Aldosterone dysregulation is considered an important contributor to hypertension that remains difficult to control with standard therapy. A phase 3 randomized, double-blind, placebo-controlled trial published in Lancet evaluated the effect of baxdrostat, a selective aldosterone synthase inhibitor, on ambulatory blood pressure in patients with Resistant Hypertension.

Adults aged 18 years or older with seated systolic blood pressure (SBP) ≥140 mm Hg and <170 mm Hg despite receiving at least three antihypertensive medications, including a diuretic, were recruited from 79 clinical sites across 22 countries. Following a two-week placebo run-in period, patients with a 24-hour ambulatory SBP ≥130 mm Hg were randomly assigned in a 1:1 ratio to receive oral baxdrostat 2 mg once daily or placebo for 12 weeks in addition to background therapy. The primary endpoint was change in 24-hour ambulatory SBP from baseline to week 12.

Of 854 screened participants, 217 patients were randomized and received baxdrostat (n=108) or placebo (n=109). The median age was 60 years, and 65% were male. At week 12, the least-squares mean change in 24-hour ambulatory SBP was −16.6 mm Hg (95% CI −18.8 to −14.3) with baxdrostat compared with −2.6 mm Hg (95% CI −4.7 to −0.4) with placebo, yielding a placebo-corrected difference of −14.0 mm Hg (95% CI −17.2 to −10.8; p<0.0001). Adverse events occurred in 52% of baxdrostat recipients and 37% of placebo recipients. Confirmed potassium levels >6 mmol/L occurred in three patients (3%) receiving baxdrostat and in none receiving placebo.

Baxdrostat significantly reduced ambulatory SBP compared with placebo in patients with resistant hypertension. These findings provide further evidence for the potential of aldosterone synthase inhibition in hard-to-control hypertension.