Valsartan/hydrochlorothiazide - A review of its pharmacology, therapeutic efficacy and place in the management of hypertension

The combination of valsartan [an angiotensin II type 1 (AT(1)) receptor blocker] and hydrochlorothiazide (a thiazide diuretic), administered once daily, has been evaluated in the treatment of patients with hypertension in clinical trials ranging in duration from 8 weeks to 3 years. These studies showed that combination treatment with valsartan 80 or 160mg and hydrochlorothiazide 12.5 or 25mg induced significant reductions from baseline in systolic blood pressure (SBP) and diastolic BP (DBP) in patients with mild to severe hypertension. Clinical trials have demonstrated that the combination of valsartan 80 or 160mg with hydrochlorothiazide 12.5 or 25mg is significantly more effective than either drug alone. Furthermore, valsartan plus hydrochlorothiazide was effective at reducing BP in patients unresponsive to monotherapy with either agent alone. Effective BP control with valsartan plus hydrochlorothiazide was maintained in long-term studies, with reductions observed after 3 months of treatment being similar to those seen after 1, 2 or 3 years. Fixed-dose valsartan/hydrochlorothiazide showed similar BP reductions to amlodipine and to valsartan plus benazepril. Valsartan/hydrochlorothiazide also provided effective 24-hour ambulatory SBP/DBP control. Headache, dizziness and fatigue were the most common adverse events occurring in clinical trials; the incidence of these events in valsartan plus hydrochlorothiazide recipients was not significantly different to that in placebo recipients. Hypokalaemia occurred in 4.5% of valsartan plus hydrochlorothiazide recipients; valsartan attenuated the hydrochlorothiazide-associated decrease in serum potassium concentrations. Conclusions: the combination of valsartan and hydrochlorothiazide is an effective treatment for patients with hypertension. Clinical trials have demonstrated that the combination is more effective than either drug alone, and is effective in patients not responding to monotherapy with either agent. Furthermore, the adverse event profile of valsartan/hydrochlorothiazide is similar to that of placebo. Unless there are compelling or specific indications for other drugs, current data support the use of valsartan/hydrochlorothiazide when patients are unresponsive to monotherapy with either agent. Results from clinical trials evaluating the effects of valsartan/hydrochlorothiazide on cardiovascular morbidity and mortality will help to further define the role of the combination in the management of hypertension.