, Volume 66, Issue 14, pp 1881–1901


A Review of its Use in the Management of Hypertension
Adis Drug Evaluation



Valsartan/hydrochlorothiazide is a fixed-dose (valsartan 80, 160 or 320mg plus hydrochlorothiazide 12.5 or 25mg) angiotensin II receptor blocker/diuretic drug combination indicated for the treatment of patients with essential hypertension not adequately controlled by monotherapy.

There is ample evidence that valsartan/hydrochlorothiazide is an effective fixed-dose combination antihypertensive agent. However, efficacy and tolerability data pertaining to the 320mg dose of valsartan in the combination are currently relatively few. There is also some evidence of potential benefits associated with the relatively favourable tolerability profile of the combination, the low occurrence of new-onset diabetes mellitus versus amlodipine and the valsartan-associated improvements in cardiac and endothelial function.

Pharmacological Properties

Valsartan is a selective antagonist of the angiotensin II type 1 receptor. This drug has established antihypertensive effects and is associated with improvements in cardiac function (reduced left ventricular mass), endothelial function (improved basal nitric oxide availability, reduced formation of reactive oxygen species, reduced C-reactive protein levels) and lipid profiles.

Hydrochlorothiazide is a thiazide diuretic which inhibits Na-Cl transport in the kidney and reduces plasma volume. It has been associated with improvements in cardiac output, mean arterial pressure, stroke volume, heart rate and total peripheral resistance in patients with hypertension. It has also been linked with dyslipidaemia, hyperglycaemia and increased risk of developing type 2 diabetes mellitus in some patients, and it may increase levels of some inflammatory biomarkers.

Coadministration of valsartan and hydrochlorothiazide does not have a clinically relevant pharmacokinetic effect on either drug. Plasma concentrations of both components increase dose-proportionally, with peak concentrations reached in 2–5 hours. The elimination half-life of the components ranges from 2.5 to 19 hours, mainly because of variability in hydrochlorothiazide values. Clearance is 2.2 L/h for valsartan and 20–22 L/h for hydrochlorothiazide. Excretion of valsartan is mainly faecal and that of hydrochlorothiazide is mainly renal. While the systemic clearance of hydrochlorothiazide is decreased in older patients, the effects of age on valsartan pharmacokinetics are not considered clinically significant. Exposure to hydrochlorothiazide is increased in patients with renal dysfunction and exposure to valsartan is increased in patients with hepatic dysfunction.

Therapeutic Efficacy

The superior antihypertensive efficacy of once-daily valsartan 80–320mg plus hydrochlorothiazide 12.5 or 25mg over the individual components has been demonstrated in well designed trials in patients with hypertension unresponsive to monotherapy or with moderate to severe hypertension.

In the only trial investigating comparative clinical cardiovascular outcomes, valsartan-and amlodipine-based therapy regimens had similar results for the primary efficacy parameter (total cardiac morbidity and mortality 10.6% vs 10.4%), despite not achieving the prespecified equivalent reduction in blood pressure (BP). Patients (aged ≥50 years) at high cardiovascular risk received increased dosages of monotherapy and then additional hydrochlorothiazide as required for a mean of 4.2 years. BP reduction and occurrence of myocardial infarction favoured amlodipine-based therapy, while the rate of new-onset diabetes mellitus favoured valsartan-based therapy. In contrast, equivalent BP reduction was seen in a 6-month comparison of valsartan-based and amlodipine-based therapy in elderly patients with moderate to severe isolated systolic hypertension.

Valsartan/hydrochlorothiazide recipients had similar BP reductions to those in patients receiving amlodipine monotherapy in two double-blind trials; a significantly greater reduction in systolic BP was seen with the higher hydrochlorothiazide dose in another double-blind trial. One single-blind trial indicated superior systolic/diastolic BP reductions with the combination. Noninferiority for valsartan/hydrochlorothiazide versus amlodipine monotherapy has been demonstrated in Black African-American patients with mild to moderate hypertension.

There are preliminary indications that valsartan/hydrochlorothiazide has generally similar antihypertensive efficacy to that of other angiotensin receptor blocker/hydrochlorothiazide combinations.


Valsartan/hydrochlorothiazide is well tolerated. Adverse events (most commonly dizziness, headache and fatigue) are generally mild and transient. Serious adverse events that have rarely been associated with the combination include orthostatic hypotension, syncope, angioneurotic oedema, angina pectoris and atrial fibrillation. The tolerability profile of the combination was superior to that of lisinopril/hydrochlorothiazide (similar efficacy profile). Hypokalaemia occurs less often with the valsartan/hydrochlorothiazide combination than with hydrochlorothiazide monotherapy or amlodipine/hydrochlorothiazide.


  1. 1.
    World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/ International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens 2003; 21: 1983–92CrossRefGoogle Scholar
  2. 2.
    Giles TD, Berk BC, Black HR, et al. Expanding the definition and classification of hypertension. J Clin Hypertens 2005 Sep; 7(9): 505–12CrossRefGoogle Scholar
  3. 3.
    Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005 Jan 15; 365: 217–23PubMedGoogle Scholar
  4. 4.
    Psaty BM, Lumley T, Furberg CD, et al. Health outcomes associated with various antihypertensive therapies used as first-line agents. JAMA 2003 May 21; 289(19): 2534–44PubMedCrossRefGoogle Scholar
  5. 5.
    Meredith PA. Angiotensin II receptor antagonists alone and combined with hydrochlorothiazide: potential benefits beyond the antihypertensive effect. Am J Cardiovasc Drug 2005; 5(3): 171–83CrossRefGoogle Scholar
  6. 6.
    Langtry HD, McClellan KJ. Valsartan/hydrochlorothiazide. Drugs 1999 May; 57(5): 751–5; discussion 756-8PubMedCrossRefGoogle Scholar
  7. 7.
    Wellington K, Faulds DM. Valsartan/hydrochlorothiazide: a review of its pharmacology, therapeutic efficacy and place in the management of hypertension. Drugs 2002; 62(13): 1983–2005PubMedCrossRefGoogle Scholar
  8. 8.
    Criscione L, de Gasparo M, Buhlmayer P, et al. Pharmacological profile of valsartan: a potent, orally active, nonpeptide antagonist of the angiotensin II AT1-receptor subtype. Br J Pharmacol 1993 Oct; 110(2): 761–71PubMedCrossRefGoogle Scholar
  9. 9.
    Verheijen I, Fierens FLP, DeBacker JP, et al. Interaction between the partially insurmountable antagonist valsartan and human recombinant angiotensin II type I receptors. Fundam Clin Pharmacol 2000; 14(6): 577–85PubMedCrossRefGoogle Scholar
  10. 10.
    Novartis Pharmaceuticals UK Ltd. Co-Diovan 80/12.5 mg, 160/ 12.5 mg/160/25 mg tablets; UK prescribing information [online]. Available from URL: http://emc.medicines.org.uk [Accessed 2006 Apr 26]
  11. 11.
    Saito F, Kimura G. Antihypertensive mechanism of diuretics based on pressure-natriuresis relationship. Hypertension 1996; 27: 914–8PubMedCrossRefGoogle Scholar
  12. 12.
    Hanefeld M, Abletshauser C. Effect of the angiotensin II receptor antagonist valsartan on lipid profile and glucose metabolism in patients with hypertension. J Int Med Res 2001 Jul; 29: 270–9PubMedGoogle Scholar
  13. 13.
    Plum J, Bunten B, Németh R, et al. Effects of the angiotensin II antagonist valsartan on blood pressure, proteinuria, and renal hemodynamics in patients with chronic renal failure and hypertension. J Am Soc Nephrol 1998 Dec; 9: 2223–34PubMedGoogle Scholar
  14. 14.
    Viberti G, Wheeldon NM, MicroAlbuminuria Reduction With VALsartan (MARVAL) study investigators. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002 Aug 6; 106(6): 672–8PubMedCrossRefGoogle Scholar
  15. 15.
    Thurmann PA, Kenedi P, Schmidt A, et al. Influence of the angiotensin II antagonist valsartan on left ventricular hypertrophy in patients with essential hypertension. Circulation 1998 Nov 10; 98(19): 2037–42PubMedCrossRefGoogle Scholar
  16. 16.
    Yasunari K, Maeda K, Watanabe T, et al. Comparative effects of valsartan versus amlodipine on left ventricular mass and reactive oxygen species formation by monocytes in hypertensive patients with left ventricular hypertrophy. J Am Coll Cardiol 2004 Jun 2; 43(11): 2116–23PubMedCrossRefGoogle Scholar
  17. 17.
    Munakata M, Nagasaki A, Nunokawa T, et al. Effects of valsartan and nifedipine coat-core on systemic arterial stiffness in hypertensive patients. Am J Hypertens 2004 Nov; 17(11): 1050–5PubMedCrossRefGoogle Scholar
  18. 18.
    Shargorodsky M, Leibovitz E, Lubimov L, et al. Prolonged treatment with the AT1 receptor blocker, valsartan, increases small and large artery compliance in uncomplicated essential hypertension. Am J Hypertens 2002 Dec; 15(12): 1087–91PubMedCrossRefGoogle Scholar
  19. 19.
    Klingbeil AU, John S, Schneider MP, et al. Effect of AT1 receptor blockade on endothelial function in essential hypertension. Am J Hypertens 2003 Feb; 16(2): 123–8PubMedCrossRefGoogle Scholar
  20. 20.
    Watanabe H, Nakagawa K, Kakihana M. Effects of valsartan on endothelial function and aortic stiffness in hypertensive patients with stroke [abstract no. P563]. Eur Heart J 2003 Aug; 24 (Suppl.): 93CrossRefGoogle Scholar
  21. 21.
    Ridker PM, Danielson E, Rifai N, et al. Valsartan, blood pressure reduction, and C-reactive protein: primary report of the Val-MARC trial. Hypertension 2006; 48: 1–7CrossRefGoogle Scholar
  22. 22.
    Ruilope LM, Malacco E, Khder Y, et al. Efficacy and tolerability of combination therapy with valsartan plus hydrochlorothiazide compared with amlodipine monotherapy in hypertensive patients with other cardiovascular risk factors: the VAST Study. Clin Ther 2005 May; 27(5): 578–87PubMedCrossRefGoogle Scholar
  23. 23.
    Benz J, Oshrain C, Henry D, et al. Valsartan, a new angiotensin II receptor antagonist: a double-blind study comparing the incidence of cough with lisinopril and hydrochlorothiazide. J Clin Pharmacol 1997 Feb; 37(2): 101–7PubMedGoogle Scholar
  24. 24.
    Hussein O, Shneider J, Rosenblat M, et al. Valsartan therapy has additive anti-oxidative effect to that of fluvastatin therapy against low-density lipoprotein oxidation: studies in hypercholesterolemic and hypertensive patients. J Cardiovasc Pharmacol 2002 Jul; 40: 28–34PubMedCrossRefGoogle Scholar
  25. 25.
    Delles C, Klingbeil AU, Schneider MP, et al. Direct comparison of the effects of valsartan and amlodipine on renal hemodynamics in human essential hypertension. Am J Hypertens 2003 Dec; 16(12): 1030–5PubMedCrossRefGoogle Scholar
  26. 26.
    Fogari R, Derosa G, Zoppi A, et al. Comparison of the effects of valsartan and felodipine on plasma leptin and insulin sensitivity in hypertensive obese patients. Hypertens Res 2005 Mar; 28(3): 209–14PubMedCrossRefGoogle Scholar
  27. 27.
    Ohbayashi Y, Tsutamoto T, Sakaguchi T, et al. Effect of an angiotensin II type 1 receptor blocker, valsartan, on neurohumoral factors in patients with hypertension: comparison with a long-acting calcium channel antagonist, amlodipine. J Cardiovasc Pharmacol 2003 Dec; 42 (Suppl. 1): S71–4PubMedCrossRefGoogle Scholar
  28. 28.
    Malacco E, Piazza S, Scandiani L, et al. Effects of valsartan/ hydrochlorothiazide and amlodipine on ambulatory blood pressure and plasma norepinephrine levels in high-risk hypertensive patients. Adv Ther 2004 May; 21(3): 149–61PubMedCrossRefGoogle Scholar
  29. 29.
    Dusing R. Effect of the angiotensin II antagonist valsartan on sexual function in hypertensive men. Blood Press 2003; 12 (Suppl. 2): 29–34CrossRefGoogle Scholar
  30. 30.
    Fogari R, Preti P, Derosa G, et al. Effect of antihypertensive treatment with valsartan or atenolol on sexual activity and plasma testosterone in hypertensive men. Eur J Clin Pharmacol 2002 Jun; 58: 177–80PubMedCrossRefGoogle Scholar
  31. 31.
    Fogari R, Preti P, Zoppi A, et al. Effect of valsartan and atenolol on sexual behavior in hypertensive postmenopausal women. Am J Hypertens 2004 Jan; 17(1): 77–81PubMedCrossRefGoogle Scholar
  32. 32.
    Rinder MR, Spina RJ, Peterson LR, et al. Comparison of effects of exercise and diuretic on left ventricular geometry, mass, and insulin resistance in older hypertensive adults. Am J Physiol Regul Integr Comp Physiol 2004 Apr 29; 287(2): R360–8PubMedCrossRefGoogle Scholar
  33. 33.
    Carter BL, Ernst ME, Cohen JD. Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability. Hypertension 2004 Jan; 43: 4–9PubMedCrossRefGoogle Scholar
  34. 34.
    Hoogerbrugge N, de Groot E, de Heide LHM, et al. Doxazosin and hydrochlorothiazide equally affect arterial wall thickness in hypertensive males with hypercholesterolaemia (the DAPHNE study). Neth J Med 2002 Oct; 60(9): 354–61PubMedGoogle Scholar
  35. 35.
    Maitland-van der Zee AH, Turner ST, Schwartz GL, et al. Demographic, environmental, and genetic predictors of metabolic side effects of hydrochlorothiazide treatment in hypertensive subjects. Am J Hypertens 2005 Aug; 18(8): 1077–83PubMedCrossRefGoogle Scholar
  36. 36.
    Schwartz GL, Turner ST, Chapman AB, et al. Interacting effects of gender and genotype on blood pressure response to hydrochlorothiazide. Kidney Int 2002 Nov; 62(5): 1718–23PubMedCrossRefGoogle Scholar
  37. 37.
    Carretta R, Trenkwalder P, Martinez F, et al. Pulse pressure responses in patients treated with valsartan and hydrochlorothiazide combination therapy. J Int Med Res 2003; 31(5): 370–7PubMedGoogle Scholar
  38. 38.
    Weisser B, Vetter H, Mengden T. Decreased blood pressure, pulse pressure and heart rate under treatment with valsartan alone or combined with hydrochlorothiazide: results of an open trial in 11447 hypertensives [in German]. Dtsch Med Wochenschr 2003 Mar 14; 128(11): 541–4PubMedCrossRefGoogle Scholar
  39. 39.
    Malacco E, Santonastaso M, Vari NA, et al. Comparison of valsartan 160 mg with lisinopril 20 mg, given as monotherapy or in combination with a diuretic, for the treatment of hypertension: the Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril (PREVAIL) study. Clin Ther 2004 Jun; 26(6): 855–65PubMedCrossRefGoogle Scholar
  40. 40.
    Flesch G, Müller P, Lloyd P. Absolute bioavailability and pharmacokinetics of valsartan, an angiotensin II receptor antagonist, in man. Eur J Clin Pharmacol 1997; 52(2): 115–20PubMedCrossRefGoogle Scholar
  41. 41.
    Israili ZH. Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. J Hum Hypertens 2000; 14 (Suppl. 1): S73–86PubMedCrossRefGoogle Scholar
  42. 42.
    Novartis Pharmaceuticals Corporation. Diovan HCT®valsartan and hydrochlorothiazide, USP; combination tablets 80mg/ 12.5mg, 160mg/12.5mg, 160mg/25mg, 320mg/12.5mg, 320mg/25mg; US prescribing information. East Hanover (NJ): Novartis, 2006Google Scholar
  43. 43.
    Novartis Pharmaceuticals Canada Inc. Diovan-HCT (valsartan and hydrochlorothiazide) tablets, 80mg/12.5mg, 160mg/ 12.5mg, and 160mg/25mg; Canadian prescribing information. Dorval, Quebec: Novartis, 2004Google Scholar
  44. 44.
    Waldmeier F, Flesch G, Muller P, et al. Pharmacokinetics, disposition and biotransformation of [14C]-radiolabelled valsartan in healthy male volunteers after a single oral dose. Xenobiotica 1997 Jan; 27(1): 59–71PubMedCrossRefGoogle Scholar
  45. 45.
    Taeschner W, Vozeh S. Appendix A: pharmacokinetic drug data. In: Speight TM, Holford NHG, editors. Avery’s Drug Treatment. 4th ed. Auckland: Adis International Limited, 1997: 1629–64Google Scholar
  46. 46.
    Beermann B, Groschinsky-Grind M. Pharmacokinetics of hydrochlorothiazide in man. Eur J Clin Pharmacol 1977 Dec 2; 12(4): 297–303PubMedCrossRefGoogle Scholar
  47. 47.
    Kalbag J, Prasad P, Redalieu E, et al. Plasma concentrations and antihypertensive effect of 10 to 160 mg doses of valsartan (VAL) in hypertensive patients [abstract no. PPDM 8140]. Pharm Res 1994; 11 (10 Suppl.): S367Google Scholar
  48. 48.
    Weir SJ, Dimmitt DC, Lanman RC, et al. Steady-state pharmacokinetics of diltiazem and hydrochlorothiazide administered alone and in combination. Biopharm Drug Dispos 1998; 19: 365–71PubMedCrossRefGoogle Scholar
  49. 49.
    Sioufi A, Marfil F, Jaouen A, et al. The effect of age on the pharmacokinetics of valsartan. Biopharm Drug Dispos 1998 May; 19: 237–44PubMedCrossRefGoogle Scholar
  50. 50.
    Prasad P, Mangat S, Choi L, et al. Effect of renal function on the pharmacokinetics of valsartan. Clin Drug Invest 1997; 13(4): 207–14CrossRefGoogle Scholar
  51. 51.
    Leidig MF, Delles C, Kuchenbecker C, et al. Pharmacokinetics of valsartan in hypertensive patients on long-term haemodialysis. Clin Drug Invest 2001; 21(1): 59–66CrossRefGoogle Scholar
  52. 52.
    Brookman LJ, Rolan PE, Benjamin IS, et al. Pharmacokinetics of valsartan in patients with liver disease. Clin Pharmacol Ther 1997 Sep; 62(3): 272–8PubMedCrossRefGoogle Scholar
  53. 53.
    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(9426): 2022–31PubMedCrossRefGoogle Scholar
  54. 54.
    Weber MA, Julius S, Kjeldsen SE, et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE trial. Lancet 2004 Jun 19; 363: 2049–51PubMedCrossRefGoogle Scholar
  55. 55.
    Benz JR, Black HR, Graff A, et al. Valsartan and hydrochlorothiazide in patients with essential hypertension. A multiple dose, double-blind, placebo controlled trial comparing combination therapy with monotherapy. J Hum Hypertens 1998 Dec; 12(12): 861–6Google Scholar
  56. 56.
    Hall WD, Montoro R, Littlejohn T, et al. Efficacy and tolerability of valsartan in combination with hydrochlorothiazide in essential hypertension. Clin Drug Invest 1998 Sep; 16(3): 203–10CrossRefGoogle Scholar
  57. 57.
    Hedner T, Reimund B, Le Breton S, et al. Valsartan and hydrochlorothiazide combination therapy (320/12.5 mg and 320/25 mg) provides effective blood pressure control in hypertensive patients inadequately controlled by monotherapy. American Society of Hypertension 21 st annual scientific meeting and exposition, May 16–20 2006, New York; Abstract no. P-165 [online]. Available from URL: http://www.ash-us.org [Accessed 2006 May 17]
  58. 58.
    Lacourciere Y, Poirier L, Hebert D, et al. Antihypertensive efficacy and tolerability of two fixed-dose combinations of valsartan and hydrochlorothiazide compared with valsartan monotherapy in patients with stage 2 or 3 systolic hypertension: an 8-week, randomized, double-blind, parallel-group trial. Clin Ther 2005 Jul; 27(7): 1013–21PubMedCrossRefGoogle Scholar
  59. 59.
    Mallion J-M, Carretta R, Trenkwalder P, et al. Valsartan/ hydrochlorothiazide is effective in hypertensive patients inadequately controlled by valsartan monotherapy. Blood Press 2003; 12 (Suppl. 1): 36–43CrossRefGoogle Scholar
  60. 60.
    Pool J, Glazer R, Weinberger M, et al. Treatment with valsartan and hydrochlorothiazide alone and in combination at doses up to 320/25 mg provides effective blood pressure control in hypertensive patients. American Society of Hypertension 21st annual scientific meeting and exposition, May 16–20 2006, New York; Abstract no. P-179 [online]. Available from URL: http://www.ash-us.org [Accessed 2006 May 17]
  61. 61.
    Schmidt A, Adam SA, Kolloch R, et al. Antihypertensive effects of valsartan/hydrochlorothiazide combination in essential hypertension. Blood Press 2001; 10(4): 230–7PubMedCrossRefGoogle Scholar
  62. 62.
    Franco RJS, Goldflus S, McQuitty M, et al. Efficacy and tolerability of the combination valsartan/hydrochlorothiazide compared with amlodipine in a mild-to-moderately hypertensive Brazilian population. Blood Press 2003; 12 (Suppl. 2): 41–7CrossRefGoogle Scholar
  63. 63.
    Palatini P, Malacco E, Fogari R, et al. A multicenter, randomized double-blind study of valsartan/hydrochlorothiazide combination versus amlodipine in patients with mild to moderate hypertension. J Hypertens 2001 Sep; 19(9): 1691–169PubMedCrossRefGoogle Scholar
  64. 64.
    Weir MR, Ferdinand KC, Flack JM, et al. A noninferiority comparison of valsartan/hydrochlorothiazide combination versus amlodipine in black hypertensives. Hypertension 2005 Sep; 46(3): 508–13PubMedCrossRefGoogle Scholar
  65. 65.
    Ruilope LM, Heintz D, Brandao AA, et al. 24-hour ambulatory blood-pressure effects of valsartan & hydrochlorothiazide combinations compared with amlodipine in hypertensive patients at increased cardiovascular risk: a VAST sub-study. Blood Press Monit 2005 Apr; 10(2): 85–91PubMedCrossRefGoogle Scholar
  66. 66.
    Zanchetti A, Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003 Jun; 21(6): 1011–53CrossRefGoogle Scholar
  67. 67.
    Pool J, Glazer R, Graff A, et al. Long-term combination treatment with valsartan and hydrochlorothiazide (320/12.5 mg and 320/25 mg) provides effective blood pressure control and is well-tolerated in hypertensive patients. American Society of Hypertension 21st annual scientific meeting and exposition, May 16–20 2006, New York; Abstract no. P-180 [online]. Available from URL: http://www.ash-us.org [Accessed 2006 May 17]
  68. 68.
    Weir MR, Aknay N, Purkayastha D, et al. Antihypertensive efficacy of valsartan and valsartan/HCTZ in elderly hypertensives: exploratory analyses of nine clinical trials. American Society of Hypertension 21st annual scientific meeting and exposition, May 16–20 2006, New York; Abstract no. P-2310 [online]. Available from URL: http://www.ash-us.org [Accessed 2006 May 17]
  69. 69.
    Azizi M, Nisse-Durgeat S, French Collaborative Group. Comparison of the antihypertensive effects of the candesartan 8 mg-hydrochlorothiazide 12.5 mg combination (C8+H) vs the valsartan 80 mg-hydrochlorothiazide 12.5 mg combination (V80+H) in patients with essential hypertension resistant to monotherapy [abstract no. P2.367]. J Hypertens 2004 Jun; 22 (Suppl. 2): S254–5Google Scholar
  70. 70.
    Malacco E, Vari N, Capuano V, et al. A randomized, double-blind, active-controlled, parallel-group comparison of valsartan and amlodipine in the treatment of isolated systolic hypertension in elderly patients: the Val-Syst study. Clin Ther 2003 Nov; 25(11): 2765–80PubMedCrossRefGoogle Scholar
  71. 71.
    White W, Punzi H, Neutel J, et al. Telmisartan plus hydrochlorothiazide (80/25 mg) has a greater antihypertensive effect than valsartan plus hydrochlorothiazide (160/25 mg) in patients with stage 1 and 2 hypertension [abstract no. P254]. Am J Hypertens 2005 May; 18 (5 pt 2): 97A [plus poster presented at the 20th Annual Scientific Meeting of the American Society of Hypertension; 2005 Dec 10–13; San Fransisco (CA)]Google Scholar
  72. 72.
    Bobrie G, Delonca J, Moulin C, et al. A home blood pressure monitoring study comparing the antihypertensive efficacy of two angiotensin II receptor antagonist fixed combinations. Am J Hypertens 2005 Nov; 18(11): 1482–8PubMedCrossRefGoogle Scholar
  73. 73.
    Palatini P, Mugellini A, Spagnuolo V, et al. Comparison of the effects on 24-h ambulatory blood pressure of valsartan and amlodipine, alone or in combination with a low-dose diuretic, in elderly patients with isolated systolic hypertension (Val-syst Study). Blood Press Monit 2004 Apr; 9(2): 91–7PubMedCrossRefGoogle Scholar
  74. 74.
    Malacco E, Palatini P, Val-Combo Investigators. The efficacy and tolerability of valsartan-based versus lisinopril-based treatment in patients with mild to moderate hypertension: the Val-Combo study [abstract no. P728]. J Hypertens 2004 Feb; 22 (Suppl. 1): 197SGoogle Scholar
  75. 75.
    Scholze J, Probst G, Bertsch K. Valsartan alone and in combination with hydrochlorothiazide in general practice: results from two postmarketing surveillance studies involving 54 928 patients with essential hypertension. Clin Drug Invest 2000 Jul; 20(1): 1–7CrossRefGoogle Scholar
  76. 76.
    Sever P. VALUE: analysis of results [letter]. Lancet 2004 Sep 11; 364: 933–4PubMedCrossRefGoogle Scholar
  77. 77.
    Hermida RC, Calvos C, Ayala DE, et al. Administration time-dependent effects of valsartan on ambulatory blood pressure in hypertensive subjects. Hypertension 2003 Sep; 42(3): 283–90PubMedCrossRefGoogle Scholar
  78. 78.
    Morgan TO, Anderson A. Different drug classes have variable effects on blood pressure depending on the time of day. Am J Hypertens 2003 Jan; 16: 46–50PubMedCrossRefGoogle Scholar
  79. 79.
    Chalmers J, Guidelines Sub-Committee. 1999 World Health Organization. International Society of Hypertension guidelines for the management of hypertension. Blood Press 1999; 8 (Suppl.1): 9–43Google Scholar
  80. 80.
    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
  81. 81.
    Williams B, Poulter NR, Brown MJ, et al. British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary. BMJ 2004 Mar 13; 328(7440): 634–40PubMedCrossRefGoogle Scholar
  82. 82.
    Cifkova R, Erdine S, Fagard R, et al. Practice guidelines for primary care physicians: 2003 ESH/ESC hypertension guidelines. J Hypertens 2003 Oct; 21(10): 1779–86PubMedCrossRefGoogle Scholar
  83. 83.
    Lindholm LH, Carlberg B, Samuelsson O. Should β blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005 Oct 29; 366: 1545–53PubMedCrossRefGoogle Scholar
  84. 84.
    Khan N, McAlister FA. Re-examining the efficacy of beta-blockers for the treatment of hypertension: a meta-analysis. CMAJ 2006 Jun 6; 174(12): 1737–42PubMedCrossRefGoogle Scholar
  85. 85.
    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: 10–7PubMedCrossRefGoogle Scholar
  86. 86.
    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 2002; 4(6): 393–404CrossRefGoogle Scholar
  87. 87.
    Douglas JG, Bakris GL, Epstein M, et al. Management of high blood pressure in African Americans. Arch Intern Med 2003 Mar 10; 163(5): 525–41PubMedCrossRefGoogle Scholar
  88. 88.
    Pickering TG, Shimbo D, Haas D. Ambulatory blood-pressure monitoring. NEJM 2006 Jun 1; 354(22): 2368–74PubMedCrossRefGoogle Scholar
  89. 89.
    Palatini P, Dorigatti F, Mugellini A, et al. Ambulatory versus clinic blood pressure for the assessment of antihypertensive efficacy in clinical trials: insights from the Val-Syst study. Clin Ther 2004 Sep; 26(9): 1436–45PubMedCrossRefGoogle Scholar
  90. 90.
    Goodman R, Lanese JW, Singson CR, et al. Symptom assessment and quality of life in hypertensive patients following modification of antihypertensive therapy to a regimen containing valsartan. J Outcomes Res 2004; 8: 1–14Google Scholar
  91. 91.
    Kjeldsen SE, Os I, Høieggen A, et al. Fixed-dose combinations in the management of hypertension: defining the place of angiotensin receptor antagonists and hydrochlorothiazide. Am J Cardiovasc Drugs 2005; 5(1): 17–22PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.Wolters Kluwer Health / AdisMairangi Bay, AucklandNew Zealand
  2. 2.Wolters Kluwer HealthConshohockenUSA

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