Advertisement

Advances in Therapy

, Volume 25, Issue 5, pp 399–411 | Cite as

Effective and safe reduction of blood pressure with the combination of amlodipine 5 mg and valsartan 160 mg in hypertensive patients not controlled by calcium channel blocker monotherapy

  • Johannes Brachmann
  • Anwar Ansari
  • Gerhard Mahla
  • Renate Handrock
  • Sven Klebs
Original Research

Abstract

Introduction

The addition of an angiotensin II receptor blocker to calcium channel blocker-based antihypertensive therapy may be associated with enhanced efficacy and reduced risk of adverse events.

Methods

This 8-week, open-label, single-arm trial evaluated the efficacy and tolerability of the combination of amlodipine and valsartan in patients not responding adequately to treatment with amlodipine or felodipine alone. Patients aged ≥18 years with moderate essential hypertension (defined as mean sitting systolic blood pressure [MSSBP] ≥160 and <180 mmHg) were treated for 4 weeks with once-daily amlodipine 5 mg or felodipine 5 mg. At week 4, patients not adequately responding were treated for an additional 4 weeks with once-daily amlodipine 5 mg plus valsartan 160 mg. Of 214 patients treated for 4 weeks with amlodipine 5 mg or felodipine 5 mg, 181 failed to achieve MSSBP <140 mmHg. These non-responders were treated for an additional 4 weeks with amlodipine 5 mg and valsartan 160 mg.

Results

A clinically and statistically significant additional reduction in MSSBP of 13.1 mmHg (95% confidence interval [CI]: 11.4, 14.7; P<0.0001) and a mean sitting diastolic blood pressure of 5.3 mmHg (95% CI: 4.3, 6.3; P<0.0001) were observed. Of patients treated with amlodipine 5 mg and valsartan 160 mg, 51.1% achieved target blood pressure levels (<140/90 mmHg) after 4 weeks. Adverse event rates were low in both treatment phases, and most were mild or moderate in severity.

Conclusion

The combination of amlodipine/valsartan was effective and well tolerated.

Keywords

amlodipine angiotensin II receptor blockers calcium channel blockers combination therapy felodipine hypertension valsartan 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217–223.PubMedGoogle Scholar
  2. 2.
    The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC). 2007 guidelines for the management of arterial hypertension. J Hypertens. 2007;25:1105–1187.CrossRefGoogle Scholar
  3. 3.
    Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206–1252.PubMedCrossRefGoogle Scholar
  4. 4.
    Ong KL, Cheung BMY, Man YB, Lau CP, Lam KSL. Prevalence, awareness, treatment, and control of hypertension among United States adults 1999–2004. Hypertension. 2007;49:69–75.PubMedCrossRefGoogle Scholar
  5. 5.
    Wolf-Maier K, Cooper RS, Kramer H, et al. Hypertension treatment and control in five European countries, Canada, and the United States. Hypertension. 2004;43:10–17.PubMedCrossRefGoogle Scholar
  6. 6.
    Basile J. The role of existing and newer calcium channel blockers in the treatment of hypertension. J Clin Hypertens (Greenwich). 2004;6:621–631.CrossRefGoogle Scholar
  7. 7.
    Prisant LM. Calcium antagonists. In: Oparil S, Weber MA, eds. Hypertension: A Companion to Brenner and Rector’s The Kidney. 2nd ed. Philadelphia: Elsevier Saunders; 2005:683–704.Google Scholar
  8. 8.
    Sica DA. Pharmacotherapy review: calcium channel blockers. J Clin Hypertens (Greenwich). 2006;8:53–56.CrossRefGoogle Scholar
  9. 9.
    Weir MR. Incidence of pedal edema formation with dihydropyridine calcium channel blockers: issues and practical significance. J Clin Hypertens (Greenwich). 2003;5:330–335.CrossRefGoogle Scholar
  10. 10.
    Gerbino PP, Shoheiber O. Adherence patterns among patients treated with fixed-dose combination versus separate antihypertensive agents. Am J Health-Syst Pharm. 2007;64:1279–1283.PubMedCrossRefGoogle Scholar
  11. 11.
    Elliott WJ. Is fixed combination therapy appropriate for initial hypertension treatment? Curr Hypertens Rep. 2002;4:278–285.PubMedCrossRefGoogle Scholar
  12. 12.
    Sica DA. Rationale for fixed-dose combinations in the treatment of hypertension: the cycle repeats. Drugs. 2002;62:443–462.PubMedCrossRefGoogle Scholar
  13. 13.
    Weber MA. Creating a combination antihypertensive regimen: what does the research show? J Clin Hypertens (Greenwich). 2003;5(4 suppl 3):12–20.CrossRefGoogle Scholar
  14. 14.
    Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet. 2000;355:637–645.PubMedCrossRefGoogle Scholar
  15. 15.
    Messerli FH. Vasodilatory edema: a common side effect of antihypertensive therapy. Am J Hypertens. 2001;14:978–979.PubMedCrossRefGoogle Scholar
  16. 16.
    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;21:220–224.PubMedGoogle Scholar
  17. 17.
    Poldermans D, Glazer R, Karagiannis S, et al. Tolerability and blood pressurelowering efficacy of the combination of amlodipine plus valsartan compared with lisinopril plus hydrochlorothiazide in adult patients with stage 2 hypertension. Clin Ther. 2007;29:279–289.PubMedCrossRefGoogle Scholar
  18. 18.
    Pickering TG, Hall JE, Appel LJ, et al. Recommendations for blood pressure measurement in humans and experimental animals: Part I: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension. 2005;45:142–161.PubMedGoogle Scholar
  19. 19.
    Blacher J, Staessen JA, Girerd X, et al. Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients. Arch Intern Med. 2000; 160:1085–1089.PubMedCrossRefGoogle Scholar
  20. 20.
    Mancia G. Blood pressure reduction and cardiovascular outcomes: past, present and future. Am J Cardiol. 2007;100(suppl):3J–9J.PubMedCrossRefGoogle Scholar
  21. 21.
    Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998;351:1755–1762.PubMedCrossRefGoogle Scholar
  22. 22.
    Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensinreceptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–860.PubMedCrossRefGoogle Scholar
  23. 23.
    Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of blood pressure control in diverse North American settings: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens (Greenwich). 2002;4:393–404.CrossRefGoogle Scholar
  24. 24.
    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;363:2022–2031.PubMedCrossRefGoogle Scholar
  25. 25.
    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 Lowing Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366:895–906.PubMedCrossRefGoogle Scholar
  26. 26.
    Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003;326:1427.PubMedCrossRefGoogle Scholar
  27. 27.
    Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed-dose combinations improve medication compliance: a metaanalysis. Am J Med. 2007;120:713–719.PubMedCrossRefGoogle Scholar
  28. 28.
    Krone W, Nägele H. Effects of antihypertensives on plasma lipids and lipoprotein metabolism. Am Heart J. 1988;116:1729–1734.PubMedCrossRefGoogle Scholar
  29. 29.
    Wilson TW, Lacourcière Y, Barnes CC, for the Canadian Cozaar Hyzaar Amlodipine Trial Study Group. The antihypertensive efficacy of losartan and amlodipine assessed with office and ambulatory blood pressure monitoring. CMAJ. 1998;159:469–475.PubMedGoogle Scholar

Copyright information

© Springer Healthcare Communications 2008

Authors and Affiliations

  • Johannes Brachmann
    • 1
  • Anwar Ansari
    • 2
  • Gerhard Mahla
    • 3
  • Renate Handrock
    • 4
  • Sven Klebs
    • 4
  1. 1.Department of CardiologyKlinikum Coburg, II. Medizinische KlinikCoburgGermany
  2. 2.Practice for Internal MedicineEinbeckGermany
  3. 3.Practice for General MedicineFeldafingGermany
  4. 4.Clinical & Regulatory AffairsNovartis Pharma GmbHNurembergGermany

Personalised recommendations