Dr. Berkant Öztürk  -  Dr. Mustafa Yenerçağ

The BedMed and BedMed-Frail randomised controlled trials - Effect of antihypertensive timing on mortality and morbidity

This summary is based on the presentation of Scott Garrison, MD, PhD (Edmonton, AL, Canada) at the ESC Congress 2024 

Objective:
The BedMed study aimed to evaluate whether bedtime antihypertensive administration reduces major adverse cardiovascular events compared with morning use.

Introduction and methods:
Blood pressure (BP) normally exhibits a circadian rhythm with relatively lower pressures during sleep. Lack of this sleep time ‘dip’ correlates strongly with adverse cardiovascular events such as myocardial infarction (MI), stroke and congestive heart failure (CHF), and BP correlates most strongly with such events when measured at night (ie, during sleep). Given some antihypertensive medications might lower sleep time BP more effectively when administered at bedtime, administration time could conceivably alter the degree of cardiovascular risk reduction these medications provide. However, previous studies on the effects of antihypertensive dose timing on cardiovascular disease risk have shown conflicting results.

In the BedMed study was a prospective, pragmatic, multicenter, blinded randomised controlled trial (RCT). 3357 Canadian primary care patients with no history of glaucoma treated by 436 primary care providers across Canada between March 2017 and December 2023 were randomized to take all their antihypertensive medications at bedtime or in the morning. Median follow-up was 4.6 years.

Because older adults are often underrepresented in RCTs, the researchers conducted a second study in a lean population at greater risk of hypotensive side effects. The BedMed-Frail study had a similar design, but participants were 776 Canadian continuing care residents. They were assigned to evening dosing or usual care (predominantly morning medication use). Median follow-up duration was 415 days.

The primary endpoint in both studies was major adverse cardiovascular events (MACE), defined as the composite outcome of all-cause death or hospitalization or emergency department (ED) visit for MI, stroke, or CHF.  Secondary endpoints included unplanned hospitalizations/emergency room visits for any reason and visual, cognitive, and fracture-related events. In the BedMed-Frail study, additional secondary endpoints included cognitive decline and skin ulceration.

Results:
In the BedMed trial, the primary endpoint of MACE occurred in 9.7% of the patients in the bedtime-dosing group and 10.3% of those in the morning-dosing group (adjusted HR: 0.96; 95% CI: 0.77–1.19; P=0.70).
There were no differences in the frequencies of hospitalization/ED visit for any reason or the safety outcomes between the 2 dosing groups.

In the BedMed-Frail trial, the primary endpoint occurred in 40.6% of the patients in the bedtime-dosing group and 41.9% of those in the morning-dosing group (adjusted HR: 0.88; 95% CI: 0.71–1.11; P=0.28).
The rates of the secondary efficacy and safety outcomes were also not different between the groups, although patients in the evening-dosing group were less frequently admitted to the hospital or ED for any reason (HR: 0.74; 95% CI: 0.57–0.96; P=0.02).

Conclusion:
The 2 Canadian BedMed trials showed no difference in the effect of bedtime versus morning dosing of antihypertensives on MACE risk reduction in primary-care patients and frail elderly. There were also no significant differences in safety outcomes.