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June 8, 2020, Editor's Note: This study is under investigation by the editor of the journal in which it was published due to inconsistencies in the data noted by others. Caution is warranted regarding applying these findings to clinical care.

Am Fam Physician. 2020;101(7):434-435

Clinical Question

Does bedtime ingestion instead of morning ingestion of hypertension medications produce better cardiovascular disease risk reduction in adults with hypertension?

Bottom Line

This study found a significant reduction in mortality and morbidity among patients who took their once-daily anti-hypertensive medications at bedtime instead of in the morning. No significant difference occurred in compliance rates between bedtime and morning ingestion times. Individual experiences may differ in clinical practice. (Level of Evidence = 1b−)


The investigators identified 19,168 adults, 18 years or older, who met standard criteria for hypertension that required prescription treatment to lower blood pressure (BP). The study participants randomly received (uncertain concealment) assignment to the intervention group or to the control group. The intervention group was told to ingest the entire daily dose of one or more prescribed BP-lowering medications at bedtime. The control group was told to ingest the entire daily dose upon waking. Clinicians provided care without restriction of choice of BP-lowering medication approved for once-daily dosing (e.g., angiotensin receptor blocker, angiotensin-converting enzyme inhibitor, calcium channel blocker, beta blocker, diuretic). Statins, aspirin, and diabetes mellitus medications were also prescribed as needed and ingested as recommended. Individuals masked to treatment group assignment assessed outcomes, including the primary composite outcome of myocardial infarction, coronary revascularization, heart failure, stroke, and cardiovascular disease death. Complete follow-up occurred for more than 99% of participants at a median of 6.3 years.

Using intention-to-treat analysis, significantly fewer patients in the bedtime group experienced the primary cardiovascular disease outcome (n = 1,752 total) compared with the morning group (adjusted hazard ratio = 0.55; 95% CI, 0.50 to 0.61; number needed to treat = 20.3; 95% CI, 17.4 to 24.3). Adverse events occurred similarly in both groups. Poor adherence was similarly reported at any visit during follow-up in both groups (approximately 3%).

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Allocation: Uncertain

Setting: Outpatient (primary care)

Reference: Hermida RC, Crespo JJ, Domínguez-Sardiña M, et al.; Hygia Project Investigators. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial [published online October 22, 2019]. Eur Heart J.

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