Baxdrostat lowered round-the-clock blood pressure in a resistant-hypertension trial

Office blood-pressure readings are a snapshot. They are taken in a clinic, at one moment, often with the white-coat effect in play. The more demanding test of a blood-pressure drug is what it does across an ordinary day and night, measured by a cuff the patient wears for 24 hours. Bax24, published in The Lancet, put baxdrostat to exactly that test in people whose hypertension had resisted several drugs already [s1].

Baxdrostat is a selective aldosterone synthase inhibitor — it blocks the enzyme that makes aldosterone, a hormone that drives salt retention and raised pressure, rather than blocking the receptor aldosterone acts on. It reached the market on the strength of seated, in-clinic readings. Bax24 asks whether the effect holds up on a round-the-clock measure.

What Bax24 did

The trial was international, phase 3, randomised, double-blind and placebo-controlled, run at 79 clinical sites in 22 countries [s1]. It enrolled adults with seated systolic pressure of 140 mm Hg or higher but below 170 mm Hg despite taking three or more antihypertensive drugs, one of them a diuretic [s1]. After a two-week placebo run-in, patients whose 24-hour ambulatory systolic pressure was 130 mm Hg or higher were randomly assigned one-to-one to 2 mg of baxdrostat or placebo once daily for 12 weeks, on top of their existing treatment [s1].

The screening funnel is worth seeing. Between 1 March 2024 and 16 April 2025, 854 patients were screened and 636 were excluded — 437 before the placebo run-in and 199 during it — leaving 217 who were randomly assigned to baxdrostat (n=108) or placebo (n=109) [s1]. That heavy attrition, much of it during a placebo run-in, is how a resistant-hypertension trial confirms that the pressure is real and not a matter of missed pills. Of those randomised, 140 (65%) were male and 77 (35%) female, 170 (78%) were White, and the median age was 60.0 years (IQR 51.0–68.0) [s1]. The trial is registered as NCT06168409 and is complete [s2].

The numbers

At 12 weeks, the least-squares mean change in 24-hour ambulatory systolic pressure was −16.6 mm Hg (95% CI −18.8 to −14.3) in the baxdrostat group (n=89) and −2.6 mm Hg (−4.7 to −0.4) on placebo (n=95) [s1]. The placebo-corrected difference was −14.0 mm Hg (95% CI −17.2 to −10.8; p<0.0001) [s1].

A 14-point placebo-adjusted fall on a 24-hour measure is a large effect for a drug added to an already-loaded regimen. Ambulatory readings tend to produce smaller placebo responses than office readings — here the placebo arm dropped just 2.6 mm Hg — which makes the separation between the groups harder to dismiss as regression to the mean or white-coat effect.

The safety signal to watch

Blocking aldosterone synthase raises the same concern that has dogged every drug acting on this pathway: potassium. Adverse events occurred in 56 (52%) of the 108 baxdrostat recipients against 40 (37%) of the 109 on placebo [s1]. A confirmed potassium level above 6 mmol/L — a level that can disturb heart rhythm — occurred in three (3%) of the baxdrostat group and in none of the placebo group [s1].

Three cases in a 12-week trial of about a hundred people is not a reason to set the drug aside, but it is the number that matters most for how it would be used. Hyperkalaemia is dose-dependent and interacts with kidney function and with other common blood-pressure drugs, and a short trial in a selected population is the most favourable setting in which to measure it. Real-world use, in people with worse kidney function and more co-prescriptions, is where the rate would be tested properly.

What it does and does not settle

Bax24 was designed to measure blood pressure, not outcomes. It does not report heart attacks, strokes, kidney events or deaths, and it was neither designed nor long enough to do so [s1]. The case that lowering pressure this much prevents those events rests on decades of evidence for blood-pressure reduction in general, not on this trial. The trial was funded by AstraZeneca, which is developing the drug [s1] — the standard caveat for an industry-run registration study, and a reason the independent replication of the ambulatory finding carries weight.

What Bax24 adds is specific and useful: the reduction baxdrostat produces is not an artefact of the clinic, and it persists across the full day and night in people whose pressure had already defeated several drugs. Whether that translates into fewer cardiovascular events, and whether the potassium signal stays manageable outside a trial, are the open questions — and only longer outcome trials can answer them.

This article is informational and does not constitute medical advice.

Sources

• [s1] Effect of baxdrostat on ambulatory blood pressure in patients with resistant hypertension (Bax24): a phase 3, randomised, double-blind, placebo-controlled trial. The Lancet, 1 March 2026. https://doi.org/10.1016/S0140-6736(25)02549-8
• [s2] A Study to Investigate the Effect of Baxdrostat on Ambulatory Blood Pressure in Participants With Resistant Hypertension. ClinicalTrials.gov identifier NCT06168409, US National Library of Medicine. https://clinicaltrials.gov/study/NCT06168409