Dose–response efficacy and safety of the aldosterone synthase inhibitor baxdrostat in resistant hypertension: a systematic review and network meta-analysis

Resistant hypertension (RH) is associated with increased cardiovascular morbidity and mortality, while available treatment options are often limited by adverse effects and inadequate blood pressure control. Because aldosterone plays a key role in RH pathophysiology, aldosterone synthase inhibition has emerged as a promising therapeutic approach. This study evaluated the efficacy and safety of different baxdrostat doses in patients with RH. This PRISMA-NMA-compliant systematic review and network meta-analysis was prospectively registered with PROSPERO. PubMed, Cochrane CENTRAL, Embase, Scopus, and ScienceDirect were searched through April 2026 for randomized, double-blind, placebo-controlled trials evaluating baxdrostat in adults with RH. A frequentist random-effects network meta-analysis compared baxdrostat doses of 0.5-2 mg with placebo. Four randomized controlled trials comprising 1,535 participants were included. In the NMA, baxdrostat 2 mg and 1 mg significantly reduced seated SBP versus placebo, whereas 0.5 mg was not significant. Direct pairwise analysis confirmed the 2 mg effect, while the 1 mg direct estimate was not statistically significant, indicating some sensitivity to the analytical approach. Both 1 mg and 2 mg reduced ambulatory SBP, but neither dose was significantly superior to the other. Only 2 mg significantly increased urinary renin. Baxdrostat 1 mg and 2 mg significantly increased overall adverse events and hyperkalemia, whereas serious adverse events were not significantly increased. Baxdrostat 2 mg produced the most consistent short-term seated SBP reduction, whereas evidence for 1 mg was less consistent across analytical approaches. Ambulatory rankings did not establish superiority of 1 mg over 2 mg, and both higher doses significantly increased hyperkalemia risk. Larger, longer-term studies are required.