Effect of diuretic dose on baxdrostat efficacy and safety in uncontrolled and resistant hypertension: a post hoc analysis of the BaxHTN trial
B Williams, M Azizi, J M Flack, J P Dwyer, J M Brown, E S W Jones, V Bhalla, V Mehta, X Li, S Perl, D S Olsson, H Shibata, J G WangAbstract
Background
In the randomised, double-blind, placebo-controlled, Phase 3 BaxHTN trial, baxdrostat reduced seated systolic blood pressure (sSBP) at Week 12 in patients with uncontrolled/resistant hypertension (uHTN/rHTN).
Purpose
This post hoc analysis of BaxHTN compared efficacy and safety of baxdrostat in patients with uHTN/rHTN who received low dose vs standard dose diuretics.
Methods
Adults enrolled in BaxHTN had sSBP ≥140–<170 mmHg despite treatment with 2 (uHTN) or ≥3 (rHTN) antihypertensive medications, including a diuretic. After a 2-week placebo run in, patients with sSBP ≥135 mmHg were randomised to baxdrostat 1 mg, 2 mg, or placebo once daily for 12 weeks. In this analysis, patients were categorised by diuretic dose into low (≤0.5 defined daily dose [DDD]: e.g. indapamide ≤1.25 mg; chlortalidone ≤12.5 mg; hydrochlorothiazide ≤12.5 mg) and standard (defined as >0.5 DDD for this analysis) dose groups. Outcomes were change from baseline in sSBP, achieving sSBP <130 mmHg and safety at Week 12.
Results
Overall, 371 patients were in the low (baxdrostat 1 mg, n=133; 2 mg, n=121; placebo, n=117) and 388 in the standard (baxdrostat 1 mg, n=121; 2 mg, n=133; placebo, n=134) dose groups. Other full analysis set patients (n=35) were not classified by diuretic dose and excluded. Mean age in both groups was 61 years. More patients in the low vs standard dose group were Asian (39.9% vs 14.7%). Baseline mean sSBP/diastolic blood pressure was 149/86 and 150/87 mmHg in the low and standard dose groups. Placebo-corrected least-squares mean change in sSBP at Week 12 in the low dose group was −10.5 mmHg (95% confidence interval: −14.5, −6.6) with baxdrostat 1 mg and −10.3 mmHg (−14.3, −6.3) with 2 mg. In the standard dose group, placebo-corrected change was −6.8 mmHg (−11.1, −2.4) with baxdrostat 1 mg and −9.3 mmHg (−13.4, −5.1) with 2 mg. Interaction p-value of diuretic dose group by treatment group=0.3346. With low dose, sSBP <130 mmHg at Week 12 was achieved by 41.4% of patients with baxdrostat 1 mg, 39.7% with 2 mg and 13.9% with placebo; with standard dose, 34.7% achieved sSBP <130 mmHg with baxdrostat 1 mg, 37.1% with 2 mg and 21.6% with placebo. Overall, serious adverse events occurred in 1.5%, 2.5% and 1.7% of patients with baxdrostat 1 mg, 2 mg and placebo, respectively, in the low dose group, and 2.5%, 4.5% and 3.7% with baxdrostat 1 mg, 2 mg and placebo, respectively, in the standard dose group. Discontinuation due to hyperkalaemia occurred in 2 patients in the low (baxdrostat 2 mg, n=2 [1.7%]) and 4 patients in the standard (baxdrostat 1 mg, n=2 [1.7%]; 2 mg, n=2 [1.5%]) dose groups.
Conclusions
In this analysis, there was no apparent difference in blood pressure response in patients with uHTN/rHTN relative to background diuretic dose. Safety profiles were similar between groups, including discontinuation due to hyperkalaemia. Further data are needed to understand baxdrostat’s effect in patients without diuretics.