Non-dipping has been related to increased end-organ injury and cardiovascular risk. Accordingly, there is growing interest in how to tailor the treatment of non-dipper hypertensives. Clinical studies have documented that dosing of angiotensin-receptor blockers (ARB) at bedtime as opposed to upon wakening increases the sleep-time relative blood pressure (BP) decline and their efficacy in lowering asleep BP. Accordingly, we investigated the antihypertensive efficacy of ARB monotherapy when dosed either on awakening or at bedtime in non-dipper hypertensive subjects.
We studied 453 untreated subjects with grade 1–2 essential hypertension (210 men and 243 women), 53.1 ± 14.2 years of age, all with a non-dipper BP profile at inclusion. Subjects were randomly assigned to receive ARB monotherapy (valsartan, 160 mg/day; olmesartan, 40 mg/day; or telmisartan, 80 mg/day) either on awakening or before bedtime. BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h before and after 12 weeks of treatment.
The reduction in awake BP was similar for both treatment-times (11.0/8.0 mmHg reduction of systolic/diastolic awake BP after ARB on awakening; 10.2/7.3 mmHg after ARB at bedtime; P > 0.293 between treatment-groups). Treatment at bedtime, however, was significantly more efficient in reducing asleep BP (18.5/11.9 mmHg reduction compared to 12.8/8.8 mmHg after morning treatment; P < 0.001). The sleep-time relative BP decline was increased by 6.9 (P < 0.001) towards a more dipping pattern after bedtime dosing, which resulted in 72% of the patients reverted to dippers. This increase in sleep-time relative BP decline was similar for all three ARB tested (P > 0.503).
Bedtime administration of ARB in non-dipper hypertensives provides a higher efficacy as compared to morning treatment in reducing the asleep BP mean, and improves the sleep-time relative BP decline towards a more dipper profile. This might be clinically relevant, as nighttime BP is a better prognostic marker of cardiovascular mortality than awake BP. These effects were comparable for all ARB tested here, despite marked differences in plasma-half-life.
University of Vigo, Vigo, Spain