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This review highlights innovative approaches in hypertension management. Aldosterone synthase inhibitors (ASIs) and non\u2010steroidal mineralocorticoid receptor antagonists improve blood pressure control and offer cardiorenal benefits while reducing adverse effects including hyperkalaemia. Endothelin receptor antagonists show promise in resistant hypertension by addressing vasoconstrictive pathways. RNA\u2010based therapies, like zilebesiran, provide a novel approach to suppress angiotensinogen, offering durable antihypertensive effects with less frequent dosing. Additional advances include AT<jats:sub>2<\/jats:sub> receptor agonists, ACE2\/Angiotensin\u2010(1\u20137)\/MAS receptor activators and NAD<jats:sup>+<\/jats:sup> boosting compounds, which target key mechanisms of vascular dysfunction and ageing\u2010related hypertension. Gut microbiome\u2010targeted therapies and fixed\u2010dose combination pills are also discussed for their potential to enhance blood pressure control and patient adherence. These emerging therapies not only aim to lower blood pressure but also address underlying pathophysiological mechanisms, offering a precision\u2010focussed approach to treatment. By critically analysing these developments, this review provides insights into how novel strategies can overcome existing challenges in hypertension management, reduce the global disease burden and improve patient outcomes.<\/jats:p>","DOI":"10.1111\/bph.70063","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T06:44:56Z","timestamp":1748933096000},"page":"3389-3410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Advancing antihypertensive drug development"],"prefix":"10.1111","volume":"182","author":[{"given":"Fay","family":"Pu","sequence":"first","affiliation":[{"name":"Intensive care units University Hospitals of Morecambe Bay NHS Foundation Trust  Kendal UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanrong","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fozia Zahir","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Cardiology Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7678-0785","authenticated-orcid":false,"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Green","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"},{"name":"Northern Care Alliance NHS Foundation Trust  Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1012-4141","authenticated-orcid":false,"given":"Hongyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.312156"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.19430"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab777"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32135-X"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000003330"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16177"},{"key":"e_1_2_17_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16179"},{"key":"e_1_2_17_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16182"},{"key":"e_1_2_17_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16180"},{"key":"e_1_2_17_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16178"},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/348730a0"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.121.17073"},{"key":"e_1_2_17_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025845"},{"key":"e_1_2_17_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.10081"},{"key":"e_1_2_17_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.156976"},{"key":"e_1_2_17_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.0728"},{"key":"e_1_2_17_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.34.5.1112"},{"key":"e_1_2_17_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01263"},{"key":"e_1_2_17_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01049-3"},{"key":"e_1_2_17_22_1","unstructured":"BavryA. 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