Summary: In 217 adults with resistant hypertension, baxdrostat 2 mg once daily reduced 24-hour ambulatory systolic blood pressure by an estimated 14.0 mm Hg more than placebo at 12 weeks (95% CI -17.2 to -10.8). Confirmed potassium above 6 mmol/L occurred in three baxdrostat recipients and none receiving placebo.
PICO Summary
| Element | Detail |
|---|---|
| Population | 217 adults with resistant hypertension despite at least three antihypertensive medicines including a diuretic; seated systolic pressure at least 140 but below 170 mm Hg at screening and 24-hour ambulatory systolic pressure at least 130 mm Hg after a placebo run-in. Recruited at 79 sites in 22 countries; median age 60 years. |
| Intervention | Baxdrostat 2 mg orally once daily, added to background antihypertensive treatment for 12 weeks; 108 participants. |
| Comparator | Matching placebo once daily with continued background antihypertensive treatment for 12 weeks; 109 participants. |
| Outcomes | Primary week-12 change in 24-hour ambulatory systolic blood pressure: -16.6 mm Hg with baxdrostat (95% CI -18.8 to -14.3; 89 evaluable) versus -2.6 mm Hg with placebo (-4.7 to -0.4; 95 evaluable). Estimated between-group difference -14.0 mm Hg (95% CI -17.2 to -10.8; P<0.0001). Missing or invalid ambulatory measurements were not imputed. Adverse events: 56/108 (52%) versus 40/109 (37%). Confirmed potassium above 6 mmol/L: 3/108 (3%) versus 0/109. Cardiovascular events were not the primary efficacy outcome. |
| Study Design | Bax24: phase 3, randomised, double-blind, placebo-controlled trial with a 2-week placebo run-in and 12-week treatment phase. Primary analysis required valid baseline and week-12 ambulatory measurements; safety included all dosed participants. Funded by AstraZeneca. ClinicalTrials.gov NCT06168409. |
Baxdrostat and 24-hour ambulatory blood pressure in resistant hypertension
Phase 3 RCT | 12 weeks
Baxdrostat lowered 24-hour ambulatory systolic blood pressure in resistant hypertension, while hyperkalaemia monitoring remained clinically important.
Expert Commentary
I regard Bax24 as convincing evidence of short-term ambulatory blood-pressure lowering in a selected resistant-hypertension population. The magnitude of the placebo-corrected reduction is clinically notable, and ambulatory measurement is a strength because it captures blood pressure beyond the clinic. However, this was not a cardiovascular outcomes trial, so fewer strokes, myocardial infarctions or deaths cannot be claimed from these results. The main limitation is the selected and incomplete primary analysis: a placebo run-in preceded randomisation, and participants without valid week-12 ambulatory measurements were not imputed. That combination warrants attention when applying the result to less closely monitored practice. The potassium signal is also important, despite the small absolute number of events. Three treated participants exceeded 6 mmol/L, compared with none receiving placebo. Can I use this with my patients? The evidence may inform specialist discussion for adults with confirmed resistant hypertension, but any clinical use must follow current local authorisation and prescribing requirements, with appropriate renal and potassium assessment. It is not a reason to replace established assessment of adherence or secondary causes. AstraZeneca sponsorship should be transparent. I would prioritise longer follow-up, complete missing-data sensitivity analyses and cardiovascular outcome evidence before treating this substantial pressure reduction as a proven long-term net benefit.
References
Azizi M, Brown JM, Dwyer JP, et al. Effect of baxdrostat on ambulatory blood pressure in patients with resistant hypertension (Bax24): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2026;407(10532):988-999. doi:10.1016/S0140-6736(25)02549-8. PMID: 41794437.
