Timing of Antihypertensive Medication Yields No Benefit in Older Adults With Frailty

Hypertension is highly prevalent in older adults, with estimates indicating that more than 70% of individuals aged 65 and older are affected. Although lowering blood pressure (BP) is a cornerstone of cardiovascular risk reduction, the optimal timing of antihypertensive medication remains an area of clinical debate. Some researchers have hypothesized that evening dosing may better align with circadian patterns of BP regulation, thereby reducing early-morning surges in cardiovascular events.³

Morning and bedtime dosage of Antihypertensive medication has no benefit.| Image credit: HBS | stock.adobe.com

To investigate this further, the BedMed-Frail trial was designed as a pragmatic, open-label randomized clinical trial. Published in JAMA Network Open, the study included 305 patients aged 70 years and older who were classified as frail using a validated electronic frailty index. Participants were recruited from 110 UK based primary care practices and were already taking at least 1 antihypertensive medication.¹

Subjects were randomly assigned to either continue their usual morning dosing or switch to evening administration. The trial’s pragmatic design allowed participants to use their existing medications without alteration, providing a more realistic representation of how patients manage therapy outside of controlled environments. Median follow-up time was approximately 2 years.¹

Findings

The primary outcome was a composite of all-cause mortality or hospitalization for myocardial infarction, stroke, or vascular death. This occurred in 24% of both the morning and bedtime dosing groups, yielding a hazard ratio of 1.00 (95% CI, 0.65-1.52). These findings suggest that bedtime dosing of antihypertensives offered no added cardiovascular benefit in this population.¹

Secondary outcomes, including self-reported falls, dizziness, and hypotensive episodes, also showed no significant differences. However, there was a slight numerical increase in falls in the bedtime group, raising concerns about the potential for nighttime hypotension.

It is important to note that adherence to therapy was high in both groups, indicating that lack of compliance was not a confounding factor.¹ These results stand in contrast to the widely publicized Hygia Chronotherapy Trial, which reported substantial cardiovascular benefits from bedtime dosing. However, the Hygia trial has come under scrutiny for its methodological limitations and potential biases, which may limit its generalizability.²

Clinical Implications

The results of BedMed-Frail have important implications for the care of older adults with hypertension, particularly those with frailty. Chronotherapy—the strategic timing of medication administration to align with biological rhythms—has been a growing area of interest. However, the utility of this approach appears to depend heavily on the population in question.¹

Adults with frailty are especially vulnerable to adverse effects such as nocturnal hypotension, imbalance, and falls. These adverse events can significantly impact quality of life and lead to hospitalization or long-term care placement.¹ For this reason, the theoretical benefits of evening dosing may be outweighed by safety concerns in this group.

Furthermore, this study highlights the value of including real-world geriatric patients in clinical research. Individuals with frailty are frequently excluded from randomized trials, yet they comprise a large and growing segment of the hypertensive population. Data from trials like BedMed-Frail offer much-needed guidance for clinicians working in primary care, geriatrics, and internal medicine.¹

Conclusion

The BedMed-Frail trial offers robust evidence that the timing of antihypertensive medications—morning versus bedtime—does not affect major cardiovascular outcomes in older adults with frailty.¹ This finding supports existing practices and encourages clinicians to prioritize safety and simplicity over theoretical benefits when treating this population.³

Although chronotherapy may still have a role in younger or more robust patients, it does not appear to offer meaningful advantages in those with frailty.¹ Future research should continue to explore how individualized treatment plans can optimize care for complex and aging patient populations, but for now, morning dosing remains a safe and effective default.

References

1. Garrison SR, Youngson ERE, Perry DA, et al. Bedtime vs morning antihypertensive medications in frail older adults. JAMA Network Open. 2025;8(5):e2513812. doi:10.1001/jamanetworkopen.2025.13812

2. Hermida RC, Crespo JJ, Domínguez-Sardiña M, et al. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. Eur Heart J. 2019;41(48):ehz754. doi:10.1093/eurheartj/ehz75‌4

3. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71(6):1269-1324. doi:10.1161/hyp.0000000000000066