Effect of baxdrostat on ambulatory blood pressure in patients with resistant

# Effect of baxdrostat on ambulatory blood pressure in patients with resistant hypertension (Bax24): a phase 3, randomised, double-blind, placebo-controlled trial *The Lancet 2026* Articles Effect of baxdrostat on ambulatory blood pressure in patients with resistant hypertension (Bax24): a phase 3, randomised, double-blind, placebo-controlled trial Michel Azizi, Jenifer M Brown, Jamie P Dwyer, John M Flack, Erica S W Jones, Raisa Kurlyandskaya, Hongjian Li, Filip Birve, Aina S Lihn, Shira Perl, Markus P Schlaich, Hirotaka Shibata, Ji-Guang Wang, Bryan Williams, for the Bax24 investigators* Summary Lancet 2026; 407: 988–99 Background Aldosterone dysregulation is an important contributor in the pathogenesis of hard-to-control hypertension. See Comment page 922 We aimed to assess the eect of baxdrostat, a selective aldosterone synthase inhibitor, on ambulatory blood pressure *Members listed in the appendix in patients with resistant hypertension. (pp 3–6) Université Paris Cité, INSERM Methods The Bax24 international, phase 3, randomised, double-blind, placebo-controlled trial recruited adults CIC1418, Paris, France (aged ≥18 years) with seated systolic blood pressure (SBP) ≥140 mm Hg and <170 mm Hg, despite receiving three or (Prof M Azizi MD); Hypertension more antihypertensive medications, including a diuretic, from 79 clinical sites (primary, secondary, and tertiary Department, Hôpital Européen Georges Pompidou, Assistance centres, in addition to research centres) in 22 countries. Following a 2-week placebo run-in period, patients with Publique–Hôpitaux de Paris, 24 h ambulatory SBP ≥130 mm Hg were randomly assigned (1:1) to receive 2 mg baxdrostat or placebo orally once Paris, France (Prof M Azizi); daily for 12 weeks, in addition to background therapy (stratified by baseline ambulatory SBP <140 mm Hg or Department of Medicine, ≥140 mm Hg). Investigators, patients, and trial sta were masked to treatment assignment. The primary endpoint Division of Cardiovascular Medicine, Brigham and was change in 24 h ambulatory SBP from baseline to week 12, assessed by analysis of covariance in patients Women’s Hospital, Boston, administered at least one dose of study medication with valid ambulatory SBP measurement at baseline and MA, USA (J M Brown MD); week 12. Missing or invalid ambulatory SBP measurements were not imputed. The safety analysis included all Division of Nephrology and patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, Hypertension, University of Utah, Salt Lake City, UT, USA NCT06168409, and is complete. (Prof J P Dwyer MD); Department of Medicine and Findings Between March 1, 2024, and April 16, 2025, 854 patients were screened, 636 were excluded (437 before the Department of Population placebo run-in and 199 during the placebo run-in) and 217 were randomly assigned to and received baxdrostat (n=108) Science and Policy, Division of General Internal Medicine, or placebo (n=109). 140 patients (65%) were male, 77 (35%) patients were female, and 170 patients (78%) were White. Hypertension Section, The median age was 60·0 years (IQR 51·0–68·0). At 12 weeks, the change from baseline in the least-squares mean Southern Illinois University, 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 Springfield, IL, USA (−4·7 to −0·4) in the placebo group (n=95); the estimated placebo-corrected dierence was −14·0 mm Hg (Prof J M Flack MD MPH); Department of Medicine, (−17·2 to −10·8; p<0·0001). Adverse events occurred in 56 (52%) of 108 patients in the baxdrostat group and 40 (37%) Division of Nephrology and of 109 patients in the placebo group. A confirmed potassium level of more than 6 mmol/L occurred in three (3%) of Hypertension, Groote Schuur the 108 baxdrostat recipients and in none of the placebo recipients. Hospital, University of Cape Town, Cape Town, South Africa (E S W Jones MD); Late-Stage Interpretation Baxdrostat significantly reduced 24 h ambulatory SBP versus placebo in patients with resistant Development, Cardiovascular, hypertension, providing further evidence of the potential of aldosterone synthase inhibition for treatment of hard-to- Renal and Metabolism, control hypertension. BioPharmaceuticals Research and Development, AstraZeneca, Warsaw, Poland Funding AstraZeneca. (R Kurlyandskaya MD); Late- Stage Development, Copyright © 2026 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 Cardiovascular, Renal and license. Metabolism, BioPharmaceuticals Research and Development, Introduction systolic blood pressure (SBP) with the selective AstraZeneca, Gaithersburg, Aldosterone dysregulation, characterised by aldosterone synthase inhibitor baxdrostat, after 12 weeks MD, USA (H Li MS, S Perl MD); inappropriately elevated aldosterone secretion relative to of treatment, in patients with uncontrolled or resistant Late-Stage Development, Cardiovascular, Renal and sodium balance, is increasingly recognised as an hypertension. Metabolism, important contributor to hard-to-control and resistant Ambulatory blood pressure monitoring is a valuable BioPharmaceuticals Research hypertension and its associated cardiovascular and renal approach to assess the blood pressure-lowering ecacy and Development, AstraZeneca, Gothenburg, complications.1–4 Pharmacological blockade of of new antihypertensive medications, specifically in Sweden (F Birve MS, aldosterone signalling can eectively reduce blood phase 2 and 3 trials. As a complement to oce blood A S Lihn MD); Dobney pressure in patients with uncontrolled or resistant pressure measurement, which is well established and Hypertension Centre, Medical hypertension.5–8 The phase 3 BaxHTN trial5 reported widely used for the diagnosis and management of School-Royal Perth Hospital Unit and Royal Perth Hospital significant reductions in placebo-adjusted seated oce hypertension, ambulatory blood pressure monitoring 988 Articles Research Foundation, Research in context University of Western Australia, Perth, WA, Australia Evidence before this study −13·3 to −2·6) with lorundrostat 50 mg daily and of −6·5 mm Hg (Prof M P Schlaich MD); We searched PubMed for papers published between Jan 1, 2010, (−11·8 to −1·2) in those up-titrated to lorundrostat 100 mg Neurovascular Hypertension & and Oct 15, 2025, using the search terms “aldosterone synthase daily. Kidney Disease Laboratory, Baker Heart and Diabetes inhibitors”, “hypertension”, “placebo”, “randomised controlled Added value of this study Institute, Melbourne, VIC, trials”, “meta-analysis”, “systematic review”, and various The Bax24 trial was designed to assess the 24 h ambulatory Australia (Prof M P Schlaich); combinations of these words with no language restrictions. Department of Cardiology and blood pressure-lowering effect of baxdrostat in patients with We aimed to identify systematic reviews and meta-analyses of Department of Nephrology, true resistant hypertension despite treatment with three or Royal Perth Hospital, Perth, blood pressure-lowering efficacy of aldosterone synthase more antihypertensive medications, including a diuretic, WA, Australia inhibitors that specifically included those with selectivity for confirmed by ambulatory blood pressure monitoring. (Prof M P Schlaich); Department aldosterone synthase (cytochrome P450 11B2, mitochondrial; of Endocrinology, Metabolism, Baxdrostat 2 mg daily added to background antihypertensive CYP11B2) versus cortisol synthase (cytochrome P450 11B1, Rheumatology and therapy was associated with the largest placebo-corrected Nephrology, Faculty of mitochondrial; CYP11B1). We identified seven meta-analyses, reductions in 24 h ambulatory SBP ever reported in patients Medicine, Oita University, Oita, two of which only included trials with the aldosterone synthase Japan (Prof H Shibata MD); with resistant hypertension, as well as very substantial inhibitor lorundrostat. Four others included trials conducted in Shanghai Institute of reductions in night-time SBP, which might provide additional settings other than hypertension or involved the non-selective Hypertension, Ruijin Hospital, benefits in reducing cardiovascular events. Furthermore, the Shanghai Jiao Tong University aldosterone synthase inhibitor osilodrostat, which was later magnitude of the placebo-corrected office SBP reduction with School of Medicine, Shanghai, developed for Cushing’s disease. A 2025 meta-analysis, China (Prof J-G Wang MD); baxdrostat was consistent with the results of the meta-analysis including four placebo-controlled trials of selective aldosterone University College London of selective aldosterone synthase inhibitors. synthase inhibitors (baxdrostat and lorundrostat) in patients Institute of Cardiovascular Science and National Institute with uncontrolled or resistant hypertension (1838 patients), Implications of all the available evidence for Health Research, UCL reported a mean reduction in office systolic blood pressure Existing data show that selective aldosterone inhibitors Hospitals Biomedical Research (SBP) of −8·21 mm Hg (95% CI −10·64 to −5·78) and in diastolic significantly reduce office blood pressure in patients with Centre, London, UK blood pressure of −3·64 mm Hg (−5·65 to −1·63) compared resistant as well as uncontrolled hypertension and are generally (Prof B Williams MD) with placebo. None of the meta-analyses reported 24 h well tolerated. Aldosterone synthase inhibitors might raise serum Correspondence to: Prof Bryan Williams, University ambulatory blood pressure reductions because only a single potassium concentrations and be associated with a functional College London Institute of trial has previously reported changes in 24 h ambulatory blood decrease in estimated glomerular filtration rate due to improved Cardiovascular Science and pressure with lorundrostat, but did not report night-time blood blood pressure control. However, data on 24 h blood pressure National Institute for Health pressure changes, a parameter most closely associated with all- lowering are scarce, and no data on night-time blood pressure Research, UCL Hospitals Biomedical Research Centre, cause and cardiovascular mortality risk. This trial (Advance- have been reported. The Bax24 study provides the most London W1T 7DN, UK HTN), which included 285 patients with either uncontrolled or comprehensive data to date on the effect of selective aldosterone bryan.williams@ucl.ac.uk resistant hypertension, reported a placebo-adjusted change in synthase inhibition with baxdrostat on 24 h and night-time See Online for appendix 24 h ambulatory SBP at 12 weeks of −7·9 mm Hg (97·5% CI blood pressure. also enables detection of so-called white-coat Methods hypertension (especially in patients with apparent Study design and participants resistant hypertension), is less prone to observer bias, is Bax24 was an international, multicentre, randomised, less aected by placebo response, and provides a full 24 h double-blind, placebo-controlled trial that enrolled circadian blood pressure profile, including nocturnal patients at 79 clinical sites (primary, secondary, and blood pressure.9 Furthermore, some studies suggest that tertiary centres in addition to research centres) in ambulatory blood pressure monitoring, especially night- 22 countries (appendix pp 7–10), as previously described.13 time blood pressure, is more strongly associated with The trial was designed by an academic executive both all-cause and cardiovascular mortality than oce committee and representatives of AstraZeneca (trial blood pressure.10–12 sponsor). Patients with treated hypertension participated Data on the eects of aldosterone synthase inhibition in the trial design. We conducted the trial in accordance on 24 h blood pressure are scarce7 and no data exist on the with the International Conference for Harmonisation eect on night-time blood pressure, which is often Good Clinical Practice guidelines, the principles of the disproportionately elevated in patients with resistant Declaration of Helsinki, and applicable laws and hypertension.9,12 We therefore conducted a dedicated, regulations. The study protocol including all amendments placebo-controlled, phase 3 trial (Bax24) to evaluate the and statistical analysis plan are included in the appendix eect of baxdrostat on 24 h and night-time ambulatory (pp 55–240). Independent ethics committees and blood pressure in patients with true resistant hypertension institutional review boards approved the protocol and confirmed by ambulatory blood pressure monitoring, as a amendments (appendix pp 11–18). An independent data fully independent study from the previously reported monitoring committee (appendix p 6) monitored the BaxHTN trial.13 safety and scientific integrity of the trial. This trial is Articles registered with ClinicalTrials.gov, NCT06168409, and is filtration rate (eGFR; calculated according to the Chronic completed. Kidney Disease Epidemiology Collaboration equation14) of Adults (aged ≥18 years) with resistant hypertension, ≥45 mL/min per 1·73 m² and serum potassium defined as a mean seated oce SBP ≥140 mm Hg and ≥3·5 mmol/L and <5·0 mmol/L. <170 mm Hg at screening despite treatment with Key exclusion criteria were use of mineralocorticoid maximally tolerated doses of three or more receptor antagonists or potassium-sparing diuretics antihypertensive medications of dierent classes within 4 weeks of screening and throughout the study; (including a diuretic) for at least 4 weeks before screening uncontrolled diabetes (glycated haemoglobin >9·5%); were eligible for inclusion. Patients with SBP levels secondary hypertension (except due to sleep apnoea or ≥170 mm Hg were excluded for safety reasons. Patients primary aldosteronism); cardiovascular or cerebro- were also required to have an estimated glomerular vascular events within the previous 6 months; and persistent atrial fibrillation. Full inclusion and exclusion criteria are provided in the appendix (pp 19–23). 854 patients assessed for eligibility Patients were recruited by investigators at participating sites. Patients’ sex (male or female), race (American Indian 636 excluded (437 before and 199 during or Alaska Native, Asian, Black or African American, placebo run-in) Native Hawaiian or Other Pacific Islander, White, 9 patient decision 2 lost to follow-up Multiple, or Other), and ethnicity (Hispanic or Latino or 1 physician decision not Hispanic or Latino) were self-reported by patients 623 screen failure and recorded by the investigators. All patients provided 1 other reason (haemolysis of blood sample and unsuccessful contact with written informed consent before enrolment. participant for repeat sampling) Randomisation and masking 218 randomly assigned Investigators used an automated interactive response technology/randomisation and trial supply management (IRT/RTSM) system to randomly assign eligible patients 1 assigned to baxdrostat 2 mg group but did at the start of the double-blind treatment period. not receive treatment Randomisation codes were computer-generated by an independent vendor and loaded into the IRT/RTSM database using a fixed randomised block size of four and 108 assigned to and received 109 assigned to and received permutation of treatments within each block. Patients baxdrostat 2 mg placebo were randomly assigned in a 1:1 ratio to 2 mg baxdrostat or placebo, stratified by mean ambulatory SBP at baseline 16 discontinued treatment 10 discontinued treatment (<140 mm Hg or ≥140 mm Hg). At the dispensing visit, 5 adverse events 4 patient decision the IRT/RTSM system provided investigators and 4 patient decision 2 non-compliance with 2 non-compliance with protocol pharmacists with the kit identification number to be protocol 1 required prohibited allocated to the patient. Baxdrostat and placebo tablets 1 required prohibited medication medication 3 other reasons were similar in labelling and appearance to ensure 4 other reasons adequate masking to treatment allocation. Treatment allocation was concealed from all investigators, patients, and trial sta until completion of the trial. 19 excluded (including 5 14 (including 5 who who withdrew) withdrew) missing or 1 invalid baseline invalid week 12 Procedures ambulatory blood ambulatory blood pressure monitoring pressure monitoring Patients were eligible for random assignment following a measurement measurements 2-week placebo run-in period if they had a mean 24 h 18 missing or invalid ambulatory SBP of ≥130 mm Hg after witnessed week 12 measurements consumption of their background antihypertensive therapy and at least an 80% adherence to placebo (based on pill counts; appendix p 23). After random assignment, patients 89 had valid ambulatory 95 had valid ambulatory blood pressure blood pressure underwent a 12-week double-blind treatment period, and a monitoring monitoring 2-week safety follow-up period (appendix p 33). Baxdrostat measurements at measurements at baseline and week 12 baseline and week 12 (2 mg) and placebo were administered orally, once daily. and were included in the and were included in the Dose reductions of the study medications were not primary endpoint primary endpoint permitted throughout the 12-week double-blind treatment analysis analysis period, but temporary or permanent discontinuations were permitted in case of hyperkalaemia, as described in the Figure 1: Trial profile Patients who discontinued from the study also accounted for some of the excluded patients. appendix (p 29). Patients remained on their background 990 Articles Baxdrostat group Placebo group Baxdrostat group Placebo group (n=108) (n=109) (n=108) (n=109) Age, years 60·0 (52·0–67·0) 61·0 (51·0–69·0) (Continued from previous column) Sex Serum potassium (mmol/L) 4·14 (0·42) 4·10 (0·43) Male 70 (65%) 70 (64%) Serum sodium (mmol/L) 140·2 (2·6) 139·9 (2·6) Female 38 (35%) 39 (36%) Serum aldosterone (ng/dL)|| 7·6 (5·2–13·2) 9·0 (5·3–12·6) Race* Plasma renin activity (ng/mL 1·2 (0·7–3·5) 0·9 (0·4–2·5) White 86 (80%) 84 (77%) per h)** Black 4 (4%) 6 (6%) Time since hypertension 10·0 (4·0–18·5) 11·0 (7·0–21·0) diagnosis, years Asian 16 (15%) 19 (17%) Background antihypertensive medications Multiple or other 2 (2%) 0 Mean number of 3·7 (3–6) 3·8 (3–6) Ethnicity* medications (range) Hispanic or Latino 25 (23%) 21 (19%) 3 56 (52%) 46 (42%) Not Hispanic or Latino 82 (76%) 84 (77%) 4 37 (34%) 41 (38%) BMI (kg/m²) 32·4 (28·4–36·1) 31·6 (27·9–35·8) 5 or more 15 (14%) 22 (20%) ≥30 70 (65%) 66 (61%) Background classes of antihypertensive medications Ambulatory systolic blood pressure (mm Hg)† Diuretic 108 (100%) 109 (100%) 24 h average 140·5 (8·4) 141·8 (11·8) Angiotensin-converting 100 (93%) 104 (95%) Night-time average 133·6 (11·0) 135·4 (14·1) enzyme inhibitor or Daytime average 144·0 (8·7) 145·0 (11·8) angiotensin receptor blocker Ambulatory diastolic blood pressure (mm Hg)† Calcium channel blocker 96 (89%) 95 (87%) 24 h average 79·7 (9·2) 80·0 (9·3) Beta blocker 49 (45%) 56 (51%) Night-time average 74·0 (9·4) 74·7 (10·1) Other†† 35 (32%) 44 (40%) Daytime average 82·6 (9·8) 82·8 (9·5) Data are n (%), mean (SD), or median (IQR). Baseline characteristics are shown for Seated blood pressure (mm Hg) all the patients who underwent randomisation and received at least one dose of baxdrostat or placebo. Percentages may not total 100 because of rounding. Systolic 146·9 (12·0) 148·3 (14·5) eGFR=estimated glomerular filtration rate. *Race and ethnic group were reported Diastolic 85·4 (11·6) 85·7 (9·2) by the patients; “multiple” and “other” race was recorded for one patient each Dipping status‡ receiving baxdrostat. †Data for 107 patients receiving baxdrostat and 109 patients receiving placebo with valid ambulatory blood pressure monitoring Dipping 34 (31%) 34 (31%) measurements at baseline. ‡Patients with at least a 10% reduction in night-time Non-dipping 73 (68%) 75 (69%) systolic blood pressure compared with daytime systolic blood pressure are Missing 1 (1%) 0 characterised as dippers. §eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation as described by Inker and eGFR (mL/min per 1·73 m²)§ 86·3 (18·1) 84·8 (19·5) colleagues.14 ¶Heart failure was documented according to the clinical record only <60 mL/min per 1·73 m² 11 (10%) 14 (13%) and was not independently evaluated or defined further (eg, as heart failure with Medical history preserved ejection fraction or heart failure with reduced ejection fraction). ||Data for 106 patients receiving baxdrostat and 103 patients receiving placebo with Type 2 diabetes 35 (32%) 39 (36%) measurements of serum aldosterone at baseline. **Data for 70 patients receiving Dyslipidaemia 27 (25%) 39 (36%) baxdrostat and 73 patients receiving placebo with measurements of plasma renin Myocardial infarction 7 (6%) 1 (1%) activity at baseline. ††Other antihypertensive medications included hydralazine (baxdrostat: six [6%]; placebo: six [6%]), alpha-1 blockers (baxdrostat: 18 [17%]; Coronary revascularisation 7 (6%) 3 (3%) placebo: 24 [22%]), and centrally acting drugs (baxdrostat: 15 [14%]; Stroke 6 (6%) 6 (6%) placebo: 19 [17%]). Sleep apnoea 6 (6%) 15 (14%) Table 1: Baseline characteristics of the modified intention-to-treat Heart failure¶ 5 (5%) 9 (8%) population Hypokalaemia 3 (3%) 3 (3%) Peripheral arterial disease 3 (3%) 4 (4%) Transient ischaemic attack 1 (1%) 1 (1%) administered at the study site after seated oce blood Primary aldosteronism 0 1 (1%) pressure was measured by trained nurses or clinical sta (Table 1 continues in next column) using the Microlife WatchBP Oce 2G device (Microlife Corporation, Taipei, Taiwan). On two visits (weeks 1 and 2 of the 12-week treatment period), for all participants, only antihypertensive medications throughout the trial, and safety laboratory measurements were done, and the study these could not be changed unless seated SBP exceeded drug was not administered at the study site.13 Blood was 170 mm Hg or diastolic blood pressure (DBP) exceeded sampled to measure serum potassium, sodium, 105 mm Hg, when rescue therapy could be administered at creatinine, aldosterone, plasma renin activity, and the investigator’s discretion. baxdrostat concentrations at a central laboratory masked The schedule of activities has been previously to treatment assignment; serum potassium was published.13 On study visit days, the study drug was simultaneously measured at a local laboratory (appendix Articles pp 28–29). Patients underwent 24 h ambulatory blood Baxdrostat group Placebo group pressure monitoring using the Microlife WatchBP O3 device (Microlife Corporation, Taipei, Taiwan) following Primary endpoint—change in 24 h ambulatory SBP from baseline to week 12* witnessed intake of background antihypertensive Number of patients 89 95 medications and study drug at both baseline and week 12. Least-squares mean (95% CI) change, mm Hg −16·6 (−18·8 to −14·3) −2·6 (−4·7 to −0·4) Ambulatory blood pressure monitoring was initiated at Least-squares mean (95% CI) placebo-corrected −14·0 (−17·2 to −10·8) ·· difference, mm Hg the last visits of the run-in and double-blind treatment p value <0·0001 ·· periods and lasted at least 25 h, which allowed a minimum Secondary endpoint—change in night-time ambulatory SBP from baseline to week 12* of 24 h of readings, given the measurements recorded within the first hour (after placement and activation of the Number of patients 89 95 device) were excluded from analysis. The ambulatory Least-squares mean (95% CI) change, mm Hg −16·0 (−18·6 to −13·4) −2·1 (−4·6 to 0·4) blood pressure monitoring device recorded blood pressure Least-squares mean (95% CI) placebo-corrected −13·9 (−17·5 to −10·3) ·· difference, mm Hg measurements every 20 min during a 16 h daytime period p value <0·0001 ·· (06:00 to 21:59) and every 30 min during an 8 h night-time Secondary endpoint—change in daytime ambulatory SBP from baseline to week 12* period (22:00 to 05:59). Ambulatory blood pressure Number of patients 89 95 monitoring assessment was considered valid when at Least-squares mean (95% CI) change, mm Hg −16·8 (−19·2 to −14·4) −2·7 (−5·1 to −0·4) least 20 h of recordings were obtained, at least 70% of the Least-squares mean (95% CI) placebo-corrected −14·1 (−17·4 to −10·7) ·· readings were recorded, and no more than 2 consecutive difference, mm Hg hours of recordings were missing. A maximum of p value <0·0001 ·· two attempts at ambulatory blood pressure monitoring Secondary endpoint—change in seated SBP from baseline to week 12* recording were conducted at baseline and at week 12. Number of patients 108 109 Additional details regarding blood pressure measurements Least-squares mean (95% CI) change, mm Hg −14·9 (−18·2 to −11·6) −4·7 (−7·9 to −1·4) are provided in the appendix (pp 26–28). Least-squares mean (95% CI) placebo-corrected −10·3 (−14·9 to −5·6) ·· difference, mm Hg Outcomes p value <0·0001 ·· The primary endpoint was the change in 24 h ambulatory Secondary endpoint—reaching 24 h ambulatory SBP <130 mm Hg at week 12† SBP from baseline to week 12. Secondary endpoints Number of patients 85 84 assessed at week 12 in hierarchical order were: change Number of patients reaching ambulatory 24-h average 60/85 (71%) 14/84 (17%) from baseline in night-time ambulatory SBP; change SBP <130 mm Hg from baseline in daytime ambulatory SBP; change from OR (95% CI) 15·2 (6·6 to 35·2) ·· baseline in seated SBP; proportion of patients reaching p value <0·0001 ·· 24 h ambulatory SBP of <130 mm Hg; change from Secondary endpoint—change in 24 h ambulatory DBP from baseline to week 12‡ baseline in 24 h ambulatory DBP; change from baseline Number of patients 89 95 in night-time ambulatory DBP; change from baseline in Least-squares mean (95% CI) change, mm Hg −8·3 (−9·7 to −6·9) −1·5 (−2·9 to −0·1) daytime ambulatory DBP; change from baseline in Least-squares mean (95% CI) placebo-corrected −6·8 (−8·8 to −4·8) ·· seated DBP; and proportion of patients reaching a difference, mm Hg nocturnal SBP dipping of at least 10%. Prespecified p value <0·0001 ·· exploratory endpoints included change from baseline in Secondary endpoint—change in night-time ambulatory DBP from baseline to week 12‡ seated SBP and DBP at weeks 4 and 8, and in serum Number of patients 89 95 aldosterone levels and plasma renin activity at weeks 4 Least-squares mean (95% CI) change, mm Hg −7·9 (−9·6 to −6·3) −1·1 (−2·7 to 0·5) and 12 (appendix pp 87–88). Least-squares mean (95% CI) placebo-corrected −6·9 (−9·1 to −4·6) ·· Safety and tolerability were evaluated up to 14 weeks difference, mm Hg (ie, including the 2-week safety follow-up after study p value <0·0001 ·· treatment) via adverse event and vital sign monitoring, Secondary endpoint—change in daytime ambulatory DBP from baseline to week 12‡ laboratory tests, and recording of adverse events of Number of patients 89 95 special interest (ie, adverse events that required clinical Least-squares mean (95% CI) change, mm Hg −8·4 (−9·9 to −6·9) −1·7 (−3·2 to −0·3) intervention for hyponatraemia, hyperkalaemia, or Least-squares mean (95% CI) placebo-corrected −6·7 (−8·8 to −4·6) ·· hypotension). For biochemical endpoints including difference, mm Hg hyperkalaemia, hyponatraemia, and eGFR decrease, we p value <0·0001 ·· report the proportion of patients with any event during Secondary endpoint—change in seated DBP from baseline to week 12‡ the trial. Number of patients 108 109 Least-squares mean (95% CI), mm Hg −7·6 (−9·5 to −5·7) −2·6 (−4·5 to −0·7) Statistical analysis Least-squares mean (95% CI) placebo-corrected −5·0 (−7·7 to −2·3) ·· We planned to randomly assign approximately difference, mm Hg 212 patients in a 1:1 ratio to receive 2 mg baxdrostat or p value 0·0003 ·· placebo. This sample size was estimated to provide (Table 2 continues on next page) 88% statistical power, assuming a mean treatment 992 Articles dierence of 6 mm Hg (SD 12 mm Hg) for the primary Baxdrostat group Placebo group endpoint (change in 24 h ambulatory SBP from baseline to week 12) and at least 75% of patients with evaluable (Continued from previous page) ambulatory blood pressure monitoring at baseline and Secondary endpoint—reaching a nocturnal SBP dipping of ≥10% at week 12§ week 12, using a two-sample t-test at a two-sided alpha Number of patients 89 95 of 0·05. Number of patients reaching a nocturnal SBP dipping of 36/89 (40%) 28/95 (29%) Data are presented as absolute values and percentage, ≥10% median and IQR, mean and SD or SE, least-squares OR (95% CI) 1·6 (0·9 to 3·0) ·· mean and 95% CI or SE, or odds ratio and 95% CI, as p value 0·15 ·· appropriate. The primary endpoint was analysed using For analyses of ambulatory blood pressure endpoints, in the baxdrostat group, one patient was excluded due to an ANCOVA with fixed eects for treatment and baseline invalid baseline ambulatory blood pressure monitoring measurement and 18 patients were excluded due to missing or invalid week 12 ambulatory blood pressure monitoring measurements; in the placebo group, 14 patients were ambulatory 24 h SBP as a covariate, using a modified excluded due to missing or invalid week 12 ambulatory blood pressure monitoring measurements. Missing data were intention-to-treat population that included all patients imputed for seated blood pressure endpoints only. DBP=diastolic blood pressure. OR=odds ratio. SBP=systolic blood who received at least one dose of the study drug. Missing pressure. *Endpoint analysed using an ANCOVA model with treatment as a factor; the covariate was baseline 24 h or invalid ambulatory blood pressure monitoring data ambulatory SBP, night-time ambulatory SBP, daytime ambulatory SBP, or seated SBP, as appropriate for the endpoint. †Endpoint analysed using a logistic regression model with treatment as a factor and baseline 24 h ambulatory SBP as a were not imputed. Thus, patients were only included in covariate; only patients with baseline 24 h ambulatory SBP of 130 mm Hg or higher were included in the analysis. the primary endpoint analysis if they had valid ‡Endpoint analysed using an ANCOVA model with treatment as a factor; the covariate was baseline 24 h ambulatory assessments at both baseline and week 12, irrespective of DBP, night-time ambulatory DBP, daytime ambulatory DBP, or seated DBP, as appropriate for the endpoint. §Endpoint analysed using a logistic regression model with treatment as a factor and baseline dipping status as a covariate. treatment discontinuation or use of rescue therapy. Patients with missing or invalid ambulatory blood Table 2: Primary and secondary endpoints in hierarchical order in the modified intention-to-treat pressure monitoring at week 12 were included in a population sensitivity analysis via multiple imputation. Secondary blood pressure outcomes were also analysed using study and were not included in the primary analysis, but ANCOVA. Secondary endpoints were assessed in the were included in the safety analysis. Overall, 26 patients modified intention-to-treat population, with ambulatory (12%) discontinued treatment for miscellaneous reasons blood pressure endpoints assessed only in patients with (figure 1), but were included in the analysis of the valid measurements at both baseline and week 12. primary endpoint if they had valid ambulatory blood Additional details regarding the analysis plan, handling pressure monitoring measurements both at baseline and of missing data, sensitivity analysis, subgroup analyses, week 12, as well as in the analysis of the secondary and post-hoc analyses are provided in the appendix endpoints. (pp 30–31). Overall, 140 patients (65%) were male and A family-wise type I error rate of 0·05 (two-sided) was 77 (35%) patients were female, 170 patients (78%) were controlled using a hierarchical testing procedure. The White, and the median age was 60·0 years (IQR 51·0–68·0). primary endpoint was tested at a two-sided alpha of 0·05. Patients in the two treatment groups had similar clinical Secondary endpoints were tested at the same level in the characteristics at baseline (table 1). Mean 24 h ambulatory order listed in the Outcomes section until a test failed to and seated oce SBP/DBP at baseline were 141/80 mm Hg reject the null hypothesis or until all listed null and 148/86 mm Hg, respectively, across groups, despite hypotheses were rejected. All analyses were performed patients receiving a mean of 3·75 (range 3–6) background using SAS version 9.4. antihypertensive medications. A total of 206 patients (95%) had adherence of 80% or more during the double-blind Role of the funding source treatment period, assessed by tablet count. Throughout The sponsor of the study (AstraZeneca) had a role in the the 12-week double-blind treatment period, three patients study design, data collection, data analysis, data (3%) in the placebo group and none in the baxdrostat interpretation, and writing of the manuscript. group received rescue antihypertensive medications. At baseline, all patients except one (in the baxdrostat Results group) had valid ambulatory blood pressure monitoring Between March 1, 2024, and April 16, 2025, 854 patients measurements. Of those, at week 12, 99 (93%) of were screened and 417 were included in the placebo 107 patients in the baxdrostat group and 100 (92%) of run-in period; 636 of the 854 patients were excluded 109 in the placebo group had ambulatory blood pressure (437 before the placebo run-in and 199 during the monitoring measurements, with 89 and 95 patients, placebo run-in). 218 patients were randomly assigned, respectively, having valid ambulatory blood pressure and 217 received at least one dose of treatment (modified monitoring at both timepoints and being included in the intention-to-treat population) with 2 mg baxdrostat primary endpoint analysis. (n=108) or placebo (n=109; figure 1). The number of At week 12, the least-squares mean change from baseline patients included in each analysis population is in 24 h ambulatory SBP without imputation was summarised in the appendix (p 44). During the study, −16·6 mm Hg (95% CI −18·8 to −14·3) in the baxdrostat five patients in each treatment arm withdrew from the group and −2·6 mm Hg (95% CI −4·7 to −0·4) in the Articles placebo group (table 2; appendix p 34). The placebo- dierence with baxdrostat versus placebo at week 12 was corrected treatment dierence was −14·0 mm Hg (95% CI significant for change from baseline in night-time −17·2 to −10·8; p<0·0001). A sensitivity analysis with ambulatory, daytime ambulatory, and seated SBP multiple imputation of missing data produced similar (appendix pp 34, 36), and for the proportion of patients results (appendix p 45). The 24 h ambulatory blood reaching 24 h ambulatory SBP <130 mm Hg. Individual pressure monitoring profiles for hourly mean SBP at changes in night-time ambulatory SBP from baseline to baseline and week 12 are shown in figure 2, and individual week 12 are shown in the appendix (p 37). In a post-hoc changes in 24 h ambulatory SBP from baseline to week 12 analysis, the proportion of patients reaching seated oce are shown in the appendix (p 35); all but four patients SBP <130 mm Hg and <140 mm Hg is shown in the treated with baxdrostat had a reduction in 24 h ambulatory appendix (p 46). The between-treatment dierence at SBP. Treatment eects for the change in 24 h ambulatory week 12 for change from baseline was also significant for SBP from baseline to week 12 were consistent across 24 h ambulatory, night-time ambulatory, daytime prespecified subgroups, including age, sex, race, ethnicity, ambulatory, and seated DBP (table 2; appendix p 38). The geographic region, baseline 24 h ambulatory SBP, baseline 24 h ambulatory blood pressure monitoring profiles for eGFR, and baseline BMI (figure 3). hourly mean DBP at baseline and week 12 are shown in The results for the secondary endpoints in hierarchical the appendix (p 39). The proportion of patients reaching order are summarised in table 2. The treatment nocturnal SBP dipping of at least 10% at week 12 was not 140 120 994 )gH mm( PBS yrotalubma naeM A Baseline Daytime Night-time 140 120 0600 0700 0800 0900 1000 1100 1200 1300 1400 1500 1600 1700 1800 1900 2000 2100 2200 2300 0000 0100 0200 0300 0400 0500 )gH mm( PBS yrotalubma naeM Placebo Baxdrostat (2 mg) B Week 12 Hour of day Figure 2: Hourly mean ambulatory systolic blood pressure profile over 24 h at baseline (A) and week 12 (B) Error bars represent SE. The daytime period was 0600 h to 2159 h; the night-time period was 2200 h to 0559 h. SBP=systolic blood pressure. Articles Baxdrostat, 2 mg Placebo Least-squares mean (number of patients) (number of patients) difference (95% CI) in 24 h ambulatory SBP, mm Hg Age, years <65 60 61 –15·3 (–19·1 to –11·6) ≥65 to <75 20 23 –9·8 (–17·4 to –2·3) ≥75 9 11 NA Sex Female 29 34 –14·8 (–20·6 to –8·9) Male 60 61 –13·6 (–17·4 to –9·8) Race Black or African American 4 5 NA Asian 14 13 –16·1 (–26·1 to –6·0) White 70 77 –13·7 (–17·2 to –10·2) Ethnicity Hispanic or Latino 21 19 –12·0 (–19·6 to –4·5) Not Hispanic or Latino 67 72 –14·1 (–17·6 to –10·5) Geographical region Asia–Pacific, Middle East, and Africa 16 20 –17·5 (–26·3 to –8·7) Americas 25 25 –12·4 (–18·8 to –6·0) Europe 48 50 –13·7 (–17·7 to –9·6) Baseline 24 h ambulatory SBP, mm Hg <140 46 49 –13·7 (–18·0 to –9·4) ≥140 43 46 –15·4 (–20·2 to –10·7) Baseline eGFR, mL/min per 1·73m2 <60 7 12 NA ≥60 82 83 –13·5 (–16·9 to –10·1) Baseline BMI, kg/m2 <30 30 33 –18·2 (–24·1 to –12·3) ≥30 59 62 –11·8 (–15·5 to –8·1) Overall 89 95 –14·0 (–17·2 to –10·8) –30 –20 –10 0 10 20 30 Favours baxdrostat Favours placebo Figure 3: Change from baseline in 24 h ambulatory systolic blood pressure at week 12 by prespecified subgroup The forest plot shows least-squares mean difference versus placebo for change from baseline in 24 h ambulatory SBP at week 12 with baxdrostat 2 mg, by subgroup. The squares denote the point estimates. Treatment difference was not analysed for subgroups with fewer than ten patients within treatment groups. Interaction p values for all the subgroup analyses were more than 0·05. eGFR=estimated glomerular filtration rate. NA=not applicable. SBP=systolic blood pressure. significantly dierent between baxdrostat and placebo (n=34; appendix p 40). The median change in aldosterone (table 2). to plasma renin activity ratio from baseline to week 12 The results for the exploratory endpoints are described was –3·5 ng/dL per ng/mL per h (IQR −8·0 to −1·9) for in the appendix (p 32). Seated SBP/DBP decreased from baxdrostat (n=36) and –0·8 ng/dL per ng/mL per h baseline to weeks 4 and 8 with baxdrostat versus placebo (IQR −6·8 to 2·8) for placebo (n=33). (appendix p 47). A total of 12 (11%) of 105 patients at During the trial, adverse events occurred in 56 (52%) of week 4 and 14 (15%) of 94 patients at week 12 had plasma 108 patients receiving baxdrostat and in 40 (37%) of concentrations of baxdrostat below the lower limit of 109 patients receiving placebo (table 3; appendix p 49). quantification (appendix p 48). The median change in Serious adverse events were reported in one patient (1%) serum aldosterone concentration from baseline to in each group (table 3; appendix p 51). There were no week 12 was −5·1 ng/dL (IQR −8·8 to −2·7) in the deaths and no cases of adrenal insuciency during the baxdrostat group (n=92) and −0·4 (−2·9 to 3·0) ng/dL in trial. The most common adverse events were hyper- the placebo group (n=91; appendix p 40), representing kalaemia, headache, and hypotension (appendix p 49). changes in median aldosterone concentration from 2 weeks after treatment discontinuation (week 14), mean baseline of −76% and +2%, respectively, approximated seated SBP/DBP was 137·7 (SD 17·5)/80·5 (12·1) mm Hg based on point estimates. The median change in plasma in the baxdrostat group (n=99) and 142·6 (18·0)/84·1 renin activity from baseline to week 12 was 1·9 ng/mL (11·8) mm Hg in the placebo group (n=105). per h (IQR 0·6 to 17·1) in the baxdrostat group (n=37) Throughout the trial, serum potassium concentration of and 0·3 (−0·3 to 1·2) ng/mL per h in the placebo group more than 6 mmol/L was recorded in a central laboratory Articles p 43). eGFR returned towards baseline 2 weeks after Baxdrostat Placebo group baxdrostat discontinuation (week 14; appendix p 43). A group (n=108) (n=109) 30% or more decrease in eGFR from baseline at any time Any serious adverse event* 1 (1%) 1 (1%) during the trial was reported in 26 (24%) of 108 patients Death 0 0 in the baxdrostat group and in five (5%) of 109 patients in Any adverse event 56 (52%) 40 (37%) the placebo group (table 3). Moderate or severe 15 (14%) 8 (7%) Severe 2 (2%) 1 (1%) Discussion Adverse event leading to discontinuation† In patients with resistant hypertension confirmed by Any  %  ambulatory blood pressure monitoring, the addition of Hyperkalaemia leading to  %  2 mg baxdrostat daily to background antihypertensive discontinuation therapy resulted in a significant placebo-adjusted Adverse event of special interest‡ reduction (−14·0 mm Hg [95% CI −17·2 to −10·8]) in 24 h Hyperkalaemia  %  % ambulatory SBP after 12 weeks of treatment. All but Hyponatraemia  %  % four patients treated with baxdrostat had a reduction in Hypotension  %  24 h ambulatory SBP at week 12 and the treatment eect Serum potassium concentration, mmol/L§ was consistent across all prespecified subgroups. >5·5 / %  % Baxdrostat was also superior to placebo for all prespecified >6·0  %  secondary hierarchical outcomes, including night-time >6·5  %  and daytime ambulatory SBP, seated oce SBP, and all More than 30% decrease in estimated 26 (24%) 5 (5%) DBP measures, except for the dipping profile, which is glomerular filtration rate at any time known to be a poorly reproducible parameter.15 Notably, from baseline to 14 weeks§ the proportion of patients reaching 24 h ambulatory SBP Data are n (%) or n/N (%). Adverse events were collected throughout the trial control (<130 mm Hg) was approximately 4-times higher (ie, up to 14 weeks and including the 2-week treatment withdrawal period). *No serious adverse event was deemed by the investigators to be related to with baxdrostat (71%) than placebo (17%; table 2). baxdrostat. †Other adverse events leading to discontinuation in the baxdrostat Baxdrostat was well tolerated, and no unexpected adverse group were hyponatraemia (1 [1%]), arthralgia (1 [1%]), and serum potassium events were observed. increase (1 [1%]). ‡Low sodium concentration, low blood pressure, and elevated potassium concentration were reported as adverse events of special interest if We implemented measures to ensure accurate they required clinical intervention. §Complete clinical chemistry treatment- identification of patients with true resistant hypertension emergent abnormalities by predefined criteria are reported in the appendix (p 52). in this trial. This rigorous quality-control process Table 3: Adverse events in the safety population excluded patients with pseudo-resistant hypertension and those with clear non-adherence to background medications, ensuring a stable background blood in five (5%) of 108 patients receiving baxdrostat (confirmed pressure that was less responsive to placebo. The placebo in three patients [3%] in a local laboratory) and none eect on SBP was small in Bax24 (−2·6 mm Hg by 24 h receiving placebo (table 3; appendix pp 52–53). Hyper- ambulatory blood pressure monitoring and −4·7 mm Hg kalaemia requiring clinical intervention (an adverse event by seated oce measurement) when compared with a of special interest) was reported in seven (6%) of trial of the aldosterone synthase inhibitor lorundrostat in 108 patients in the baxdrostat group and in one (1%) of patients with uncontrolled hypertension,7 which reported 109 patients in the placebo group (table 3). Hypokalaemia an unexpectedly large placebo-associated 24 h ambulatory (serum potassium concentration <3·5 mmol/L) occurred SBP reduction (−7·4 mm Hg at 12 weeks). Moreover, in in two (2%) of 104 patients in the baxdrostat group and our trial, witnessed intake of background and study 11 (11%) of 104 patients in the placebo group (appendix therapy at both baseline and 12 weeks standardised the p 52). primary endpoint assessment. Standardisation of drug Hyponatraemia requiring clinical intervention (adverse intake using directly observed therapy prior to baseline event of special interest) was reported in one (1%) patient and week 12 ambulatory blood pressure monitoring in each group (table 3). Hyponatraemia <130 mmol/L enabled detection of a reduction in 24 h ambulatory SBP was recorded in four (4%) of 108 patients in the baxdrostat that exceeded the oce SBP reduction, consistent with group and in two (2%) of 109 patients in the placebo that observed in an ambulatory substudy of the BaxHTN group (appendix p 52). trial,5 but in contrast to the typical pattern observed in Changes in potassium and sodium concentrations antihypertensive drug trials.16,17 This finding might reflect with baxdrostat occurred predominantly in the first attenuation of the white-coat eect, but might also relate 2 weeks, with levels returning towards baseline 2 weeks to the study design, in which ambulatory blood pressure after the end of treatment (appendix pp 41–42). The mean monitoring was performed after directly observed change in eGFR from baseline to week 12 was therapy, whereas seated oce blood pressure measure- −8·7 mL/min per 1·73 m² (SD 14·0) for baxdrostat and ments were obtained pre-dose, at trough (ie, 12−24 h −0·4 (9·7) mL/min per 1·73 m² for placebo (appendix after the last medication intake). Finally, the unexpectedly 996 Articles large nocturnal blood pressure reduction observed with mean daytime and night-time SBP with baxdrostat help baxdrostat (−16·0 mm Hg), comparable in magnitude to preserve the normal 24 h circadian rhythm. the daytime SBP reduction (−16·8 mm Hg), contributed Consistent with the known pharmacological eects of to an overall amplification of the 24 h SBP reduction mineralocorticoid receptor antagonists and aldosterone across the circadian cycle. synthase inhibitors,6–8,24–26 treatment with baxdrostat was We focused on 24 h ambulatory blood pressure in the associated with increases in serum potassium Bax24 study because it is more strongly associated with concentrations. The rise in serum potassium mainly all-cause and cardiovascular mortality than conventional occurred within 2 weeks of baxdrostat treatment, oce blood pressure, with night-time blood pressure remained stable thereafter during the 12-week treatment most strongly associated with mortality.10,12 Our previous period, and progressively declined 2 weeks after drug phase 3 BaxHTN study,5 conducted in patients with discontinuation. The magnitude and temporal pattern of uncontrolled or resistant hypertension, primarily this eect was comparable to that reported in the evaluated the ecacy of baxdrostat in reducing seated BaxHTN trial.5 The incidence of confirmed and clinically oce SBP and included exploratory ambulatory blood significant hyperkalaemia (>6·0 mmol/L) was low (3%; pressure assessments that showed large reductions in table 3) and consistent with the low rates of severe 24 h and night-time ambulatory blood pressure relative hyperkalaemia reported in both the BaxHTN5 and to placebo after 12 weeks of treatment. The present study, lorundrostat trials.7,8,26 However, these trials largely fully independent from BaxHTN and conducted in enrolled patients with preserved renal function and patients with true resistant hypertension only, confirms therefore at low baseline risk of hyperkalaemia. Finally, these substantial reductions in both 24 h and night-time in our trial the incidence of hyponatraemia was low, and ambulatory blood pressure. The reductions in ambulatory there were no cases of adrenal insuciency. SBP in this trial are the largest observed in a randomised As previously observed with inhibition of aldosterone, controlled trial of any therapeutic intervention to date in eGFR decreased by a mean of 8·7 (SD 14·0) mL/min per patients with true resistant hypertension.18–20 Moreover, 1·73 m² during the trial, mainly within 2−4 weeks of the magnitude of the placebo-corrected oce SBP baxdrostat treatment, but recovered towards baseline decrease with baxdrostat is consistent with the results of within 2 weeks after discontinuation of baxdrostat, a 2025 meta-analysis of selective aldosterone synthase consistent with a reversible functional eGFR change due inhibitors.21 To contextualise our findings with respect to to changes in renal perfusion pressure.27,28 Notably, the the potential eect of the ambulatory blood pressure absolute decrease in eGFR observed in Bax24 is changes we observed with 2 mg baxdrostat, an consistent with renal function changes reported with observational study with almost 60 000 patients lorundrostat26 and with findings from the PATHWAY-2 followed-up for a median of 9·7 years quantified the trial,6 in which an eGFR decline of 9·7 mL/min per eect of a 1 SD increase in 24 h (9·5 mm Hg) and night- 1·73 m² was reported after 12 weeks of treatment with time (11·5 mm Hg) ambulatory SBP.10 All-cause mortality the mineralocorticoid receptor antagonist spironolactone increased by 30% and 36% per SD increase for 24 h and (25−50 mg daily) in patients with resistant hypertension. night-time SBP, respectively, and cardiovascular Such early decreases in eGFR in the short term have mortality increased by 41% for 24 h SBP and 46% for been reported after initiation of the non-steroidal night-time SBP.10 However, to confirm a causal mineralocorticoid receptor antagonist finerenone, or relationship between the substantial reductions in sodium-glucose cotransporter 2 inhibitors added to ambulatory blood pressure with baxdrostat, and clinical background treatment with renin-angiotensin-system outcomes, longer-term outcome studies are required. blockers, which have been demons trated to have Our study adds to the growing body of evidence that long-term renoprotective eects in proteinuric aldosterone dysregulation is a key factor in the nephropathies.29 Ongoing phase 3 trials are assessing the pathogenesis of hard-to-control and resistant hypert- ecacy and safety of baxdrostat in combination with ension.1–8 Over 12 weeks, baxdrostat lowered serum dapagliflozin on kidney outcomes in patients with aldosterone concentrations by approximately 76% and chronic kidney disease and high blood pressure increased plasma renin activity, findings consistent with (NCT06268873, NCT06742723) and on develop ment of inhibition of aldosterone synthase and the enhanced heart failure and risk of cardiovascular death renal excretion of sodium. Resistant hypertension is (NCT06742723, NCT06677060). Meanwhile, similarly to known to be a sodium-retaining state,22 which contributes what has been recommended with the use of to night-time blood pressure elevation despite treatment mineralocorticoid antagonists, our results suggest that with background diuretic therapy. The substantial night- once approved for clinical use, monitoring of patients time blood pressure lowering with baxdrostat in our trial treated with aldosterone synthase inhibitors will be shows that this increase in night-time blood pressure is clinically important soon after initiation. reversible with aldosterone synthase inhibition, and the Our study has limitations. The proportion of women long half-life of baxdrostat (approximately 30 h)23 might and Black patients was lower than observed in clinical contribute to this eect. Moreover, similar reductions in practice, but the patient characteristics were broadly Articles representative of those with resistant hypertension.12,30 ProKidney, Intercept, Ionis, Ipsen, JucaBio, Lilly, Novotech, ReCor Our primary outcome analysis only included patients Medical, Transcend, ValenzaBio, and Remegen; honoraria from with valid ambulatory blood pressure monitoring data at Vanderbilt University Medical Center and Tufts Medicine; support for meeting attendance from AstraZeneca and Intercept; has patents both baseline and 12 weeks; however, a sensitivity planned, issued, or pending with Corventum; has a leadership role on analysis with imputation of missing or invalid ambulatory the Collaborative Study Group and Corventum; stock options with blood pressure monitoring data for the whole modified Acelyrin, Alumis, ValenzaBio, PathEx, Venostent, Teucer, Corventum, intention-to-treat population showed similar results. We Innovative Renal Care, Ephla Bio, and Biorasi; and receipt of equipment or other services from AstraZeneca and Novo Nordisk. JMF reports did not perform chemical adherence testing for sitting on the AstraZeneca Executive Committee for baxdrostat clinical background antihypertensive therapy in blood or urine, trials; grant funding from Recor Medical, SoniVie, Mineralys, and but tablet counts and baxdrostat drug concentrations AstraZeneca; royalties or licences from UptoDate; consulting fees from (consistent with those observed in earlier studies with AstraZeneca, Casana, Recor Medical, and Idorsia; and payment for expert testimony from Teva. ESWJ reports sitting on the AstraZeneca baxdrostat5,23) suggested good adherence to therapy Executive Committee for baxdrostat clinical trials. RK, HL, FB, ASL, and throughout the study. Finally, our study was only 12 weeks SP are employed by AstraZeneca and hold stocks in AstraZeneca. in duration; however, long-term safety and ecacy in MPS reports consulting fees from AstraZeneca, Medtronic, Eli Lilly, hypertension are being evaluated in the BaxHTN and Idorsia, and Abbott; honoraria from AstraZeneca, Medtronic, Abbott, and Boehringer Ingelheim; support for meeting attendance from BaxAsia (NCT06344104) trials,5,13 and in long-term AstraZeneca; and a leadership role in Hypertension Australia and World renoprotection and cardioprotection trials. Hypertension League. HS and J-GW report sitting on the AstraZeneca In conclusion, in the Bax24 trial, the addition of 2 mg Executive Committee for baxdrostat clinical trials. BW reports chairing baxdrostat daily to background antihypertensive therapy the AstraZeneca Executive Committee for baxdrostat clinical hypertension trials; grant funding from the National Institute for for patients with true resistant hypertension confirmed Health Research University College Hospitals Biomedical Research by ambulatory blood pressure monitoring resulted in Centre; consulting fees from Alynylam, Roche, Novartis, and Antlia; substantial reductions in 24 h and night-time ambulatory and is the Chief Scientific and Medical Ocer and Board member for the British Heart Foundation. SBP at 12 weeks compared with placebo. Although steroidal (spironolactone and eplerenone) and non- Data sharing Data underlying the findings described in this manuscript can be steroidal (finerenone) mineralocorticoid receptor requested in accordance with AstraZeneca’s data sharing policy antagonists have demonstrated clinical benefits in described online at https://www.astrazenecaclinicaltrials.com/our- selected populations with heart failure or chronic kidney transparency-commitments/. Data for studies directly listed on Vivli disease, selective aldosterone synthase inhibitors such as can be requested through Vivli at https://www.vivli.org. Data for studies not listed on Vivli can be requested through Vivli at https:// baxdrostat represent a promising new treatment strategy vivli.org/members/enquiries-about-studies-not-listed-on-the-vivli- for patients with hard-to-control hypertension. Dedicated platform/. The AstraZeneca Vivli member page is also available outcomes trials will be needed to determine whether outlining further details: https://vivli.org/ourmember/astrazeneca. these blood pressure reductions translate into improved Acknowledgments long-term cardiovascular and renal outcomes. The Bax24 trial was funded by AstraZeneca. BW is supported by the National Institute for Health Research University College London Hospitals Contributors Biomedical Research Centre. We thank the patients who participated in the MA, JMB, JMF, ESWJ, ASL, SP, MPS, HS, J-GW, and BW participated in Bax24 trial, as well as the investigators, clinical trial personnel, and research the conceptualisation and development of the study design. HL and FB teams who participated in this trial. We also acknowledge the contribution performed the programming and analysed the data. MA, RK, HL, FB, of George Bakris (died June, 2024), who provided substantial support as ASL, and BW accessed and verified the data. JPD, RK, HL, FB, ASL, part of our trial steering committee before and during the trial. Medical MPS, SP, and BW conducted the research process, provided study writing and editing support for the development of this manuscript, under resources, and performed data curation activities. MA, JPD, SP, and BW the direction and guidance of the authors, was provided by had oversight and leadership responsibility for the research. MA and Lois Roberts-Grant, Jane Murphy, and Mary Sayers of Ashfield BW developed the initial draft of the manuscript. All authors had access MedComms, an Inizio Company, in accordance with Good Publications to all the included data and interpreted the data, including the Practice guidelines. This support was funded by AstraZeneca. visualisation of the data. All authors participated in the development and review of this manuscript, had final responsibility for the decision to References submit for publication, and are accountable for the accuracy and 1 Brown JM, Underwood PC, Ferri C, et al. Aldosterone dysregulation integrity of this work. with aging predicts renal vascular function and cardiovascular risk. Hypertension 2014; 63: 1205–11. Declaration of interests 2 Brown JM, Siddiqui M, Calhoun DA, et al. The unrecognized MA reports sitting on the AstraZeneca Executive Committee for prevalence of primary aldosteronism: a cross-sectional study. baxdrostat clinical trials; grant funding from Novartis, Recor, and Ann Intern Med 2020; 173: 10–20. SoniVie; consulting fees from Novartis, Recor, AstraZeneca, Alnylam, 3 Monticone S, D’Ascenzo F, Moretti C, et al. 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HTN TRIO): a randomised, multicentre, single-blind, sham- controlled trial. Lancet 2021; 397: 2476–86. --- [PDF原文](https://sci-net.xyz/storage/7932541/59b96fc59e673b516a297cbbd90a38fb99a4ba9e78489153e6f23f164e1e5238/Effect-of-baxdrostat-on-ambulatory-blood-pressure-in-patients-with-resistant-hypertension.pdf) DOI: 10.1016/S0140-6736(25)02549-8