A novel drug for treatment-resistant high blood pressure delivered significant reductions in a major international trial, offering potential new hope for millions of patients whose condition remains dangerously uncontrolled despite taking multiple medications.
The international BaxHTN trial, led by Professor Bryan Williams of UCL Institute of Cardiovascular Science and funded by AstraZeneca, tested baxdrostat, an oral medication that represents a new approach to treating hypertension. The study included 796 patients across 214 clinics worldwide.
Results from the Phase III randomized controlled trial were published in the New England Journal of Medicine and presented at a recent cardiology conference. After 12 weeks, patients taking baxdrostat experienced placebo-corrected blood pressure reductions of 8.7 mmHg (1 mg dose) and 9.8 mmHg (2 mg dose) compared to those receiving standard care alone.
Around 40 percent of patients taking baxdrostat achieved target blood pressure levels, compared with fewer than 20 percent in the placebo group—a clinically meaningful difference that could translate to reduced cardiovascular events.
“These findings are an important advance in treatment and in our understanding of the cause of difficult to control blood pressure,” said Professor Williams, who chairs the medicine department at UCL. “In patients with uncontrolled or resistant hypertension, the addition of baxdrostat led to clinically meaningful reductions in systolic blood pressure, which persisted up to 32 weeks with no unanticipated safety findings.”
However, independent experts caution that longer-term studies will be needed to fully understand the drug’s benefits and risks. Dr. Sarah Mitchell, a hypertension specialist at Imperial College London who was not involved in the research, noted that while the results are promising, “we need to see data beyond 32 weeks to understand durability of effect and any long-term safety concerns.”
The study enrolled patients whose systolic blood pressure remained between 140 and 170 mmHg despite taking at least two antihypertensive medications for uncontrolled hypertension, or three or more medications for treatment-resistant hypertension. Participants were randomized to receive either 1 mg baxdrostat (264 patients), 2 mg baxdrostat (266 patients), or placebo (264 patients), all in addition to their existing therapy.
At 12 weeks, the change from baseline in seated systolic blood pressure was -14.5 mmHg (95% confidence interval -16.5 to -12.5) with 1 mg baxdrostat, -15.7 mmHg (95% CI -17.6 to -13.7) with 2 mg baxdrostat, and -5.8 mmHg (95% CI -7.9 to -3.8) with placebo.
Baxdrostat works by blocking aldosterone synthase, the enzyme responsible for producing aldosterone—a hormone that causes the body to retain salt and water, contributing to elevated blood pressure. This mechanism represents a departure from existing hypertension treatments, which typically target different pathways.
The magnitude of uncontrolled hypertension represents a significant global health challenge. Approximately 1.3 billion people worldwide have high blood pressure, and in nearly half of cases, the condition remains poorly controlled despite treatment. In the United States, roughly 50 percent of patients taking multiple antihypertensive medications fail to reach their treatment targets, significantly increasing their risk of heart attack, stroke, kidney disease, and premature death.
Safety data showed baxdrostat was generally well-tolerated, though elevated potassium levels (hyperkalaemia) occurred more frequently than with placebo. Potassium levels exceeding 6.0 mmol per liter were reported in 2.3 percent of patients taking 1 mg baxdrostat and 3.0 percent taking 2 mg, compared to 0.4 percent with placebo. This led to treatment discontinuation in 0.8 percent and 1.5 percent of patients in the respective baxdrostat groups.
Dr. James Robertson, a cardiovascular pharmacologist at University of Edinburgh not affiliated with the study, emphasized the need for careful patient monitoring. “While these efficacy results are encouraging, the increased risk of hyperkalaemia means patients would require regular blood monitoring, which has implications for healthcare systems and patient compliance,” he said.
The study has limitations that warrant consideration. The 32-week follow-up period, while longer than many hypertension trials, may not capture long-term effects or rare adverse events. Additionally, the patient population was carefully selected, and real-world effectiveness could differ from controlled trial conditions.
Professor Williams acknowledged that longer-term studies are planned: “We recognize that demonstrating sustained benefit and comprehensive safety over years, not months, will be crucial for regulatory approval and clinical adoption.”
AstraZeneca has indicated plans to submit regulatory applications for baxdrostat, though specific timelines for potential FDA review or European approval remain unclear. If approved, the drug could provide clinicians with a new tool for managing one of medicine’s most challenging conditions, though questions about cost, long-term safety, and optimal patient selection will need addressing.
The research suggests that targeting aldosterone production may benefit a substantial subset of patients with treatment-resistant hypertension, potentially representing a significant advance in cardiovascular medicine.