Titre du document / Document title

Valsartan /hydrochlorothiazide : A review of its use in the management of hypertension

Auteur(s) / Author(s)

WAGSTAFF Antona J. ^{(1 2)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Wolters Kluwer Health I Adis, Auckland, NOUVELLE-ZELANDE
⁽²⁾ Wolters Kluwer Health, Conshohocken, Pennsylvania, ETATS-UNIS

Résumé / Abstract

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 Valsartan is a selective antagonist of the angiotensin II type 1 receptor. This drug Properties 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.

Revue / Journal Title

Drugs   ISSN 0012-6667   CODEN DRUGAY 

Source / Source

2006, vol. 66, n^o14, pp. 1881-1901 [21 page(s) (article)] (91 ref.)

Langue / Language

Anglais

Editeur / Publisher

Adis International, Auckland, NOUVELLE-ZELANDE  (1962) (Revue)

Mots-clés anglais / English Keywords

Renin angiotensin system ; Octapeptide ; Peptide hormone ; Cardiovascular disease ; Thiazide ; Sulfanilamide derivatives ; Tetrazole derivatives ; AT1 angiotensin receptor ; Biphenyl derivatives ; Angiotensin antagonist ; Angiotensin II ; Aminoacid ; Pharmacotherapy ; Diuretic ; Antihypertensive agent ; Monograph ; Pharmacokinetics ; Toxicity ; Drug combination ; Human ; Hypertension ; Clinical management ; Treatment ; Bibliographic review ; Review ; Hydrochlorothiazide ; Valsartan ;

Mots-clés français / French Keywords

Benzothiadiazine dérivé ; Sartan dérivé ; Valine dérivé ; Système renin angiotensine ; Octapeptide ; Hormone peptide ; Appareil circulatoire pathologie ; Thiazide ; Sulfamides ; Tétrazole dérivé ; Récepteur angiotensine AT1 ; Biphényle dérivé ; Antagoniste angiotensine ; Angiotensine II ; Aminoacide ; Pharmacothérapie ; Diurétique ; Antihypertenseur ; Monographie ; Pharmacocinétique ; Toxicité ; Association médicamenteuse ; Homme ; Hypertension artérielle ; Conduite à tenir ; Traitement ; Revue bibliographique ; Article synthèse ; Hydrochlorothiazide ; Valsartan ;

Mots-clés espagnols / Spanish Keywords

Sistema renin angiotensina ; Octapéptido ; Hormona péptido ; Aparato circulatorio patología ; Tiazida ; Sulfamidas ; Tetrazol derivado ; Receptor angiotensina AT1 ; Bifenilo derivado ; Antagonista angiotensina ; Angiotensina II ; Aminoácido ; Farmacoterapia ; Diurético ; Antihipertensivo ; Monografía ; Farmacocinética ; Toxicidad ; Asociación medicamentosa ; Hombre ; Hipertensión arterial ; Actitud médica ; Tratamiento ; Revista bibliográfica ; Artículo síntesis ; Hidroclorotiazida ; Valsartán ;

Localisation / Location

INIST-CNRS, Cote INIST : 15326, 35400015885289.0080