Does taking BP medicine at night (vs morning) result in fewer cardiovascular events?

Evidence summary

Recent UK study shows no difference by timing

A 2022 UK prospective, randomized, multicenter trial assigned 21,104 predominantly White adults (58% men) with hypertension to take their usual antihypertensive medication either in the morning (6 am to 10 am) or evening (8 pm to midnight).¹ A computer algorithm randomized patients, but neither the patients nor the investigators were masked to allocation.

All patient baseline characteristics were equivalent between groups. If troubled by nocturia, patients in the evening group taking diuretics were told to take only the diuretic earlier (6 pm) and subsequently to change to morning if they experienced persistent bothersome symptoms. More patients in the evening administration group than in the morning administration group reported having to change the time of day that they took their diuretic (546 [5.2%] vs 71 [0.7%]; P < .0001).

The median follow-up was 5.2 years. Data were collected at regular intervals through patient completion of online questionnaires and researcher analysis of ­National Health Service data on hospitalization and death. The intention-to-treat analysis showed no difference in the primary outcome (a composite of vascular death, nonfatal myocardial infarction, or nonfatal stroke) between the evening and morning administration groups (0.69 events vs 0.72 events per 100 person-years; hazard ratio [HR] = 0.95; 95% CI, 0.83-1.10; P = .53).

The controversial Hygia Project favored evening

Prior to the UK study was the Hygia Chronotherapy Trial, a prospective, controlled, multicenter study conducted within the primary care setting in Spain. Caucasian Spanish adults (N = 19,168; mean age, 61 years; 56% men) with hypertension were randomly assigned to take all prescribed antihypertensive medication either at bedtime or upon waking.²

The Hygia Project initially sought to establish the value of ambulatory blood pressure monitoring (ABPM) compared to office blood pressure (BP) monitoring and to explore the prognostic value of sleeping BP.³ The study objectives evolved over time. The randomization process was not clearly described,^2,3 but multiple randomizations were alluded to. The authors stated that “for any of these chronotherapy trials” randomizations were done separately for “each participating center” and “randomization of participants to treatment-time regimen is done separately for each hypertension medication or combination being tested.”

A 2022 UK multicenter trial found no difference between the evening and morning administration groups in a composite outcome of vascular death, nonfatal myocardial infarction, or nonfatal stroke.

The baseline characteristics of patients in the evening and morning administration groups were similar, but statistically significant differences existed in BMI (29.6 vs 29.7; P = .030) and sleep-time systolic BP percent decline (9.3 vs 9.0; P < .001). Mean baseline 48-hour BP was 132/77 mm Hg. Hypertension was defined as an awake systolic BP ≥ 135 mm Hg or diastolic BP ≥ 85 mm Hg, or asleep systolic BP ≥ 120 mm Hg or diastolic BP ≥ 70 mm Hg. BP readings were confirmed with 48-hour ABPM. Exclusion criteria included pregnancy, a history of substance use disorder, night-shift work, and cardiovascular disease (defined as unstable angina, heart failure, life-threatening arrhythmia, atrial fibrillation, kidney failure, and grade III-IV retinopathy).

Prescribers were free to prescribe medicines from 5 classes (diuretic, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or beta-blocker) as they thought appropriate, were encouraged to use fixed-dose combination pills, and were told not to use split (eg, twice per day) dosing. Annual ­48-hour ABPM was completed, and patients’ electronic health records were analyzed by blinded investigators. Median follow-up was 6.3 years, and only 84 participants failed to complete the minimum 1-year participation requirement.

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