Full Phase 3 Results Indicate Reduced Blood Pressure With Baxdrostat in Hypertension

At the European Society of Cardiology (ESC) Congress 2025, investigators from AstraZeneca presented full trial results from the phase 3 BaxHTN trial, demonstrating that baxdrostat induced statistically meaningful and clinically significant reductions in mean seated systolic blood pressure (SBP) at either 1- or 2-mg doses compared with placebo at 12 weeks in patients with uncontrolled or resistant hypertension receiving standard of care. The results, which were first announced in July 2025 with the release of top-line data, were also published in The New England Journal of Medicine and announced in a news release from AstraZeneca.^1,2

Hypertension is a major contributor to adverse cardiovascular outcomes. | Image Credit: ©interstid - stock.adobe.com

Baxdrostat, an investigational, highly selective, oral small molecule drug, inhibits aldosterone synthase, a major contributor to hypertension through promotion of sodium and water retention. Elevated aldosterone levels in the body can make elevated blood pressure complicated to treat and heighten the risk of adverse cardiovascular events, including heart attack. With the potential to act as a first-in-class and potent treatment option, baxdrostat offers numerous advantages compared with the standard of care. Most pertinently, it can lower aldosterone levels without impacting cortisol, a hormone in the adrenal glands that helps regulate stress responses in the body.^1-3

Full BaxHTN Data Demonstrates Major Blood Pressure Reductions

According to the full BaxHTN results, baxdrostat met all primary and secondary end points in the trial. There was a significant reduction from baseline in mean seated SBP—15.7 mmHg—at week 12 (95% CI, –17.6 to –13.7), whereas the placebo-adjusted reduction was 9.8 mmHg (95% CI, –12.6 to –7.0; P < .001) for patients treated with the 2-mg dose of baxdrostat. For those administered the 1-mg dose, the absolute reduction from baseline was 14.5 mmHg (95% CI, –16.5 to –12.5), and the placebo-adjusted reduction was 8.7 mmHg (95% CI, –11.5 to –5.8; P < .001).¹

Compared with the reduction in mean seated SBP with placebo (5.8 mmHg [95% CI, –7.9 to –3.8]), both doses of baxdrostat were significantly more effective at reducing SBP. Importantly, these results were consistent in both treatment-resistant and uncontrolled subgroups of hypertension, the investigators reported.¹

Confirmatory secondary end points with baxdrostat were also successfully met. These end points included demonstration of durable long-term blood pressure reductions with a 2-mg baxdrostat dose. Furthermore, each dose of baxdrostat induced significant reductions in diastolic blood pressure while nearly tripling the odds of patients reaching a target SBP of less than 130 mmHg compared with placebo.¹

A prespecified exploratory analysis in a subgroup of patients was conducted to investigate reductions in ambulatory nighttime SBP compared with placebo. According to this analysis, baxdrostat was found to meaningfully reduce 24-hour and ambulatory nighttime SBP­­—the 2-mg dose lowered 24-hour SBP by 16.9 mmHg (95% CI, –25.6 to –8.3), while the pooled 2-mg and 1-mg doses reduced nighttime SBP by 11.7 mmHg (95% CI, –19.5 to -3.8). More research is necessary to better elucidate the impacts of baxdrostat on nighttime SBP; in this regard, the phase 3 Bax24 trial, which is set to evaluate 24-hour ambulatory effects of baxdrostat on SBP, is expected to have results available by the end of 2025.¹

“Achieving a nearly 10 mmHg placebo-adjusted reduction in systolic blood pressure with baxdrostat in the BaxHTN phase 3 trial is exciting, as this level of reduction is linked to substantially lower risk of heart attack, stroke, heart failure, and kidney disease,” primary study investigator Bryan Williams, MD, chair of medicine at University College London, said in the news release regarding the trial’s efficacy data. “These data show that aldosterone plays a greater role in hard-to-control hypertension than previously recognized, underscoring the importance of baxdrostat’s novel mechanism of action and potential impact for the millions of people living with hard-to-control hypertension despite being on multiple treatments.”¹

Safety of Baxdrostat and Implications for Patients

In critical findings, baxdrostat was well-tolerated among the patient population, and there were no unanticipated safety indications, according to the study researchers. As for any observed adverse events (AEs), there were low rates of confirmed hyperkalemia (> 6 mmol/L) in both dose groups compared with placebo. Hyperkalemia is characterized by abnormally high levels of potassium in the blood; with symptoms including abdominal pain and diarrhea, pharmacists will be integral in monitoring patients taking baxdrostat for these possible complications.^1,4

Despite the appearance of hyperkalemia, the safety profile of baxdrostat was consistent with its mechanism of action, and most instances of AEs were mild. Based on these observations, baxdrostat stands to present as a safe, novel option for reducing SBP in patients with uncontrolled hypertension if approved in the future.¹

Millions of individuals in the United States live with hypertension, and about half of those who utilize multiple therapies remain harboring uncontrolled blood pressure. Baxdrostat has the potential to transform the treatment paradigm for uncontrolled or resistant hypertension and could provide relief to individuals utilizing a series of different drugs to control their hypertension. Pharmacists will play an essential role in counseling patients on baxdrostat’s use and dosage if the drug is eventually approved by the FDA.^1,5

“The BaxHTN phase 3 results demonstrate baxdrostat’s potential in tackling one of the toughest challenges in cardiovascular care, which is hypertension that is hard to control despite multiple therapies.”¹

REFERENCES

1. Baxdrostat demonstrated statistically significant and clinically meaningful reduction in systolic blood pressure in patients with hard-to-control hypertension in the BaxHTN Phase III trial. AstraZeneca. News Release. Released August 30, 2025. Accessed September 8, 2025. https://www.astrazeneca-us.com/media/press-releases/2025/Baxdrostat-demonstrated-statistically-significant-and-clinically-meaningful-reduction-in-systolic-blood-pressure-in-patients-with-hard-to-control-hypertension-in-the-BaxHTN-Phase-III-trial.html

2. Halpern L. Baxdrostat Reduces Systolic Blood Pressure in Uncontrolled, Treatment-Resistant Hypertension. Pharmacy Times. Published July 31, 2025. Accessed September 8, 2025. https://www.pharmacytimes.com/view/baxdrostat-reduces-systolic-blood-pressure-in-uncontrolled-treatment-resistant-hypertension

3. Cleveland Clinic. Cortisol. Last Updated February 17, 2025. Accessed September 8, 2025. https://my.clevelandclinic.org/health/articles/22187-cortisol

4. Cleveland Clinic. Hyperkalemia (High potassium). Last Updated May 11, 2023. Accessed September 8, 2025. https://my.clevelandclinic.org/health/diseases/15184-hyperkalemia-high-blood-potassium#symptoms-and-causes

5. Carey RM, Sakhuja S, Calhoun DA, et al. Prevalence of Apparent Treatment-Resistant Hypertension in the United States. Hypertension. 2019;73(2):424-431. doi:10.1161/HYPERTENSIONAHA.118.12191