Cureus. 2026 Feb 23;18(2):e104160. doi: 10.7759/cureus.104160. eCollection 2026 Feb.
ABSTRACT
Resistant hypertension (RH) is characterized by persistently elevated blood pressure despite treatment with three or more antihypertensive agents, including a diuretic. Excess production of aldosterone is a key contributor to this condition. Baxdrostat is a novel, highly selective aldosterone synthase inhibitor that reduces aldosterone synthesis without affecting cortisol production. This systematic review and meta-analysis evaluated the efficacy and safety of baxdrostat in patients with RH. Following a preregistered PROSPERO protocol (CRD420251038564) and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus through December 2025 for randomized controlled trials (RCTs) comparing baxdrostat with placebo in adults with RH. Primary efficacy outcomes were changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Primary safety outcomes included adverse events and hyperkalemia. Data were pooled using random-effects models. Risk of bias was assessed using Cochrane RoB 2, and evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Three RCTs (the BrigHTN trial, the BaxHTN trial, and the HALO trial) involving 1,318 patients were included. Pooled analysis demonstrated that baxdrostat significantly reduced SBP compared with placebo (mean difference (MD): -7.93 mmHg; 95% CI: -12.64 to -3.21; I² = 84%; high-certainty evidence). DBP was also significantly reduced (MD: -3.49 mmHg; 95% CI: -5.18 to -1.81; I² = 68%; high certainty). Dose-dependent effects were observed, with greater reductions at 2 mg. There was no significant difference in overall adverse events (risk ratio (RR): 1.05; 95% CI: 0.95-1.16) or serious adverse events (RR: 1.10; 95% CI: 0.70-1.73). However, baxdrostat increased hyperkalemia risk (serum potassium ≥5.5 mmol/L) (RR: 2.87; 95% CI: 1.61-5.11; moderate certainty), although most cases were mild and manageable. Baxdrostat provides clinically meaningful blood pressure reductions in RH with a favorable safety profile. Its highly selective, cortisol-sparing mechanism offers a promising therapeutic option that directly targets aldosterone dysregulation in RH.
PMID:41909295 | PMC:PMC13019122 | DOI:10.7759/cureus.104160