Promising new drug for people with stubborn high blood pressure: NEJM

A new treatment has been shown to significantly lower blood pressure in people whose levels stay dangerously high, despite taking several existing medicines, according to the results of a Phase III clinical trial led by a UCL Professor.

Globally around 1.3 billion people have high blood pressure (hypertension), and in around half of cases the condition is uncontrolled or treatment resistant. These individuals face a much greater risk of heart attack, stroke, kidney disease, and early death. In the UK the number of people with hypertension is around 14 million.

The international BaxHTN trial, led by Professor Bryan Williams (UCL Institute of Cardiovascular Science) and sponsored by AstraZeneca, assessed the new drug baxdrostat -which is taken as a tablet – with participation from nearly 800 patients across 214 clinics worldwide.

The study was supported by the NIHR Biomedical Research Centre at UCLH.

Results are being presented today (Saturday 30th August) at the European Society of Cardiology (ESC) Congress 2025 in Madrid and are being simultaneously published in the New England Journal of Medicine.

The trial results showed that, after 12 weeks, patients taking baxdrostat (1 mg or 2 mg once daily in pill form) saw their blood pressure fall by around 9-10 mmHg more than placebo – a reduction large enough to cut cardiovascular risk. About 4 in 10 patients reached healthy blood pressure levels, compared with fewer than 2 in 10 on placebo.

Principal Investigator, Professor Williams, who is presenting the results at ESC, said: “Achieving a nearly 10 mmHg reduction in systolic blood pressure with baxdrostat in the BaxHTN Phase III trial is exciting, as this level of reduction is linked to substantially lower risk of heart attack, stroke, heart failure and kidney disease.”

How baxdrostat works

Blood pressure is strongly influenced by a hormone called aldosterone, which helps the kidneys regulate salt and water balance.

Some people produce too much aldosterone, causing the body to hold onto salt and water. This aldosterone dysregulation pushes blood pressure up and makes it very difficult to control.

Addressing aldosterone dysregulation has been a key effort in research over many decades, but it has been so far difficult to achieve.

Baxdrostat works by blocking aldosterone production, directly addressing this driver of high blood pressure (hypertension).

Professor Williams, Chair of Medicine at UCL, said: “These findings are an important advance in treatment and in our understanding of the cause of difficult to control blood pressure.

“Around half of people treated for hypertension do not have it controlled, however this is a conservative estimate and the number is likely higher, especially as the target blood pressure we try to reach is now much lower than it was previously.*

“In patients with uncontrolled or resistant hypertension, the addition of baxdrostat 1mg or 2mg once daily to background antihypertensive therapy led to clinically meaningful reductions in systolic blood pressure, which persisted up to 32 weeks with no unanticipated safety findings.

“This suggests that aldosterone is playing an important role in causing difficult to control blood pressure in millions of patients and offers hope for more effective treatment in the future.”

Historically higher income Western countries were reported to have far higher levels of hypertension; however, largely due to changing diets (adding less salt to food), the numbers of people living with the condition is now far higher in Eastern and lower income countries. More than half of those affected live in Asia, including 226 million people in China and 199 million in India.

Professor Williams added: “The results suggest that this drug could potentially help up to half a billion people globally – and as many as 10 million people in the UK alone, especially at the new target level for optimal blood pressure control.”

Reference:

John M. Flack, Michel Azizi, Jenifer M. Brown, Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension, New England Journal of Medicine, DOI: 10.1056/NEJMoa2507109.