, Volume 68, Issue 3, pp 373–381 | Cite as


Fixed-Dose Combination in Hypertension
Adis Drug Profile


  • ▴ Amlodipine, a dihydropyridine calcium channel blocker, and valsartan, an angiotensin II receptor blocker, are established antihypertensive agents. Fixed-dose combinations of amlodipine/valsartan are available in several European countries and in the US. Individual dose titration with amlodipine and valsartan is generally recommended before changing to the fixed-dose combination.

  • ▴ Amlodipine/valsartan, at approved dosage regimens, achieved significantly greater reductions in mean sitting diastolic and systolic blood pressure (BP) than amlodipine or valsartan monotherapy, or placebo in two randomized, double-blind, factorial trials in patients with mild to moderate hypertension.

  • ▴ Approximately 80–90% of patients receiving approved dosages of amlodipine/valsartan achieved a response, defined as a mean sitting diastolic BP <90 mmHg or a ≥10 mmHg reduction from baseline.

  • ▴ Subgroup analyses of data from the two trials showed that the antihypertensive efficacy of amlodipine/valsartan in the elderly, Black patients and those with stage 2 hypertension was consistent with that observed in the overall study population.

  • ▴ Marked reductions in BP were also observed in patients whose BP was previously uncontrolled on monotherapy (with various antihypertensives) who were switched (without washout) to amlodipine/valsartan in a phase IIIb-IV study.

  • ▴ Amlodipine/valsartan was generally well tolerated in clinical trials. In particular, the incidence of peripheral oedema was significantly lower in patients receiving amlodipine/valsartan than in those treated with amlodipine monotherapy.


Amlodipine Valsartan HCTZ Peripheral Oedema Moderate Hypertension 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Acknowledgements and Disclosures

The manuscript was reviewed by: J.P. Baguet, Department of Cardiology and Hypertension, Grenoble University Hospital, Grenoble, France; L. Frost, Department of Medicine and Clinical Institute, Silkeborg Hospital, Aarhus University Hospital, Silkeborg, Denmark; M.F. O’Rourke, St Vincent’s Clinic, Carlinghurst, New South Wales, Australia; D. Poldermans, Erasmus Medisch Centrum Rotterdam, Rotterdam, The Netherlands.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was also offered an opportunity to comment on this article. Changes resulting from any comments received were made on the basis of scientific and editorial merit.


  1. 1.
    Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003 May 21; 289(19): 2560–72PubMedCrossRefGoogle Scholar
  2. 2.
    Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007 Jun; 25(6): 1105–87PubMedCrossRefGoogle Scholar
  3. 3.
    Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multientre randomised controlled trial. Lancet 2005 Sep 10; 366(9489): 895–906PubMedCrossRefGoogle Scholar
  4. 4.
    European Medicines Agency (EMEA). Summary of product characteristics: Exforge® (amlodipine/valsartan) film-coated tablets [online]. Available from URL: [Accessed 2007 Aug 13]
  5. 5.
    Novartis. Exforge® (amlodipine and valsartan) prescribing information. East Hanover (NJ): Novartis Pharmaceuticals Corp., 2007 Apr [online]. Available from URL: [Accessed 2007 Sep 14]
  6. 6.
    Top C, Cingözbay BY, Terekeci H, et al. The effects of valsartan on insulin sensitivity in patients with primary hypertension. J Int Med Res 2002; 30(1): 15–20PubMedGoogle Scholar
  7. 7.
    Ram CVS, Ames RP, Applegate WB, et al. Double-blind comparison of amlodipine and hydrochlorothiazide in patients with mild to moderate hypertension. Clin Cardiol 1994; 17: 251–6PubMedCrossRefGoogle Scholar
  8. 8.
    Scheen AJ. Prevention of type 2 diabetes mellitus through inhibition of the renin-angiotensin system. Drugs 2004; 64(22): 2537–65PubMedCrossRefGoogle Scholar
  9. 9.
    Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertenisve drugs: a network meta-analysis. Lancet 2007 Jan 20; 369: 201–7PubMedCrossRefGoogle Scholar
  10. 10.
    Abuissa H, Jones PG, Marso SP, et al. Angiotensin-converting enzyme inhibitors or angiotenisn receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials. J Am Coll Cardiol 2005; 46(5): 821–6PubMedCrossRefGoogle Scholar
  11. 11.
    Bakris G, Molitch M, Hewkin A, et al. Differences in glucose tolerance between fixed-dose antihypertensive drug combinations in people with metabolic syndrome. STAR Investigators. Diabetes Care 2006; 29: 2592–7PubMedCrossRefGoogle Scholar
  12. 12.
    Haria M, Wagstaff AJ. Amlodipine: a reappraisal of its pharmacological properties and therapeutic use in cardiovascular disease. Drugs 1995; 50(3): 560–86PubMedCrossRefGoogle Scholar
  13. 13.
    Markham A, Goa KL. Valsartan: a review of its pharmacology and therapeutic use in essential hypertension. Drugs 1997; 54(2): 299–311PubMedCrossRefGoogle Scholar
  14. 14.
    Thürmann PA. Valsartan: a novel angiotensin type 1 receptor antagonist. Expert Opin Pharmacother 2000 Jan; 1(2): 337–50PubMedCrossRefGoogle Scholar
  15. 15.
    Maeda T, Kato M, Tajima A, et al. Additive effect of valsartan on exercise tolerance in hypertensive patients treated with amlodipine [abstract no. PO4-154]. J Hypertens 2006 Dec 1; 24 Suppl. 6: 399Google Scholar
  16. 16.
    Fogari R, Preti P, Mugellini A, et al. Valsartan amlodipine combination and prevention of atrial fibrillation recurrence in hypertensive diabetic patients [abstract no. 3695]. Circulation 2006 Oct 31; 114 (18 Suppl. II): 789–90Google Scholar
  17. 17.
    de Champlain J, Karas M, Assouline L, et al. Effects of valsartan or amlodipine alone or in combination on plasma catecholamine levels at rest and during standing in hypertensive patients. J Clin Hypertens 2007 Mar; 9(3): 168–78CrossRefGoogle Scholar
  18. 18.
    Leenen FHH, Nwachuku CE, Black HR, et al. Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial. Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group. Hypertension 2006; 48: 374–84PubMedCrossRefGoogle Scholar
  19. 19.
    Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure. The CAMELOT study: a randomized controlled trial. JAMA 2004 Nov 10; 292(18): 2217–26PubMedCrossRefGoogle Scholar
  20. 20.
    Pitt B, Byington RP, Furberg CD, et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation 2000; 102: 1503–10PubMedCrossRefGoogle Scholar
  21. 21.
    Williams B, Lacy PS, Thorn SM, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes. CAFE Investigators. Circulation 2006; 113: 1213–25PubMedCrossRefGoogle Scholar
  22. 22.
    Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. Valsartan Heart Failure Trial (Val-HeFT) Investigators. N Engl J Med 2001 Dec 6; 345(23): 1667–75PubMedCrossRefGoogle Scholar
  23. 23.
    Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004 Jun 19; 363: 2022–31PubMedCrossRefGoogle Scholar
  24. 24.
    Maggioni AP, Latini R, Carson PE, et al. Valsartan reduces the incidence of atrial fibrillation in patients with heart failure: results from the valsartan heart failure trial (Val-HeFT). Am Heart J 2005; 149: 548–57PubMedCrossRefGoogle Scholar
  25. 25.
    Mochizuki S, Dahlöf B, Shimizu M, et al. Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study. Lancet 2007 Apr 28; 369: 1431–9PubMedCrossRefGoogle Scholar
  26. 26.
    Pfeffer MA, McMurray JJV, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. Valsartan in Acute Myocardial Infarction (VALIANT) Trial Investigators. N Engl J Med 2003 Nov 13; 349(20): 1893–906PubMedCrossRefGoogle Scholar
  27. 27.
    Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension. Clin Ther 2007 Apr; 29(4): 563–80PubMedCrossRefGoogle Scholar
  28. 28.
    Smith TR, Philipp T, Vaisse B, et al. Amlodipine and valsartan combined and as monotherapy in stage 2, elderly, and black hypertensive patients: subgroup analyses of 2 randomized, placebo-controlled studies. J Clin Hypertens 2007 May; 9(5): 355–64CrossRefGoogle Scholar
  29. 29.
    Allemann Y, Fraile B, Lambert M, et al. Efficacy of the combination of amlodipine and valsartan in hypertensive patients uncontrolled on previous monotherapy: the EX-FAST study. J Clin Hypertens. Epub in advance Feb 2008Google Scholar
  30. 30.
    Fogari R, Zoppi A, Derosa G, et al. Effect of valsartan addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients. J Hum Hypertens 2007 Mar; 21(3): 220–4PubMedGoogle Scholar
  31. 31.
    Poldermans D, Glazer R, Karagianniss S, et al. Tolerability and blood pressure-lowering efficacy of the combination of amlodipine plus valsartan compared with lisinopril plus hydrochlorothiazide in adult patients with stage 2 hypertension. Clin Ther 2007 Feb; 29(2): 279–89PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Wolters Kluwer Health ¦ AdisMairangi Bay, North Shore 0754, AucklandNew Zealand
  2. 2.Wolters Kluwer HealthConshohockenUSA

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