Key Points
- Baxdrostat, a highly selective aldosterone synthase inhibitor, reduced systolic blood pressure as compared with placebo among patients with resistant hypertension in the BrigHTN trial. Efficacy and safety data are needed for individuals with uncontrolled hypertension.
- In this randomized, double-blind, placebo-controlled, phase 2 clinical trial, treatment with baxdrostat did not meet primary endpoint of statistically significant change from baseline in mean seated SBP versus placebo in patients with uncontrolled hypertension
Over half of individuals with hypertension have uncontrolled blood pressure. Identification of novel therapies to reduce blood pressure are needed for individuals unable to reach target goals. Baxdrostat is a highly selective aldosterone synthase inhibitor which reduces aldosterone levels. In the prior BrigHTN phase 2 trial, baxdrostat reduced systolic blood pressure in a dose dependent manner when compared to placebo in patients with treatment-resistant hypertension. Additional efficacy and safety data are needed for individuals with uncontrolled hypertension.
This multicenter, randomized, double-bind, phase 2 trial enrolled individuals with a mean systolic blood pressure of 140 mmHg or higher on a stable regimen of an ACEi or ARB alone or in combination with a thiazide diuretic or calcium channel blocker and randomized them in a 1:1:1:1 fashion to placebo, baxdrostat 0.5 mg, baxdrostat 1mg, or baxdrostat 2mg. Individuals with a mean systolic blood pressure ≥ 180 mmHg, a body mass index of >50 kg/m2, or an estimated glomerular filtration rate < 30 mL/min/1.73 m2 were excluded. The primary outcome was change from baseline in mean seated systolic blood pressure after 8 weeks of treatment.
A total of 249 patients were enrolled, and 227 completed the study. The average age was 60 years of age and just under half of them were female. The average systolic blood pressure and diastolic blood pressures at baseline were 147 mmHg and 83 mmHg, respectively. The primary endpoint of placebo-corrected systolic blood pressure change was not met at any baxdrostat dose. There was a large 16.6 mmHg reduction in mean systolic blood pressure from baseline among the placebo recipients. No significant difference in the secondary endpoint of placebo-corrected diastolic blood pressure occurred with any baxdrostat dose. The number of participants achieving a seated systolic blood pressure goal of less than 130 mmHg at 8 weeks was similar among the groups. Despite >95% adherence suggested by dosing records by pill counts, 36% of participants in the 2 mg arm had plasma baxdrostat levels of <0.2 ng/mL indicating non-adherence.
In conclusion, baxdrostat at any dose did not provide a statistically significant change from baseline in mean seated systolic blood pressure when compared to placebo among individuals with uncontrolled hypertension. When presenting their findings at ACC.23, Dr. Deepak Bhatt noted that baxdrostat appeared to have generally a favorable safety profile and a post-hoc analysis revealed a placebo-corrected reduction in systolic blood pressure of 7.9 mmHg among patients adherent to the highest dose of baxdrostat, which requires confirmation in future trials.
