Antihypertensives at Night: When You Snooze, You Lose?

Typically, antihypertensive medications are taken in the morning. But typically does not always equal correct! Preliminary studies have documented that a more appropriate approach would be to take them (or at least some of them) at bedtime.¹

The MAPEC Study (Spanish: Monitorizacion Ambulatoria para Prediccion de Eventos Cardiovasculares; English: Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Events) was designed to test the hypothesis that bedtime dosing of one or more antihypertensives not only provides better blood pressure control, but also allows for improved cardiovascular risk reduction.¹

A total of 2156 hypertensive patients (1044 men and 1112 women) were randomized into 2 groups. Those in Group 1 took all their medications upon awakening. Those in Group 2 took one or more of these medications at bedtime.

The medication choices were as follows:

. From the angiotensin receptor blocker category
   Valsartan(Drug information on valsartan)
   Telmisartan(Drug information on telmisartan)
   Olmesartan
. From the available ACE inhibitors
   Ramipril
   Spirapril (not used in the US)
. From the calcium channel blockers
   Amlodipine(Drug information on amlodipine)
   Nifedipine(Drug information on nifedipine);
. One beta-blocker (nebivolol)
. One diuretic (torasemide)

All those enrolled had blood pressures taken with an ambulatory device protocol that checked pressure at 20-minute intervals from 7 AM until 11 PM and at the 30-minute intervals through the night for 48 hours (one cycle of checks). Additionally, their physical activity was monitored by “wrist actigraphy.” The device also ensured that night equalled sleep and cessation of all physical activities. These assessments were repeated annually, and more frequently, actually quarterly, if adjustments to reach target BP were necessary.

There were no baseline differences between Groups 1 and 2. On followup, the night medication group demonstrated lower sleep blood pressures, a higher sleep time blood pressure decline, a reduced prevalence of non-dipping, and a higher prevalence of controlled ambulatory BP. Median followup was 5.6 years.

Let me take a moment to explain the strange term “non-dipping.” If blood pressure does not drop 10% or more during the night (called non-dipping), that person has a higher cardiovascular risk.

The bedtime medication takers also had a lower relative risk of total cardiovascular events (0.39 [0.29-0.51]). The cardiovascular events included death from a cardiovascular cause, myocardial infarction, ischemic stroke, and hemorrhagic stroke.

The research group then specifically looked at daytime versus nighttime medication pattern for blood pressure in hypertensive patients with type 2 diabetes.² Again, treatment with 1 or more antihypertensive medications at bedtime rather than in the AM resulted in improved ambulatory blood pressure control as well as reduced cardiovascular morbidity and mortality.

The first reference contains ample citations that document a nighttime medication pattern is successful and beneficial for blood pressure lowering. Since earlier generation beta-blockers have appropriately been used less frequently for blood pressure control, it was good to see that nebivolol(Drug information on nebivolol)—a beta-1 selective blocker with nitric oxide-mediated vasodilatory properties—was chosen for the study. It works better than beta-blockers without the additional vasodilatory effect.³

I was impressed that something as simple as changing a once daily medication from AM to PM ingestion --and something that doesn’t cost anything extra -- could be this successful. With a plethora of once-a-day blood pressure medications, this AM to PM change should be easy to accomplish. While awaiting further studies, the change will probably help- — and it surely won’t hurt.     

References:
1. Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010; 27:1629-1651.
2. Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of time of day of blood pressure-lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes. Diabetes Care. 2011; 34:1270-1276.
3. Weiss RJ, Saunders E, Greathouse M. Efficacy and tolerability of nebivolol in stage I-II hypertension: a pooled analysis of data from three randomized , placebo-controlled monotherapy trials. Clin Ther. 2011; August 23rd [e pub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/21864908