Spanish researchers who followed nearly 20,000 patients for a median of six years found that patients who took their medications at bedtime cut their overall risk of dying from cardiovascular causes during the study nearly in half compared with those taking the drugs in the morning, according to a report in European Heart Journal.
“The time of day when you take your blood pressure-lowering medication counts,” said lead author Ramon Hermida, a professor and director of the bioengineering and chronobiology labs at the University of Vigo.
“Beyond greater reduction of asleep blood pressure - the most significant marker of cardiovascular disease risk - the mechanisms involved so far are just hypothesis, mainly dealing with well-documented circadian rhythms in determinants of around-the-clock blood pressure variability,” Hermida said in an email. “The beneficial effects of bedtime therapy on (kidney) function and lipid profile documented in our study may also play a significant role.”
With earlier studies showing mixed results, Hermida’s team designed a large randomized study that could provide conclusive evidence on whether it made a difference when blood pressure medications were taken. They recruited 19,084 hypertensive patients - 10,614 men and 8,470 women - who were randomly assigned to take their blood pressure-lowering medications first thing in the morning or at bedtime.
The volunteers all wore ambulatory blood pressure measuring devices, which kept track of blood pressure 24 hours a day.
The researchers found, after accounting for factors like age, gender, type 2 diabetes, chronic kidney disease, smoking, cholesterol levels and previous cardiovascular events, that it made a big difference when patients took their medications.
At their final evaluation, patients who took their medications at night had significantly lower LDL cholesterol, higher HDL cholesterol and lower sleeping blood pressure.
During follow-up, 3,246 volunteers experienced a cardiovascular event: 274 had heart attacks, 302 had procedures to open clogged arteries, 521 were diagnosed with heart failure, 345 had a stroke and 310 died from a cardiovascular cause.
Risk of these events, and of dying from them, was significantly lower in the bedtime group. Those who took their medications at bedtime were 45% less likely to die of cardiovascular causes overall, 56% less likely to die of cardiovascular disease, 61% less likely to die of hemorrhagic stroke and 46% less likely to die of ischemic stroke - the more common kind.
Those taking medications at bedtime were also 34% less likely to have a heart attack, 40% less likely to need a procedure to widen clogged arteries, 42% less likely to develop heart failure and 49% less likely to have a stroke.
The new findings are “remarkable,” said Dr. Matthew Muldoon, a professor of medicine and director of the University of Pittsburgh’s UPMC Heart and Vascular Institute Hypertension Center. “This is a huge impact. I’ve never seen anything like it.”
For perspective, Muldoon said, when a new drug to treat blood pressure or cholesterol came on the market and showed a 30% decrease in cardiovascular events, “it was good enough to give those treatments out.”
The new study is showing an even bigger effect just from manipulating the time the medication is given, Muldoon said.
“Hypertension experts have come to believe that nighttime blood pressure is probably the most important blood pressure to control,” Muldoon noted. “Yet, American researchers have never tested this. I think American researchers have been missing the boat.”
Circadian rhythms may play a big role, Muldoon said, adding that during sleep our blood pressure is at its lowest. “It rises briskly in the hour before we wake up and peaks shortly after that.”
“It could be that dosing at bedtime is the only way you can control that surge in the first couple of hours when you wake up,” Muldoon said.
Medications tend to be most effective for three to 15 hours, so if you take them in the morning, they’re clearly wearing off during the most important hours, Muldoon said.