Dad Allah, Bakht Kinza, Tahir Haris Bin, Arham Muhammad, Goel Anika, Ahmad Malik Maaz, Raza Soban, Qadri Syeda Hafsa, Rathi Diya, Javed Saad, Hamdani Syed Shah Qasim, Arshad Hasnan, Abubakar F N U, Awais Muhammad Nauman, Nizam Muhammad Abdullah
Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Pakistan.
Lahore General Hospital, Lahore, Pakistan.
J Clin Hypertens (Greenwich). 2025 Sep;27(9):e70155. doi: 10.1111/jch.70155.
This systematic review and meta-analysis evaluated the efficacy and safety of lorundrostat in adults with uncontrolled hypertension. Following PRISMA guidelines and PROSPERO registration (CRD420251088503), five databases were systematically searched through July 2025 for randomized controlled trials comparing lorundrostat with placebo in this population. The primary outcome was change in systolic blood pressure (SBP), while secondary outcomes included diastolic blood pressure, severe BP events, and adverse effects. Three RCTs comprising 1568 participants across 10 study arms were included. Lorundrostat significantly reduced 24-h ambulatory SBP (mean difference [MD]: -7.45 mmHg; 95% CI: -12.54 to -2.36; p = 0.0041; p = 0%) and diastolic BP (MD: -3.49 mmHg; 95% CI: -5.56 to -1.41; p = 0.0010; I = 0%). While office SBP showed a non-significant reduction in the primary analysis (MD: -13.55 mmHg; p = 0.077; I = 94%), it became statistically significant in a sensitivity analysis (MD: -9.08 mmHg; p < 0.0001). Lorundrostat also significantly lowered the risk of severely elevated BP events (odds ratio [OR]: 0.37; 95% CI: 0.17-0.81; p = 0.028). Adverse effects included an increased risk of hyperkalemia (OR: 3.22; p < 0.001) and hyponatremia (OR: 2.16; p = 0.037), with no significant difference in serious adverse events between groups. In conclusion, lorundrostat demonstrates significant reductions in both ambulatory and diastolic BP in patients with uncontrolled hypertension, with a generally tolerable safety profile. Hyperkalemia and hyponatremia remain notable risks. Further long-term trials are warranted to validate its sustained efficacy and safety.
本系统评价和荟萃分析评估了洛伦德司他对血压控制不佳的成年人的疗效和安全性。遵循PRISMA指南和PROSPERO注册要求（CRD420251088503），系统检索了5个数据库，截至2025年7月，查找在该人群中比较洛伦德司他与安慰剂的随机对照试验。主要结局是收缩压（SBP）的变化，次要结局包括舒张压、严重血压事件和不良反应。纳入了3项随机对照试验，共1568名参与者，分布在10个研究组中。洛伦德司他显著降低了24小时动态收缩压（平均差值[MD]：-7.45mmHg；95%置信区间：-12.54至-2.36；p = 0.0041；I² = 0%）和舒张压（MD：-3.49mmHg；95%置信区间：-5.56至-1.41；p = 0.0010；I² = 0%）。虽然在初步分析中诊室收缩压的降低不显著（MD：-13.55mmHg；p = 0.077；I² = 94%），但在敏感性分析中具有统计学意义（MD：-9.08mmHg；p < 0.0001）。洛伦德司他还显著降低了严重血压升高事件的风险（比值比[OR]：0.37；95%置信区间：0.17 - 0.81；p = 0.028）。不良反应包括高钾血症风险增加（OR：3.22；p < 0.001）和低钠血症风险增加（OR：2.16；p = 0.037），两组间严重不良事件无显著差异。总之，洛伦德司他在血压控制不佳的患者中显著降低了动态血压和舒张压，安全性总体可耐受。高钾血症和低钠血症仍是值得关注的风险。需要进一步进行长期试验以验证其持续的疗效和安全性。
