Key result
Lorundrostat lowers systolic BP by ~8 mmHg vs placebo in uncontrolled hypertension.
Why the study?
Uncontrolled hypertension persists despite three or more antihypertensive medications, and novel therapeutic options like lorundrostat need evaluation for efficacy and safety.
Does lorundrostat reduce systolic blood pressure in adult patients with uncontrolled hypertension?
Meta-Analysis (n=1,568)
Does lorundrostat reduce systolic blood pressure in adult patients with uncontrolled hypertension?
Lorundrostat provides significant systolic and diastolic blood pressure reduction in patients with uncontrolled hypertension, though it is associated with increased risks of hyperkalemia and hypotension.
May add a novel option for uncontrolled hypertension; extends RCT evidence for aldosterone synthase inhibition while flagging hypotension and hyperkalemia risks.
Background: Uncontrolled hypertension (UH), a severe form of hypertension, persists despite the use of three or more antihypertensive medications. Its growing prevalence, particularly in patients with comorbidities, necessitates novel therapeutic options. Lorundrostat, a selective aldosterone synthase inhibitor, presents a promising mechanism of action by directly reducing aldosterone synthesis while sparing cortisol production, potentially offering an effective and safer alternative to mineralocorticoid receptor antagonists. Objectives: Three randomized controlled trials (RCTs) comprising 1568 participants were included to evaluate the efficacy and safety of lorundrostat in adults with UH as a primary objective, with a decrease in diastolic blood pressure and the incidence of hyperkalemia, hypotension, and serious adverse events, including life-threatening conditions, hospitalization, significant disability, and events resulting in death, as secondary outcomes of the study. Methods: A systematic search of PubMed, Embase, ScienceDirect, Cochrane, and ClinicalTrials.gov up to July 2025 was conducted per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included RCTs compared lorundrostat to placebo in adult patients with resistant/UH. Outcomes were pooled using a random-effects model. Meta-regression explored moderators, including age, BMI, and comorbidities. Adverse events were more frequent in the lorundrostat group [risk ratio (RR) = 1.41], with notable risks of hypotension (RR = 3.10) and hyperkalemia (RR = 7.31), though serious adverse events were not significantly increased (RR = 1.28). Conclusion: Lorundrostat demonstrates significant antihypertensive efficacy and a manageable safety profile in UH patients. Larger, long-term trials are warranted to further validate its safety across broader populations and complete its efficacy profile, emphasizing the unknown long-term cardiovascular outcomes of the intervention.
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Kumar et al. (2026) conducted a meta-analysis in Uncontrolled hypertension (n=1,568). Lorundrostat vs. Placebo was evaluated on Change in systolic blood pressure from baseline (MD -8.40 mmHg, 95% CI -9.81, -6.99, p=<0.00001). Lorundrostat significantly reduced systolic blood pressure by a mean difference of 8.40 mmHg compared to placebo in adults with uncontrolled hypertension.
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