Taking blood-pressure pills at night, rather than in the morning, may better control hypertension and significantly reduce the risk of heart attack and stroke.
The results of the five-year study add to the growing evidence that tailoring the timing and dosage of medications to the body's biological rhythms may help drugs work better and with fewer side effects, the researchers said.
The research also highlighted the importance of sleep-time blood pressure, the most sensitive predictor of a person's risk of death from cardiovascular disease over a five-year period.
In healthy people, blood pressure dips at night, by 10 percent to 20 percent. "Nondippers," whose blood pressure doesn't fall as it should at night, are more vulnerable to cardiovascular events such as heart attack and stroke, the researchers said.
"This study confirms sleep-time blood pressure as the most relevant predictor of cardiovascular risk," said lead researcher Ramon C. Hermida, director of the bioengineering and chronobiology laboratories at the University of Vigo, Spain.
"Sleep-time blood pressure is best reduced when medication is taken at bedtime," Hermida said. "Thus, this effect of the proper timing for dosing seems to be directly related to the documented reduction in cardiovascular events."
For the study, published recently in the journal Chronobiology International, Hermida and his team randomly assigned 2,156 men and women with high blood pressure (average age 56) to one of two treatment groups.
One group took one or more of their blood-pressure medications at bedtime. The other group took all their pills either upon awakening or with breakfast, the recommendation most physicians give their patients.
The researchers monitored the volunteers' blood pressure at 20- and 30-minute intervals, depending on time of day, for 48 hours at the beginning of the study and at least once a year for its duration.
Unlike the standard blood-pressure reading taken in a doctor's office, this round-the-clock tracking -- called ambulatory blood-pressure monitoring (ABPM) -- gives a clearer picture of a person's blood pressure both during the day and the important sleep-time period.
After more than five years of follow-up, those who took at least one of their blood-pressure pills at night seemed to reap significant benefits. Sixty-two percent had controlled blood pressure over the 24-hour period, compared to 53 percent of those who took all their pills in the morning. Moreover, only 34 percent of this group were "nondippers," vs. 62 percent of the morning-medications group, the study authors said.
Those who routinely took at least one of their blood-pressure medicines at night experienced only one-third of the cardiovascular events -- including angina, stroke and heart attack -- suffered by those who swallowed all their blood-pressure pills in the morning, the study found.
"The results of the study indicate that the way we diagnose and treat hypertension needs to be completely reevaluated," said Michael Smolensky, co-author of an accompanying journal article and an adjunct professor in the department of biomedical engineering at the University of Texas at Austin.
One reason blood-pressure medications are more effective when taken before bed: They prevent the release of chemicals synthesized during the sleep span that raise blood pressure to abnormal levels, said Smolensky, the journal's editor. Synchronizing blood-pressure medications to the circadian body clock "optimizes the medications' therapeutic benefit and sometimes lessens their unwanted side effects," he said.
This is not the first study to show the benefits of night-time dosing of blood-pressure medications, Smolensky said. "However, it is the first in which ABPM was done very frequently and also included a morning treatment comparison group to properly evaluate the merits of the bedtime dosing strategy."
People most likely to benefit from taking their pills at night include those whose high blood pressure occurs secondary to another condition, such as metabolic syndrome, type 2 diabetes, sleep apnea or other sleep disorders, heart failure or kidney disease, said Smolensky.
"They are most likely to be nondippers," he said.
However, those who now take their pills in the morning should not begin taking them at night without their doctor's knowledge, said Hermida. "There is a risk for nocturnal hypotension [abnormally low blood pressure] which could increase the risk of stroke."
SOURCES: Ramon C. Hermida, Ph.D., director, Bioengineering and Chronobiology Labs, University of Vigo, Spain; Michael Smolensky, adjunct professor, department of biomedical engineering, University of Texas at Austin, and editor, Chronobiology International; Oct. 5, 2010, Chronobiology International