高血圧治療薬バクスドロスタットの有効性と安全性：3つの第2/3相ランダム化比較試験の系統的レビューとメタアナリシス

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 = 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 = 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.