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

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.