#Grand Rounds

Hygia Chronotherapy Trial Results: Is it Better to Take Blood Pressure Medications at Night?

BACKGROUND AND PURPOSE:

Previous research has demonstrated BP improvement when medications are taken at night rather than during the day
Hermida et al. (European Heart Journal, 2019), sought to evaluate if bedtime medication also impacted cardiovascular disease (CVD) risk

Multicenter, controlled, randomized trial (RCT)
- Hygia Chronotherapy Trial: Network of 40 primary care centers in Northern Spain
Participants with confirmed hypertension diagnosis
- SBP means: Awake ≥135 mmHg | Asleep ≥120 mmHg
- DBP means: Awake ≥85 mmHg | Asleep ≥70 mmHg
- On medications to control BP (ARB, ACEI, CCB, β-blocker, and/or diuretic)
Interventions
- Bedtime dosing: All medications at bedtime
- Daytime dosing: All medications upon awakening
Study design
- Ambulatory blood pressure (ABP) monitoring for 48 h at inclusion and at every scheduled clinic visit
- Hazard ratio (HRs) adjusted to address confounders
Primary outcome
- Major CVD event: CVD death | MI | Coronary revascularization | Heart failure | Stroke)

19,084 hypertensive patients were included | Follow-up 6.3 year median | 1752 participants experienced a major CVD event
- 10,614 men/8470 women | 60.5 ± 13.7 years of age
- Bedtime group: 9552
- Awakening group: 9532
Bedtime group had a lower risk of
- Major CVD event (P<0.001): HR 0.55 (95% CI, 0.50 to 0.61)
- CVD death (P < 0.001): HR 0.44 (95% CI, 0.34 to 0.56)
- Myocardial infarction (P < 0.001): HR 0.66 (95% CI, 0.52–0.84)
- Coronary revascularization (P < 0.001): HR 0.60 (95% CI, 0.47 to 0.75)
- Heart failure (P < 0.001): HR 0.58 (95% CI, 0.49 to 0.70)
- Stroke (P < 0.001): HR 0.51 (95% CI, 0.41–0.63)
There were no differences in adverse events between groups

Patients that took their hypertension medications at bedtime vs upon awakening had not only better BP control, but had lower risk for major CVD events
Limitations of the study include
- Restriction to Caucasians and therefore further studies need to be performed to determine generalizability to other populations
- Clinicians chose medications, although one of the strengths of the study is that results reflect actual practice

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