Efficacy and safety of nighttime dosing of antihypertensives: review of the literature and design of a pragmatic clinical trial.

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 at particularly high risk. Several studies have found that bedtime dosing of antihypertensive agents reduces sleep blood pressure and improves the dipping pattern in nondippers. One small study and 2 substudies of diabetes and chronic kidney disease suggest that bedtime dosing of ≥ 1 antihypertensives significantly reduced CV events. A Cochrane review of 5 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 antihypertensive agents that evaluate CV events need to be conducted. The authors describe a randomized controlled pragmatic trial that is being planned at the University of Iowa and Duke University. Patients with hypertension and other comorbid conditions will be randomized to either continue morning dosing of all antihypertensive agents or to switch their nondiuretic medications to bedtime dosing. Patients will be followed for 36 to 42 months. This study will determine whether nighttime dosing reduces CV risk when compared with traditional morning dosing of antihypertensive agents.