Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension

作者：John M. Flack, Michel Azizi, Jenifer M. Brown, Jamie P. Dwyer, Jakub Fronczek, Erika Jones, Daniel S Olsson, Shira Perl, Hirotaka Shibata, Jiguang Wang, Ulrica Wilderäng, Janet Wittes, Bryan Williams · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2507109 · 被引用次数：134 · 研究领域：Hormonal Regulation and Hypertension、Blood Pressure and Hypertension Studies、Renin-Angiotensin System Studies

BACKGROUND: Aldosterone dysregulation plays an important pathogenic role in hard-to-control hypertension. In several studies, baxdrostat, an aldosterone synthase inhibitor, reduced the seated systolic blood pressure of patients with uncontrolled or resistant hypertension. METHODS: In this phase 3, multinational, double-blind, randomized, placebo-controlled trial, we recruited patients with a seated systolic blood pressure of between 140 mm Hg and less than 170 mm Hg despite the receipt of stable treatment with two antihypertensive medications (uncontrolled hypertension) or three or more such medications (resistant hypertension), including a diuretic. After a 2-week placebo run-in period, we randomly assigned patients with a seated systolic blood pressure of 135 mm Hg or more in a 1:1:1 ratio to receive baxdrostat at a dose of 1 mg, baxdrostat at a dose of 2 mg, or placebo once daily for 12 weeks. The primary end point was the change in seated systolic blood pressure from baseline to week 12. RESULTS: A total of 796 patients underwent randomization and 794 received 1-mg baxdrostat (264 patients), 2-mg baxdrostat (266 patients), or placebo (264 patients) in addition to background therapy. At 12 weeks, the change from baseline in the least-squares mean seated systolic blood pressure was -14.5 mm Hg (95% confidence interval [CI], -16.5 to -12.5) with 1-mg baxdrostat, -15.7 mm Hg (95% CI, -17.6 to -13.7) with 2-mg baxdrostat, and -5.8 mm Hg (95% CI, -7.9 to -3.8) with placebo. The...