Dose–Response Relationships and Comparative Efficacy of Aldosterone Synthase Inhibitors in Resistant Hypertension: A Comprehensive Network Meta-Analysis and Meta-Regression

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Resistant or uncontrolled hypertension (n=3253). Intervention: Baxdrostat vs. Placebo. Primary outcome: Mean change in systolic blood pressure (SBP) (MD -13.8 mmHg, 95% CI -17.5 to -10.1).

Q: What does this research mean for the field?

Baxdrostat 2 mg once daily provides the greatest reduction in systolic blood pressure among aldosterone synthase inhibitors in patients with resistant hypertension, achieving a mean reduction of -13.8 mmHg versus placebo. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Kareem A. Mohamed; Mohamed Nasser Elshabrawi; Hossam Albeyoumi; Mohamed Khalil; Ahmed AlGhazawy; Youssof Eshac; Atef Akoum; Ibrahim Kamal; Y Sattar; Ashesh Das; Mohammed Rahouma; Akshay Kumar

doi:10.3390/jcm15124477

June 9, 2026Journal of Clinical MedicineOpen Access

Dose–Response Relationships and Comparative Efficacy of Aldosterone Synthase Inhibitors in Resistant Hypertension: A Comprehensive Network Meta-Analysis and Meta-Regression

View Full Paper

Ask AI

Bookmark

Share

Key result

Baxdrostat 2 mg daily leads aldosterone synthase inhibitors, cutting SBP by ~14 mmHg versus placebo.

MD -13.8 mmHg
95% CI -17.5 to -10.1
n=3,253

Figures

Why the study?

Resistant hypertension is often driven by dysregulated aldosterone production, creating a need to synthesize evidence on the comparative efficacy, optimal dosing, and dose-response relationships of novel aldosterone synthase inhibitors.

Do aldosterone synthase inhibitors reduce systolic blood pressure in adult patients with resistant or uncontrolled hypertension?

Study Design

Type

Meta-Analysis (n=3,253)

Structured PICO

Do aldosterone synthase inhibitors reduce systolic blood pressure in adult patients with resistant or uncontrolled hypertension?

P

Population

3,253 adults with resistant or uncontrolled hypertension across 8 randomized controlled trials, followed for 6 to 12 weeks.

I

Intervention

Aldosterone synthase inhibitors (ASIs) including baxdrostat, lorundrostat, and osilodrostat at various dosing regimens (e.g., baxdrostat 1 mg or 2 mg QD, lorundrostat 12.5 mg to 100 mg QD, osilodrostat up to 2 mg QD), added to stable background antihypertensive therapy.

C

Comparator

Placebo or alternative aldosterone synthase inhibitor regimens, with both groups on stable background antihypertensive therapy.

O

Outcome

Mean change in systolic blood pressure (SBP) compared to placebo at 6–8 weeks and 12 weeks.surrogate

Main Result

Mean Difference: -13.8 (95% CI -17.5–-10.1)

Aldosterone synthase inhibitors, particularly baxdrostat and lorundrostat, offer robust, dose-dependent reductions in systolic blood pressure in patients with resistant hypertension, establishing them as a promising novel therapeutic class.

Limitations

Short follow-up duration of the included trials (6-12 weeks) limits conclusions regarding long-term cardiovascular outcomes
Patient populations were relatively homogeneous and lacked individuals with advanced chronic kidney disease or significant comorbidities
Limited direct head-to-head comparisons among different aldosterone synthase inhibitors
Focused primarily on office and ambulatory blood pressure endpoints without evaluating surrogate markers of end-organ damage
Limited efficacy and safety data available for patients older than 75 years
Lack of cost-effectiveness analyses
Short follow-up durations (6–12 weeks) limiting conclusions regarding long-term cardiovascular outcomes
Substantial between-study heterogeneity in the baxdrostat trials (I² = 51.9%) resulting in wide predictive intervals
Small sample sizes in some treatment arms (e.g., Osilodrostat 2 mg QD N=13)

Implication

Supports baxdrostat for resistant hypertension; extends RCT evidence for aldosterone synthase inhibitors as a novel class.

Abstract

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.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Mohamed et al. (2026) conducted a meta-analysis in Resistant or uncontrolled hypertension (n=3,253). Baxdrostat vs. Placebo was evaluated on Mean change in systolic blood pressure (SBP) (MD -13.8 mmHg, 95% CI -17.5 to -10.1). Baxdrostat 2 mg once daily demonstrated the greatest antihypertensive efficacy among aldosterone synthase inhibitors, achieving a mean systolic blood pressure reduction of 13.8 mmHg versus placebo.

synapsesocial.com/papers/6a2ba2448101cf8926f01584 https://doi.org/10.3390/jcm15124477

Topics

Hypertension management

View Full Paper

Ask AI

Bookmark

Share

Dose–Response Relationships and Comparative Efficacy of Aldosterone Synthase Inhibitors in Resistant Hypertension: A Comprehensive Network Meta-Analysis and Meta-Regression

Figures

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

Dose–Response Relationships and Comparative Efficacy of Aldosterone Synthase Inhibitors in Resistant Hypertension: A Comprehensive Network Meta-Analysis and Meta-Regression

Figures

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Keep reading

Topics

Keep reading