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Antihypertensive medications are better taken before bed than are upon awakening in the morning, according to a Spanish multicenter trial.

Night-time blood pressure (BP) drug regimens nearly halved risk of cardiovascular disease (CVD) death, MI, coronary revascularization, heart failure, or stroke compared with day-time regimens over a median of 6.3 years (adjusted HR 0.55, 95% CI 0.50-0.61).

Each component of the primary CVD endpoint significantly favored night-time antihypertensive use, too, reported the Hygia Chronotherapy Trial team led by Ramón Hermida, PhD, of the University of Vigo, Spain, in a paper published online in the .

Taking these drugs at bedtime left patients with better BP control on ambulatory BP monitoring, lower average systolic BP while asleep (114.7 vs 118.0 mm Hg, P<0.001), and no loss of systolic BP-lowering efficacy while awake (129.2 vs 129.5 mm Hg, P=0.294), compared with those taken in the morning.

Moreover, BP medications taken at night also resulted in greater sleep-time relative systolic BP declines (12.2% vs 8.5%, P<0.001) and, in turn, a lower prevalence of non-dipping (37.5% vs 50.3%, P<0.001).

A progressive decrease in mean asleep systolic BP was the most significant predictor of reduced CVD risk after adjustment, according to Hermida and colleagues.

Thus, the benefits of taking BP-lowering medications at bedtime may be in part due to better BP control during sleep through improved targeting of underlying circadian rhythm-organized biological mechanisms, they concluded.

"This speaks to the idea that taking all of your medications at once, in the morning, doesn't work for all the people. Commonly, people coming into the clinic, they'll say they're not taking their meds," said John Higgins, MD, MPhil, of McGovern Medical School at The University of Texas Health Science Center at Houston, who was not involved in the study.

"Patients will often say, especially people who are still in the workforce and active, that when they take all their medications in the morning, they almost feel a crash where they're really low in energy and it's hard to do things, like concentrate," he commented in an interview with MedPage Today.

Higgins said he has instructed patients to take some antihypertensive medications in the morning and some in the evening -- some even during lunchtime -- even before this study. By not taking all the drugs at once, patients can avoid the big dips in energy that may trigger compensatory mechanisms, he suggested.

The trial also reinforces the value of ambulatory BP monitoring and shows that sleeping BP is a better barometer of heart health and wellness, Higgins concluded.

"The better that barometer is, the better off we are going to be," he said. "And if taking medications at night looks like the way to do that, then maybe we really need to think seriously about when patients should be taking these medications."

The Hygia Chronotherapy Trial was set in primary care and included more than 19,000 patients with hypertension (55.6% men and 60.5 years on average). They were asked to make clinic visits at least annually, each time having ambulatory BP monitoring performed over 48 hours.

With 1:1 randomization to take BP drugs at bedtime or upon awakening, the two groups had no baseline differences. Adherence to their medications was similar as well.

Angiotensin receptor blockers and angiotensin converting enzyme inhibitors were the most common monotherapies prescribed. By the end of the study, the group taking medications in the evening reported taking slightly fewer hypertension medications with no increase in adverse effects.

Notably, bedtime regimen patients showed better renal function and an improved lipid profile of reduced LDL cholesterol and higher HDL cholesterol.

Whether the results of this trial can be generalized to other groups is unknown given that these were all Caucasian Spaniards, Hermida's group acknowledged.

Even so, the findings corroborate and build upon other studies that have reported reductions in CVD risk due to a bedtime schedule of these medications, said the authors, citing the , , and MAPEC trials.

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