Efficacy and Safety of Aldosterone Synthase Inhibitor Baxdrostat in Resistant Hypertension

Background: Resistant hypertension remains a major unmet clinical challenge despite optimized multidrug therapy. Aldosterone dysregulation plays a central role in its pathophysiology. Baxdrostat, a selective aldosterone synthase inhibitor, has emerged as a novel therapeutic strategy. This meta-analysis evaluated its pooled efficacy and safety across randomized controlled trials. Methods: We conducted a systematic review and random-effects meta-analysis of six randomized controlled trials to evaluate the dose-specific efficacy and safety of baxdrostat in resistant hypertension. Results: A total of six randomized controlled trials comprising 1,319 patients were included in the pooled analysis. Of these, 923 patients received baxdrostat (2 mg, n=399; 1 mg, n=394; 0.5 mg, n=130), and 396 received placebo. The pooled population represented a high-risk resistant hypertension cohort, with a weighted mean age of 61.2 years, mean BMI of 31.7 kg/m 2 , 58.9% male participants, 38.5% with diabetes, and a baseline systolic blood pressure (SBP) of 148.6 mmHg. In the primary efficacy analysis, baxdrostat 2 mg demonstrated a statistically significant placebo-corrected reduction in SBP at 12 weeks (–7.99 mmHg; 95% CI, –12.57 to –3.41; P < 0.001), with moderate to substantial heterogeneity (I 2 = 72.8%). The 1 mg and 0.5 mg doses showed smaller, non-significant reductions in SBP. Regarding safety, baxdrostat was associated with a significantly increased risk of severe hyperkalemia (K > 6.0 mmol/L) compared with placebo (RR 5.46; 95% CI, 1.22-14.47; I 2 = 0.0%), although absolute event rates were low. Conclusions: In patients with resistant hypertension, baxdrostat 2 mg was associated with reduced systolic blood pressure compared with placebo. These findings support selective aldosterone synthase inhibition as a promising therapeutic strategy for resistant hypertension, although careful potassium monitoring remains necessary.