AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Blood Pressure-Lowering Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension: A Systematic Review, Meta-Analysis, and Dose-Response Analysis with Trial Sequential Analysis
By Warraich K, Rasool MM, Murtaza M et al.
Background: Resistant and uncontrolled hypertension carries high cardiovascular and renal risk, with aldosterone excess as a central driver. Baxdrostat, a highly selective aldosterone synthase (CYP11B2) inhibitor, was recently approved, yet prior syntheses pooled only a subset of trials or combined agents. We provide the first synthesis of the complete five-trial baxdrostat program using dose-response modeling and trial sequential analysis (TSA). Methods: Per PRISMA with PROSPERO registration (CRD420261281409), five databases were searched through May 2026 for RCTs of baxdrostat versus placebo in resistant or uncontrolled hypertension. Twelve outcomes were pooled by random-effects meta-analysis (REML, Hartung-Knapp), with one-stage dose-response modeling, TSA against pre-specified minimal clinically important differences (MCIDs), and GRADE. Results: Five RCTs (1,730 participants, 11 arms) were included. Baxdrostat reduced seated SBP (–6.71 mmHg; 95% CI –9.43 to –3.99; p<0.001) and DBP (–3.02 mmHg; 95% CI –4.50 to –1.55; p=0.001), with a linear gradient of 3.61 mmHg per 1 mg and the largest effect at 2 mg (–9.14 mmHg). Twenty-four-hour ambulatory SBP fell by 14.31 mmHg (95% CI –16.83 to –11.78; p=0.002; I ² =0%), though based on three comparisons and considered supportive. The TSA-adjusted seated SBP estimate (–5.24 mmHg) exceeded the 5 mmHg MCID, confirming statistically firm, clinically relevant efficacy. More patients achieved SBP <130 mmHg (RR 1.51; 95% CI 1.05-2.17; p=0.031). Serum aldosterone fell by 3.86 ng/dL with a plateau near 1 mg, while plasma renin activity rose by 5.49 ng/mL/h. Baxdrostat increased hyperkalemia (RR 4.39; 95% CI 2.05-9.40; p=0.002) and hyponatremia (RR 3.10; 95% CI 1.65-5.83; p=0.008), both dose-dependent, with a mean eGFR decline of 5.61 mL/min/1.73 m ² . Serious adverse events were not significantly increased. GRADE certainty ranged from low to high. Conclusions: Baxdrostat produces significant, dose-dependent reductions in seated and ambulatory blood pressure with a tolerable short-term profile dominated by monitorable electrolyte disturbances. Aldosterone suppression plateaued at lower doses, whereas blood pressure reduction continued at higher doses, suggesting that mechanisms beyond circulating aldosterone suppression may contribute to blood pressure lowering.