Lorundrostat for Patients with Uncontrolled Hypertension: A Systematic Review with Meta-Analysis and Trial Sequential Analysis
Abstract
BACKGROUND
The efficacy and safety of lorundrostat, a selective aldosterone synthase inhibitor, in patients with uncontrolled hypertension remain unclear. This meta-analysis aimed to evaluate its effects on blood pressure and risk of hyperkalemia.
METHODS
PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were systematically searched through July 2025 for randomized controlled trials comparing lorundrostat with placebo. Pooled mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI) were estimated using a random-effects model with the Restricted Maximum Likelihood estimator. Trial Sequential Analysis (TSA) was conducted to assess the conclusiveness of safety evidence.
RESULTS
Three RCTs including 1,060 patients were identified. Lorundrostat significantly reduced systolic blood pressure at 50 mg (MD, -9.08 mmHg; 95% CI, -13.14 to -5.03) and 100 mg (MD, -11.41 mmHg; 95% CI, -15.97 to -6.85), and diastolic blood pressure at 50 mg (MD, -3.48 mmHg; 95% CI, -5.98 to -0.98). However, lorundrostat increased the risk of hyperkalemia at 50 mg (RR, 6.56; 95% CI, 1.53-28.12; NNH=71) and 100 mg (RR, 10.37; 95% CI, 2.44-44.03; NNH=42). TSA confirmed hyperkalemia at 100 mg as the only conclusive harm signal, while other safety outcomes remained inconclusive.
CONCLUSIONS
Lorundrostat effectively lowered blood pressure but increased dose-dependent risk of hyperkalemia. These findings support its potential as a novel therapy for uncontrolled hypertension, while…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,060 participants or records.
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