Efficacy and Safety of Baxdrostat for Hypertension: A Systematic Review and Meta‐Analysis of Three Phase 2/3 Randomized Controlled Trials
Rahul Falodia, Ehsanullah Alokozay, Mohammad Idrees, Darsh Paghdar, Ali Msheik, Taha Alam, Saeedullah ZadranABSTRACT
Background
Baxdrostat is a selective aldosterone synthase (CYP11B2) inhibitor for treatment‐resistant and uncontrolled hypertension, evaluated in phase 2/3 RCTs.
Objectives
To estimate pooled placebo‐corrected reductions in seated office and ambulatory SBP, characterize the dose–response relationship, assess cortisol selectivity, and quantify hyperkalemia risk.
Methods
We conducted a systematic review and meta‐analysis of phase 2/3 randomized, double‐blind, placebo‐controlled trials of baxdrostat in hypertension, searching MEDLINE/PubMed, EMBASE, ClinicalTrials.gov, and NEJM.org to March 2026. The primary outcome was placebo‐corrected change in seated office SBP, analyzed using random‐effects meta‐analysis (REML) with metafor in R. Risk of bias and certainty were evaluated using Cochrane RoB 2.0 and GRADE, respectively.
Results
Three RCTs (BrigHTN, BaxHTN, Bax24; N = 1285) were included. The pooled seated SBP reduction was −9.44 mmHg (95% CI: −11.09 to −7.79; I 2 = 0.0%), with dose subgroup estimates of −8.57 mmHg (1 mg) and −10.11 mmHg (2 mg) and a clear dose–response in BrigHTN (slope −4.2 mmHg/mg; R 2 = 0.96). Bax24 demonstrated a 24 h ambulatory SBP reduction of −14.0 mmHg (95% CI: −17.2 to −10.8). Serum cortisol was unsuppressed at all doses, while the pooled OR for potassium ≥ 6.0 mmol/L was 5.14 (95% CI: 1.76 to 14.97). GRADE certainty was moderate for seated SBP, low to moderate for ambulatory outcomes, and low for hyperkalemia.
Conclusions
Baxdrostat produces meaningful, selective BP reductions across hypertensive populations. Hyperkalemia is manageable with structured monitoring. Certainty is limited by a few trials, a short follow‐up, and safety imprecision. Long‐term cardiovascular outcome data are needed before guideline incorporation.