Home > Cardiology > ACC 2023 > Miscellaneous > Baxdrostat in patients with uncontrolled hypertension

Baxdrostat in patients with uncontrolled hypertension

Presented By
Dr Deepak Bhatt, Icahn School of Medicine at Mount Sinai, NY, USA
ACC 2023
Phase 2, HALO

In the placebo-controlled phase 2 HALO trial, baxdrostat did not achieve a statistically significant change from baseline in mean seated systolic blood pressure (SBP) in patients with uncontrolled hypertension. The placebo effect in this study was substantial. In a post-hoc analysis, SBP was significantly lowered in patients adherent to the highest dose of 2 mg.

The results of the phase 2 HALO study (NCT05137002) were highly anticipated since there have not been any new agents to treat uncontrolled hypertension in well over a decade, said Dr Deepak Bhatt (Icahn School of Medicine at Mount Sinai, NY, USA) [1]. Baxdrostat is a highly selective aldosterone synthase inhibitor. Its efficacy and safety were evaluated in the randomised, double-blind, placebo-controlled, multicentre, phase 2 HALO trial. The participants had to be on a stable regimen of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), an ACEi/ARB plus a thiazide diuretic, or an ACEi/ARB plus a calcium channel blocker, and have a mean seated SBP ≥140 mmHg. The primary endpoint was change from baseline in mean seated SBP after 8 weeks of treatment. A total of 249 patients were randomised 1:1:1:1 to baxdrostat 0.5 mg, 1 mg, 2 mg, or placebo; 227 completed the trial.

The primary endpoint was not met with any baxdrostat dose. SBP change was -17.0, -16.0, and -19.8 mmHg in the 0.5 mg, 1 mg, and 2 mg groups, respectively, but there was also a large decrease (-16.6 mmHg) in the placebo group (see Figure).

Figure: Placebo-corrected change from baseline in mean seated SBP at 8 weeks [1]

Similarly, none of the baxdrostat doses were associated with a significant difference in placebo-corrected diastolic blood pressure (DBP), which was a secondary endpoint. Change in DBP at 8 weeks did not significantly differ either; nor did the percentage of patients achieving a seated SBP response <130 mmHg at 8 weeks. Baxdrostat significantly reduced serum aldosterone levels at all doses. The treatment was well tolerated.

Dr Bhatt explained that a post-hoc analysis was done in patients who were adherent to the highest baxdrostat dose of 2 mg. The reason was that 20 of 54 (36%) patients in the 2 mg arm who completed 8 weeks of treatment had baxdrostat levels <0.2 ng/dL, indicating non-adherence (despite dosing records by pill count showing >95% adherence in all groups). This subgroup analysis suggested a placebo-corrected SBP reduction of 7.9 mmHg in patients adherent to baxdrostat 2 mg.

  1. Bhatt DL, et al. Results from a phase 2, double-blind, placebo-controlled trial evaluating the efficacy and safety of baxdrostat in patients with uncontrolled hypertension. Session 403-08, ACC Scientific Session 2023, 4–6 March, New Orleans, USA.


Copyright ©2023 Medicom Medical Publishers

Posted on