Key Points:
- Blood pressure follows a circadian rhythm, peaking after waking and dipping during sleep. While elevated nocturnal pressures are associated with adverse cardiovascular events, it is uncertain whether taking anti-hypertensive medication in the evening improves outcomes.
- BedMed and BedMed-Frail were pragmatic trials that randomized community-dwelling adults and nursing home residents, respectively, to their once-daily anti-hypertensives either before bed or in the morning.
- There were no differences in major cardiovascular or safety events between the two groups in either trial.
Night-time hypertension and an exaggerated morning surge in blood pressure is associated with an increased risk in cardiovascular events. Therefore, evening dosing of anti-hypertensive medication may be a more effective treatment strategy than morning-only administration. Previous research comparing morning vs. evening dosing, however, was of varying quality and provided conflicting results.1,2
On August 31st 2024, the principalresults of the BedMed and BedMed-Frail trials were presented at ESC Congress 2024. The purpose of these studies were to determine the safety and efficacy of bedtime vs. morning dosing of blood pressure medications in community-dwelling adults as well as those who reside in nursing homes, a frail population that have historically been excluded from prior studies on this topic.
The open-label pragmatic BedMed trial randomized 3,357 adult primary care patients in Canada who were prescribed at least one once-daily anti-hypertensive to take these medications exclusively in the morning or before bed. The primary outcome was a composite of major adverse cardiovascular events (MACE: all-cause death or stroke, myocardial infarction, or heart failure). Secondary outcomes included any unplanned emergency department visit or hospitalization, and visual-, cognitive-, or fall-related events. The mean age was 67 years; 56% were female. Over a median of 4.6 years there was no difference in MACE (9.7% in the bedtime group vs. 10.3% in the morning group; aHR 0.96 [95% CI 0.77-1.19]; p=0.7) or in the secondary safety outcomes.
BedMed frail similarly randomized 776 nursing home residents, with a median age of 88 years; 72% were female. Again, no differences were found in MACE between the evening group or the morning group (40.6% vs. 41.9%; aHR 0.88 [0.71-1.11]; p=0.3). Unplanned hospital visits were lower in the evening administration group (aHR 0.74 [0.57, 0.96]; p=0.02), but no significant differences were found in any of the other secondary or safety outcomes.
Professor Scott Garrison from the University of Alberta, Edmonton, Canada, concluded: “While evening dosing was safe, it conveyed no additional advantages…We found no difference in MACE, nor in potential hypotensive, visual, cognitive or other safety events in a general population and importantly, in frail older patients, a subgroup who are generally excluded from clinical trials. We can now dismiss the treatment timing as being important and advise patients to take their BP medication when they are least likely to forget.”
- Mackenzie IS, Rogers A, Poulter NR, et al. Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial. The Lancet. 2022;400(10361):1417-1425. doi:10.1016/S0140-6736(22)01786-X
- Stergiou G, Brunström M, MacDonald T, et al. Bedtime dosing of antihypertensive medications: systematic review and consensus statement: International Society of Hypertension position paper endorsed by World Hypertension League and European Society of Hypertension. J Hypertens. 2022;40(10):1847-1858. doi:10.1097/HJH.0000000000003240