Baxdrostat reduces 24-hour blood pressure in resistant hypertension by 14 mmHg

AHA 2025 – In the phase 3 Bax24 trial, baxdrostat 2 mg reduced 24-hour average ambulatory systolic blood pressure compared with placebo at 12 weeks in patients with treatment-resistant hypertension.

This summary focuses on the presentation of Bryan Williams, MD (London, UK) at the AHA Scientific Sessions 2025 - Effect of Baxdrostat on 24-Hour Average Ambulatory Blood Pressure in Patients with Resistant Hypertension: The Bax24 Trial.

Introduction and methods

Aldosterone dysregulation is an important contributor to the development of treatment-resistant and uncontrolled hypertension. Baxdrostat is an oral, highly selective aldosterone synthase inhibitor that was shown to reduce seated office systolic blood pressure (SBP) compared with placebo in patients with treatment-resistant hypertension in a previous phase 2 trial. In the phase 3 Bax24 (Effect of Baxdrostat on 24-Hour Average Ambulatory Blood Pressure in Patients with Resistant Hypertension) trial, the effect on 24-hour average ambulatory SBP, safety, and tolerability of baxdrostat were investigated in patients with treatment-resistant hypertension.

The Bax24 trial was an international, double-blind, placebo-controlled, parallel-group RCT in which 218 patients with treatment-resistant hypertension at screening and 24-hour average ambulatory SBP ≥130 mmHg at randomization were enrolled. Treatment-resistant hypertension was defined as seated office SBP 140–169 mmHg despite treatment with 3 antihypertensive agents of different classes, including a diuretic, at optimal doses. Participants were randomized to baxdrostat 2 mg once daily or placebo for 12 weeks. Exclusion criteria were known secondary causes of hypertension, such as renal artery stenosis, uncontrolled or untreated hyperthyroidism or hypothyroidism, pheochromocytoma, Cushing’s syndrome, and aortic coarctation.

The primary endpoint was the change in 24-hour average ambulatory SBP from baseline to 12 weeks. Key secondary endpoints included changes from baseline to 12 weeks in nighttime/daytime average ambulatory SBP, 24-hour average ambulatory diastolic BP, and seated office SBP.

Main results

• At 12 weeks, the least-squares (LS) mean change in 24-hour average ambulatory SBP was –16.6 mmHg (95%CI: –18.8 to –14.3) in patients treated with baxdrostat and –2.6 mmHg (95%CI: –4.7 to –0.4) in patients receiving placebo (difference: –14.0 mmHg; 95%CI: –17.2 to –10.8; P<0.0001).
• Baxdrostat treatment also resulted in clinically meaningful reductions in nighttime average ambulatory SBP (placebo-adjusted LS mean change: –13.9 mmHg; 95%CI: –17.5 to –10.3; P<0.0001), daytime average ambulatory SBP (placebo-adjusted LS mean change: –14.1 mmHg; 95%CI: –17.4 to –10.7; P<0.0001), and seated office SBP (placebo-adjusted LS mean change: –10.3 mmHg; 95%CI: –14.9 to –5.6; P<0.0001), as well as 24-hour average ambulatory diastolic BP (placebo-adjusted LS mean change: –6.8 mmHg; 95%CI: –8.8 to –8.4; P<0.0001).
• In addition, a larger proportion of patients treated with baxdrostat achieved 24-hour average ambulatory SBP <130 mmHg compared with placebo-treated patients (70.6% vs. 16.7%; OR: 15.2; 95%CI: 6.6–35.2; P<0.0001).
• Baxdrostat was generally well tolerated, and its safety profile was consistent with that seen in another trial with baxdrostat, in patients with uncontrolled or treatment-resistant hypertension (BaxHTN trial).

Conclusion

In the Bax24 trial, 12-week treatment with baxdrostat 2 mg reduced 24-hour average ambulatory SBP by 14 mmHg compared with placebo in patients with treatment-resistant hypertension. Additionally, 71% of the baxdrostat-treated patients met the guideline target (<130 mmHg), compared with 17% of the placebo-treated patients. Baxdrostat was generally well tolerated.

- Our reporting is based on information provided on the AstraZeneca website and publication of the study design at ClinicalTrials.gov -