巴多司他治疗未控制及难治性高血压的疗效与安全性

Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension.

作者信息

Flack John M, Azizi Michel, Brown Jenifer M, Dwyer Jamie P, Fronczek Jakub, Jones Erika S W, Olsson Daniel S, Perl Shira, Shibata Hirotaka, Wang Ji-Guang, Wilderäng Ulrica, Wittes Janet, Williams Bryan

机构信息

Departments of Medicine and Population Science and Policy, Division of General Internal Medicine, Hypertension Section, Southern Illinois University, Springfield.

Université Paris Cité, INSERM Centre d'Investigation Clinique 1418, Paris.

出版信息

N Engl J Med. 2025 Aug 30. doi: 10.1056/NEJMoa2507109.

DOI:10.1056/NEJMoa2507109

PMID:40888730

Abstract

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 estimated difference from placebo (placebo-corrected difference) was -8.7 mm Hg (95% CI, -11.5 to -5.8) with 1-mg baxdrostat and -9.8 mm Hg (95% CI, -12.6 to -7.0) with 2-mg baxdrostat (P<0.001 for both comparisons). A potassium level of more than 6.0 mmol per liter was reported in 6 patients (2.3%) with 1-mg baxdrostat, in 8 patients (3.0%) with 2-mg baxdrostat, and in 1 patient (0.4%) with placebo.

CONCLUSIONS

Among patients with uncontrolled or resistant hypertension, the addition of baxdrostat to background therapy resulted in a significantly lower seated systolic blood pressure at 12 weeks than placebo. (Funded by AstraZeneca and others; BaxHTN ClinicalTrials.gov number, NCT06034743.).

摘要

背景

醛固酮失调在难以控制的高血压中起重要致病作用。在多项研究中，醛固酮合酶抑制剂巴曲司他降低了未控制或难治性高血压患者的坐位收缩压。

方法

在这项3期、多国、双盲、随机、安慰剂对照试验中，我们招募了尽管接受了两种抗高血压药物（未控制的高血压）或三种或更多此类药物（难治性高血压）包括利尿剂的稳定治疗，但坐位收缩压仍在140 mmHg至低于170 mmHg之间的患者。在为期2周的安慰剂导入期后，我们将坐位收缩压为135 mmHg或更高的患者按1:1:1的比例随机分配，分别接受每日一次剂量为1 mg的巴曲司他、剂量为2 mg的巴曲司他或安慰剂，共12周。主要终点是从基线到第12周坐位收缩压的变化。

结果

共有796例患者进行了随机分组，794例患者在接受背景治疗的基础上，分别接受1 mg巴曲司他（264例患者）、2 mg巴曲司他（266例患者）或安慰剂（264例患者）治疗。在第12周时，1 mg巴曲司他组的最小二乘均值坐位收缩压较基线变化为-14.5 mmHg（95%置信区间[CI]，-16.5至-12.5），2 mg巴曲司他组为-15.7 mmHg（95%CI，-17.6至-13.7），安慰剂组为-5.8 mmHg（95%CI，-7.9至-3.8）。与安慰剂相比的估计差异（安慰剂校正差异），1 mg巴曲司他组为-8.7 mmHg（95%CI，-11.5至-5.8），2 mg巴曲司他组为-9.8 mmHg（95%CI，-12.6至-7.0）（两组比较P均<0.001）。1 mg巴曲司他组有6例患者（2.3%）、2 mg巴曲司他组有8例患者（3.0%）、安慰剂组有1例患者（0.4%）报告血钾水平高于6.0 mmol/L。