Two New Studies: No Cardiovascular Advantage for Bedtime Dosing of Once-Daily Blood Pressure Medications

In 2023 hypertension played a role in nearly 664,500 deaths in the United States, including cardiovascular events (such as heart attack and stroke).[1] Therefore, controlling hypertension through healthy lifestyle modifications and, if necessary, use of blood pressure-lowering (antihypertensive) medications is critical to reducing the risk of cardiovascular complications.

Patients with hypertension usually are advised to take their once-daily antihypertensive medications in the morning (morning dosing), as was done in the clinical trials that supported the approval of these drugs. In recent years, however, this practice has been challenged by advocates for bedtime dosing, who argue that taking these medications before bed would ensure that blood pressure dips at night, which may offer additional cardiovascular-protection benefits.[2]

In the May 2023 issue of Worst Pills, Best Pills News, we discussed the findings of the TIME clinical trial,[3] which showed no greater benefit of evening dosing over morning dosing of once-daily antihypertensive medications in terms of major cardiovascular outcomes.[4]

Two new related open-label, randomized clinical trials also demonstrated no additional benefit for bedtime dosing of once-daily antihypertensive medications in terms of reducing the risk of major cardiovascular events or decreasing safety outcomes.[5],[6] These new findings lend support to the results of the TIME study and indicate that the time of taking blood pressure medications does not matter as much as the consistency in taking these medications.

Called BedMed and BedMed Frail, the new trials were publicly funded, in part, by the Canadian Institutes of Health Research. The first trial was larger, focused on primary-care patients, and published in JAMA in June 2025. The second trial was limited to elderly nursing home residents and was published in May 2025 in JAMA Network Open.

The BedMed trial

The main BedMed trial enrolled 3,357 Canadian adult primary-care participants with hypertension who were taking at least one of any type of once-daily antihypertensive medication (including diuretics); 54% were taking a single medication. The mean age of these participants was 67 years, and 56% of them were women. The trial did not include any participants with glaucoma or sleep-disrupting shift work. The trial staff randomized 1,677 participants to take all their once-daily antihypertensive medications at bedtime and the remaining 1,680 participants to take their medications upon waking.

After a median follow-up of 4.6 years, participants in both groups had similar rates of death or major cardiovascular events (hospitalization or emergency-department visit for stroke, acute coronary syndrome or heart failure), estimated at 2.3 and 2.4 events per 100 patient-years in the bedtime- and morning-dosing groups, respectively.

Furthermore, the two groups did not differ on the safety outcomes, which included falls or fractures and diagnosis of glaucoma or cognitive decline at 18 months of follow-up.

The BedMed Frail trial

The second trial involved a cohort of 776 Canadian nursing home residents with hypertension who were taking at least one once-daily antihypertensive medication. The median age across the cohort was 88 years, and 86% of the participants had some degree of dementia. Morning dosing was the usual care in the nursing homes of the participants; therefore 394 participants were randomized to bedtime dosing and the remaining 382 participants continued with their morning dosing. The trial had a similar design to the larger BedMed trial except that its median follow-up was only 415 days (1.1 years).

Like the main trial, the BedMed Frail trial did not find any additional cardiovascular benefit for the nighttime dosage. Specifically, the rate for the primary outcome of death or major adverse cardiovascular events was not statistically significant between participants in the two groups: 29.4 and 31.5 events per 100 patient-years in the bedtime- and morning-dosing groups, respectively.

Furthermore, there were no differences between participants in both groups on safety outcomes: falls or fractures, decubitus ulcers, and worsening cognition or behavioral problems.

What You Can Do

If you take antihypertensive drugs and have glaucoma, do not take these drugs at bedtime; doing so can drop blood pressure too low during sleep, which may cause damage to the optic nerve in the eyes. Otherwise, discuss with your clinician the best time to take your drugs knowing that current evidence shows that morning and evening/bedtime administration of once-daily antihypertensive medications likely will not impact your cardiovascular outcomes. What matters most is to take your medications regularly at a convenient time for you that is best for your schedule and would minimize any adverse effects, if applicable. Do not stop any of your medications without consulting your clinician first.

It also is important to rely on healthy lifestyle modifications as a first-line approach for managing hypertension. These modifications include abstaining from smoking, avoiding or at least limiting alcohol consumption, avoiding long-term stress, consuming a healthy diet (particularly the Dietary Approaches to Stop Hypertension [DASH] diet or the Mediterranean diet), increasing potassium intake from foods (such as beet greens and Swiss chard)[7] and reducing sodium intake, losing extra weight, engaging in at least 30 minutes of moderate physical activity (such as cycling, dancing, jogging, swimming or walking) every day and getting enough quality sleep at night.[8]
 

References

[1] Centers for Disease Control and Prevention. High blood pressure facts. January 28, 2025. https://www.cdc.gov/high-blood-pressure/data-research/facts-stats/index.html. Accessed October 6, 2025.

[2] Li H, Sun R, Li Y, et al. Controversies in hypertension therapy: bedtime dosing or daytime dosing? J Hypertens. 2025;43(7):1126-1135.

[3] 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. Lancet. 2022;400(10361):1417-1425.

[4] Timing of once-daily blood pressure medications does not influence cardiovascular outcomes, study finds. Worst Pills, Best Pills News. May 2023. https://www.worstpills.org/newsletters/view/1534. Accessed October 6, 2025.

[5] Garrison SR, Bakal JA, Kolber MR, et al. Antihypertensive medication timing and cardiovascular events and death: The BedMed randomized clinical trial. JAMA. 2025;333(23):2061-2072.

[6] 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.

[7] Potassium: An essential but often overlooked nutrient. Worst Pills, Best Pills News. November 2021. https://www.worstpills.org/newsletters/view/1430. Accessed October 6, 2025.

[8] Mayo Clinic Staff. 10 ways to control high blood pressure without medication. July 12, 2022. https://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/high-blood-pressure/art-20046974. Accessed October 6, 2025.