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Novel antihypertensive agents for resistant hypertension: what does the future hold?

Hypertension Research volume 45, pages 1918–1928 (2022)Cite this article

Abstract

Finding complementary compelling novel therapeutic agents for better control of blood pressure in people with resistant hypertension is moving into unchartered territory. The latest therapeutic developments explore approaches in the clinical arena that were either not examined or could only be examined in animal models two decades ago. Four main mechanisms have now been explored and operationalized in drug development: (a) mineralocorticoid receptor blockade using a nonsteroidal structure with many fewer side effects, (b) an aminopeptidase A inhibitor that has central effects on vasopressin, (c) a combined endothelin A and B receptor blocker and (d) an aldosterone synthase inhibitor devoid of glucocorticoid activity. All these agents are either completing Phase II development and starting Phase III or are involved in the ongoing recruitment of Phase III trials. Additionally, novel agents use antisense inhibition to block angiotensinogen development in the liver. These agents are discussed only for completeness, as they are still in Phase II trial development. Last, another agent that was initially being developed as an antihypertensive and once the data were reviewed by the company clearly showed efficacy as a heart failure agent was sacubitril/valsartan, which was ultimately approved. However, there are some discussions about reinvigorating the quest for an indication for hypertension, although no such steps have been formally initiated.

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  1. Department of Medicine, Am Heart Assoc. Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, IL, USA

    Vincent D. Salvador & George L. Bakris

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VDS—None; GLB is supported by T32 NIH grant DK07011 and is a consultant to Bayer, KBP Biosciences, Ionis, Alnylam, Astra Zeneca, Quantum Genomics, Horizon, Novo Nordisk, Dia Medica Therapeutics, and InRegen.

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Salvador, V.D., Bakris, G.L. Novel antihypertensive agents for resistant hypertension: what does the future hold?. Hypertens Res 45, 1918–1928 (2022). https://doi.org/10.1038/s41440-022-01025-9

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