BP medication timing: Bedtime or daytime, the effect’s the same

For adults with hypertension being treated in the primary care setting, taking their blood pressure (BP)-lowering medications at bedtime is safe but confers no additional cardiovascular protection as opposed to taking them in the morning, according to the results of the BedMed trial.

Bedtime administration of BP-lowering meds did not result in reduced incidence of the composite primary outcome of all-cause death or hospitalization/emergency department (ED) visit for stroke, acute coronary syndrome, or heart failure over a median follow-up of 4.6 years when compared with morning administration (2.3 vs 2.4 per 100 patient-years, respectively; adjusted hazard ratio, 0.96, 95 percent confidence interval [CI], 0.77–1.19; p=0.70). [JAMA 2025;doi:10.1001/jama.2025.4390]

The same was true for all individual components of the primary outcome and for all predefined subgroups, including sex, age, frailty status, polypharmacy, comorbidities, and antihypertensive medication class, among others.

Likewise, results for the safety outcomes did not differ between the bedtime and morning dosing groups. These included the incidence of nonvertebral and hip fractures, falls, new glaucoma diagnosis, and cognitive decline at 18 months, among others.

BP levels not different

Twenty-four-hour ambulatory blood pressure monitoring data collected over a median of 9.6 months into the trial showed no significant differences in mean daytime systolic BP (133.8 vs 136.2 mm Hg; p=0.15) and mean daytime diastolic BP (75.2 vs 75.6 mm Hg; p=0.72) between the bedtime and morning dosing groups.

Meanwhile, overnight mean systolic BP was significantly lower with bedtime vs morning dosing (116.5 vs 123.9 mm Hg; difference, −7.4 mm Hg, 95 percent CI, −11.2 to −3.7; p<0.001), as was overnight mean diastolic BP (62.9 vs 65.5 mm Hg; difference, −2.7 mm Hg, 95 percent CI, −4.9 to −0.4; p=0.02).

Daytime BP control, as defined by the American College of Cardiology/American Heart Association 2017 guidelines (<130/80 mm Hg), was achieved in 41.1 percent of participants in the bedtime dosing group and in 32.5 percent of those in the morning dosing group, with the difference not reaching significance (p=0.12).

Overall, the data showed that antihypertensive medication administration time does not affect the risks and benefits of BP-lowering medication, said the BedMed investigators. When to take the medication should be guided by patient preferences instead, they added.

Conflicting evidence

“Normal BP exhibits circadian modulation, being lower during sleep, and sleep-time BP is a better predictor of adverse cardiovascular events than is BP measured during the day. Conceivably, high BP might convey greater cardiovascular risk at night because daytime and sleep-time metabolic states are different,” the investigators explained.

“Given that antihypertensive medications might preferentially lower overnight BP if administered at bedtime, administration time might influence the degree of cardiovascular risk reduction these medications convey,” they continued.

The potential for improved outcomes with nighttime dosing was supported by two earlier randomized controlled trials, MAPEC and Hygia. These trials indicated significant benefits, including a 61-percent and 45-percent reduction in major adverse cardiovascular events and a 57-percent and 45-percent decrease in all-cause death, respectively, when medication was taken at bedtime. [Chronobiol Int 2010;27:1629-1651; Eur Heart J 2020;41:4565-4576]

However, two other studies—the large randomized trial TIME and the small crossover study HARMONY—produced conflicting results. TIME showed no difference in major cardiovascular outcomes between morning and evening BP medication administration over 4 years. Likewise, HARMONY indicated no significant difference in 24-hour or clinic BP measurements when participants switched between morning and evening dosing. [Lancet 2022;400:1417-1425; Hypertension 2018;72:870-873]

“After the initial dramatic results observed in the MAPEC and Hygia trials, attempts by other research groups to corroborate the initial findings were not able to do so, raising serious questions,” according to Dr Sandra Taler from the Mayo Clinic in Rochester, Minnesota, US, in an accompanying editorial. [JAMA 2025;doi:10.1001/jama.2025.7286]

“The most important finding, that BP medication administration at night did not affect cardiovascular event rates or survival, is clear,” Taler said.

She emphasized that the finding extends to older, frail individuals, in whom nighttime BP medication dosing was thought to be potentially harmful, as lower BP levels could exacerbate other conditions such as glaucoma or orthostatic hypotension. She pointed to the data from the BedMed-Frail trial, which showed that bedtime dosing had no significant effect on death rates, falls, fractures, ulcers, or cognitive issues. [JAMA Netw Open 2025;doi:10.1001/jamanetworkopen.2025.13812]

“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,” Taler said. “Regular dosing and use of long-acting medications should be emphasized and may better address concerns related to BP variability.”

BedMed population

The open-label, pragmatic BedMed trial included 3,357 community-dwelling adult patients with hypertension (median age 67 years, 56.4 percent female) recruited via 436 primary care clinicians across five Canadian provinces. These participants had to be taking at least one once-daily antihypertensive medication (53.7 percent on monotherapy).

Of the participants, 1,677 were randomly assigned to take all once-daily antihypertensive medications at bedtime and 1,680 to take their medications in the morning. At 6 months, 83 percent of once-daily bedtime antihypertensives and 95 percent of once-daily morning antihypertensives were self-reported to be taken as assigned. Adherence to allocation decreased gradually with time, but at 72 months, when at its lowest, one or more once-daily antihypertensive was still taken per allocation by 70 percent of participants in the bedtime dosing group and by 88 percent of those in the morning dosing group.