Hot Line 4: BaxHTN
31 Aug 2025
Hot Line ESC Congress 2025 Baxdrostat in patients with uncontrolled or resistant hypertension: BaxHTN
According to Professor Bryan Williams (University College London - London, UK), the BaxHTN trial “set out to confirm the impact and safety of the selective aldosterone synthase inhibitor, baxdrostat, in a broad group of patients whose blood pressure (BP) remained uncontrolled despite being on multiple treatments.”
This international phase III trial included patients with a seated systolic BP (SBP) ≥140 and <170 mmHg despite treatment with maximally tolerated doses of two antihypertensives (uncontrolled hypertension) or at least three antihypertensives (resistant hypertension), including a diuretic, for ≥4 weeks before screening.
Part 1 was presented, a 12-week double-blind period in which 796 patients were randomised to receive baxdrostat 1 mg, baxdrostat 2 mg or placebo once daily.
For the primary endpoint at week 12, placebo-adjusted reductions in seated SBP from baseline were –8.7 mmHg with baxdrostat 1 mg and –9.8 mmHg with baxdrostat 2 mg (both p<0.0001).
Improvement of seated SBP with baxdrostat were consistent across prespecified subgroups, including uncontrolled and resistant hypertension. In an exploratory analysis, mean ambulatory 24-hour and night-time average SBP reductions were substantial with baxdrostat 2 mg (placebo-adjusted reductions of –16.9 and –11.7 mmHg, respectively). The proportion of patients with controlled SBP (<130 mmHg) was 39.4% with baxdrostat 1 mg, 40% with baxdrostat 2 mg and 18.7% with placebo.
Any serious adverse events were reported in 1.9% of patients in the baxdrostat 1 mg group, 3.4% in the baxdrostat 2 mg group and 2.7% in the placebo group over 12 weeks. Hyperkalaemia led to discontinuation in 0.8% of patients on baxdrostat 1 mg and 1.5% on baxdrostat 2 mg, with confirmed hyperkalaemia >6 mmol/l occurring in 1% of patients in both baxdrostat groups. There were no reports of adrenocortical insufficiency.
Prof. Williams concluded: “These BaxHTN trial findings are an important advance in treatment and in our understanding of the cause of hard-to-control BP. In patients with uncontrolled or resistant hypertension, the addition of baxdrostat 1 mg or 2 mg once daily to background antihypertensive therapy led to clinically meaningful reductions in SBP, with no unanticipated safety findings. This suggests that aldosterone is playing an important role in causing hard-to-control BP and offers hope for more effective treatment in the future.”
