Exceeding the Limits of Daily Medication? Astra's New Drug Baxdrostat Lowers Blood Pressure More Than Twice as Much as Standard Medication in Resistant Hypertension

"No more medication can be added," "It won't go down." A new drug taken once daily may change the landscape of real-world treatment for such "stubborn hypertension." AstraZeneca's baxdrostat, presented at the European Society of Cardiology (ESC 2025), showed a strong signal of lowering blood pressure by an average of 15.7mmHg in the global late-stage trial (BaxHTN), when added to conventional treatment. The placebo showed a reduction of 5.8mmHg, with a placebo-adjusted difference of about 10mmHg. The company aims to apply for approval within 2025, potentially adding a new dimension to the "final push" in antihypertensive treatment. NDTV ProfitESCARDIO

What's new — Cutting off at the "source"

Baxdrostat is an aldosterone synthase (CYP11B2) inhibitor. It suppresses the production itself of the hormone "aldosterone," which promotes salt and water retention, differing from drugs like spironolactone that block receptors. Excess aldosterone tends to increase with age, contributing to the difficulty in lowering blood pressure even with multiple drugs. Experts point out that "the role of aldosterone in the pathology of hypertension is greater than expected." NDTV Profit

Key points of the trial — Clear differences in 12 weeks

In BaxHTN, once-daily doses of 1mg/2mg both showed statistically significant blood pressure reductions at 12 weeks. The additional reduction in the 2mg group was an average of 15.7mmHg, while the placebo showed 5.8mmHg. Analyses published in NEJM and presented in the conference hotline reported a placebo-adjusted difference of approximately 10mmHg. The reduction was reproducible in 24-hour blood pressure, and some UK media reported that the proportion of patients reaching target blood pressure doubled. Bloomberg.comESCARDIOThe Guardian

Patient scale — "About 10% of adults" are resistant

Hypertension that remains uncontrolled despite standard treatments, known as resistant or poorly controlled, affects about 10% of adults, according to an editorial in NEJM. It is a major cause of death risk factors such as stroke, heart failure, and kidney failure, and even a 10mmHg reduction in blood pressure directly correlates with a reduced risk of events. Therefore, the effect size in this case is clinically significant. NDTV Profit

Safety — Attention to early hyperkalemia

Regarding side effects, about 3% hyperkalemia at high doses was reported, with a tendency to appear **mostly early in administration (within 2 weeks)**. Monitoring potassium levels and managing interactions with concomitant medications (ACE inhibitors/ARBs, diuretics, etc.) are key points in implementation. Long-term safety and cardiovascular outcomes (stroke, heart failure, kidney events) are yet to be evaluated. NDTV Profit

Prospects for approval and commercialization

AstraZeneca commented on considering application within the year. Analysts estimate peak sales to be in the billions of dollars, envisioning its integration into the core of the cardio-renal-metabolic portfolio. The key in real-world settings will be the stratification and access (pricing and insurance coverage) of "who benefits." NDTV ProfitInvestors.com

Competition and the "two giants" scenario — Tablets vs. Injections

• Lorundrostat (Mineralys): Another ASi (aldosterone synthase inhibitor), showing promising data such as a 12-week placebo-adjusted difference of 11.7mmHg in trials like Launch-HTN/Advance-HTN. Mineralys Therapeutics, Inc.

• Zilebesiran (Roche/Alnylam): Twice-yearly administration is also considered for this siRNA injection. A long-term trial involving cardiovascular outcomes as the primary focus, involving approximately 11,000 multinational participants, is set to begin within the year. It poses a challenge to medication adherence issues. Business WireESCARDIO

Summary of reactions at the venue and on social media

• The official NEJM journal announced the publication of the BaxHTN paper on X, significantly increasing its visibility within the clinical community. X (formerly Twitter)

• The American College of Cardiology (ACC) also noted the joint presentation of baxdrostat and zilebesiran at the ESC hotline, raising the momentum for the entire field. X (formerly Twitter)

• From interventional cardiovascular specialists, there were posts suggesting that "the indication for renal denervation might relatively decrease with this data." Active discussions continue on whether the treatment map will be rewritten. X (formerly Twitter)

• On Reddit, a thread for sharing news among patients and the general public was created, featuring comments with varying degrees of enthusiasm, such as "Good news for those whose blood pressure doesn't go down despite more medication" and "Safety assessment is yet to come." Reddit

What will change — Strategy to capture the "last 10mmHg"

In hypertension treatment, "step-up" is the basic approach, but the clinical challenge is often the last 10mmHg. Factors such as salt sensitivity, aging, declining kidney function, and decreased adherence are intertwined. ASi (aldosterone synthase inhibitor) directly addresses this bottleneck. Being a once-daily tablet is also an advantage. On the other hand, the rise of the siRNA camp, which seeks to "structurally solve" adherence issues with twice-yearly injections, encourages differentiated use according to patient type in real-world settings. The GuardianBusiness Wire

Checklist of discussion points from here

1. Long-term safety: Management of hyperkalemia, impact on kidney function, and appropriateness of long-term endocrine intervention. NDTV Profit

2. Outcomes: Confirmation of benefits in event suppression (stroke/heart failure/kidney events). siRNA is moving towards large trials with outcomes as the primary focus. Business Wire

3. Stratification: Subgroups with high aldosterone activity, comorbid kidney function and diabetes, differences in Asian populations. sciencemediacentre.org

4. Real-world: Additional effects and cost-effectiveness under multiple drug combinations, initial monitoring system. Investors.com

Summary

Baxdrostat, as a leading candidate for the "source approach" to resistant hypertension, has shown compelling numbers with a double-digit mmHg placebo-adjusted difference. The competition with lorundrostat and the conceptually different zilebesiran signifies the arrival of an era where patients have "choices." However, only after long-term safety evaluation and outcome verification can it be called the "new standard." The possibility of updating the common sense of antihypertensive treatment is high from late 2025 to 2026. ##