美国克利夫兰医学中心Steven E. Nissen团队研究了Lorundrostat在未控制高血压患者中的疗效和安全性。相关论文于2025年4月23日发表在《新英格兰医学杂志》上。

醛固酮失调有助于高血压。Lorundrostat是一种醛固酮合成酶抑制剂，但其在高血压患者中的有效性和安全性数据有限。

在这项多中心、双盲、随机、安慰剂对照试验中，研究组将接受2 - 5种降压药物治疗且在就诊期间血压测量值为140/90 mm Hg或更高的参与者分配给接受标准化降压治疗方案3周的患者。随后，24小时平均动态血压为130/80毫米汞柱或更高的参与者被分配接受安慰剂，稳定剂量为每天50毫克的Lorundrostat（稳定剂量组），或起始剂量为每天50毫克的Lorundrostat，如果4周后收缩压为130毫米汞柱或更高，则增加到每天100毫克（剂量调整组）。主要终点是从基线到第12周的24小时平均收缩压变化，评估为每个Lorundrostat组与安慰剂的最小二乘平均差异（安慰剂调整的变化）。关键次要终点是24小时平均收缩压从基线到第4周的变化，评估为联合Lorundrostat组的安慰剂调整变化。

共有285名参与者接受随机分组；94人被分配到稳定剂量组，96人被分配到剂量调整组，95人被分配到安慰剂组。平均年龄为60岁，150名参与者（53%）是黑人。12周后，稳定剂量组24小时平均收缩压的最小二乘平均变化为15.4 mm Hg，剂量调整组为13.9 mm Hg，安慰剂组为7.4 mm Hg。稳定剂量组经安慰剂调整后的血压变化为- 7.9毫米汞柱（97.5%置信区间，- 13.3至- 2.6），剂量调整组为- 6.5毫米汞柱（97.5%置信区间，- 11.8至- 1.2）。经安慰剂调整后，联合Lorundrostat组从基线到第4周的24小时平均收缩压变化为- 5.3 mm Hg （95% CI, - 8.4至- 2.3）。稳定剂量组有5名（5%）参与者钾水平高于6.0 mmol / l，剂量调整组有7名（7%）参与者钾水平高于6.0 mmol / l，安慰剂组没有参与者钾水平高于6.0 mmol / l。

研究结果表明，在未控制和治疗难治性高血压患者中，Lorundrostat比安慰剂更能降低24小时平均血压。

附：英文原文

Title: Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension

Author: Luke J. Laffin, Branko Kopjar, Carrie Melgaard, Kathy Wolski, Jessica Ibbitson, Shivani Bhikam, Matthew R. Weir, Elizabeth O. Ofili, Reena Mehra, James M. Luther, Debbie L. Cohen, Ashish Sarraju, Michael J. Wilkinson, John M. Flack, David Rodman, Steven E. Nissen

Issue&Volume: 2025-04-23

Abstract:

BACKGROUND

Aldosterone dysregulation contributes to hypertension. Lorundrostat is an aldosterone synthase inhibitor, but data on its efficacy and safety in patients with hypertension are limited.

METHODS

In this multicenter, double-blind, randomized, placebo-controlled trial, we assigned participants who were receiving two to five antihypertensive medications and had a blood-pressure measurement of 140/90 mm Hg or higher obtained during an office visit to undergo a standardized antihypertensive regimen for 3 weeks. Subsequently, participants with an average 24-hour ambulatory blood pressure of 130/80 mm Hg or higher were assigned to receive placebo, lorundrostat at a stable dose of 50 mg daily (the stable-dose group), or lorundrostat at a starting dose of 50 mg daily, with an increase to 100 mg daily if systolic blood pressure was 130 mm Hg or higher after 4 weeks (the dose-adjustment group). The primary end point was the change in 24-hour average systolic blood pressure from baseline to week 12, assessed as the least-squares mean difference from placebo (the placebo-adjusted change) in each lorundrostat group. A key secondary end point was the change in 24-hour average systolic blood pressure from baseline to week 4, assessed as the placebo-adjusted change in the combined lorundrostat groups.

RESULTS

A total of 285 participants underwent randomization; 94 were assigned to the stable-dose group, 96 to the dose-adjustment group, and 95 to the placebo group. The mean age was 60 years, and 150 participants (53%) were Black. After 12 weeks, the least-squares mean change in 24-hour average systolic blood pressure was 15.4 mm Hg in the stable-dose group, 13.9 mm Hg in the dose-adjustment group, and 7.4 mm Hg in the placebo group. The placebo-adjusted change in blood pressure was 7.9 mm Hg (97.5% confidence interval [CI], 13.3 to 2.6) in the stable-dose group and 6.5 mm Hg (97.5% CI, 11.8 to 1.2) in the dose-adjustment group. The placebo-adjusted change in 24-hour average systolic blood pressure from baseline to week 4 in the combined lorundrostat groups was 5.3 mm Hg (95% CI, 8.4 to 2.3). A potassium level above 6.0 mmol per liter occurred in 5 participants (5%) in the stable-dose group, 7 participants (7%) in the dose-adjustment group, and no participants in the placebo group.

CONCLUSIONS

Lorundrostat was associated with greater reductions in 24-hour average blood pressure than placebo in participants with uncontrolled and treatment-resistant hypertension.

DOI: NJ202504230000001

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2501440