Chronotherapy in Hypertension: A Systematic Review and Meta-Analysis Comparing Asian and Non-Asian Populations on the Effects of Antihypertensive Dosing Time, Ambulatory Blood Pressure and Cardiovascular Outcomes

Abstract

Background: Hypertension is a major global health burden and a leading cause of cardiovascular morbidity and mortality. Despite effective antihypertensive therapies, optimal blood pressure (BP) control remains inadequate worldwide (Kario et al., 2019). Circadian variations influence BP, and insufficient nocturnal decline (“nondipping”) increases cardiovascular risk. Chronotherapy, the timed administration of antihypertensive medication, may enhance 24-hour BP control and clinical outcomes. Objective: To evaluate the effects of morning versus bedtime antihypertensive medication dosing on ambulatory BP parameters and major adverse cardiovascular events (MACE). Methods: A systematic literature search was conducted in PubMed, Google Scholar, HERDIN, and Cochrane Library, yielding 1,246 records. After duplicate removal and relevance screening, 86 full-text articles were assessed for eligibility. Seventy-one studies were excluded mainly for non-randomized designs, incomplete data, or absence of direct comparison between bedtime and morning dosing. Ultimately, 11 randomized controlled trials (RCTs) fulfilled the inclusion criteria and were included in the meta-analysis. Results: Bedtime dosing resulted in significantly greater reductions in 24-hour and nighttime systolic BP (approximately 2–3 mmHg) than morning dosing. Subgroup analyses showed enhanced BP-lowering effects among Asian populations, potentially reflecting genetic and circadian influences. Conclusion: Bedtime administration of antihypertensive medications is a safe and feasible chronotherapeutic approach that improves nocturnal BP control, especially in patients with nondipping or nocturnal hypertension. Although major cardiovascular benefits remain unconfirmed, this strategy supports personalized hypertension management and warrants validation in larger outcome trials.