Efficacy and Safety of Baxdrostat in Treatment-Resistant and Uncontrolled Hypertension

Introduction: Baxdrostat is a selective aldosterone synthase (CYP11B2) inhibitor evaluated in three phase 2/3 randomized controlled trials (RCTs) for treatment-resistant and uncontrolled hypertension. However, no dedicated quantitative synthesis has characterized its blood pressure-lowering efficacy, dose-response relationships, and safety profile. Research Question: Among patients with treatment-resistant or uncontrolled hypertension, what is the pooled placebo-corrected effect of baxdrostat on seated office and ambulatory systolic blood pressure, what dose-response relationship is observed, does it preserve cortisol selectivity, and what is the risk of clinically significant hyperkalemia? Methods: We conducted a systematic review and meta-analysis of phase 2/3 randomized, double-blind, placebo-controlled trials of baxdrostat in hypertension. MEDLINE/PubMed, EMBASE, ClinicalTrials.gov, and NEJM.org were searched without restriction to March 2026. The primary outcome was placebo-corrected change in seated office SBP. Random-effects meta-analysis (REML) was performed using the metafor package in R. Risk of bias was assessed using Cochrane RoB 2.0. Results: Three RCTs (BrigHTN, BaxHTN, Bax24; N = 1,285; five study arms) were included. The pooled placebo-corrected reduction in seated SBP was –9.44 mmHg (95% CI: –11.09 to –7.79; I 2 = 0.0%). Dose subgroup estimates were –8.57 mmHg (1 mg) and –10.11 mmHg (2 mg). A clear dose-response relationship was observed in BrigHTN (slope –4.2 mmHg/mg; R 2 = 0.96). Bax24 demonstrated a 24-hour ambulatory SBP reduction of –14.0 mmHg (95% CI: –17.2 to –10.8). Serum cortisol was not suppressed at any dose in any trial. The pooled odds ratio for potassium ≥6.0 mmol/L was 5.14 (95% CI: 1.76 to 14.97). Conclusions: Baxdrostat produces clinically meaningful, reproducible, and selective reductions in blood pressure across diverse hypertensive populations. While risk for hyperkalemia is increased, it is manageable with monitoring. The evidence certainty is high, however, long-term cardiovascular outcome data are needed before guideline incorporation.