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Review
. 2025 Sep;27(9):e70155.
doi: 10.1111/jch.70155.

Efficacy and Safety of Lorundrostat in Uncontrolled Hypertension: A Systematic Review and Meta-Analysis

Allah Dad  1 , Kinza Bakht  1 , Haris Bin Tahir  2 , Muhammad Arham  1 , Anika Goel  3 , Malik Maaz Ahmad  4 , Soban Raza  4 , Syeda Hafsa Qadri  5 , Diya Rathi  5 , Saad Javed  6 , Syed Shah Qasim Hamdani  7 , Hasnan Arshad  8 , F N U Abubakar  9 , Muhammad Nauman Awais  10 , Muhammad Abdullah Nizam  11
Affiliations
Review

Efficacy and Safety of Lorundrostat in Uncontrolled Hypertension: A Systematic Review and Meta-Analysis

Allah Dad et al. J Clin Hypertens (Greenwich). 2025 Sep.

Abstract

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; p2 = 0%) and diastolic BP (MD: -3.49 mmHg; 95% CI: -5.56 to -1.41; p = 0.0010; I2 = 0%). While office SBP showed a non-significant reduction in the primary analysis (MD: -13.55 mmHg; p = 0.077; I2 = 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.

Keywords: aldosterone synthase inhibitor; blood pressure; lorundrostat; meta‐analysis; randomized controlled trial; systematic review; uncontrolled hypertension.

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Conflict of interest statement

The authors declare no conflicts of interest related to this study. All authors have reviewed and approved the final manuscript.

Figures

FIGURE 1
FIGURE 1
Preferred reporting items for systematic reviews and meta‐analyses (PRISMA) flowchart illustrating the study selection process.
FIGURE 2
FIGURE 2
Forest plot of change in office systolic blood pressure with lorundrostat versus control. IV, inverse variance; SD, standard deviation.
FIGURE 3
FIGURE 3
Leave‐one‐out sensitivity analysis of the change in office systolic blood pressure with lorundrostat versus control. MD, mean difference.
FIGURE 4
FIGURE 4
Forest plot of change in office systolic blood pressure in lorundrostat (single arm analysis). IV, inverse variance; MD, mean difference; SD, standard deviation.
FIGURE 5
FIGURE 5
Forest plot of change in 24 h ambulatory systolic blood pressure with lorundrostat versus control. IV, inverse variance; MD, mean difference; SD, standard deviation.
FIGURE 6
FIGURE 6
Forest plot of change in office diastolic blood pressure with lorundrostat versus control. IV, inverse variance; MD, mean difference; SD, standard deviation.
FIGURE 7
FIGURE 7
Forest plot of risk of severely elevated blood pressure with lorundrostat versus control. IV, inverse variance; OR, odds ratio.
FIGURE 8
FIGURE 8
Forest plot of hyperkalemia risk with lorundrostat versus control. IV, inverse variance; OR, odds ratio.
FIGURE 9
FIGURE 9
Forest plot of hypotension risk with lorundrostat versus control. IV, inverse variance; OR, odds ratio.
FIGURE 10
FIGURE 10
Forest plot of the risk of hyponatremia requiring dose modification with lorundrostat versus control. IV, inverse variance; OR, odds ratio.
FIGURE 11
FIGURE 11
Forest plot of the risk of any adverse event with lorundrostat versus control. IV, inverse variance; OR, odds ratio.
FIGURE 12
FIGURE 12
Forest plot of the risk of overdose events with lorundrostat versus control. IV, inverse variance; OR, odds ratio.
FIGURE 13
FIGURE 13
Forest plot of the risk of eGFR reduction requiring dose modification with lorundrostat versus control. IV, inverse variance; OR, odds ratio.
FIGURE 14
FIGURE 14
Forest plot of the risk of serious adverse events with lorundrostat versus control. IV, inverse variance; OR, odds ratio.
FIGURE 15
FIGURE 15
Forest plot of the risk of severe adverse events with lorundrostat versus control. IV, inverse variance; OR, odds ratio.
See this image and copyright information in PMC

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