Key take-aways
- Many patients with hypertension do not have their blood pressure under control, despite treatment with multiple medications.
- The BaxHTN trial investigated the efficacy and safety of the selective aldosterone synthase inhibitor, baxdrostat, in patients with uncontrolled or treatment-resistant hypertension.
- Treatment with baxdrostat 1 mg or 2 mg once daily resulted in statistically significant reductions in systolic blood pressure vs. placebo with no unanticipated safety findings.
Madrid, Spain – 30 August 2025: Baxdrostat 1 mg or 2 mg once daily led to statistically significant reductions in blood pressure compared with placebo at 12 weeks in patients with uncontrolled or treatment-resistant hypertension, according to a late-breaking trial presented in a Hot Line session today at ESC Congress 2025.1
Despite the use of multiple medications, many people with hypertension do not achieve target blood pressure (BP) levels associated with cardiovascular disease risk reduction.2 In uncontrolled hypertension, elevated BP persists despite treatment with two or more medications, while in resistant hypertension, BP remains high despite three or more medications.
Principal Investigator, Professor Bryan Williams from University College London, UK, explained the background to the BaxHTN trial: “Aldosterone is a well-known driver of hypertension, but for decades, scientists have struggled to block its production in a precise way. Baxdrostat is one of the first therapies to do so selectively, showing meaningful BP reductions in uncontrolled or resistant hypertension.3 With the phase III BaxHTN trial, we set out to confirm the impact and safety of baxdrostat in a broader group of patients whose BP remains uncontrolled despite being on multiple treatments.”
The phase III BaxHTN trial was conducted at 214 clinical sites across multiple countries. Eligible participants were adults with ≥140 and <170 mmHg seated systolic BP (SBP) 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 a 12-week double-blind period in which 796 patients were randomised 1:1:1 to receive baxdrostat 1 mg, baxdrostat 2 mg or placebo once daily. The primary efficacy endpoint was the difference in mean change from baseline in seated SBP at week 12 with baxdrostat (1 mg or 2 mg separately) and placebo. Part 2 was a 12-week open-label period in which patients were re-randomised: 483 to receive baxdrostat 2 mg and 245 to standard-of-care. Part 3 was a double-blind randomised withdrawal period in which 257 patients from the baxdrostat 2 mg group were re-randomised 2:1 to baxdrostat 2 mg or placebo for 8 weeks. An open-label period for longer term safety analysis, from week 32 to week 52 is ongoing (part 4).
In total, 794 patients received at least one dose of baxdrostat and were analysed in part 1 (primary endpoint). They had a mean age of 62 years and 39% were women. In total, 27% had uncontrolled hypertension and 73% had resistant hypertension. At baseline, mean seated SBP and diastolic BP (DBP) were 149 mmHg and 85 mmHg, respectively. The median number of antihypertensives was 3.
For the primary endpoint at week 12, placebo-adjusted reductions in seated SBP from baseline were −8.7 mmHg for the 1 mg dose and −9.8 mmHg for the 2 mg dose (both p<0.0001). Changes 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) after 12 weeks of treatment.
The proportion of patients with controlled SBP (<130 mmHg) after 12 weeks was 39.4% with baxdrostat 1 mg, 40% with baxdrostat 2 mg and 18.7% with placebo.
Seated SBP at the end of part 2, when all patients received baxdrostat 2 mg, was 133 mmHg. Thereafter, at the end of the 8-week randomised withdrawal period (part 3), patients who received placebo/standard-of-care had a mean SBP increase (+1.4 mmHg), while those who continued on baxdrostat 2 mg had a further reduction (−3.7 mmHg; p=0.0016) at week 32.
Regarding safety, 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 in part 1. 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.
Professor 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.”
ENDS