Abstract
This study was undertaken to evaluate the effects on blood pressure of hydrochlorothiazide (HCTZ) 12.5 mg added to valsartan 160 mg or to olmesartan 20 mg in hypertensive patients. After a 2-wk placebo period, 130 patients, aged 35 to 75 y, with diastolic blood pressure (DBP) ≥99 and <110 mm Hg were randomly assigned to olmesartan 20 mg once daily or to valsartan 160 mg once daily according to a prospective, parallel-arm study design. After 4 wk of monotherapy, patients whose BP was not controlled (DBP ≥90 mm Hg) were given combination treatment with HCTZ 12.5 mg for an additional 4 wk. At the end of the placebo period and at the end of each treatment period, clinical and ambulatory BP measurements were recorded. At the end of the combination therapy period, venous blood samples were drawn 2, 4, and 24 h after drug intake for evaluation of HCTZ plasma concentrations. Both combinations induced a greater ambulatory BP reduction than monotherapy. However, mean reduction from baseline in the valsartan/HCTZ-treated patients (-21.5/-14.6 mm Hg for 24 h, -21.8/-14.9 mm Hg for daytime, and -20.4/-13.7 mm Hg for nighttime systolic blood pressure [SBP]/DBP) was greater than in the olmesartan/HCTZ-treated patients (-18.8/-12.3 mm Hg for 24 h, -19.3/-12.8 mm Hg for daytime, and -17.4/-10.6 mm Hg for nighttime SBP/DBP). The difference between the effects of the 2 treatments was significant (P<.01). In particular, compared with monotherapy, the add-on effect of HCTZ 12.5 mg was significantly greater in the valsartan group than in those treated with olmesartan; the difference was more evident for nighttime BP values. Plasma concentrations of HCTZ were significantly greater with valsartan than with olmesartan at each determination time (P<.05). These findings suggest that the addition of HCTZ 12.5 mg to valsartan 160 mg monotherapy produces a greater BP reduction than the addition of the same dose of HCTZ to olmesartan 20 mg monotherapy.
Similar content being viewed by others
References
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; 289: 2560–2572.
Guidelines Committee. 2003. European Society of Hypertension/European Society of Cardiology guidelines for the management of arterial hypertension.J Hypertens. 2003; 21: 1011–1053.
Turnbull F. Effects of different blood-pressure lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials.Lancet. 2003; 362: 1527–1535.
Staessen JA, Wang JG, Thijs L. Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until March 1, 2003.J Hypertens. 2003; 21: 1055–1076.
Hansson L, Zanchetti A, Carruthers SG, et al, for the HOT study group. 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.
UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38.BMJ. 1998; 317: 703–713.
Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G, for the Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin converting enzyme inhibitor, ramipril, on cardiovascular events in high risk patients.N Engl J Med. 2000; 342: 145–153.
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT).JAMA. 2002; 288: 2981–2997.
Moser M, Black HR. The role of combination therapy in the treatment of hypertension.Am J Hypertens. 1998; 11: 73S-78S.
Sica DA. Rationale for fixed dose combinations in the treatment of hypertension: the cycle repeats.Drugs. 2002; 62: 443–462.
Waeber B. Combination therapy with ACE-inhibitors/angiotensin II receptor antagonists and diuretics in hypertension.Expert Rev Cardiovasc Ther. 2003; 1: 43–50.
Palatini P. Combination therapy in the management of hypertension: focus on angiotensin receptor blockers combined with diuretics.J Clin Hypertens. 2005; 7: 96–101.
Kjeldsen SE, Os I, Hoieggen A, Beckey K, Gleim GW, Oparil S. Fixed-dose combinations in the management of hypertension: defining the place of angiotensin receptor antagonists and hydrochlorothiazide.Am J Cardiovasc Drugs. 2005; 5: 17–22.
Sica DA. Pharmacotherapy review: angiotensin receptor antagonists.J Clin Hypertens. 2005; 7: 681–684.
Meredith PA. Angiotensin II receptor antagonists alone and in combination with hydrochlorothiazide: potential benefits beyond the antihypertensive effect.Am J Cardiovasc Drugs. 2005; 5: 171–183.
Hansson L, Hedner T, Dahlof B. Prospective, randomized, open, blinded end-point (PROBE) study: a novel design for intervention trials.Blood Press. 1992; 1: 113–114.
Groppelli A, Omboni S, Ravogli A, et al. Validation of the Spacelabs 90202 and 90207 devices for ambulatory blood pressure monitoring by comparison with intra-arterial resting and ambulatory measurements.J Hypertens. 1991; 9(suppl 3): S334-S335.
Parati G, Bosi S, Castellano M, et al. Guidelines for 24-hour non-invasive ambulatory blood pressure monitoring: report from a working group of the Italian Society of Hypertension.High Blood Press. 1995; 4: 168–174.
Omboni S, Parati G, Zanchetti A, Mancia G. Calculation of trough:peak ratio of antihypertensive treatment from ambulatory blood pressure: methodological aspects.J Hypertens. 1995; 13: 1105–1112.
Rizzoni D, Castellano M, Muiesan ML, Porteri E, Agabiti-Rosei E. Beyond trough:peak ratio. A new index of the smoothness of the antihypertensive effect of a drug.High Blood Press. 1997; 6: 110–115.
Parati G, Omboni S, Rizzoni D, Agabiti-Rosei E, Mancia G. The smoothness index: a new, reproducible and clinically relevant measure of the homogeneity of the blood pressure reduction with treatment for hypertension.J Hypertens. 1998; 16: 1685–1691.
Sabanathan K, Castelden CM, Adam HK, Ryan J, Fitzimmons TJ. A comparative study of the pharmacokinetics and pharmacodynamics of atenolol, hydrochlorothiazide and amiloride in normal young and elderly subjects and elderly hypertensive patients.Eur J Clin Pharmacol. 1987; 32: 53–60.
Wellington K, Faulds DM. Valsartan/hydrochlorothiazide: a review of its pharmacology, therapeutic efficacy and place in the management of hypertension.Drugs. 2002; 62: 1983–2005.
Mallion JM, Caretta R, Trenkwalder P, et al. Valsartan/hydrochlorothiazide is effective in hypertensive patients inadequately controlled by valsartan monotherapy.Blood Press. 2003; 12(suppl 1): 36–43.
Palatini P, Mugellini A, Spagnuolo V, et al. Comparison of the effects on 24-hour 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; 9: 91–97.
Chrysant SG, Chrysant GS. Antihypertensive efficacy of olmesartan medoximil alone and in combination with hydrochlorothiazide.Expert Opin Pharmacother. 2004; 5: 657–667.
Sellin L, Stegbauer J, Laeis P, Rump LC. Adding hydrochlorothiazide to olmesartan dose dependently improves 24-hour blood pressure and response rates in mild-to-moderate hypertension.J Hypertens. 2005; 23: 2083–2092.
Rump LC, Ambrosioni E, Burnier M, Horl W, Rabelink AJ. Initial combination therapy with olmesartan/hydrochlorothiazide in moderate to severe hypertension.J Hum Hypertens. 2006; 20: 299–301.
Markham A, Goa KL. Valsartan: a review of its pharmacology and therapeutic use in essential hypertension.Drugs. 1997; 54: 299–311.
Nussberger J, Koike H. Antagonizing the angiotensin II subtype I receptor: focus on olmesartan medoximil.Clin Ther. 2004; 26(suppl A): A21-A27.
Stamler R. Implications of the INTERSALT Study.Hypertension. 1991; 17(suppl 1): I16-I20.
Lewington S, Clarke R, Qizilbash N, et al, for the Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.Lancet. 2002; 360: 1903–1913.
Palatini P, Penzo M, Racioppa A, et al. Clinical relevance of night-time blood pressure and daytime blood pressure variability.Arch Intern Med. 1992; 152: 1855–1860.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fogari, R., Zoppi, A., Mugellini, A. et al. Hydrochlorothiazide added to valsartan is more effective than when added to olmesartan in reducing blood pressure in moderately hypertensive patients inadequately controlled by monotherapy. Adv Therapy 23, 680–695 (2006). https://doi.org/10.1007/BF02850307
Issue Date:
DOI: https://doi.org/10.1007/BF02850307