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Introduction <p>Lorundrostat, a highly selective aldosterone synthase inhibitor, has emerged as a promising therapeutic agent for uncontrolled and treatment-resistant hypertension. This meta-analysis evaluates the effectiveness and safety of lorundrostat in patients with uncontrolled and treatment-resistant hypertension.</p> Methodology <p>A comprehensive electronic database search was conducted across electronic databases—PubMed, Google Scholar, and Cochrane, as well as ClinicalTrials.gov, from inception till 2 July 2025, which yielded 482 articles. 3 articles met the eligibility criteria and were included in the meta-analysis. Statistical analysis was carried out via RevMan version 5.4.</p> Results <p>Three RCTs included 1556 patients,1161 patients were allocated to the lorundrostat group, and 395 patients to the placebo group. The mean age of participants was 61.9(10.3) years, 53% were male. The meta-analysis showed a significant reduction in systolic blood pressure [Mean Difference (MD) -7.54, 95% Confidence Interval (CI) -9.70 to -5.38; p-value &lt; 0.00001, I<sup>2</sup> = 0%] and diastolic blood pressure (MD=-3.57, CI 95% [-5.23, -1.91], <i>p</i> &lt; 0.0001, I<sup>2</sup> = 0%) in comparison to placebo accompanied by a reduction in serum aldosterone levels. Intermediate and high doses demonstrated statistically significant systolic blood pressure reductions, while low dose failed to show any significant reduction in blood pressure. There was an increased incidence of any grade adverse events, including hyperkalemia, hyponatremia, and symptomatic hypotension, but there was no significant difference in the incidence of serious adverse events.</p> Conclusion <p>Lorundrostat shows statistically substantial reduction in systolic and diastolic blood pressure, with a tolerable short-term safety profile including elevated but often controllable side effects. These findings support lorundrostat as a possible exploratory alternative for uncontrolled and treatment-resistant hypertension, awaiting confirmation from longer-term investigations.</p>

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Lorundrostat for Uncontrolled and Treatment-Resistant Hypertension: a Systematic Review and Meta-Analysis of Efficacy and Safety Outcomes

  • 期刊论文

  • 发表日期：

    2026年4月29日

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  • Maheen Gohar,
  • Mahnoor Aamir,
  • Manahil Gohar,
  • Muhammad Owais

摘要

Introduction

Lorundrostat, a highly selective aldosterone synthase inhibitor, has emerged as a promising therapeutic agent for uncontrolled and treatment-resistant hypertension. This meta-analysis evaluates the effectiveness and safety of lorundrostat in patients with uncontrolled and treatment-resistant hypertension.

Methodology

A comprehensive electronic database search was conducted across electronic databases—PubMed, Google Scholar, and Cochrane, as well as ClinicalTrials.gov, from inception till 2 July 2025, which yielded 482 articles. 3 articles met the eligibility criteria and were included in the meta-analysis. Statistical analysis was carried out via RevMan version 5.4.

Results

Three RCTs included 1556 patients,1161 patients were allocated to the lorundrostat group, and 395 patients to the placebo group. The mean age of participants was 61.9(10.3) years, 53% were male. The meta-analysis showed a significant reduction in systolic blood pressure [Mean Difference (MD) -7.54, 95% Confidence Interval (CI) -9.70 to -5.38; p-value < 0.00001, I2 = 0%] and diastolic blood pressure (MD=-3.57, CI 95% [-5.23, -1.91], p < 0.0001, I2 = 0%) in comparison to placebo accompanied by a reduction in serum aldosterone levels. Intermediate and high doses demonstrated statistically significant systolic blood pressure reductions, while low dose failed to show any significant reduction in blood pressure. There was an increased incidence of any grade adverse events, including hyperkalemia, hyponatremia, and symptomatic hypotension, but there was no significant difference in the incidence of serious adverse events.

Conclusion

Lorundrostat shows statistically substantial reduction in systolic and diastolic blood pressure, with a tolerable short-term safety profile including elevated but often controllable side effects. These findings support lorundrostat as a possible exploratory alternative for uncontrolled and treatment-resistant hypertension, awaiting confirmation from longer-term investigations.