Baxdrostat Proves Role of Aldosterone Inhibition in Hypertension, With Jenifer Brown, MD

Baxdrostat, AstraZeneca’s investigational aldosterone synthase inhibitor, significantly reduced systolic blood pressure in patients with uncontrolled and resistant hypertension, according to results of the phase 3 BaxHTN trial presented at the 2025 European Society of Cardiology Congress.1
The trial randomized 794 patients with seated systolic blood pressures between 140 mm Hg and <170 mm Hg, all receiving stable background therapy, to baxdrostat 1 mg, baxdrostat 2 mg, or placebo once daily for 12 weeks. At study completion, patients on baxdrostat demonstrated substantial reductions in seated systolic blood pressure compared with placebo: -14.5 mm Hg for 1 mg, -15.7 mm Hg for 2 mg, versus -5.8 mm Hg with placebo. Hyperkalemia >6 mmol/L occurred in 2.3% of patients on 1 mg, 3% on 2 mg, and 0.4% on placebo.1
An editorial in the New England Journal of Medicine by Tomasz Guzik, MD, PhD, highlighted three clinical takeaways. First, baxdrostat achieved reductions in blood pressure comparable to spironolactone and other aldosterone synthase inhibitors, despite concomitant RAAS blockade and near-universal diuretic use, suggesting potential to overcome aldosterone breakthrough. Second, biochemical changes emerged early but were generally well managed, with few discontinuations for hyperkalemia. Third, during randomized withdrawal, blood pressure rebounded only modestly, hinting at possible physiologic resets in sodium balance or vascular tone that could support durable control.2
“It’s exciting, because now we’re looking at a completely new class of blood pressure medication,” said Jenifer Brown, MD, of Brigham and Women’s Hospital, in an interview with HCPLive. “Beyond just being a new class, it’s targeting aldosterone, which we believe is a prevalent and important driver of hypertension and cardiovascular disease. The benefits appeared consistent across subgroups, suggesting a broad role for aldosterone antagonists.”
Investigators concluded that baxdrostat represents a promising therapeutic option for patients with uncontrolled or resistant hypertension, potentially broadening long-term strategies for cardiovascular protection.1

References

1. Flack J, Azizi M, Brown J, et al. Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension. N Engl J Med. August 30, 2025. Accessed August 30, 2025. DOI: 10.1056/NEJMoa2507109.

2. Guzik T, Tomaszewski M. Aldosterone Synthase Inhibition for Hypertension. N Engl J Med. August 30, 2025. Accessed August 30, 2025. DOI: 10.1056/NEJMe2511533.