Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial

TLDR

Bedtime administration of antihypertensive medication may enhance nocturnal blood‑pressure dipping and lower cardiovascular risk. The Hygia Chronotherapy Trial evaluated whether taking all antihypertensive drugs at bedtime, instead of upon awakening, reduces cardiovascular disease risk in hypertensive patients. In this multicentre, prospective study, 19,084 adults were randomized 1:1 to bedtime or morning dosing and underwent 48‑hour ambulatory blood‑pressure monitoring at baseline and annually over a median 6.3‑year follow‑up. Bedtime dosing reduced the hazard of major cardiovascular events by 45% (HR 0.55, 95% CI 0.50–0.61) and improved nocturnal blood‑pressure control, leading to markedly lower rates of CVD death, myocardial infarction, revascularization, heart failure, and stroke.

Abstract

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.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)].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.ClinicalTrials.gov, number NCT00741585.