Bedtime vs Morning Dosing of Blood Pressure Meds Shows No Benefit in Frail Elderly

New research showed no difference in the benefits of administering antihypertensive medications at bedtime vs. in the morning among frail older adults.1

“This RCT found that among frail older adults residing in Alberta nursing homes, those switching once-daily antihypertensive medications to bedtime had similar rates of all-cause death, stroke, acute coronary syndrome, or heart failure as those continuing largely morning antihypertensive use,” investigators, led by Scott R. Garrison, MD, PhD, from Pragmatic Trials Collaborative at University of Alberta, wrote.1 “The same was true for the hypothesized adverse effects of falls and fractures, decubitus ulcers, and worsening cognition or behavioral problems.”

Blood pressure typically drops at night, and bedtime readings often predict cardiovascular risk more than daytime measurements. This indicates that elevated blood pressure at night shows a greater cardiovascular risk.

Antihypertensive medications may favorably lower overnight blood pressure when administered at bedtime. Several randomized clinical trials have shown large reductions in cardiovascular events when antihypertensive medications are taken at bedtime rather than in the morning—one trial reported a 61% reduction, while another found a 45% reduction.2,3

Conversely, a randomized clinical trial and an observational study had reported no difference in mortality and morbidity with administration time.4,5 Conflicting evidence leaves uncertainty surrounding the best time to take antihypertensive medication.

Investigators conducted BedMed-Frail to assess the effect of bedtime vs morning administration of antihypertensive medications on major cardiovascular events and death in frail older adults.1 They also aimed to assess potentially ischemic or hypotensive adverse events.

The multicenter, open-label, pragmatic randomized clinical trial recruited participants from 13 continuing care facilities, including wards (n = 17), long-term (n = 14), and supportive-living wards (n = 3), in Canada from May 25, 2020, to September 18, 2023. The sample included 776 older adults (mean age, 88 years) with hypertension and ≥ 1 once-daily antihypertensive medication. Participants had ≥ 2 health system encounters with a hypertension diagnosis from 2002 onwards.

Among the sample, 72.4% were female, 85.6% had dementia, 47.3% with diabetes, and 39.6% with coronary artery disease. Participants were randomized 1:1 to receive once-daily hypertensive medications at either bedtime (intervention; n = 394) or per usual care control (often morning use; n = 382).

The primary outcome was the first occurrence of all-cause death or hospitalization or emergency department visit for stroke, acute coronary syndrome, or heart failure. Secondary outcomes included all-cause unplanned hospitalizations or emergency department visits, falls and fractures, decubitus ulcers, and worsening cognition or behavioral problems.

Participants were followed up until February 29, 2024, with a median follow-up of 415 days (IQR, 251 – 735). The team analyzed the data from March to August 2024.

Among primary outcome events, 91.6% were deaths. The team found no difference for bedtime vs usual care administration in a modified intention-to-treat analysis (29.4 vs 31.5 events per 100 patient-years; adjusted hazard ratio [aHR], 0.88; 95% confidence interval [CI], 0.71-1.11; P = .28). Outcomes of falls and fractures, decubitus ulcers, and worsening cognition or behavioral problems also showed no difference in patients taking hypertensive medications at bedtime vs morning.

The only outcome that showed a difference in administration time was all-cause unplanned hospitalizations and emergency department visits, which favored bedtime (22.6 vs 30.0 events per 100 patient-years; aHR, 0.74; 95% CI, 0.57-0.96; P = .02)

“These findings suggest that for frail older adults, administration time likely has little influence on the benefits and risks of antihypertensive medications,” investigators wrote.1

References

1. Garrison SR, Youngson ERE, Perry DA, et al. Bedtime vs Morning Antihypertensive Medications in Frail Older Adults: The BedMed-Frail Randomized Clinical Trial. JAMA Netw Open. 2025;8(5):e2513812. doi:10.1001/jamanetworkopen.2025.13812.

2. Hermida RC, Ayala DE, Mojón A, Fernández JR. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010;27(8):1629-1651. doi:10.3109/07420528.2010.510230

3. Hermida RC, Crespo JJ, Domínguez-Sardiña M, et al; Hygia Project Investigators. Bedtime hypertension treatment improves cardiovascular risk reduction: the hygia chronotherapy trial. Eur Heart J. 2020;41(48):4565-4576. doi:10.1093/eurheartj/ehz754

4. Mackenzie IS, Rogers A, Poulter NR, et al; TIME Study Group. 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. Lancet. 2022;400(10361):1417-1425. doi:10.1016/S0140-6736(22)01786-X

5. de la Sierra A, Ruilope LM, Martínez-Camblor P, et al. Impact of timing of antihypertensive treatment on mortality: an observational study from the Spanish Ambulatory Blood Pressure Monitoring Registry. J Hypertens. 2024;42(2):260-266. doi:10.1097/HJH.0000000000003581