Abstract Body: Background: Lorundrostat is a novel drug that offers a new treatment alternative for resistant hypertension. It is a potent and selective inhibitor of Aldosterone Synthase, an enzyme that catalyzes the final steps for Aldosterone Synthesis.
Hypothesis: Lorundrostat significantly reduces systolic blood pressure in patients with uncontrolled or treatment-resistant hypertension compared to placebo, with a favorable safety and tolerability profile across varying doses.
Methodology: We found 67 studies on our initial search across PubMed, Embase, Scopus & Cochrane Library from inception until May 2025. After exclusion of studies by deduplication, Title/Abstract screening, and full text screening, we finalized 2 Randomized Controlled Trials, with one trial having two cohorts. All the enrolled patients in trials were adults (≥18 years) with resistant hypertension, either being treated with Lorudrostat or a placebo. The Risk Ratios (RRs) for adverse events, Mean Differences for change in Blood Pressures, and their corresponding 95% confidence intervals (CIs) were pooled with the random effects model.
Results: The analysis encompassed the total sample size of 485 patients. Lorundrostat significantly reduced mean systolic blood pressure by 6.96 mm Hg (95% CI: –10.12 to –3.79, p < 0.001). The risk of adverse events was non-significantly elevated with lorundrostat (RR 1.40, 95% CI: 0.99–1.97, p = 0.054). Similarly, the severe adverse events did not differ significantly between the two groups (RR 2.24, 95% CI: 0.28 -- 17.81, p = 0.237). Analysis of other events also showed a non-significant trend, such as hyperkalemia (RR 5.54, 95% CI: 0.30–101.63, p = 0.127) and hypotension (RR 2.03, 95% CI: 0.43–9.63, p = 0.191). There was no evidence of heterogeneity among all the outcomes in the studies, therefore emphasizing the consistency of our results.
Conclusion: Lorundrostat significantly reduces systolic blood pressure in patients with treatment-resistant hypertension and maintains a comparable safety profile to placebo across multiple dosing regimens. Nevertheless, further research is imperative to yield evidence, verify long-term safety, and ascertain the most effective dosing strategies.