Efficacy of Aldosterone Synthase Inhibitor for Uncontrolled or Resistant Hypertension

NYU Langone Health Med-Lit Review

Clinical Question: For patients with uncontrolled or resistant hypertension, does the addition of baxdrostat result in a significantly lower systolic blood pressure than placebo?

Background: Resistant hypertension—typically defined as blood pressure above goal despite the use of three or more antihypertensives, including a diuretic at maximally tolerated doses—affects roughly 10% of patients with hypertension and is associated with elevated cardiovascular risk. Aldosterone dysregulation contributes importantly to its pathophysiology. Baxdrostat, a selective aldosterone synthase inhibitor, has been investigated as a potential therapy to improve blood pressure control in this population.

Study Design: A Phase 3, double-blind, randomized, placebo-controlled trial

Setting: Multinational

Synopsis: This study recruited patients who had a systolic blood pressure of 140 to 170 mmHg despite taking a stable regimen of two antihypertensives (uncontrolled hypertension) or three or more antihypertensives, including a diuretic (resistant hypertension). A total of 796 patients underwent randomization to receive 1 mg baxdrostat, 2 mg baxdrostat, or placebo in addition to background antihypertensive therapy.

At 12 weeks, the estimated difference from placebo was -8.7 mmHg (95% CI, -11.5 to -5.8) with 1 mg baxdrostat, and -9.8 mmHg (95% CI, -12.6 to -7.0) with 2 mg baxdrostat. Hyperkalemia with a potassium level over 6.0 occurred in 2.3% of patients with 1 mg baxdrostat, 3.0% with 2 mg baxdrostat, and 0.4% with placebo. Other adverse effects observed included hyponatremia, hypotension, and a decrease in GFR.

Bottom Line: The addition of baxdrostat for patients with uncontrolled and resistant hypertension resulted in a reduction in systolic blood pressure at 12 weeks as compared to placebo.

Citation: Flack JM, et al. Efficacy and safety of baxdrostat in uncontrolled and resistant hypertension. N Engl J Med. 2025;393(14):1363-1374. doi: 10.1056/NEJMoa2507109.

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Dr. Ng is a hospitalist and a medical unit director at NYU Langone Hospital-Long Island and a clinical assistant professor in the department of internal medicine at NYU Grossman Long Island School of Medicine, both in Mineola, New York.