BrigHTN: Baxdrostat for Resistant Hypertension

November 2022 NEJM

Aldosterone physiology.

Aldosterone, a hormone crucial for blood pressure regulation, plays a significant role in promoting salt and water retention by the kidneys. Excessive levels of aldosterone can lead to hypertension. The enzyme responsible for the synthesis of aldosterone is aldosterone synthase (AS), which bears a striking 93% similarity to cortisol synthase (CS, CYP11B1), an enzyme vital for maintaining human physiology and vitality.

Baxdrostat, an aldosterone reducer.

Inhibiting aldosterone synthase presents a promising approach to treating hypertension. However, it is key to ensure selective inhibition to avoid compromising cortisol production. Recently, researchers have identified Baxdrostat as a highly selective AS inhibitor that does not interfere with cortisol synthesis. The specificity of Baxdrostat in inhibiting aldosterone synthase over cortisol synthase is 100:1.

Baxdrostat clinical trial.

The findings of a phase 2 BrigHTN clinical trial were published in the New England Journal of Medicine in February 2023. This study aimed to compare the efficacy of Baxdrostat with a placebo in treating patients with difficult-to-control hypertension. The primary endpoint was the change in systolic blood pressure from baseline to week 12. The trial involved approximately 250 patients who completed the study. 

Results of the trial.

The results showed a clinically significant decrease in systolic blood pressure ranging from 8-11 mmHg in the Baxdrostat group compared to the placebo group. Notably, no instances of adrenocortical insufficiency were observed in individuals receiving Baxdrostat, and the side effect profile was similar between the two groups.

Summary.

Baxdrostat is effective in reducing blood pressure in patients with resistant hypertension. This represents a significant stride towards obtaining FDA approval for Baxdrostat as a treatment for individuals who urgently require successful control of stubborn hypertension.

Dr. Tashko