Duration of Antihypertensives Taken Regardless: New Trials

LONDON – Two new trials have confirmed that the time of day does not matter when it comes to taking antihypertensive drugs.

The two BedMed and BedMed-Frail trials, presented at the European Society of Cardiology (ESC) Congress, showed no difference in death or cardiovascular events between patients who took their antihypertensive medication at night and those who did not. in the morning.

Timing of antihypertensive medications became an issue when Spanish researchers reported the results of the 2010 MAPEC trial and the 2019 Hygia Chronotherapy Trial, which showed a significant reduction in cardiovascular events when the drugs antihypertensives are taken at bedtime rather than during treatment. in the morning.

To see if this finding could be confirmed, other groups conducted similar experiments.

Results from the first of these, the 2022 TIME trial, showed no difference between morning and evening antihypertensive doses.

And now two BedMed studies show the same result, which should settle the issue, said Scott Garrison, MD, PhD, of the University of Alberta in Edmonton, Canada, who was the trial’s principal investigator. two.

“We are the second group of two groups of independent researchers to contradict the findings of the Spanish group. I think we can now say with confidence that the benefits and risks of antihypertensive drugs do not differ from the time of day they are used ,” he said.

The question of when antihypertensive drugs are taken is due to the observation that high blood pressure at night causes a greater risk of heart disease and stroke than high blood pressure during the day, Garrison explained. This led to the suggestion that taking an antihypertensive drug at bedtime might do a better job of lowering blood pressure overnight, which would translate into a reduction in cardiovascular events.

BedMed Trials

In the BedMed trial, 3357 patients with high blood pressure in Canada were randomly assigned to take their antihypertensive medication at bedtime or in the morning. Most patients were taking one (54%) or two (33%) antihypertensive medications once a day.

The BedMed-Frail trial had a similar design but involved 776 patients from 17 nursing homes in Alberta. In both trials, patients with a history of glaucoma were excluded.

Both trials showed no harm, but also no benefit of taking antihypertensives before bed instead of in the morning.

The primary outcome in both trials was death or hospitalization for acute myocardial infarction, stroke, or heart attack.

In the BedMed trial, over a follow-up period of up to 6 years, more patients who took their medication at bedtime than in the morning had a primary event (9.7% vs 10.3%; [HR]0.96; 95% CI, 0.77–1.19).

In the BedMed-Frail trial, with a follow-up period of 42 months, the primary event rates were 40.6% in the sleep group and 41.9% in the morning group (HR, 0.88; 95% CI , 0.71–1.11).

There was no difference between bedtime dosing and morning dosing in terms of safety events, which included postural hypotension, falls, and adverse effects related to vision and cognition.

“Together, the BedMed trials, along with TIME, resolve the uncertainty about whether or not antihypertensive prescription should be strongly recommended, and show that it is not,” Garrison said.

People should take their antihypertensives at a time that suits them best, he added.

Some medications have side effects that are time-related. For example, calcium blockers tend to cause swelling in the ankles when taken in the morning, while diuretics tend to make patients wake up at night needing to urinate when taken before bed.

And some people may want to take their blood pressure medication at different times so that they can take all of their medication at once.

“Our findings suggest that blood pressure-medication timing can be adjusted in any way people like, and that medication should be taken whenever it’s convenient and inconvenient. that it can be forgotten,” Garrison said.

‘A hotly debated topic’

The timing of antihypertensive medication has been a very controversial topic in recent years, said Isla Mackenzie, MD, of the University of Dundee, United Kingdom, who spoke about the BedMed trial at the ESC Hotline conference.

The MAPEC and Hygia trials showed “what many consider to be an immeasurably large benefit” in cardiovascular outcomes by taking antihypertensive medications at night. However, the methods of those tests have been questioned.

In the TIME trial, there was no difference between bedtime and morning antihypertensive dosing in terms of the primary end point of heart disease, myocardial infarction, and stroke; The HR of 0.95 was very similar to that reported in the BedMed trials.

Both BedMed tests were well-designed and well-designed, and had very good safety data. It was great to see the BedMed-Frail trial being conducted on patients from nursing homes, an underserved population, Mackenzie said.

Now that there are three trials showing similar results, “I advise my patients to take their antihypertensive medication at a regular time of day when they will better remember to take their tablets,” Mackenzie said.