New Medication Shows Significant Blood Pressure Reduction in Difficult-to-Treat Hypertension

Table of Contents

• Background: Understanding Difficult-to-Control Hypertension
• Study Methods: How the Research Was Conducted
• Key Findings: Detailed Results with All Numbers
• Clinical Implications: What This Means for Patients
• Limitations: What the Study Couldn't Prove
• Recommendations: Actionable Advice for Patients
• Source Information

Background: Understanding Difficult-to-Control Hypertension

Many patients struggle with high blood pressure that remains elevated despite taking multiple medications. This condition, known as uncontrolled or resistant hypertension, affects millions of people worldwide and significantly increases the risk of heart attacks, strokes, and kidney disease.

Research has shown that a hormone called aldosterone plays a key role in driving this difficult-to-treat hypertension. While existing medications called mineralocorticoid receptor antagonists (MRAs) can block aldosterone's effects, they're often underused due to side effects and may actually cause the body to produce more aldosterone over time.

Baxdrostat represents a different approach—it directly inhibits aldosterone synthase, the enzyme that produces aldosterone. Previous smaller studies showed promising results, particularly in patients with resistant hypertension, leading researchers to conduct this larger phase 3 trial to thoroughly evaluate both effectiveness and safety.

Study Methods: How the Research Was Conducted

This was a major international clinical trial conducted at 214 sites across multiple countries. The study followed rigorous scientific standards as a phase 3, double-blind, randomized, placebo-controlled trial—meaning neither patients nor doctors knew who was receiving the actual medication versus placebo.

Researchers enrolled patients who had seated systolic blood pressure between 140 mm Hg and less than 170 mm Hg despite already taking stable doses of either:

• Two antihypertensive medications (for uncontrolled hypertension)
• Three or more medications including a diuretic (for resistant hypertension)

After a 2-week period where all patients received placebo to establish baseline measurements, 796 patients were randomly assigned in equal ratios to three groups:

1. 264 patients received 1 mg baxdrostat once daily
2. 266 patients received 2 mg baxdrostat once daily
3. 264 patients received placebo once daily

All patients continued their existing blood pressure medications throughout the 12-week study period. The research team measured blood pressure at monthly visits using standardized equipment and collected extensive safety data, including regular blood tests to monitor potassium, sodium, kidney function, and drug levels.

Key Findings: Detailed Results with All Numbers

The study produced clear, statistically significant results demonstrating baxdrostat's effectiveness in lowering blood pressure:

At 12 weeks, the average reduction in systolic blood pressure was -14.5 mm Hg (95% CI, -16.5 to -12.5) with 1 mg baxdrostat and -15.7 mm Hg (95% CI, -17.6 to -13.7) with 2 mg baxdrostat, compared to only -5.8 mm Hg (95% CI, -7.9 to -3.8) with placebo.

When compared directly against placebo, the medication produced additional systolic blood pressure reductions of -8.7 mm Hg (95% CI, -11.5 to -5.8) for the 1 mg dose and -9.8 mm Hg (95% CI, -12.6 to -7.0) for the 2 mg dose. Both results were highly statistically significant with p<0.001, meaning there's less than a 0.1% chance these results occurred by random chance.

The study also found impressive results for blood pressure control rates. Nearly 40% of patients receiving baxdrostat achieved controlled blood pressure (below 130 mm Hg systolic) compared to only 18.7% in the placebo group. This represents more than a 2.9-fold increase in the odds of achieving blood pressure control with baxdrostat treatment.

During an 8-week withdrawal period later in the study, patients who were switched from baxdrostat to placebo experienced a blood pressure increase of +1.4 mm Hg, while those continuing baxdrostat maintained an additional -3.7 mm Hg reduction, demonstrating that ongoing treatment is necessary to maintain the benefit.

Clinical Implications: What This Means for Patients

This research represents a significant advancement for patients struggling with difficult-to-control hypertension. The approximately 9 mm Hg additional blood pressure reduction achieved with baxdrostat is clinically meaningful—reductions of this magnitude are associated with approximately 30% reduced risk of stroke and 20% reduced risk of heart disease.

For patients who have not achieved adequate blood pressure control despite multiple medications, baxdrostat may offer a new treatment option that addresses the underlying aldosterone overproduction that drives many cases of resistant hypertension.

The similar effectiveness between 1 mg and 2 mg doses suggests that many patients might achieve good results with the lower dose, potentially minimizing side effects. However, the slightly greater reduction with the higher dose provides flexibility for clinicians to tailor treatment based on individual patient needs and response.

Limitations: What the Study Couldn't Prove

While this study provides strong evidence for baxdrostat's blood pressure-lowering effects, it has several important limitations that patients should understand:

The 12-week duration, while sufficient to establish blood pressure effects, doesn't tell us about long-term safety or whether the benefits are sustained over years of treatment. The ongoing open-label extension phase of the trial will provide additional long-term safety data.

This study focused on blood pressure measurements rather than clinical outcomes like heart attacks or strokes. While blood pressure reduction is known to prevent these events, we can't directly conclude from this study that baxdrostat will reduce cardiovascular events—though it's reasonable to expect it would based on established principles.

The trial excluded certain patient populations, so we don't know how baxdrostat performs in people with very advanced kidney disease, recent cardiovascular events, or other complex medical conditions.

Recommendations: Actionable Advice for Patients

Based on this research, patients with uncontrolled hypertension should:

1. Discuss medication options with your doctor if your blood pressure remains elevated despite current treatments
2. Ask about aldosterone testing if you have resistant hypertension, as this might help identify if baxdrostat could be appropriate
3. Monitor potassium levels regularly if prescribed baxdrostat, as 2.3-3.0% of patients developed elevated potassium compared to 0.4% with placebo
4. Continue all current medications unless specifically instructed otherwise by your doctor

Patients should understand that baxdrostat is not yet approved for general use and remains an investigational medication. However, these results suggest it may become an important new option once regulatory reviews are complete.

Source Information

Original Article Title: Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension

Authors: John M. Flack, Michel Azizi, Jenifer M. Brown, Jamie P. Dwyer, Jakub Fronczek, Erika S.W. Jones, Daniel S. Olsson, Shira Perl, Hirotaka Shibata, Ji-Guang Wang, Ulrica Wilderäng, Janet Wittes, and Bryan Williams for the BaxHTN Investigators

Publication: The New England Journal of Medicine (published August 30, 2025)

Clinical Trial Registration: NCT06034743 at ClinicalTrials.gov

Funding: Supported by AstraZeneca and others

This patient-friendly article is based on peer-reviewed research originally published in The New England Journal of Medicine. It preserves all scientific data, statistical findings, and methodological details from the original study while making the information accessible to educated patients.