2 patients were exposed to valsartan (80, 160 and 320mg) and concomitant hydrochlorothiazide (12.5 and 25mg). Two factorial trials compared various combinations of 80/12.5mg, 80/25mg, 160/12.5mg, 160/25mg, 320/12.5mg and 320/25mg with their respective components and placebo. The combination of valsartan and hydrochlorothiazide resulted in additive placebo-adjusted decreases in systolic and diastolic blood pressure at trough of 14-21/8-11mmHg at 80/12.5mg to 320/25mg, compared to 7-10/4-5mmHg for valsartan 80mg to 320mg and 5-11/2-5mmHg for hydrochlorothiazide 12.5mg to 25mg, alone.
Three other controlled trials investigated the addition of hydrochlorothiazide to patients who did not respond adequately to valsartan 80mg to valsartan 320mg, resulted in the additional lowering of systolic and diastolic blood pressure by approximately 4-12/2-5mmHg.
The maximal antihypertensive effect was attained 4 weeks after the initiation of therapy, the first time point at which blood pressure was measured in these trials.
In long-term follow-up studies (without placebo control) the effect of the combination of valsartan and hydrochlorothiazide appeared to be maintained for up to two years. The antihypertensive effect is independent of age or gender. The overall response to the combination was similar for Black and non-Black patients.
There was essentially no change in heart rate in patients treated with the combination of valsartan and hydrochlorothiazide in controlled trials.
Valsartan: The antihypertensive effects of valsartan were demonstrated principally in 7placebo-controlled, 4- to 12-week trials (one in patients over 65) of dosages from 10 to 320mg/day in patients with baseline diastolic blood pressures of 95-115. The studies allowed comparison of once-daily and twice-daily regimens of 160mg/day; comparison of peak and trough effects; comparison (in pooled data) of response by gender, age, and race; and eva luation of incremental effects of hydrochlorothiazide.
Administration of valsartan to patients with essential hypertension results in a significant reduction of sitting, supine, and standing systolic and diastolic blood pressure, usually with little or no orthostatic change.
In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs at approximately 2hours, and maximum reduction of blood pressure is achieved within 6hours. The antihypertensive effect persists for 24hours after dosing, but there is a decrease from peak effect at lower doses (40mg) presumably reflecting loss of inhibition of angiotensin II. At higher doses, however (160mg), there is little difference in peak and trough effect. During repeated dosing, the reduction in blood pressure with any dose is substantially present within 2 weeks, and maximal reduction is generally attained after 4weeks. In long-term follow-up studies (without placebo control) the effect of valsartan appeared to be maintained for up to two years. The antihypertensive effect is independent of age, gender or race. The latter finding regarding race is based on pooled data and should be viewed with caution, because antihypertensive drugs that affect the renin-angiotensin system (that is, ACE inhibitors and angiotensinII blockers) have generally been found to be less effective in low-renin hypertensives (frequently Blacks) than in high-renin hypertensives (frequently Whites). In pooled, randomized, controlled trials of Diovan that includ |
