Key result
Baxdrostat consistently lowers systolic blood pressure regardless of background diuretic dosing.
Why the study?
The efficacy and safety of baxdrostat in patients with uncontrolled or resistant hypertension receiving low-dose versus standard-dose background diuretics had not been compared.
Does background diuretic dose (low dose vs standard dose) modify the efficacy and safety of baxdrostat 1 mg or 2 mg once daily in reducing seated systolic blood pressure at Week 12 in adults with uncontrolled or resistant hypertension?
RCT (n=759)
Double-blind
Randomised
Does background diuretic dose (low dose vs standard dose) modify the efficacy and safety of baxdrostat 1 mg or 2 mg once daily in reducing seated systolic blood pressure at Week 12 in adults with uncontrolled or resistant hypertension?
Baxdrostat 1 mg and 2 mg effectively lowered systolic blood pressure with a consistent safety profile in patients with uncontrolled or resistant hypertension regardless of whether they were receiving low-dose or standard-dose background diuretics.
Baxdrostat lowers sSBP across low- and standard-dose diuretic backgrounds; extends Phase 3 data but requires prospective confirmation before practice change.
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.
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Williams et al. (2026) conducted an RCT in Uncontrolled and resistant hypertension (n=759). Baxdrostat vs. Placebo (stratified by low vs standard background diuretic dose) was evaluated on Placebo-corrected least-squares mean change from baseline in seated systolic blood pressure (sSBP) at Week 12 (MD -10.5 mmHg (low-dose, 1 mg); -10.3 mmHg (low-dose, 2 mg); -6.8 mmHg (standard-dose, 1 mg); -9.3 mmHg (standard-dose, 2 mg), 95% CI -14.5 to -6.6, p=0.3346 for interaction). Baxdrostat (1 mg and 2 mg) reduced placebo-corrected sSBP at Week 12 similarly in low (-10.5 and -10.3 mmHg) and standard (-6.8 and -9.3 mmHg) diuretic dose groups (P_interaction=0.3346).
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