Efficacy and Safety of Nighttime Dosing of Antihypertensives: Review of the Literature and Design of a Pragmatic Clinical Trial

Abstract

Blood pressure exhibits circadian variability and nighttime blood pressure is one of the best predictors of cardiovascular (CV) events. Adults with hypertension who lack a nighttime dipping pattern are particularly at high risk. Several studies have found that bedtime dosing of antihypertensives reduces sleep blood pressure and improves the dipping pattern in nondippers. One small study and two sub-studies in diabetes and chronic kidney disease suggest that bedtime dosing of one or more antihypertensives significantly reduced CV events. A Cochrane review of five studies found no difference in adverse events between morning and evening dosing. However, several evaluations in ophthalmology have found that nocturnal arterial hypotension precipitated ocular vascular disorders such as ischemic optic neuropathy. Some authors have suggested that additional studies of nighttime dosing of antihypertensives that evaluate CV events need to be conducted. We describe a randomized controlled pragmatic trial that is being planned at the University of Iowa and Duke University. Subjects with hypertension and other co-morbid conditions will be randomized to either continue morning dosing of all antihypertensives or to switch their non-diuretic medications to bedtime dosing. Subjects will be followed for 36–42 months. This study will determine if nighttime dosing reduces CV risk when compared to traditional morning dosing of antihypertensives.

Chronotherapy of Hypertension: Current State of the Scientific Problem

“…[37] одной из важнейших причин яв-ляется чрезмерная сложность для рутинной практики методологии хронотерапии под контролем СМАД, в то время как до сих пор нет полной ясности с целевыми значениями офисного АД даже при стандартном лече-нии АГ. Безусловно, доказательная база хронотерапии нуждается в пополнении; до настоящего времени мно-гие исследования в этой области имеют существенные ограничения: помимо указанных выше [14], это -от-сутствие полноценных групп контроля, произвольный анализ подгрупп пациентов, проблемы с верификацией конечных точек [37,48].…”

“…падения, переломы). B. Carter и соавт., G. Parati также обращают внимание на опасность ухуд-шения течения уже имеющихся глазных болезней (глаукома, ишемическая оптическая нейропатия) [48,49].…”

Is Evening Dosing of Antihypertensive Therapy Ready for Prime Time?

“…Accordingly, a rigorously conducted randomized controlled trial 36 to 42 months in duration comparing morning dosing of all antihypertensive medications vs administration of all nondiuretic medications at bedtime is currently being planned. 11 The analysis by Roush and colleagues 3 reported in this issue of the Journal adds important new information to the growing body of evidence that CVD risk reduction is more impressively lowered with evening compared with morning dosing of antihypertensive medications. Thus, the preponderance of evidence, at present, has aligned in favor of nocturnal dosing of once-daily antihypertensive medications.…”

Treatment in the Morning versus Evening (TIME) Study: Feasibility of an Online Study

“…Further studies are needed to establish the optimal time of dosing for hypertensive patients [10,11]. The Treatment in Morning versus Evening (TIME) study aims to determine whether evening dosing is indeed more effective than morning dosing of antihypertensive at preventing cardiovascular events such as heart attacks and strokes.…”