Recent advances in the treatment of resistant hypertension
Main Article Content
Abstract
Resistant hypertension accounts for approximately 10-20% of all hypertensive patients and represents a population at particularly high risk of cardiovascular, renal, and cerebrovascular events, imposing a substantial burden on global healthcare systems. Despite the use of optimized combination therapy, many patients still fail to achieve target blood pressure levels, underscoring the urgent need for novel therapeutic strategies. Two emerging approaches have recently shown significant promise: renal sympathetic denervation (RDN) - an interventional procedure that provides sustained blood pressure reduction in selected patients; and aldosterone synthase inhibitors (ASI) - particularly Baxdrostat, a selective inhibitor of the CYP11B2 enzyme, which has demonstrated potent, durable, and well-tolerated antihypertensive effects in several phase III clinical trials, including BaxHTN, BaxAsia, and Bax24. These advances offer new perspectives for the management of resistant hypertension, paving the way toward personalized and mechanism-targeted therapy.
Article Details
Keywords
Resistant hypertension, renal sympathetic denervation, aldosterone synthase inhibitor, Baxdrostat
References
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21. Dey S, Frishman WH, Aronow WS. Baxdrostat: an aldosterone synthase inhibitor for the treatment of systemic hypertension. Cardiology in Review. 2025; 33(3): 243-245. Doi.org/10.1097/crd.0000000000000595.
22. Flack JM, Azizi M, Brown JM, et al. Baxdrostat for uncontrolled and resistant hypertension: rationale and design of the Phase 3 clinical trials BaxHTN, BaxAsia, and Bax24. Hypertension Research. 2025: 1-13. Doi.org/10.1038/s41440-025-02297-7.
23. Ando H. Baxdrostat and the future of aldosterone-targeted therapy. Hypertension Research. 2025: 1-2. Doi.org 10.1038/s41440-025-02415-5.
24. Syed HR, Bhatia K, Dasgupta I, Ferro A. The state of renal sympathetic denervation for the management of patients with hypertension: A systematic review and meta-analysis. Eur Heart J. 2021; 42(15): 1440-1450. doi:10.1093/eurheartj/ehaa932.
25. Mahfoud F, Böhm M, Schmieder R, Narkiewicz K, Ewen S, Ruilope L, et al. Effects of renal denervation on kidney function and long-term outcomes: 3-year follow-up from the Global SYMPLICITY Registry. Eur Heart J. 2019; 40(42): 3474-3482. doi:10.1093/eurheartj/ehz118.
2. World HO. Global report on hypertension: the race against a silent killer. World Health Organization; 2023.
3. Brant LCC, Passaglia LG, Pinto-Filho MM, de Castilho FM, Ribeiro ALP, Nascimento BR. The burden of resistant hypertension across the world. Current Hypertension Reports. 2022; 24(3): 55-66. Doi.org/10.1007/s11906-022-01173-w.
4. Noubiap JJ, Nansseu JR, Nyaga UF, Sime PS, Francis I, Bigna JJ. Global prevalence of resistant hypertension: a meta-analysis of data from 3.2 million patients. Heart. 2019; 105(2): 98-105. Doi.org/10.1136/heartjnl-2018-313599.
5. Alsharari R, Shantsila E, Lip GY, Shantsila A. Revisiting the diagnosis of ‘resistant hypertension’: What should we do nowadays’. Journal of human hypertension. 2022; 36(4): 337-340. Doi.org/10.1038/s41371-021-00631-3.
6. Dogra S, Shah S, Gitzel L, et al. Baxdrostat: a novel aldosterone synthase inhibitor for treatment resistant hypertension. Current Problems in Cardiology. 2023; 48(11): 101918. Doi.org/10.1016/j.cpcardiol.2023.101918.
7. Flack JM, Azizi M, Brown JM, et al. Baxdrostat Efficacy and Safety in Uncontrolled and Resistant Hypertension. The New England journal of medicine. 2025. Doi:10.1056/NEJMoa2507109.
8. Jones DW, Ferdinand KC, Taler SJ, et al. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. JACC. 2025; Doi.org/10.1161/CIR.0000000000001356.
9. John William Mcevoy, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension: Developed by the task force on the management of elevated blood pressure and hypertension of the European Society of Cardiology (ESC) and endorsed by the European Society of Endocrinology (ESE) and the European Stroke Organisation (ESO). European heart journal. 2024: 3912-4018. Doi.org/10.1093/eurheartj/ehae178.
10. Huỳnh Văn Minh và cộng sự. Khuyến cáo chẩn đoán và điều trị tăng huyết áp. 2022;
11. Jafari E, Cooper-DeHoff RM, Effron MB, Hogan WR, McDonough CW. Characteristics and predictors of apparent treatment-resistant hypertension in real-world populations using electronic health record-based data. American Journal of Hypertension. 2024; 37(1): 60-68. Doi.org/10.1093/ajh/hpad084.
12. Ebinger JE, Kauko A, FinnGen, Bello NA, Cheng S, Niiranen T. Apparent treatment-resistant hypertension associated lifetime cardiovascular risk in a longitudinal national registry. European journal of preventive cardiology. 2023;30(10):960-968. Doi.org/10.1093/eurjpc/zwad066
13. Coccina F, Pierdomenico AM, Cuccurullo C, Pizzicannella J, Trubiani O, Pierdomenico SD. Ambulatory resistant hypertension and risk of heart failure in the elderly. Diagnostics. 2023; 13(9): 1631. Doi.org/10.3390/diagnostics13091631.
14. Kaczmarski KR, Sozio SM, Chen J, Sang Y, Shafi T. Resistant hypertension and cardiovascular disease mortality in the US: results from the National Health and Nutrition Examination Survey (NHANES). BMC nephrology. 2019; 20(1): 138. Doi.org/10.1186/s12882-019-1315-0.
15. Nguyễn Thị Tố Vân. Tuân thủ dùng thuốc ở người cao tuổi bị tăng huyết áp: Tổng quan hệ thống và phân tích gộp. Tạp chí Y học Việt Nam. 2025; 547(1). Doi.org/10.51298/vmj.v547i1.12926.
16. Reinhold Kreutz. 2024 European Society of Hypertension clinical practice guidelines for the management of arterial hypertension. European journal of internal medicine. 2024; 126: 1-15. Doi.org/10.1016/j.ejim.2024.05.033.
17. Azizi M, Sharp AS, Fisher ND, et al. Patient-level pooled analysis of endovascular ultrasound renal denervation or a sham procedure 6 months after medication escalation: the RADIANCE clinical trial program. Circulation. 2024; 149(10): 747-759. Doi.org/10.1161/circulationaha.123.066941.
18. Mancia Chairperson. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH). Journal of hypertension. 2023; 41(12): 1874-2071. Doi: 10.1097/HJH.0000000000003480.
19. Cicero AF, Tocci G, Avagimyan A, et al. Aldosterone Synthase Inhibitors for Resistant Hypertension: Pharmacological Insights-A Systematic Review: Arrigo. FG Cicero et al. Drugs. 2025: 1-25. Doi.org/10.1007/s40265-025-02229-2.
20. Schiffrin EL. Effects of aldosterone on the vasculature. Hypertension. 2006; 47(3): 312-318. Doi.org/10.1161/01.hyp.0000201443.63240.a7.
21. Dey S, Frishman WH, Aronow WS. Baxdrostat: an aldosterone synthase inhibitor for the treatment of systemic hypertension. Cardiology in Review. 2025; 33(3): 243-245. Doi.org/10.1097/crd.0000000000000595.
22. Flack JM, Azizi M, Brown JM, et al. Baxdrostat for uncontrolled and resistant hypertension: rationale and design of the Phase 3 clinical trials BaxHTN, BaxAsia, and Bax24. Hypertension Research. 2025: 1-13. Doi.org/10.1038/s41440-025-02297-7.
23. Ando H. Baxdrostat and the future of aldosterone-targeted therapy. Hypertension Research. 2025: 1-2. Doi.org 10.1038/s41440-025-02415-5.
24. Syed HR, Bhatia K, Dasgupta I, Ferro A. The state of renal sympathetic denervation for the management of patients with hypertension: A systematic review and meta-analysis. Eur Heart J. 2021; 42(15): 1440-1450. doi:10.1093/eurheartj/ehaa932.
25. Mahfoud F, Böhm M, Schmieder R, Narkiewicz K, Ewen S, Ruilope L, et al. Effects of renal denervation on kidney function and long-term outcomes: 3-year follow-up from the Global SYMPLICITY Registry. Eur Heart J. 2019; 40(42): 3474-3482. doi:10.1093/eurheartj/ehz118.