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This persistent gap reflects a combination of patient-related factors, including poor adherence, physician-related factors such as therapeutic inertia, health system limitations, and intrinsic shortcomings of current pharmacological therapies. Existing antihypertensive agents are effective at the population level but are limited by interindividual variability in response, incomplete targeting of underlying pathophysiological mechanisms, adverse effects, and insufficient 24-hour BP control. These limitations highlight a mismatch between the heterogeneous nature of hypertension and the largely empirical approach to treatment. Recent advances in systems biology, digital health, and artificial intelligence will offer opportunities for improved patient stratification and more individualized therapy in the future. In parallel, renewed drug development has led to novel approaches targeting both nontraditional pathways, such as endothelin receptor antagonism or more selective modulation within established systems, eg, particularly the inhibition of aldosterone. Future progress will require integration of improved implementation strategies for hypertension management with the development of more effective, better tolerated, and mechanism-based therapies to improve hypertension treatment and achieve optimal blood pressure control and outcomes.<\/jats:p>","DOI":"10.1093\/ajh\/hpag084","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:49:34Z","timestamp":1784116174000},"page":"S5-S10","source":"Crossref","is-referenced-by-count":0,"title":["The imperative for improved antihypertensives"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4818-211X","authenticated-orcid":false,"given":"Reinhold","family":"Kreutz","sequence":"first","affiliation":[{"name":"Institute of Clinical Pharmacology and Toxicology, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Charit\u00e9-Universit\u00e4tsmedizin Berlin , 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