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Key advances in antihypertensive treatment

Nature Reviews Cardiology volume 9, pages 276–285 (2012)Cite this article

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Abstract

Although various effective treatments for hypertension are available, novel therapies to reduce elevated blood pressure, improve blood-pressure control, treat resistant hypertension, and reduce the associated cardiovascular risk factors are still required. A novel angiotensin-receptor blocker (ARB) was approved in 2011, and additional compounds are in development or being tested in clinical trials. Several of these agents have innovative mechanisms of action (an aldosterone synthase inhibitor, a natriuretic peptide agonist, a soluble epoxide hydrolase inhibitor, and an angiotensin II type 2 receptor agonist) or dual activity (a combined ARB and neutral endopeptidase inhibitor, an ARB and endothelin receptor A blocker, and an endothelin-converting enzyme and neutral endopeptidase inhibitor). In addition, several novel fixed-dose combinations of existing antihypertensive agents were approved in 2010–2011, including aliskiren double and triple combinations, and an olmesartan triple combination. Upcoming fixed-dose combinations are expected to introduce calcium-channel blockers other than amlodipine and diuretics other than hydrochlorothiazide. Finally, device-based approaches to the treatment of resistant hypertension, such as renal denervation and baroreceptor activation therapy, have shown promising results in clinical trials. However, technical improvements in the implantation procedure and devices used for baroreceptor activation therapy are required to address procedural safety concerns.

Key Points

  • In 2010–2011, one novel antihypertensive—azilsartan—as well as several novel fixed-dose combinations of existing antihypertensive agents, including aliskiren double and triple combinations and an olmesartan triple combination were approved

  • Novel antihypertensive compounds in clinical development include an aldosterone synthase inhibitor, a natriuretic peptide agonist, and a soluble epoxide hydrolase inhibitor

  • An angiotensin II type 2 receptor agonist—compound 21—is in preclinical development

  • Novel antihypertensives with dual activity, including an angiotensin-receptor blocker and neutral endopeptidase inhibitor, an angiotensin-receptor blocker and endothelin receptor A blocker, and an endothelin-converting enzyme and neutral endopeptidase inhibitor, are in clinical development

  • Upcoming fixed-dose combinations of antihypertensives are expected to include calcium-channel blockers other than amlodipine, and diuretics other than hydrochlorothiazide (which are included in the current combinations)

  • Nonpharmacological approaches for the treatment of resistant hypertension—renal denervation and baroreceptor activation—have shown promising results in clinical trials

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Figure 1: Schematic representation of renal sympathetic denervation.
Figure 2: Schematic representation of baroreflex activation therapy.

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Acknowledgements

This work was supported by the EUREKA's Eurostars program of the EU and by the grant VEGA 1/0831/09 from the Scientific and Grant Agency of the Slovak Republic.

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Authors and Affiliations

  1. Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, Bratislava, 811 08, Slovakia

    Ludovit Paulis

  2. Center for Cardiovascular Research, Charité-Universitätsmedizin, Hessische Strasse 3–4, Berlin, 10115, Germany

    Ulrike M. Steckelings & Thomas Unger

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L. Paulis and T. Unger researched the data for the article, provided a substantial contribution to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission. U. M. Steckelings provided a substantial contribution to discussions of the content, and reviewed and/or edited the manuscript before submission.

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Correspondence to Thomas Unger.

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T. Unger declares that he has acted as a consultant or speaker and has a modest financial interest in Vicore Pharma. M. U. Steckelings declares that she has acted as a consultant and has received research supplies from Vicore Pharma. L. Paulis declares no competing interests.

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Paulis, L., Steckelings, U. & Unger, T. Key advances in antihypertensive treatment. Nat Rev Cardiol 9, 276–285 (2012). https://doi.org/10.1038/nrcardio.2012.33

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