Aldosterone synthase inhibitors (ASIs) have emerged as a potential therapeutic option for patients with uncontrolled or treatment-resistant hypertension by targeting CYP11B2, the enzyme involved in aldosterone synthesis. A systematic review and network meta-analysis presented at the ESH 2026 evaluated the efficacy and safety of ASIs in adults with uncontrolled or treatment-resistant hypertension. Randomized controlled trials comparing ASIs with placebo were identified through searches of PubMed, Scopus, Cochrane, and Web of Science through September 2025.
The analysis included five randomized controlled trials involving 2,639 patients across 29 countries. The primary endpoint was change in office systolic blood pressure (OSBP). Secondary endpoints included office diastolic blood pressure (ODBP), ambulatory systolic blood pressure (ASBP), serum aldosterone, plasma renin activity (PRA), potassium and sodium levels, and estimated glomerular filtration rate (eGFR).
Findings
- Aldosterone synthase inhibitors were associated with greater reductions in office systolic blood pressure compared with placebo (mean difference [MD], –8.58 mmHg; 95% confidence interval [CI], –9.91 to –7.25; I²=0%).
- Baxdrostat 2 mg demonstrated the greatest reduction in office systolic blood pressure (MD, –10.32 mmHg; 95% CI, –13.50 to –7.14).
- Baxdrostat 2 mg also achieved the greatest reductions in office diastolic blood pressure (MD, –4.27 mmHg) and ambulatory systolic blood pressure (MD, –17.00 mmHg).
- Treatment with ASIs reduced serum aldosterone levels and increased PRA.
- ASI therapy was associated with lower eGFR (MD, –6.88 mL/min/1.73 m²), while dose-dependent renal and electrolyte effects were most pronounced with lorundrostat 100 mg.
The findings suggest that ASIs effectively lowered blood pressure in patients with uncontrolled or treatment-resistant hypertension, with baxdrostat 2 mg demonstrating the most favorable efficacy profile in this analysis. Renal function and electrolyte monitoring remain important during therapy, particularly with higher doses.
