No difference in MACE risk with evening versus morning dosing of antihypertensives

This summary is based on the presentation of Scott Garrison, MD, PhD (Edmonton, AL, Canada) at the ESC Congress 2024 - The BedMed and BedMed-Frail randomised controlled trials - Effect of antihypertensive timing on mortality and morbidity.

Introduction and methods

High overnight blood pressure increases the risk of MI and stroke compared with high daytime blood pressure. This raises the question whether taking once-daily antihypertensive medication at bedtime is better than the conventional morning dosing. However, previous studies on the effects of the timing of antihypertensive dosing on CVD risk have shown conflicting results.

In the BedMed trial, a prospective, pragmatic, multicenter, open-label, blinded-endpoint RCT, 3357 Canadian primary-care patients, with no history of glaucoma, were randomized to take all their antihypertensive medications at bedtime or in the morning. Median follow-up time was 4.6 years.

As older adults are often underrepresented in RCTs, the researchers conducted a second trial in a frail population at greater risk of hypotensive adverse events. The BedMed-Frail trial had a similar design except that 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.

In both trials, the primary endpoint was MACE, defined as a composite outcome of all-cause mortality, or hospitalization or emergency department (ED) visit for ACS/MI, stroke, or congestive HF. Secondary endpoints included unplanned hospitalization/ED visits for any reason and visual-, cognitive-, and fracture-related events. In the BedMed-Frail trial, additional secondary endpoints included cognitive decline and skin ulceration.

Main 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. Professor Garrison therefore advised patients to take their antihypertensive medications whenever is most convenient for them or when they are least likely to forget this.

- Our reporting is based on the information provided at the ESC Congress 2024 -