Article Impact Level: HIGH Data Quality: STRONG Summary of New England Journal of Medicine, NEJMoa2507109. https://doi.org/10.1056/NEJMoa2507109 Dr. John M. Flack et al.
Points
- Baxdrostat, a novel aldosterone synthase inhibitor, was evaluated in patients whose high blood pressure was uncontrolled or resistant to treatment with multiple existing medications.
- The Phase 3 BaxHTN trial randomized nearly 800 participants to receive 1 mg of baxdrostat, 2 mg of baxdrostat, or a placebo for 12 weeks.
- After 12 weeks, baxdrostat significantly lowered systolic blood pressure by approximately 9 to 10 mm Hg more than the placebo group, a clinically meaningful reduction.
- The drug works by directly blocking the production of the hormone aldosterone, which contributes to high blood pressure by causing the body to retain salt and water.
- A notable side effect was an increased incidence of high potassium levels, reported in 2-3% of patients on baxdrostat compared to 0.4% of those on placebo.
Summary
The Phase 3 BaxHTN trial evaluated the efficacy and safety of baxdrostat, an aldosterone synthase inhibitor, in patients with uncontrolled or resistant hypertension. This multinational, double-blind, randomized, placebo-controlled study enrolled patients with a seated systolic blood pressure between 140 mm Hg and less than 170 mm Hg despite stable treatment with two or more antihypertensive medications. A total of 794 patients were randomly assigned in a 1:1:1 ratio to receive once-daily baxdrostat at a dose of 1 mg, 2 mg, or placebo for 12 weeks in addition to their existing background therapy. The primary endpoint was the change in seated systolic blood pressure from baseline to week 12.
At 12 weeks, the least-squares mean change from baseline in seated systolic blood pressure was –14.5 mm Hg (95% CI, –16.5 to –12.5) with 1-mg baxdrostat and –15.7 mm Hg (95% CI, –17.6 to –13.7) with 2-mg baxdrostat, compared to –5.8 mm Hg (95% CI, –7.9 to –3.8) with placebo. The placebo-corrected differences were –8.7 mm Hg (95% CI, –11.5 to –5.8) for the 1-mg dose and –9.8 mm Hg (95% CI, –12.6 to –7.0) for the 2-mg dose (P<0.001 for both comparisons). These clinically meaningful reductions persisted for up to 32 weeks.
Regarding safety, the incidence of hyperkalemia (potassium level >6.0 mmol per liter) was higher in the treatment arms. Hyperkalemia was reported in 6 patients (2.3%) receiving 1-mg baxdrostat and in 8 patients (3.0%) receiving 2-mg baxdrostat, compared to 1 patient (0.4%) in the placebo group. The study concludes that baxdrostat significantly lowers blood pressure in patients with uncontrolled or resistant hypertension, supporting the pathogenic role of aldosterone dysregulation in this population and offering a potential new therapeutic option.
Link to the article: https://www.nejm.org/doi/10.1056/NEJMoa2507109
References
Aminde, L. N., Islam, F. M. A., Cheng, V. E., Saad, C., Li, Y., & Schutte, A. E. (2025). Poor accuracy of blood pressure measurement images online: Implications for public health education. Hypertension, HYPERTENSIONAHA.125.25064. https://doi.org/10.1161/HYPERTENSIONAHA.125.25064
