1. Compared to placebo, baxdrostat showed a dose-dependent reduction in blood pressure in patients with treatment-resistant hypertension.
2. Baxdrostat was not associated with deaths, serious adverse events, or adrenocortical insufficiency.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Hypertension is a leading risk factor for developing cardiovascular diseases, stroke, and death worldwide. While effective medications exist, 10% of patients have treatment-resistant hypertension. This means hypertension which persists despite the use of three distinct antihypertensives. The guidelines recommend adding a fourth agent, typically spironolactone, which is an aldosterone receptor antagonist. This medication, however, carries dose-limiting adverse events. Aldosterone synthase represents a novel yet elusive therapeutic target, due to its similarity to an enzyme required for cortisol synthesis. Baxdrostat is a newly developed specific aldosterone synthase inhibitor. The current study was a phase two trial to assess the efficacy and safety of baxdrostat in managing treatment-resistant hypertension. It was shown that, compared to a placebo, baxdrostat being added to patients’ current regimen resulted in a dose-dependent reduction in systolic and diastolic blood pressures. Its safety profile was also acceptable, with no drug-related serious adverse events and no adrenocortical insufficiency. Overall, despite its limited sample size and follow-up, the study demonstrated that baxdrostat was efficacious and safe in managing treatment-resistant hypertension and warrants further investigation into this novel therapy.
Click here to read the study in NEJM
In-Depth [randomized controlled trial]: The current study was a phase two randomized, double-blind, placebo-controlled, dose-ranging trial to assess the efficacy and safety of baxdrostat in managing treatment-resistant depression. Adults 18 years of age or older with treatment-resistant hypertension and a mean resting blood pressure of at least 130/80 mmHg were included. Exclusion criteria were a mean blood pressure of 180/110 mmHg or higher, an estimated glomerular filtration rate (GFR) of 45 or lower, or uncontrolled diabetes. A total of 275 patients were randomized 1:1:1:1 to receive baxdrostat 0.5mg, 1mg, 2mg, or a placebo once daily. The primary outcome was the change in mean systolic blood pressure from baseline to 12 weeks in the baxdrostat groups compared to placebo. At 12 weeks, the changes from baseline in systolic blood pressure were -20.3 mmHg, -17.5 mmHg, -12.1 mmHg, and -9.4 mmHg in the baxdrostat 2mg, 1mg, 0.5mg, and placebo groups, respectively. The difference in the change from baseline in systolic blood pressure between the baxdrostat 2mg and placebo groups was -11.0 mmHg (95% Confidence Interval [CI], -16.4 to -5.5; p=0.003), and the difference between the baxdrostat 1mg and placebo groups was -8.1 mmHg (95% CI, -13.5 to -2.8; p=0.003). The difference in the change from baseline in diastolic blood pressure was -5.2 mmHg (95% CI, -8.7 to -1.6) between the baxdrostat 2mg and placebo groups. The most common adverse events were urinary tract infections, hyperkalemia, headache, and fatigue. The rates of these events did not differ between groups and no adrenocortical insufficiency occurred. These results demonstrated that baxdrostat resulted in dose-dependent reductions in systolic and diastolic blood pressures among patients with treatment-resistant hypertension while maintaining an acceptable safety profile.
Image: PD
©2023 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.
