MADRID, Spain - Backsdorastat (Astrazeneca), a research aldosterone synthase inhibitor, significantly lowers blood pressure when added to background therapy in patients with uncontrolled or resistant hypertension, according to results from the Phase III BaxHTN trial.
By 12 weeks, coordinate Systolic BP was 8.7 mm Hg lower at Baxdrostat at a dose of 1 mg, and 9.8 mm Hg lower at 2 mg dose after explaining the placebo effect (p Both were reported in Brian Williams, Maryland (London University College, UK), here in 2025. Therapeutic effects were shown to last for at least 32 weeks.
Baxdrostat has been well tolerated without unexpected safety issues, Williams said.
Survey results, It's also published online in New England Journal of Medicineenter the details about the area Topline Results Released in July.
"This is a potential game changer for patients, because at this point, despite the best efforts of clinicians and available drugs, at least 50% of patients have no control over blood pressure, even in the most developed healthcare system," Williams said at a press conference.
According to Sidney Smith JR, MD (UNC School of Medicine, Chapel Hill, NC), the results show a "real promise" and leads guidelines efforts at the National Institutes of Health, the American Heart Disease/American Heart Association's National Heart Institute and the Blood Institute.
Smith had several questions about how resistance to treatment was determined in the trial and whether home BP measurements were used.
"These were early results, but they looked very good," he told TCTMD, adding that the timing of their publications was by chance. in Latest US Hypertension Guidelines Earlier this month, Smith helped write, "We increased our focus on aldosterone. In general, 20-25% of patients with resistant hypertension have hyperaldosteronism."
The importance of aldosterone for hypertension could exceed this resistance group, Smith said he notes that aldosterone levels are gradually increasing with age. Professional organizations in the US and Europe "are suggested outside this group that calls the need to monitor patients for a long period of time," he said. "The focus is increasing."
Touching a similar point, Williams said, "There's a perception that this is not a niche issue affecting a small number of people. This is the core issue that explains a considerable amount of the uncontrolled hypertension there."
Addressing dysregulation of aldosterone
Dysregulation of aldosterone plays an important role in both difficult-to-treat hypertension and organ damage associated with high BP, BaxHTN investigators said. Older mineralocorticoid receptor antagonists (MRAs) like spironolactone block the effects of aldosterone, but their use for this purpose is limited by dose-dependent side effects, Williams said.
New aldosterone synthase inhibitors, including Baxdrostat and Lorundrostat (Mineralys Therapeutics), are designed to improve safety and treat stubborn hypertension. In the phase II test, Baxdrostat yields mixed results; Brightonincluding patients with treatment-resistant hypertension, halopatients with uncontrolled hypertension were included.
The Phase III BAXHTN trial, conducted at 214 sites in 29 countries, included both types of patients. Investigators enrolled adults who had systolic BP of less than 140 to 170 mm hg despite stable treatment with two antihypertensive agents (uncontrolled) or three or more antihypertensive (resistant) (resistant). Participants also had an estimated glomerular filtration rate of at least 45 ml/min/min1.73 m Normal potassium levels (3.5-5.0 mmol/L). Those currently using MRA or potassium-saving diuretics have been excluded.
After a 2-week placebo break-in period, 796 patients (mean age 61 years, 62% of men) with coordinate BP of ≥135 mm Hg were randomized once daily for 12 weeks for 12 days. It then went on to have a 12-week open-label treatment period followed by an 8-week withdrawal period. Patients taking Baxdrostat 2 mg were then randomized to continue their treatment or take a placebo.
Most patients (73%) had resistant hypertension, with the rest being classified into an uncontrolled category. At baseline, the mean BP was 149/87 mm Hg and potassium was 4.2 mmol/L. Participants took an average of three antihypertensive medications at the start of the study.
Changes in seated systolic BP from baseline from 12 weeks (primary endpoint) were -5.8 mm Hg for placebo, -14.5 mm Hg for Baxdrostat 1 mg, and -15.7 mm Hg for Baxdrostat 2 mg, with similar effects in various subgroups.
"This is consistent with the hypothesis that aldosterone plays a fundamental role in the production of control hypertension in all patients, both with uncontrolled resistant hypertension," Williams said.
At the beginning of the randomised withdrawal phase of the trial, the mean positional systolic BP was 133 mm Hg. Over the next 8 weeks, there was a slight increase in BP (+1.4 mm Hg) in patients taking placebo, and further decreased in patients with Baxdrostat 2 mg (-3.7 mm Hg), with estimated differences between the groups of -5.7 mm Hg. Williams said it was reflexive about both the slow offset of Baxdrostat's effectiveness and the continued reduction in BP in treatments up to 32 weeks.
These were early results, but they looked very good. Sydney Smith
Additional exploratory analyses showed that Baxdrostat reduced serum aldosterone concentrations (approximately 60% at low doses and 65% at high doses, resulting in a significant reduction in outpatient BP in a subset of patients who underwent such monitoring. A placebo-corrected fall for systolic BP for 24 hours had a lower dose of Baxdrostat, respectively, with waterfalls of 14.6 and 16.9 mm Hg, respectively, from baseline to 12 weeks. Furthermore, after placebo correction in the pooled Baxdrostat group, the mean nighttime systolic BP reduced by 11.7 mm Hg.
Treatment is well tolerated, with most adverse events being mild and no cases of adrenal failure, Williams reported, adding that potassium levels above 6.0 mmol/l were 0.4% for placebo, 2.3% for backsdostat 1 mg and 3.0% for Baxdrostat 2 mg. The most common adverse events were hyperkalemia, hyponatremia, hypotension, muscle convulsions, and dizziness, all of which were more common in Baxdrostat.
When Baxdrostat is started, potassium increases by about 10%. "You need to monitor potassium at least after the first two weeks of treatment. Almost all the changes happen in the first two weeks," Williams said. "The doctors themselves are very familiar with this because they sometimes see it with ACE inhibitors or angiotensin receptor blockers, and they are also found in older drugs they have used in the past, such as spironolactone, to block this pathway.
At this point, there is no major safety concern at this point, pointing out that the Baxdrostat profile is similar to that of other antihypertensive agents.
Where does baxdrostat fit?
Research debate Thomas Guzic, MD (Scottish, University of Scotland, Scotland, and the University of Jagielonia School of Medicine, Krakow, Poland), said it was difficult or non-olt.
Aldosterone is an important player. This scenario is nejm editorial with Maciej Tomaszewski, MD (University of Manchester and University of Manchester National Health Services Foundation Trust, UK).
It is important to note about Baxhtn's findings, he said, that the reduction in BP due to Baxdrostat occurred in patients already in intensive care for hypertensive, and was achieved along with expected changes in potassium and renal function. He added that cancellation due to hyperkalemia was rare. "Of course they guarantee vigilance and I think surveillance of laboratory parameters will be shown before and after treatment begins."
We handle that medicine. . . It not only lowers blood pressure, but it actually changes the underlying disease trajectory. Thomas Guzic
However, the most interesting findings of the trial came from a randomised withdrawal period, Guzic said. "It's very interesting because it shows minimal rebound despite drug clearance. [are seeing a] Resetting a physiological or pathophysiological mechanism (resetting sodium handling or another mechanism," he explained.
This needs to be understood further, he continued, "it shows that we are dealing with drugs that not only lower blood pressure, but actually change the trajectory of the underlying disease."
Guzic raised questions about where it would fit into the treatment of resistant hypertension if Baxdrostat was approved.
Williams said it would probably be used as an add-on therapy for the type of patient studied at Baxhtn, but he highlighted the wider possibilities.
"I think our findings are really consistent with the idea that aldosterone plays a much more important role in the evolution of hypertension in more patients than we previously recognized," he said. "My view was that what we often call essential hypertension is often supported by salt handling and abnormalities in sodium sensitivity. The salt-sensitive master regulator is actually aldosterone.
He predicted that Baxdrostat would eventually be used in the course of treatment. "This mechanism is at the heart of what we described as essential hypertension.