August 30, 2025
3 min read
Key takeaways:
- Baxdrostat led to substantial BP lowering, with 40% of patients with uncontrolled hypertension reaching BP of less than 130 mm Hg.
- Treatment was well-tolerated.
Adding baxdrostat to background antihypertensive therapy led to substantial reductions in seated systolic blood pressure after 12 weeks of treatment among patients with uncontrolled or resistant hypertension.
The results of the phase 3, multinational, double-blind, randomized, placebo-controlled BaxHTN trial of baxdrostat (AstraZeneca), an aldosterone synthase inhibitor, in patients with uncontrolled or resistant hypertension were presented at the European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine.
Baxdrostat led to substantial BP lowering, with 40% of patients with uncontrolled hypertension reaching BP of less than 130 mm Hg. Image: Adobe Stock
“Hypertension is a huge problem. [Hypertension] impacts over a billion people worldwide, and hundreds of millions of people don’t have their blood pressure controlled, and so they’re experiencing unnecessary extra risk for heart attack, stroke, heart failure, kidney disease and dementia,” Jenifer M. Brown, MD, cardiologist at Brigham and Women’s Hospital, told Healio. “Parallel with that, we have come to understand the importance of aldosterone, a hormone that we know is helping us to retain sodium and fluid and drive high blood pressure, but also drive those heart outcomes. … That’s really the motivation for the development of this new class of drugs called aldosterone synthase inhibitors, which specifically target production of aldosterone to try to address one of these underlying drivers of blood pressure that’s hard to control.”
For the BaxHTN trial, researchers enrolled 796 adults with seated systolic BP of 140 mm Hg to 170 mm Hg despite treatment with two antihypertensive medications, which the researchers defined as uncontrolled hypertension, or three or more antihypertensive medications, which defined resistant hypertension, including a diuretic. The average age was about 60 years and the cohort was mostly men and white.
After a 2-week placebo run-in period, patients were randomly assigned to once-daily baxdrostat 1 mg, baxdrostat 2 mg or placebo for 12 weeks.
The primary end point was the change in seated systolic BP by week 12.
Bryan Williams
“This is a potential game changer for patients. Because, despite the best efforts of clinicians and the drugs they have available, at least 50% of patients … don’t have their blood pressure controlled,” Bryan Williams, OBE, MD, FMedSci, professor and chair of medicine at University College London and chief scientific and medical officer at the British Heart Foundation, said during a press conference. “This should provide a treatment that’s more effective because it targets the core mechanism, helping to reduce their future risk of heart disease, stroke, kidney disease and potentially dementia.”
Efficacy of baxdrostat
At 12 weeks, change in mean seated systolic BP was –14.5 mm Hg (95% CI, –16.5 to –12.5) for patients assigned baxdrostat 1 mg, –15.7 mm Hg (95% CI, –17.6 to –13.7); with baxdrostat 2 mg and –5.8 mm Hg (95% CI, –7.9 to –3.8) with placebo.
The researchers reported the placebo-corrected difference was –8.7 mm Hg with baxdrostat 1 mg (95% CI, –11.5 to –5.8; P < .001) and –9.8 mm Hg for baxdrostat 2 mg (95% CI, –12.6 to –7; P < .001).
Moreover, approximately 40% of participants achieved BP control, with systolic BP of less than 130 mm Hg, with baxdrostat vs. 18.7% of those assigned to placebo, according to the results.
In an exploratory substudy designed to assess the impact of baxdrostat on 24-hour ambulatory BP, baxdrostat 1 mg and 2 mg conferred mean BP reductions of –13.7 mm Hg and –16 mm Hg, respectively, compared with a 1 mm Hg increase with placebo. The mean difference in ambulatory night-time average systolic BP was 11.7 mm Hg lower with baxdrostat compared with placebo, Williams said.
“The magnitude of change of blood pressure was remarkably consistent across every subgroup. his is consistent with the hypothesis that aldosterone is playing a fundamental role in the generation of difficult-to-control hypertension,” Williams said during the press conference.
Safety of baxdrostat
Adverse events occurred in 47.3% of patients assigned baxdrostat 1 mg, 44.7% assigned baxdrostat 2 mg and 41.3% assigned placebo.“The most common adverse events were elevations in potassium, and low sodium values tend to be present by about 2 weeks and then stable after that in the trial,” Brown told Healio. “Less than 2% to 3% of patients who had elevations in potassium needed a clinical intervention, and a small fraction of patients ended up needing to discontinue therapy. The adverse events were as expected and there were generally mild amounts of electrolyte abnormalities.”
A potassium level of more than 6 mmol/L occurred in 2.3% of patients assigned baxdrostat 1 mg, 3% assigned baxdrostat 2 mg and 0.4% assigned to placebo. Mild hyponatremia occurred in 19.1%, 22.8% and 7%, respectively.
“It’s exciting to have a new class of medications for BP after decades without new medication classes, and to have one that we think really targets a driver of high BP,” Brown told Healio.
Reference:
Sources/Disclosures
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Williams B, et al. Hot line 4. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2025; Madrid (hybrid meeting).
Disclosures:
The BaxHTN trial was funded by AstraZeneca. Brown reports serving on the BaxHTN trial steering committee. Williams reports receiving honoraria from Medtronic and Servier; consulting for Antila Bioscience, AstraZeneca and Novartis; and serving as investigator on clinical trials for AstraZeneca, Eli Lilly and Company and Novartis.
