This research is Trending!
Effect of baxdrostat on ambulatory blood pressure in patients with resistant hypertension (Bax24): a phase 3, randomised, double-blind, placebo-controlled trial
Michel AziziJenifer M. BrownJamie P. DwyerJohn M FlackErica S W JonesRaisa KurlyandskayaHongjian LiFilip BirveAina S. LihnShira PerlMarkus P. SCHLAICHHirotaka ShibataJi-Guang WangBryan WilliamsCesar ZaidmanSonia SassoneMiguel CuencaDiego ArakakiMariano I. ChahinMaría Andrea SteinacherFredy Ferre PacoraJuan LoureyroJun YangMarkus P. SCHLAICHTine De BackerHans T KindtP. DelmotteBlagovest StoimenovKiril DzhomanovKrassimir CvetkovDimitar RaevStefan NaydenovShivinder JollyJohn VyselaarLuis NoronhaDaniel GaudetA. Shekhar PandeyJennifer RingroseYves RobitailleJiri VeselyJiri KrupickaLadislav BusakJitka PruchovaWolfgang JungmairSebastian CremerMarkus van der GietStephan H. SchirmerSpasija ParizovaMichael DoumasGeorge StergiouKonstantinos TsioufisZoltán Miklós JáraiAndrás VorobcsukTibor KissGizella PapAndras Csaba NagyAttila FarkasDesmond SamuelMohd Faiz Faizul FauziMohamad Muslim JamianLouie TiradorGabriel JocsonMarek RajzerAndrzej JanuszewiczAndrzej TykarskiMichał HoffmannJan Zbigniew PerugaEdyta ZbrochPiotr SobierajAbdulmajid MukhtarTalal AljabbaryPeter KrajčiJán FedačkoPeter FulopLesley BurgessGulam LatiffJulián Segura de la MorenaJosé Antonio García DonaireMiguel Camafort BabkowskiAlejandro de la SierraJavier Sobrino MartínezAnna Oliveras SerranoFernando MartinezManuel Gorostidi PérezFrancisco Fuentes JimenezChern-En ChiangKang-Ling WangYen-Wen WuI-Chang HsiehPraew KotruchinYongkasem VorasettakarnkijWeranuj RoubsanthisukPrin VathesatogkitKrit LeemasawatHilmi Erdem SumbulÖzge Turgay YıldırımÇAĞRI YAYLAOzkan Gungorİsmail KoçyiğitAuditi Naziat
Key result
Baxdrostat reduces 24-hour ambulatory SBP by ~14 mm Hg versus placebo in resistant hypertension.
- difference -14.0 mm Hg
- 95% CI -17.2 to -10.8
- P<0.0001
- n=217
Why the study?
Aldosterone dysregulation is an important contributor to hard-to-control hypertension, prompting assessment of the selective aldosterone synthase inhibitor baxdrostat on ambulatory blood pressure in resistant hypertension.
Does baxdrostat reduce 24 h ambulatory systolic blood pressure in adults with resistant hypertension?
Key Points
- This research aims to evaluate the effectiveness of baxdrostat on reducing ambulatory blood pressure in patients with resistant hypertension.
- Phase 3, randomised, double-blind, placebo-controlled trial.
- Patients with resistant hypertension received either 2 mg baxdrostat or placebo for 12 weeks, alongside existing antihypertensive therapy.
- Primary endpoint was the change in 24-hour ambulatory systolic blood pressure from baseline to week 12.
- The baxdrostat group showed a significant reduction in 24-hour ambulatory systolic blood pressure by –16.6 mm Hg compared to –2.6 mm Hg in the placebo group.
- The placebo-corrected difference was –14.0 mm Hg with a p-value of less than 0.0001.
- Adverse events were reported in 52% of the baxdrostat group compared to 37% in the placebo group.
Study Design
Type
RCT (n=217)
Blinding
Double-blind
Randomization
1:1
Multicenter
Yes
Structured PICO
Does baxdrostat reduce 24 h ambulatory systolic blood pressure in adults with resistant hypertension?
P
Population
217 adults (aged ≥18 years) with resistant hypertension (seated systolic blood pressure ≥140 mm Hg and <170 mm Hg despite receiving ≥3 antihypertensive medications including a diuretic, and 24 h ambulatory SBP ≥130 mm Hg), median age 60.0 years, 65% male, multinational (22 countries).
I
Intervention
Baxdrostat 2 mg orally once daily for 12 weeks, in addition to background therapy.
C
Comparator
Matching placebo orally once daily for 12 weeks, in addition to background therapy.
O
Outcome
Change in 24 h ambulatory systolic blood pressure (SBP) from baseline to week 12.surrogate
Main Result
Effect estimate: difference -14.0 mm Hg (95% CI -17.2 to -10.8)
Absolute Event Rate: -16.6% vs -2.6%
p-value: p=<0.0001
In patients with resistant hypertension, the selective aldosterone synthase inhibitor baxdrostat significantly reduced 24-hour ambulatory systolic blood pressure compared to placebo over 12 weeks.
Discussion
No takes yet. Share an insight, caveat, or question.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The landmark results from Bax24 Phase III trial demonstrate that patients with the hardest-to-control hypertension treated with baxdrostat achieved a highly clinically meaningful 14 mmHg placebo-adjusted reduction in 24-hour systolic blood pressure, which could transform treatment practice. It's remarkable to see this magnitude of reduction coupled with the fact that just over 70% of baxdrostat patients achieved guideline targets, consistently over 24 hours.”
“The Bax24 results show that a once-daily baxdrostat regimen can deliver highly clinically meaningful reductions in 24-hour systolic blood pressure, including in the morning when patients are at greater risk of heart attack and stroke. These results are groundbreaking and together with the BaxHTN results mean we have the potential to change our treatment approach for the many patients whose hypertension remains uncontrolled despite current therapies.”
SBSharon BarrEVP BioPharmaceuticals R&D, AstraZeneca
“The Bax24 data demonstrate the significant impact that baxdrostat's long half-life and highly selective inhibition of aldosterone synthase can have in improving 24-hour and overnight blood pressure for patients with resistant hypertension. Patients with elevated night-time blood pressure are especially vulnerable to cardiovascular events, including heart attack and stroke. Together with the results from BaxHTN, these findings demonstrate the potential of baxdrostat to redefine what is possible for the millions of patients whose hypertension remains uncontrolled despite current therapies.”
Implication
Opens new treatment axis for resistant hypertension; confirms efficacy of selective aldosterone synthase inhibition in Phase 3 RCT.
Abstract
Summary Background Aldosterone dysregulation is an important contributor in the pathogenesis of hard-to-control hypertension. We aimed to assess the effect of baxdrostat, a selective aldosterone synthase inhibitor, on ambulatory blood pressure in patients with resistant hypertension. Methods The Bax24 international, phase 3, randomised, double-blind, placebo-controlled trial recruited adults (aged ≥18 years) with seated systolic blood pressure (SBP) ≥140 mm Hg and <170 mm Hg, despite receiving three or more antihypertensive medications, including a diuretic, from 79 clinical sites (primary, secondary, and tertiary centres, in addition to research centres) in 22 countries. Following a 2-week placebo run-in period, patients with 24 h ambulatory SBP ≥130 mm Hg were randomly assigned (1:1) to receive 2 mg baxdrostat or placebo orally once daily for 12 weeks, in addition to background therapy (stratified by baseline ambulatory SBP <140 mm Hg or ≥140 mm Hg). Investigators, patients, and trial staff were masked to treatment assignment. The primary endpoint was change in 24 h ambulatory SBP from baseline to week 12, assessed by analysis of covariance in patients administered at least one dose of study medication with valid ambulatory SBP measurement at baseline and week 12. Missing or invalid ambulatory SBP measurements were not imputed. The safety analysis included all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT06168409, and is complete. Findings Between March 1, 2024, and April 16, 2025, 854 patients were screened, 636 were excluded (437 before the placebo run-in and 199 during the placebo run-in) and 217 were randomly assigned to and received baxdrostat (n=108) or placebo (n=109). 140 patients (65%) were male, 77 (35%) patients were female, and 170 patients (78%) were White. The median age was 60·0 years (IQR 51·0–68·0). At 12 weeks, the change from baseline in the least-squares mean 24 h ambulatory SBP 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) in the placebo group (n=95); the estimated placebo-corrected difference was −14·0 mm Hg (−17·2 to −10·8; p<0·0001). Adverse events occurred in 56 (52%) of 108 patients in the baxdrostat group and 40 (37%) of 109 patients in the placebo group. A confirmed potassium level of more than 6 mmol/L occurred in three (3%) of the 108 baxdrostat recipients and in none of the placebo recipients. Interpretation Baxdrostat significantly reduced 24 h ambulatory SBP versus placebo in patients with resistant hypertension, providing further evidence of the potential of aldosterone synthase inhibition for treatment of hard-to-control hypertension. Funding AstraZeneca.
Cite This Study
Azizi et al. (2026) conducted an RCT in resistant hypertension (n=217). baxdrostat vs. placebo was evaluated on change in 24 h ambulatory SBP from baseline to week 12 (difference -14.0 mm Hg, 95% CI -17.2 to -10.8, p=<0.0001). Baxdrostat significantly reduced 24 h ambulatory systolic blood pressure compared to placebo (difference -14.0 mm Hg; 95% CI -17.2 to -10.8; p<0.0001) in patients with resistant hypertension.