Annals of medicine and surgery (2012) · 2026
Efficacy and safety of lorundrostat in uncontrolled hypertension: a systematic review, meta-analysis, and meta-regression.
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Kumar Sumet, Arif Janjua Arshia, Kumar Laksh, Muhammad Ebtehaj Ali Sheikh, Ahmed Hanzlah, Babar Rayan, Imtiaz Sheikh Rumaisa, Mohammad Ali Sana, Qazi Hadia, Hanif Fatima, Gul Khizra, Sarwar Ali Ayesha, Umme Rubab Bukhari Shehzadi, Raja Adarsh, Chaulagain Aayush
Аннотация
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.
RESULTS: Three RCTs (n = 1568) met inclusion criteria. Lorundrostat significantly reduced systolic blood pressure [mean difference (MD) = -8.40 mmHg, 95% confidence interval (CI) (-9.81, -6.99), P < 0.00001, I 2 = 0%] and diastolic blood pressure [MD = -3.84 mmHg, 95% CI (-5.06, -2.63), P < 0.00001, I 2 = 0%]. 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.
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.
RESULTS: Three RCTs (n = 1568) met inclusion criteria. Lorundrostat significantly reduced systolic blood pressure [mean difference (MD) = -8.40 mmHg, 95% confidence interval (CI) (-9.81, -6.99), P < 0.00001, I 2 = 0%] and diastolic blood pressure [MD = -3.84 mmHg, 95% CI (-5.06, -2.63), P < 0.00001, I 2 = 0%]. 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.