AIMS: The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction.
METHODS AND RESULTS: In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of =1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio-adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event-of the primary CVD outcome [0.55 (95% CI 0.50-0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34-0.56)], myocardial infarction [0.66 (0.52-0.84)], coronary revascularization [0.60 (0.47-0.75)], heart failure [0.58 (0.49-0.70)], and stroke [0.51 (0.41-0.63)].
CONCLUSION: Routine ingestion by hypertensive patients of =1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.
TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00741585.
|Family Medicine (FM)/General Practice (GP)|
|General Internal Medicine-Primary Care(US)|
I actually already read (and liked) this article! Dr William White discussed this concept years ago at a symposium. It makes physiologic sense.
Patients in this trial are similar to patients seen by many primary care practitioners and closely resemble clinical practice. The trial supports a change in taking anti-hypertensive medications at bedtime.
A large and well done practice-changing study that will affect management of a very common condition.
A large study with compelling results but would like to see this reproduced in US.
The clinical issue is one of importance to all primary care practitioners. HTN is one of the commonest primary care problems, and the "treatment" here - telling patients to take their medicine at night instead of in the morning - is so easy to be trivial. And the reported benefits are huge - RR of 0.58! - and come at no cost, not even increased postural hypotension, or, I guess, the inconvenience of having to get up at night to urinate (in a population in whom almost 50% of the patients are on a diuretic). It sounds too good to be true, which usually makes me think it may not be true. I would zero in on the adjustments they made in the outcomes analysis. Why does a trial that randomizes 20,000 people need to be adjusted for baseline differences between groups? I thought that was the goal of the randomization. At any rate, this is one trial I would need to see repeated before I made wholesale changes in how I prescribed these drugs.
Amazing results from a cost-free intervention and no apparent downside.