Chronotherapy for Hypertension: A Meta-Analysis and Systematic Review of RCTs

The aim of this study was to evaluate the efficacy of chronotherapy for patients with essential hypertension with a range of clinical characteristics.

We searched the PubMed, EMBASE, and Cochrane Library databases for randomized controlled trials of antihypertensive therapies in which patients were randomized to morning or evening administration. The primary outcomes of the included studies were ambulatory blood pressure (BP) parameters and patient characteristics, including age, body mass index, percentage of female participants, and drug ingestion, which were described in subgroup analyses.

In total, 56 studies were included in the analyses. Meta-analyses and subgroup analyses revealed that specific populations of patients benefited more from bedtime dosing than from morning dosing in both 24-h or 48-h ambulatory systolic BP (SBP) and nighttime SBP, including (1) groups aged < 60 years, (2) those with body mass index ≥ 30 kg/m², (3) studies with ≥ 50% female participants, and (4) patients receiving antihypertensive calcium channel blockers. However, when controversial data by Hermida et al. were omitted, the effects of BP controls were observed in patients with overweight, particularly obesity. Furthermore, calcium channel blockers contributed to an obvious reduction in nighttime SBP with chronotherapy.

Chronotherapy for hypertension may not be completely ineffective, and the clinical program and timing of medication administration can be selected according to the patient's clinical characteristics. Registration PROSPERO identifier number CRD42021292795.