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Fixed-Dose Combinations in the Management of Hypertension

Defining the Place of Angiotensin Receptor Antagonists and Hydrochlorothiazide

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Abstract

We discuss combination therapy with angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics in light of the independent actions of both types of agents, and the adverse effects of both agents independently and in the context of the physiologic synergy achieved in using these agents together. ARBs counteract many of the adverse events associated with the use of thiazide diuretics and have been shown to reduce the occurrence of new-onset diabetes mellitus. We also review outcome trials in patients with hypertension (such as LIFE [Losartan Intervention For Endpoint reduction in hypertension], VALUE [Valsartan Antihypertensive Long-term Use Evaluation], and SCOPE [Study on COgnition and Prognosis in the Elderly]), in which losartan, valsartan, and candesartan cilexetil were used in combination with hydrochlorothiazide. Fixed combination ARB/hydrochlorothiazide agents make sense as initial therapy for patients in whom BP is >20/ 10mm Hg above goal.

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Acknowledgments

A. Hɶggen has received honoraria from Bayer and Merck. I. Os has received honoraria for lectures from Amgen, GlaxoSmithKline, Merck Sharp & Dohme, Sanofi-Synthelabo, Bristol Myers Squibb, and Pfizer. S.E. Kjeldsen has received honoraria from AstraZeneca, Bayer, Merck, Novartis, Pharmacia, and Pfizer for various speaking and research activities. G.W. Gleim and K. Beckey are employees of Merck Research Labs.

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Authors and Affiliations

  1. Department of Cardiology, Ullevaal University Hospital, Oslo, NO-0407, Norway

    Sverre E. Kjeldsen

  2. Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA

    Sverre E. Kjeldsen

  3. Institute of Pharmacotherapy, University of Oslo Medical School, Oslo, Norway

    Ingrid Os

  4. Department of Nephrology, Ullevaal University Hospital, Oslo, Norway

    Ingrid Os & Aud Høieggea

  5. Merck Research Labs, West Point, Pennsylvania, USA

    Kim Beckey & Gilbert W. Gleim

  6. University of Alabama Vascular Biology and Hypertension Program, Birmingham, Alabama, USA

    Suzanne Oparil

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  1. Sverre E. Kjeldsen
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Kjeldsen, S.E., Os, I., Høieggea, A. et al. Fixed-Dose Combinations in the Management of Hypertension. Am J Cardiovasc Drugs 5, 17–22 (2005). https://doi.org/10.2165/00129784-200505010-00003

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