Summary: In BaxHTN, adding baxdrostat to background treatment reduced seated systolic blood pressure more than placebo at 12 weeks. Placebo-corrected effects were -8.7 mm Hg with 1 mg and -9.8 mm Hg with 2 mg; potassium above 6.0 mmol/L was more frequent with active treatment.
PICO Summary
| Element | Detail |
|---|---|
| Population | 796 adults with uncontrolled or resistant hypertension were randomised; 794 received treatment. Screening seated systolic pressure was 140 to below 170 mm Hg despite at least two antihypertensive medicines including a diuretic. Randomisation followed a two-week placebo run-in and required systolic pressure of at least 135 mm Hg. |
| Intervention | Baxdrostat 1 mg or 2 mg orally once daily for 12 weeks in addition to background therapy. Treated groups: n=264 and n=266 respectively. |
| Comparator | Matching placebo once daily with background antihypertensive treatment; n=264 treated. This was not a direct comparison with a mineralocorticoid receptor antagonist. |
| Outcomes | Primary endpoint: change in seated systolic pressure at 12 weeks. Least-squares mean changes were -14.5 mm Hg with 1 mg, -15.7 with 2 mg and -5.8 with placebo. Placebo-corrected differences were -8.7 mm Hg (95% CI -11.5 to -5.8) and -9.8 mm Hg (95% CI -12.6 to -7.0), both P<0.0001 in the full report. Potassium above 6.0 mmol/L occurred in 6/262 (2.3%), 8/263 (3.0%) and 1/262 (0.4%) respectively; these laboratory denominators differ from the treated-group totals. Cardiovascular event reduction was not the primary efficacy outcome. |
| Study Design | BaxHTN: multinational phase 3, double-blind, placebo-controlled randomised trial with 1:1:1 allocation and 12-week primary follow-up. NCT06034743. Funded by AstraZeneca and others. It is distinct from Bax24, which studied 24-hour ambulatory pressure in a separate trial. |
Expert Commentary
I regard BaxHTN as convincing evidence that aldosterone synthase inhibition can lower office blood pressure in a selected population with difficult-to-control hypertension. Both doses separated from placebo, and the confidence intervals support a clinically relevant short-term effect. The result should nevertheless be described as a blood-pressure result, not as proof of fewer strokes, heart-failure admissions or deaths. Can I use this with my patients? The findings are relevant to specialist evaluation of adults resembling the enrolled population, but treatment decisions still require current regulatory information, assessment of secondary causes and attention to existing therapy. This report does not establish superiority to established mineralocorticoid receptor antagonists because those drugs were not the randomised comparator. The potassium signal is central to the appraisal rather than an incidental safety footnote. Patients selected for a monitored trial after a run-in period may differ from those seen in routine practice, particularly where adherence or biochemical surveillance is difficult. AstraZeneca funding also warrants transparent consideration when interpreting the programme. I would keep the office-pressure findings here separate from the ambulatory-pressure results in Bax24, avoiding accidental mixing of populations or effect estimates. Longer comparative studies should establish durability, clinically important outcomes and the practical burden of safe biochemical monitoring.
References
Flack JM, Azizi M, Brown JM, et al. Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension. N Engl J Med. 2025;393(14):1363-1374. doi:10.1056/NEJMoa2507109. PMID: 40888730.
