Antihypertensive Drugs More Effective When Taken at Night

Nocturnal hypertension is more common among patients with chronic kidney disease (CKD) who may thus experience greater effects of time medications for hypertension. This randomized controlled, open-label trial compares the effect of bedtime vs. morning administration of BP medications on a composite of cardiovascular disease (CVD) outcomes and BP control.

Among patients with CKD and hypertension, taking at least 1 antihypertensive medication at bedtime significantly improves BP control, with an associated decrease in risk for CVD events, according to new research.

Ramón C. Hermida, PhD, and colleagues from the Bioengineering and Chronobiology Laboratories at the University of Vigo, Campus Universitario, Spain, published their findings and, according to the researchers, the beneficial effect of taking BP medication at night has been previously documented, but "the potential reduction in [CVD] risk associated with specifically reducing sleep-time BP is still a matter of debate."

The current prospective study sought to investigate in hypertensive patients with CKD whether bedtime treatment with hypertension medications better controls BP and reduces CVD risk compared with treatment on waking.

The study included 661 patients with CKD who were randomly assigned either to take all prescribed hypertension medications on awakening or to take at least 1 of them at bedtime. Ambulatory BP at 48 hours was measured at least once a year and/or at 3 months after any adjustment in treatment.

The composite measure of cardiovascular events used included death, myocardial infarction, angina pectoris, revascularization, heart failure, arterial occlusion of lower extremities, occlusion of the retinal artery, and stroke. The investigators controlled their results for sex, age, and diabetes.

Patients were followed for a median of 5.4 years; during that time, patients who took at least 1 BP-lowering medication at bedtime had approximately one third of the CVD risk compared with those who took all medications on awakening (adjusted hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.21 - 0.46; P < .001).

A similar significant reduction in risk with bedtime dosing was noted when the composite CVD outcome included only cardiovascular death, myocardial infarction, and stroke (adjusted HR, 0.28; 95% CI, 0.13 - 0.61; P < .001). Patients taking their medications at bedtime also had a significantly lower mean BP while sleeping, and a greater proportion of these patients had ambulatory BP control (56% vs. 45%; P = .003).

The researchers estimate that for each 5-mm-Hg decrease in mean sleep-time systolic BP, there was a 14% reduction in the risk for cardiovascular events during follow-up (P < .001).

According to Dr. Hermida and colleagues, "treatment at bedtime is the most cost-effective and simplest strategy of successfully achieving the therapeutic goals of adequate asleep BP reduction and preserving or re-establishing the normal 24-hour BP dipping pattern."

The authors suggest that a potential explanation for the benefit of nighttime treatment may be associated with the effect of nighttime treatment on urinary albumin excretion levels. "We previously demonstrated that urinary albumin excretion was significantly reduced after bedtime, but not morning, treatment with valsartan," they note. In addition, this reduction was independent of 24-hour changes of BP, but correlated with a decline in BP during sleep.

• In patients with CKD, taking blood pressure-lowering medications at bedtime vs. taking them on awakening is associated with a significant reduction in CV events.
• The best predictor of reduced CV risk in patients with CKD taking antihypertensive medications at bedtime is sleep time systolic BP.

J Am Soc Nephrol. Published online October 24, 2011