Efficacy of the Selective Aldosterone Synthase Inhibitor Baxdrostat for the Treatment of Resistant Hypertension
ypertension is the leading modifiable risk factor for cardiovascular disease worldwide. Resistant hypertension refers to elevated blood pressure (BP) that does not respond adequately to at least three antihypertensive medications of different classes including a diuretic.1 It is estimated that resistant hypertension affects about 10% of all patients with hypertension.2
Aldosterone synthase, the enzyme involved in the biosynthesis of aldosterone, has a fundamental role in regulating BP and has been a target for treating hypertension. Selective inhibition of aldosterone synthase is challenging because of its similarity to the enzyme involved in cortisol synthesis.3 The BrigHTN trial studied the use of baxdrostat, a selective inhibitor of aldosterone synthase, for the treatment of resistant hypertension.4
In this multicenter, placebo-controlled phase 2 trial, 275 patients with resistant hypertension with a mean BP ≥130/80 mm Hg were randomized to either receive baxdrostat (0.5 mg, 1 mg, or 2 mg) once daily or placebo for 12 weeks. The primary outcome was the change in systolic BP (SBP) from baseline to 12 weeks. The SBP change was -20.3 mm Hg, -17.5 mm Hg, and -12.1 mm Hg in the baxdrostat 2 mg, 1 mg, and 0.5 mg group, respectively, and -9.4 mm Hg in the placebo group. The difference in SBP change between the baxdrostat 2 mg group and placebo was -11 mm Hg (95% CI, -16.4 to -5.5; P<0.001) and -8.1 mm Hg (95% CI, -13.5 to -2.8; P=0.003) between the 1 mg and placebo group. There were no adverse events or occurrences of adrenocortical insufficiency.
The BrigHTN trial provides evidence that selective inhibition of aldosterone synthase leads to a substantial dose-dependent reduction in BP among patients with resistant hypertension and that baxdrostat may be a new tool for the treatment of resistant hypertension. The benefits and safety of baxdrostat need to be confirmed in a phase 3 trial over a longer period.
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