Optimal timing for antihypertensive dosing: focus on valsartan

Abstract

Some specific features of the 24 h blood pressure (BP) pattern are linked to the progressive injury of target tissues and the triggering of cardiac and cerebrovascular events. In particular, many studies show the extent of the nocturnal BP decline relative to the diurnal BP mean (the diurnal/nocturnal ratio, an index of BP dipping) is deterministic of cardiovascular injury and risk. Normalization of the circadian BP pattern is considered to be an important clinical goal of pharmacotherapy because it may slow the advance of renal injury and avert end-stage renal failure. The chronotherapy of hypertension takes into account the epidemiology of the BP pattern, plus potential administration-time determinants of the pharmacokinetics and dynamics of antihypertensive medications, as a means of enhancing beneficial outcomes and/or attenuating or averting adverse effects. Thus, bedtime dosing with nifedipine gastrointestinal therapeutic system (GITS) is more effective than morning dosing, while also reducing significantly secondary effects. The dose-response curve, therapeutic coverage, and efficacy of doxazosin GITS are all markedly dependent on the circadian time of drug administration. Moreover, valsartan administration at bedtime as opposed to upon wakening results in improved diurnal/nocturnal ratio, a significant increase in the percentage of patients with controlled BP after treatment, and significant reductions in urinary albumin excretion and plasma fibrinogen. Chronotherapy provides a means of individualizing treatment of hypertension according to the circadian BP profile of each patient, and constitutes a new option to optimize BP control and reduce risk.

Increased nighttime blood pressure or nondipping profile for prediction of cardiovascular outcomes

“…49 Patients assigned to receive one of their antihypertensive medicines at bedtime showed a further ambulatory BP reduction than did those receiving all drugs in the morning, whereas dippers increased from 16 to 57% in the former group. In another parallel study, 50 on 200 nondipper hypertensive patients, 3 months of monotherapy with an angiotensin receptor blocker in the evening led to a significantly greater mean decrease in nocturnal BP, whereas 59% of patients in this treatment group managed to control their nighttime BP compared with only 33% of patients receiving the drug in the morning. Till date, two large prospective randomized control trials have implemented nighttime administration of 51 ramipril was administered once daily at bedtime and resulted in an outstanding benefit on CV morbidity and mortality in high-vascular-risk subjects.…”

Administration–time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension

“…Three studies [33][34][35]49] explored the differential efficacy of valsartan monotherapy (160 mg/day) when routinely taken upon awakening or at bedtime. In an initial study on stage 1 and stage 2 essential hypertension patients, the highly significant attenuation of the 48 h SBP/DBP means was treatment-time independent (Table 1).…”

A chronobiological policy to decrease the burden of hypertension and obesity in low- and middle-income population

“…However, the 24-h pattern was preserved. In the other hand, Hermida et al (2007), studying the effect of AT1-receptor blocker (valsartan), showed the same reduction in the 24-h pattern of BP independent of the time of dosing.…”

“…Moreover, in chronopharmacology there are evidences that support the idea that drugs used to treat hypertension may be directed toward input pathways to the central clock, output pathways, or peripheral oscillators, all of which normally result in the expressions of rhythmicity that was discussed in this review and summarized in Figure 2. In spite that antihypertensive drugs have rarely been taking using the circadian variation in human, some studies have been support a circadian, time-dependent, dose-response relationship in the use of antihypertensive drugs to control BP (Hermida et al 2007).…”

“…Antihypertensive drugs have rarely been studied in relation to possible circadian variation. However, some studies support a circadian, time-dependent, dose-response relationship in the use of antihypertensive drugs to control BP (Hermida et al 2007). …”