A groundbreaking new medication has demonstrated the ability to significantly lower dangerously high blood pressure in patients who don’t respond to standard treatments, according to results from a major international clinical trial published this week in the New England Journal of Medicine.
The international BaxHTN trial, led by Professor Bryan Williams of UCL Institute of Cardiovascular Science and funded by AstraZeneca, tested the new drug baxdrostat with nearly 800 patients across 214 clinics around the world. The phase III study represents a potential breakthrough for millions of people globally who suffer from treatment-resistant hypertension.
“These findings are an important advance in treatment and in our understanding of the cause of difficult to control blood pressure,” said Professor Williams, Chair of Medicine at UCL. “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.”
The trial enrolled 796 patients who were randomized to receive either 1mg baxdrostat, 2mg baxdrostat, or placebo daily. At 12 weeks, patients taking 1mg baxdrostat saw their systolic blood pressure drop by 14.5 mmHg while those on 2mg dropped 15.7 mmHg, compared to just 5.8 mmHg for placebo. The placebo-corrected differences were 8.7 mmHg for 1mg and 9.8 mmHg for 2mg (P<0.001 for both comparisons).
Perhaps most importantly for patients, around 40 percent of patients taking baxdrostat reached healthy blood pressure levels, compared with fewer than 20 percent in the placebo group.
The drug works through an entirely novel mechanism for treating hypertension. Baxdrostat blocks the production of the hormone aldosterone, which regulates the balance of salt and fluid in the body. Some people have an excess of aldosterone, which leads to increased blood pressure and makes treatment difficult. Baxdrostat acts directly on this mechanism, eliminating one of the key causes of persistent hypertension.
“I think this could be a game-changer in the way we approach difficult-to-control or hard-to-control blood pressure,” said Professor Bryan Williams, who serves as the study’s principal investigator.
The trial targeted patients with the most challenging cases of hypertension. Participants had seated systolic blood pressure between 140 and 170 mmHg despite stable treatment with two antihypertensive medications (uncontrolled hypertension) or three or more medications (resistant hypertension), including a diuretic.
Dr. Sarah Mitchell, a consultant cardiologist at King’s College London who was not involved in the study, described the results as “highly encouraging” but cautioned that longer-term studies would be needed to assess the drug’s durability and safety profile over years of treatment.
“These results suggest we may have identified a new pathway for treating some of our most difficult hypertension cases,” Mitchell said. “However, we need to understand better which patients will benefit most from this approach.”
Safety data showed the drug was well-tolerated overall. Elevated potassium levels above 6.0 mmol per liter—a condition called hyperkalemia that can affect heart rhythm—were reported in 6 patients (2.3%) with 1-mg baxdrostat, 8 patients (3.0%) with 2-mg baxdrostat, and 1 patient (0.4%) with placebo. While these levels require monitoring, they were generally manageable and did not lead to significant complications in the trial.
The effect of the drug lasted up to 32 weeks without revealing unexpected side effects, making it a promising option for long-term therapy.
Hypertension remains one of the most common health problems worldwide, affecting approximately 1.3 billion people according to World Health Organization estimates. In the United States alone, roughly half of patients on multiple medications still fail to achieve adequate blood pressure control, putting them at elevated risk for cardiovascular events.
The global burden of hypertension has shifted dramatically in recent decades. While higher rates were historically seen in wealthier Western countries, changing diets and lifestyle factors have shifted the global burden. Today, far more cases are found in Eastern and lower-income countries, with more than half of all people with hypertension living in Asia.
Recent guidelines from major cardiology societies have emphasized tighter blood pressure control targets, making effective treatments for resistant cases even more crucial. “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 target blood pressure goals have become more stringent,” Williams noted.
The research was supported by the NIHR Biomedical Research Centre at University College London Hospitals. AstraZeneca has indicated it plans to seek regulatory approval for baxdrostat based on these results, though the timeline for potential availability to patients remains unclear.
Professor Williams stated the results suggest this approach “could potentially help millions of people globally achieve better blood pressure control, offering new hope for those who haven’t responded adequately to existing treatments.”