Kamal, Ibrahim

Background: Resistant hypertension represents a significant clinical challenge, often driven by dysregulated aldosterone production. Aldosterone synthase inhibitors (ASIs) are a novel therapeutic class designed to directly suppress aldosterone biosynthesis. This study aimed to synthesize evidence regarding the comparative efficacy, optimal dosing, and dose–response relationships of three ASIs—baxdrostat, lorundrostat, and osilodrostat—for the treatment of resistant hypertension. Methods: A systematic review and network meta-analysis (NMA) were conducted following PRISMA 2020 guidelines. We searched PubMed, Web of Science, and CENTRAL for randomized controlled trials (RCTs) published up to 31 October 2025. The primary outcome was the mean change in systolic blood pressure (SBP) compared to placebo. We utilized a frequentist random-effects model, characterized dose–response relationships via meta-regression, and ranked treatments using the Surface Under the Cumulative Ranking Curve (SUCRA). Results: The analysis included 8 RCTs comprising 3253 participants. Baxdrostat 2 mg once daily demonstrated the greatest antihypertensive efficacy with a mean SBP reduction of −13.8 mmHg (95% CI: −17.5 to −10.1) versus placebo, followed by Lorundrostat 100 mg (−12.5 mmHg) and Baxdrostat 1 mg (−11.5 mmHg). SUCRA analysis identified Baxdrostat as the highest-ranked treatment (83.0%), followed by Lorundrostat (67.8%) and Osilodrostat (55.5%). Dose–response meta-regression revealed strong linear correlations for Baxdrostat (R2 = 0.91), Osilodrostat (R2 = 0.81), and Lorundrostat (R2 = 0.80). Conclusions: ASIs, particularly Baxdrostat and Lorundrostat, offer robust blood pressure reductions in patients with resistant hypertension. The strong linear dose–response relationships suggest these agents have a favorable therapeutic window for titration. While effective, clinical implementation requires careful monitoring for adverse events.

Background/Objectives: Esaxerenone, a novel non-steroidal mineralocorticoid receptor antagonist, has shown promising results in the treatment of essential hypertension (HTN). This study aims to comprehensively analyze the effectiveness of esaxerenone to control BP in patients with essential HTN. Methods: A systematic search was performed on PubMed, Scopus, Web of Science (WOS), and Cochrane Library from inception until January 2025 for randomized controlled trials (RCTs) comparing esaxerenone with standard HTN usual care. The primary outcome of interest was mean changes in sitting systolic (SBP) and diastolic blood pressure (DBP). Other secondary outcomes were mean changes in 24 h-SBP and 24 h-DBP, and target BP achievement. Safety outcomes, such as adverse events and increased levels of potassium/uric acid, were also assessed. Results: Our meta-analysis included four studies with a total of 1981 patients, all conducted in Japan. Esaxerenone demonstrated dose-dependent blood pressure reductions. At 5 mg, sitting DBP decreased by 4.22 mmHg (95% CI −8.72 to 0.29; p = 0.07) and SBP by 9.07 mmHg (95% CI −17.69 to −0.45; p = 0.04), while the 1.25 mg dose showed smaller, non-significant reductions. For 24 h measurements, only the 5 mg dose achieved significant reductions. Target BP achievement increased by 48% overall (RR 1.48, 95% CI 1.11 to 1.96; p = 0.007), with stronger effects at 5 mg (RR 2.05, 95% CI 1.03 to 4.08; p = 0.04). Esaxerenone significantly reduced nocturnal SBP by 10.62 mmHg (95% CI −14.01 to −7.23; p < 0.001). Conclusions: In patients with essential HTN, esaxerenone was shown to be safe and well-tolerated compared with usual care. Long-term data on safety is warranted.