Efficacy and Safety of Lower- versus Higher-Dose Baxdrostat in Adults with Resistant or Uncontrolled Hypertension, Including a CKD-Enriched Population: An Indirect Subgroup Comparison from Placebo-Controlled Trials — A Systematic Review and Meta-Analysis with GRADE Assessment
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https://doi.org/10.71079/ASIDE.EN.06242026Abstract
Background: Baxdrostat is a selective aldosterone synthase inhibitor proposed for the treatment of resistant and uncontrolled hypertension. However, evidence regarding the safety and efficacy of low doses (0.5–1 mg) and high doses (2–4 mg) compared with placebo remains limited.
Methods: Major bibliographic databases were searched for randomized controlled trials (RCTs) through January 2026. Eligible RCTs compared baxdrostat with placebo. Pooled effect estimates were calculated using mean difference (MD) or risk ratio (RR) with 95% confidence intervals (CIs).
Results: Three RCTs involving patients with resistant or uncontrolled hypertension were included. Baxdrostat significantly reduced systolic blood pressure at low dose [MD: −7.81 mmHg (95% CI: −10.28, −5.33); p<0.001] and high dose [MD: −9.85 mmHg (95% CI: −12.02, −7.69); p<0.001]. Diastolic blood pressure was also significantly reduced at low dose [MD: −2.99 mmHg (95% CI: −5.11, −0.87); p=0.006] and high dose [MD: −4.18 mmHg (95% CI: −5.50, −2.86); p<0.001]. Baxdrostat decreased serum aldosterone and eGFR and increased plasma renin activity, serum potassium, adverse events, and hyperkalemia risk.
Conclusions: Compared with placebo, baxdrostat lowered systolic and diastolic blood pressure in adults with resistant or uncontrolled hypertension, including a CKD-enriched population. The apparent lack of a dose-response difference is based on indirect subgroup analyses of only three trials and should be considered hypothesis-generating rather than evidence of dose equivalence. Hyperkalemia occurred more frequently with baxdrostat, while other safety outcomes remained imprecise. Larger head-to-head dose-comparison trials are needed.
Keywords:
Baxdrostat, Aldosterone synthase inhibitor, Resistant hypertension, Uncontrolled hypertension, Meta-analysisReferences
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Data Availability Statement
All data extracted from the included trials are reported in this article and its supplementary information files. To support independent reproduction, the study-level extracted dataset (per-trial means, standard deviations, event counts, and arm-level sample sizes for every outcome reported here) and the R analysis script used to generate every pooled estimate, forest plot, Baujat plot, and GRADE judgment have been made available as a supplementary computational appendix named “R analysis”
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Copyright (c) 2026 Ahmed L Youseif, Mohamed Eldahrawy, Abdallah Al Ghnaimat, Alaa Ashraf Mohamed, Mohamed Nabil Hamouda, Karim A Khalil, Ahmed F Younis
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Article history
- Received
- 7 Mar 2026
- Received in revised form
- 16 May 2026
- Accepted
- 7 Jun 2026
- Published
- 24 Jun 2026
