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 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.
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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.
SOURCE: https://bit.ly/2pIrUHw European Heart Journal, online
October 22, 2019.
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