully controlled by mineralocorticoid receptor antagonists. Aldosterone synthase inhibitors (ASIs) directly suppress aldosterone production. We evaluated the efficacy and safety of ASIs for blood pressure (BP) control.

methodWe performed a Bayesian network meta-analysis of randomised controlled trials (RCTs) assessing systolic (SBP) and diastolic BP (DBP) in adults with hypertension. Major databases were searched to 2025. Treatment effects were summarised as mean differences (MDs) with 95% credible intervals (CrIs), and treatment rankings were determined using the surface under the cumulative ranking curve (SUCRA). Risk of bias was assessed using the Cochrane RoB V.2.0 tool.

resultsSix RCTs including 2149 patients were analysed. Risk of bias assessment using RoB2 showed that four studies were at low risk of bias, and two studies had some concerns. Compared with placebo, Baxdrostat 2 mg once a day significantly reduced SBP (MD -11.0 mm Hg; 95% CrI -21.0 to -0.30), while Osilodrostat 1 mg once a day significantly reduced both SBP (MD -7.6 mm Hg; 95% CrI -14.0 to -0.73) and DBP (MD -5.4 mm Hg; 95% CrI -10.0 to -0.69). Lorundrostat 50 mg once a day also reduced SBP significantly (MD -9.1 mm Hg; 95% CrI -17.0 to -1.7). SUCRA rankings confirmed these findings, with Baxdrostat 2 mg once a day ranking highest for SBP reduction (77%) and Osilodrostat 1 mg two times per day ranking highest for DBP reduction (84%). Most adverse events were mild, serious events were infrequent and no drug-related deaths were reported.

conclusionASIs significantly reduce BP with generally favourable tolerability. Osilodrostat and Baxdrostat demonstrated the most consistent efficacy across outcomes, while Lorundrostat also showed potential benefit. This analysis supports the use of ASIs as effective alternatives for BP reduction. Further large-scale and long-term RCTs are needed to validate these findings and guide clinical decision-making. PROSPERO REGISTRATION NUMBER: PROSPERO CRD420251024035.