Taking antihypertensive medications at bedtime rather than in the morning is safe for adults with hypertension in primary care and for frail older nursing home patients, but it does not reduce cardiovascular risk or all-cause death in either group, according to recently published results from the BedMed trial in JAMA and BedMed-Frail trial in JAMA Network Open.

In the BedMed open-label trial led by Scott R. Garrison, MD, PhD, et al., from 2017 to 2022, 436 primary care clinicians in Canada recruited 3,357 adults with hypertension taking one or more once-daily antihypertensive medication were randomized to bedtime (n=1,677) or morning (n=1,680) administration of their medication. Their median age was 67 years, 56% were women and 54% were on monotherapy.

The composite primary outcome included all-cause death and hospitalization/emergency department (ED) visits for stroke, acute coronary syndrome or heart failure. Results showed that over the median 4.6 years of follow-up there was a similar rate for the primary outcome: 2.3 per 100 patient-years in the bedtime group vs. 2.4 per 100 patient-years in the morning group (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.77-1.19).

Findings also showed no difference in individual components of the primary outcome, falls or fractures, new glaucoma diagnoses, or cognitive decline between groups. Of note, administration time affected neither the benefits nor the risks of antihypertensive medication.

In the BedMed-Frail trial, also led by Garrison and colleagues and using the same primary composite outcome, 776 Canadian nursing home residents with hypertension recruited from 13 facilities were randomized to either bedtime (n=394) or usual care (mainly morning use; n=382) once-daily antihypertensive medications. Their median age was 88 years, 73% were women and 86% had some degree of dementia.

Over the median 1.1 years of follow-up, 293 of 320 primary outcome events were deaths. Findings in a modified intention-to-treat analysis showed no difference in primary outcomes for bedtime compared with usual care (29.4 vs. 31.5 events per 100 patient-years; aHR, 0.88; 95% CI, 0.71-1.11).

Results also showed no difference between groups for other outcomes; however, all-cause unplanned hospitalization and ED visits were lower in the bedtime group (22.6 vs. 30.0 events per 100 patient-years; aHR, 0.74).

In an accompanying editorial comment, Sandra J. Taler, MD, writes that data from the current trials "disprove the maxim that medications must be dosed in the morning." Furthermore, loosening the rules on time of dosing may facilitate better supervision by caregivers, who may be able to provide assistance or oversight later in the day due to other responsibilities. "At the end of the day, timing of medications doesn't matter as much as consistency in taking them."