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Previous results have indicated that valsartan administration at bedtime as opposed to upon wakening improves the day/night ratio of blood pressure (BP) (nocturnal decline of BP relative to the diurnal mean) towards a more dipper pattern without loss in 24-hour efficacy [Hypertension. 2003;42:283-290]. Some studies have found differential effects of antihypertensive drugs according to the dipping status of the patients. Accordingly, we investigated the administration time-dependent antihypertensive efficacy of valsartan in non-dipper patients. We studied 190 non-dipper patients with grade 1-2 essential hypertension (72 men), 53.9 13.2 years of age, randomly assigned to receive single daily valsartan monotherapy (160 mg/day) either upon awakening or at bedtime. BP was measured by ambulatory monitoring at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 hours before and after 3 months of therapy. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of BP on a per subject basis. The highly significant BP reduction after 3 months of treatment with valsartan (P 0.001) was slightly larger after bedtime dosing of valsartan (13.0 and 8.1 mm Hg reduction in the 24-hour mean of systolic and diastolic BP after valsartan on awakening; 15.2 and 10.6 mm Hg when valsartan was administered at bedtime). The day/night ratio was unchanged after valsartan on awakening (0.4 and 0.7 for systolic and diastolic BP; P 0.309). This ratio was significantly increased (7.2 and 7.1 for systolic and diastolic BP, P 0.001) when valsartan was administered at bedtime, which resulted in 75% of the patients reverted to dippers, a significant increase in the percentage of patients with controlled BP after treatment, and a significant reduction in urinary albumin excretion. Independently of dosing time, 160 mg/day valsartan monotherapy efficiently reduces BP for the entire 24 hours of the day. In hypertensive patients who are non-dippers at baseline, dosing time with valsartan should be chosen at bedtime, for increased efficacy during nocturnal resting hours, improved renal function, and the potential associated reduction in cardiovascular risk.

Treatment of non-dipper essential hypertension with bedtime administration of valsartan