CONFERENCE UPDATES: ESC 2025

Baxdrostat reduces SBP in uncontrolled and resistant hypertension: Results from the phase 3 BaxHTN trial

CARDIOLOGY
27 Oct 2025

STUDY DESIGN

Individuals with uncontrolled or resistant hypertension face a significant risk of cardiovascular complications, mortality, and negative renal outcomes.1 Aldosterone dysregulation plays a crucial role in the development of uncontrolled and resistant hypertension, as well as in the organ damage associated with hypertension.1 Although mineralocorticoid receptor antagonists (MRAs) can attenuate aldosterone-mediated damage, their clinical application is limited by dose-dependent adverse effects.1 Baxdrostat is a highly selective and potent aldosterone synthase inhibitor.1 Its efficacy and safety in patients with uncontrolled or resistant hypertension were assessed in the phase 3 BaxHTN trial.1

The BaxHTN trial is a double-blind, randomized, placebo-controlled study incorporating a 12-week double-blind phase, followed by an open-label period and a randomized withdrawal (RWD) phase.1 The trial enrolled 794 adult patients with uncontrolled (27%) or resistant (73%) hypertension.1 The mean age of participants was 61 years, and 62% were men.1 Key inclusion criteria were mean seated systolic blood pressure (SBP) of 140mmHg-169mmHg despite stable therapy with ≥2 antihypertensive agents (uncontrolled hypertension) or ≥3 agents (resistant hypertension), including a diuretic, for ≥4 weeks before screening, estimated glomerular filtration rate (eGFR) ≥45mL/min/1.73m², and serum potassium ≥3.5mmol/L and <5.0mmol/L.1 Patients were excluded if they were using MRAs or potassium-sparing diuretics, had secondary hypertension, uncontrolled diabetes, cardiovascular or cerebrovascular events within 6 months, or persistent atrial fibrillation.1

Participants were randomized 1:1:1 to receive baxdrostat 1mg once daily (n=264), baxdrostat 2mg once daily (n=266), or placebo (n=264), in addition to their background antihypertensive therapy, for 12 weeks.1 This initial phase (part 1) was followed by a 12-week open-label phase (part 2) designed to collect safety data: patients already on 2mg continued treatment, while those previously on 1mg or placebo were re-randomized to either 2mg or standard-of-care therapy, providing a comparator for longer-term safety.1 In part 3, an 8-week double-blind withdrawal phase (weeks 24-32), patients receiving 2mg baxdrostat were re-randomized to continue treatment or switch to placebo.1 Part 4, which is still ongoing, is a 20-week open-label phase collecting additional safety data.1

The primary endpoint was the change in seated office SBP from baseline to week 12 (during the double-blind, placebo-controlled period).1 The key secondary endpoint was the change in SBP during the randomized withdrawal phase (weeks 24-32), whilst the key exploratory endpoint was the mean 24-hour and night-time ambulatory SBP.1

FINDINGS

Primary endpoint:
  • The primary endpoint was the change in seated office SBP from baseline to week 121
  • At 12 weeks, baxdrostat achieved significantly greater reductions in SBP compared with placebo; the least-squares mean change in SBP was -14.5mmHg (95% CI: -16.5 to -12.5) with baxdrostat 1mg, -15.7mmHg (95% CI: -17.6 to -13.7) with baxdrostat 2mg, and -5.8mmHg (95% CI: -7.9 to -3.8) with placebo1
  • The placebo-corrected differences were -8.7mmHg (95% CI: -11.5 to -5.8) for 1mg and -9.8mmHg (95% CI: -12.6 to -7.0) for 2mg (p<0.0001 for both)1
  • Reductions in seated SBP at week 12 with baxdrostat 2mg were consistent across all prespecified subgroups, irrespective of age, sex, race, baseline hypertension status, eGFR, or body mass index1

Key secondary endpoint:
  • The key secondary endpoint was the change in SBP during the randomized withdrawal phase (weeks 24-32)1
  • From week 24 to 32, the change in seated SBP was -3.7mmHg (95% CI: -5.5 to -1.9) with baxdrostat 2mg and +1.4mmHg (95% CI: -1.2 to 4.0) with placebo, indicating a between-group difference of -5.1mmHg (95% CI: -8.3 to -1.9; p=0.0016)1
  • The effect of baxdrostat on SBP offset gradually, with continued SBP reduction observed through week 32 in the 2mg group1

Key exploratory endpoint:
  • The key exploratory endpoint presented was the mean 24-hour and night-time ambulatory SBP1
  • In an ambulatory blood pressure monitoring sub-study involving 56 participants, baxdrostat substantially reduced both 24-hour and night-time systolic blood pressure1
  • Reductions in 24-hour average SBP were -13.7mmHg with 1mg and -16.0mmHg with 2mg, corresponding to placebo-corrected differences of -14.6mmHg and -16.9mmHg, respectively1
  • For night-time average SBP, baxdrostat lowered SBP by -12.1mmHg, compared with -0.4mmHg in the placebo group, yielding a placebo-corrected difference of -11.7mmHg1

Safety:
  • Adverse events (AEs) were generally mild, and no unexpected safety signals were observed1
  • The most common AEs were hyperkalemia, hyponatremia, hypotension, muscle spasms and dizziness1
  • Hyperkalemia with serum potassium >6.0mmol/L occurred in only 1.1% of patients receiving baxdrostat1

 

Get access to our exclusive articles.