Experimental drug could change high blood pressure treatment

High blood pressure that will not budge despite multiple medications is a daily frustration for patients and clinicians. A new pill called Baxdrostat takes a different tack by turning down a hormone that keeps pressure high.

Baxdrostat is designed for people whose numbers stay above the goal even when they take a careful mix of standard drugs. It targets a key biological switch without affecting other hormones that the body needs.

Baxdrostat and high blood pressure

Doctors use the term resistant hypertension when blood pressure remains above target while taking three or more medicines, including a water pill. Many people live in this tough category, and the health risks stack up quickly.

One driver is aldosterone, a hormone that tells the kidneys to hold onto salt and water. Too much aldosterone raises blood volume, tightens blood vessels, and pushes pressure higher.

Baxdrostat blocks aldosterone synthase, the enzyme that makes aldosterone, so the body produces less of it.

In earlier research, this approach reduced aldosterone while leaving cortisol unchanged, which matters because cortisol helps the body manage stress, inflammation, and metabolism.

Doctors have long used mineralocorticoid receptor blockers to blunt aldosterone’s effects. Those drugs help many people but can be limited by rises in blood potassium and other side effects.

BaxHTN hypertension trial

The latest evidence comes from BaxHTN, a global randomized study that compared Baxdrostat 1 milligram, Baxdrostat 2 milligrams, and a placebo on top of usual therapy for 12 weeks.

The BaxHTN trial enrolled adults with seated clinic pressures that remained high despite standard treatments.

Participants had seated systolic blood pressure of between 140 and 170 millimeters of mercury at the start.

They represented two groups: those uncontrolled on two drugs and those resistant on three or more drugs including a diuretic.

Hypertension changed with Baxdrostat

At 12 weeks, the BaxHTN trial showed larger drops in seated systolic blood pressure with Baxdrostat than with placebo.

Compared with placebo, the 1 milligram dose lowered systolic pressure by 8.7 millimeters of mercury, and the 2 milligram dose lowered it by 9.8 millimeters of mercury.

Those reductions came on top of current therapy, which matters in a population already taking several medicines.

Confirmed hyperkalemia, defined in the study as potassium above 6.0 millimoles per liter, occurred in 2.3 percent of patients on 1 milligram, 3.0 percent on 2 milligrams, and 0.4 percent on placebo.

Comparison to earlier studies

Before BaxHTN, the BrigHTN phase 2 trial in treatment resistant patients found Baxdrostat improved blood pressure control over placebo.

This lent support to using the new strategy in the harder-to-treat group. Those data encouraged the larger, phase 3 program.

By contrast, the HALO phase 2 trial in patients with uncontrolled hypertension did not show a significant difference between Baxdrostat and placebo over eight weeks.

This result linked to an unusually strong placebo effect and adherence issues at some sites. BaxHTN addressed many of those concerns with stricter procedures, longer follow-up, and a broader patient mix.

Safety and tradeoffs

Any drug that lowers aldosterone can push potassium up. The BaxHTN safety data show that risk exists, but most cases were manageable with standard monitoring and adjustments.

Clinicians already watch potassium in people on certain diuretics or ACE inhibitors. The same routine makes sense here, especially in patients with kidney disease or those who take supplements that raise potassium.

Why Baxdrostat matters

Every few points of systolic pressure matter for long-term risk of heart attack, stroke, heart failure, and kidney disease.

A therapy that reliably trims around 9 to 10 millimeters of mercury on top of usual care could help many patients finally cross the finish line.

“Achieving a nearly 10 mm Hg placebo-adjusted reduction in systolic blood pressure with Baxdrostat in the BaxHTN phase 3 trial is exciting,” said Bryan Williams, MD, chair of medicine at University College London.

“This level of reduction is linked to substantially lower risk of heart attack, stroke, heart failure, and kidney disease,” he added. Williams is the primary study investigator and a leading hypertension specialist.

What to watch next

Baxdrostat is taken once daily, which fits the routines of people already juggling morning and evening pills. If approved, it would be added to existing regimens rather than replacing proven therapies.

Researchers are also studying longer term outcomes and ambulatory readings to understand around-the-clock effects.

Results from other Baxdrostat trials will clarify whether specific subgroups benefit most and how the drug fits alongside diuretics, calcium channel blockers, and blockers of the renin angiotensin system.

Baxdrostat may be a game changer

People whose blood pressure sits stubbornly over 140 millimeters of mercury in the clinic, despite their taking a smart combination of drugs, are the immediate focus.

That includes those with a strong aldosterone signal who cannot tolerate high dose mineralocorticoid receptor blockers.

The approach may also be useful for patients whose blood pressure spikes at night, a pattern tied to aldosterone in many studies.

Dosing that keeps hormone production tamped down across a full day could blunt these surges and smooth daily averages.

This is a study drug for now, so doctors cannot prescribe it outside trials until regulators complete their review.

Discussions about candidacy will look at current medications, kidney function, and baseline potassium.

People on potassium sparing diuretics, salt substitutes that contain potassium chloride, or high dose supplements need careful supervision. Routine blood tests will remain part of the plan to keep treatment safe and effective.

The study is published in The New England Journal of Medicine.

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