Whether the timing of administering antihypertensive medication affects major adverse cardiovascular events (MACEs) is highly uncertain due to conflicting results from randomized trials.¹ While the MAPEC trial in 2010 and Hygia trial in 2019 showed significant reductions in MACE (61% and 45% respectively) when blood pressure (BP) medications were taken at bedtime instead of conventional morning use, the TIME trial in 2022 showed no additional benefit in doing so.¹ The BedMed and BedMed-Frail trials were thus conducted to investigate these contradictory findings in a hypertensive primary care population, as well as in older, hypertensive patients living in continuing care wards.¹ The outcomes of the trials were presented at the ESC Congress 2024 by Professor Scott Garrison from the University of Alberta in Canada.¹

The BedMed trial was a prospective, open, blinded-endpoint assessment study where 3,357 hypertensive patients from 5 Canadian provinces were recruited and randomized 1:1 to bedtime BP medication (n=1,677) or morning BP medication (n=1,680).¹ 76.5% of participants were recruited from 436 primary care providers while the rest were recruited from a social media campaign.¹ Participants included were patients diagnosed with hypertension, taking at least 1 once-daily BP medication, community-dwelling, and at least 19 years of age.¹ Those with glaucoma, sleep-disrupting shift work, or considered palliative or unable to consent were excluded from the study.¹ The median age of patients was 67 years and both the bedtime and morning groups were balanced in the number and type of BP medications used.¹ Participants were followed up at 1 week, 6 weeks, 6 months, and every 6 months thereafter by telephone or e-mail survey.¹

The BedMed-Frail trial had a similar design but recruited hypertensive patients from 17 continuing care wards in Alberta who were randomized 1:1 to take all once-daily BP medications at bedtime (n=394) or continue taking their BP medications at the usual timing (n=382), which was largely morning use by default.¹ The median age of participants in this trial was 88 years and both groups were balanced in the number and type of BP medications used.¹

The primary outcome for both trials was all-cause death or hospitalization/emergency department (ED) visit for stroke, acute coronary syndrome, or MACE.¹ The secondary efficacy outcomes for both trials were each component of the primary outcome as well as all-cause unplanned hospitalization/ED visit.¹ Secondary safety outcomes for the BedMed trial were postural hypotension-related (non-vertebral fracture, hip fracture, falling, syncope, lightheadedness), vision-related (new glaucoma diagnosis, self-reported worsening of vision), and cognition-related (cognitive decline at 18-months, new impairment consistent with dementia, nursing home admission).¹ Secondary safety outcomes for the BedMed-Frail trial focused on falls and fractures (non-vertebral fracture, fall in the last 30 days), cognitive and behavioral (deteriorated cognition, problem behaviors, use of anti-psychotic medication, physical restraints, anti-anxiety medication, or sleeping pill), skin ulcerations, and urinary incontinence.¹

Among patients who had 1 once-daily BP medication in the BedMed trial, 83% of the bedtime group adhered to taking their medication at the allocated time compared to 95% in the morning group at 6 months.¹ For those with ≥1 once-daily BP medication, 88% of the bedtime group adhered to the allocation compared to 97% of morning participants, although this gradually fell over time with the lowest adherence being 70% vs. 88% at 6 years.¹ Adherence to allocation was also the lowest for those taking diuretics at bedtime.¹

After a median follow-up of 4.6 years in the BedMed trial, no significant differences in the primary outcome were found between the two groups hazard ratio ([HR]=0.96; 95% CI: 0.77-1.19; p=0.70), with 163 events occurring in the bedtime group (2.30/100 patient-years) compared with 173 events in the morning group (2.44/100 patient-years).¹ No difference in any secondary outcome was observed between the bedtime and morning groups.¹ The results were similar in BedMed-Frail trial with no significant differences observed in the primary outcome (HR=0.88; 95% CI: 0.71-1.11; p=0.28) nor the secondary outcomes between the two treatment arms.¹

In conclusion, for hypertensive patients with no history of glaucoma, anti-hypertensive medications can be safely taken at bedtime, although no additional cardiovascular benefit is conveyed from doing so.¹ Prof. Garrison thus recommended taking blood pressure medications whenever one is least likely to forget to do so.

Professor Scott Garrison
University of Alberta,
Canada

“Blood pressure medication should be taken whenever you are least likely to forget it”