BaxHTN: Baxdrostat Achieves Primary Endpoint in Treating Hypertension

Baxdrostat, AstraZeneca’s investigational aldosterone synthase inhibitor for the treatment of uncontrolled and resistant hypertension, achieved its primary endpoint of change in seated systolic blood pressure compared to placebo in the phase 3 BaxHTN trial.1

Presented at the 2025 European Society of Cardiology Congress in Madrid, Spain, on August 30, 2025, the trial showed a significantly lower seated systolic blood pressure at 12 weeks in patients assigned to baxdrostat added to background therapy versus those assigned to placebo. According to investigators, these data represent a step towards broader protection against hypertension, targeting mitigation of aldosterone-driven fibrosis, renal damage, and vascular injury, as well as avoidance of cortisol effects.1,2

“It’s exciting, because now we’re looking at a completely new class of blood pressure medication with these aldosterone synthase inhibitors,” said trial investigator Jenifer Brown, MD, a cardiovascular specialist at Brigham and Women's Hospital, in an interview with HCPLive. “And beyond just being a new class, it’s targeting a hormone, aldosterone, that we think is a really prevalent and important driver of high blood pressure that doesn’t just lead to sodium and fluid retention, but also potentially directly to cardiovascular disease.”

The phase 3, multinational, double-blind, randomized, placebo-controlled BaxHTN trial included patients with seated systolic blood pressures between 140 mm Hg and <170 mm Hg. Additionally, patients must have received stable treatment with 2 antihypertensive medications (uncontrolled hypertension) or ≥3 such medications (resistant hypertension), including a diuretic.1

After a 2-week placebo run-in period, investigators randomly assigned patients with a seated systolic blood pressure of ≥135 mm Hg in a 1:1:1 ratio to baxdrostat 1mg, baxdrostat 2mg, or placebo daily for 12 weeks. A total of 264 patients received baxdrostat 1mg, 266 received baxdrostat 2mg, and 264 received placebo, in addition to background therapy.1

At 12 weeks, investigators noted a change from baseline in least-squares mean seated systolic blood pressure of -14.5 mm Hg (95% CI, -16.5 to -12.5) with 1mg baxdrostat. The 2mg group saw a change of -15.7 mm Hg (95% CI, -17.6 to -13.7), and the placebo group saw a change of -5.8 mm Hg (95% CI, -7.9 to -3.8). Additionally, a potassium level of >6 mmol per liter was reported in 6 patients (2.3%) with baxdrostat 1mg, in 8 patients (3%) with baxdrostat 2mg, and in 1 patient (0.4%) with placebo.1

"Aldosterone is a well-known driver of hypertension, but for decades, scientists have struggled to block its production in a precise way," said Bryan Williams, MB.BS, in a press release by the ESC. "Baxdrostat is one of the first therapies to do so selectively, showing meaningful BP reductions in uncontrolled or resistant hypertension."3

In a related editorial published in NEJM, Tomasz Guzik, MD, PhD, highlighted 3 distinct clinical messages from the trial. First, baxdrostat’s lowering of systolic blood pressure was similar to that of spironolactone and other aldosterone synthase inhibitors. This occurred on top of existing RAAS blockades and near-universal diuretic use, highlighting the potential of these inhibitors to overcome aldosterone breakthrough in salt-retaining hypertension.2

Second, adverse biochemical changes emerged within 2 weeks and were monitored by lab checks at baseline, at 1 to 2 weeks, and after 4 weeks. Discontinuations due to hyperkalemia were rare, indicating a solid safety profile. Finally, durability was established during the randomized-withdrawal phase, which saw blood pressure rise only modestly despite drug clearance. This suggests physiological resets of sodium balance or vascular tone. These results could support steadier blood-pressure control and reduced rescue therapy.2

References

1. Flack J, Azizi M, Brown J, et al. Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension. N Engl J Med. August 30, 2025. Accessed August 30, 2025. DOI: 10.1056/NEJMoa2507109.

2. Guzik T, Tomaszewski M. Aldosterone Synthase Inhibition for Hypertension. N Engl J Med. August 30, 2025. Accessed August 30, 2025. DOI: 10.1056/NEJMe2511533.

3. European Society of Cardiology. Blood-pressure reductions with baxdrostat in patients with uncontrolled or resistant hypertension. News Release. August 30, 2025. Accessed August 30, 2025.