Differing effects of awakening versus bedtime valsartan administration on urinary albumin excretion in hypertensive patients

Previous results have indicated that valsartan dosed at bedtime as opposed to upon wakening improves the day/night ratio of blood pressure (BP) towards a more dipper pattern without loss in 24-hour efficacy [Hypertension. 2003;42:283–290]. Urinary albumin excretion (UAE) in non-dippers has been shown to be significantly greater than in dippers [Am J Hypertens. 1994;7:23–29]. Moreover, the reduction of UAE provides renal protection and reduces cardiovascular risk [Lancet. 2001;357:1601–1608]. We hypothesized that improving the day/night BP ratio could further reduce UAE in hypertensive patients. We studied 123 previously untreated non-proteinuric patients with grade 1–2 essential hypertension (50 men and 73 women), 51.0±11.4 years of age, randomly assigned to receive valsartan (160 mg/d) as a monotherapy 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 consecutive hours before and after 3 months of therapy. The patients collected their urine during the first 24 hours of ambulatory monitoring. 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 significant BP reduction after 3 months of valsartan was similar for both treatment times (13.9 and 9.1 mm Hg reduction in the 24-hour mean of systolic and diastolic BP after valsartan on awakening; 15.2 and 10.3 mm Hg after valsartan at bedtime). The day/night BP ratio was unchanged after valsartan on awakening, but significantly increased by 5.4% when valsartan was administered before bedtime. UAE was significantly reduced, mainly after bedtime treatment (31% reduction). This reduction was independent of the 24-hour BP decrease, but highly correlated with the decrease of nocturnal BP (r=0.326, P=0.007) and with the increase in day/night BP ratio, mainly after bedtime treatment (r=0.395, P=0.002). Bedtime valsartan administration improves the day/night BP ratio to a more dipper profile This results in further decrease of UAE as compared to morning dosing, and could thus reduce cardiovascular risk, a hypothesis that deserves further prospective investigation.