Study Title: Baxdrostat in Uncontrolled and Resistant Hypertension

Presented at: ESC 2025

Link: https://esc365.escardio.org/presentation/312167

Prepared by: Dr. Kemal Göçer

Introduction
Impaired aldosterone synthesis is a major cause of difficult-to-control hypertension. This study evaluated the efficacy and safety of baxdrostat, a selective aldosterone synthase inhibitor.

Methods
This phase 3, multicenter, randomized, double-blind, placebo-controlled study included a total of 794 patients with systolic blood pressure between 140 and 170 mmHg despite treatment with at least two or three different antihypertensive drugs and diuretics. After a two-week placebo run-in period, patients were randomized into three arms: baxdrostat 1 mg, baxdrostat 2 mg, and placebo. The primary endpoint was the change in sitting systolic blood pressure at week 12.

Results
At week 12, the mean change in systolic blood pressure was –14.5 mmHg in the baxdrostat 1 mg group, –15.7 mmHg in the baxdrostat 2 mg group, and –5.8 mmHg in the placebo group. The difference compared to placebo was –8.7 and –9.8 mmHg, respectively, and was statistically significant for both doses. A similar additional reduction was observed in the resistant hypertension subgroup. The decrease in diastolic blood pressure was between –3.3 and –3.9 mmHg. The proportion of patients whose blood pressure fell below 130 mmHg was approximately 40% in the baxdrostat groups and 19% in the placebo group. A partial rebound in blood pressure was observed when baxdrostat was discontinued in the randomized withdrawal phase.

Safety
Most adverse events were mild. Hyperkalemia and hyponatremia were more common in the baxdrostat arms compared to placebo. Approximately 2–3% of patients had serum potassium levels above 6 mmol/L. A mean decrease of 7 mL/min/1.73 m² in glomerular filtration rate was observed, but this change partially reversed when the drug was discontinued. The rates of serious adverse events were low and similar across all groups.

Conclusion
When added to standard therapy in patients with uncontrolled or resistant hypertension, baxdrostat provided an additional 9–10 mmHg reduction in systolic blood pressure at 12 weeks, and its safety profile was generally acceptable. This effect is of a magnitude that could make an important contribution to reducing cardiovascular risk.