Efficacy and Safety of Baxdrostat in the Management of Uncontrolled Hypertension: A Systematic Review and Meta-Analysis

BACKGROUND: Uncontrolled hypertension remains challenging. This meta-analysis evaluated baxdrostat, a selective aldosterone synthase inhibitor, in patients with uncontrolled hypertension, focusing on dose-response for blood pressure (BP) reduction. METHODS: We searched databases through March 2026 for randomized controlled trials (RCTs) comparing baxdrostat with placebo in patients with uncontrolled hypertension. Subgroup analysis used a 2 mg/day cutoff; continuous dose-response meta-analysis was performed for seated systolic BP. RESULTS: Five RCTs were included. Compared with placebo, baxdrostat was associated with a greater reduction in seated systolic BP (mean difference: -6.25 mm Hg; 95% CI: -8.75 to -3.74), seated diastolic BP (mean difference: -2.92 mm Hg; 95% CI: -4.41 to -1.42), 24-hour ambulatory systolic BP (mean difference: -14.38 mm Hg; 95% CI: -17.21 to -11.54), and mean nocturnal systolic BP (mean difference: -13.19 mm Hg; 95% CI: -16.46 to -9.91). The BP control rate (defined as the proportion of patients achieving a post-treatment seated systolic BP < 130 mm Hg) was higher with baxdrostat (relative risk [RR]: 1.74; 95% CI: 1.23 to 2.46). Serum aldosterone was reduced (mean difference: -3.49 ng/dL; 95% CI: -4.30 to -2.69). Hyperkalemia risk was elevated (RR: 5.59; 95% CI: 3.47 to 9.02). Both low- (<2 mg) and high-dose (≥2 mg) baxdrostat lowered systolic/diastolic BP, but only high-dose improved BP control rate. Dose-response analysis showed a linear relationship: each 1 mg increase reduced seated systolic BP by 3.31 mm Hg. CONCLUSION: Baxdrostat is effective for uncontrolled hypertension with a linear dose-response effect, but led to an increased risk of hyperkalemia.