Abstract 4366587: Chronotherapy in Hypertension: A Meta-Analysis of the Cardiovascular Effects of Bedtime Versus Morning Antihypertensive Administration

Abstract

Introduction/Background: With the prevalence of cardiovascular comorbidities in the current era, anti-hypertensive therapy has become a mainstay in clinical practice. However, the optimal timing for the dosage of antihypertensive medication remains a subject of ongoing debate and research. Research Questions/Hypothesis: This meta-analysis evaluates whether the bedtime dosing of antihypertensive medication improves cardiovascular outcomes compared to morning dosing. Methods/Approach: We conducted an extensive literature search across three databases (PubMed, Cochrane, and ScienceDirect) to compile relevant trials published till May 2025. All statistical analyses have been done using RevMan. Dichotomous outcomes were summarized as risk ratios (RRs) with 95% confidence intervals (CIs), estimated using the Cochran–Mantel–Haenszel method. Furthermore, the random effects model was applied to account for inter-study heterogeneity. Results/Data: Seven randomized-controlled trials involving a total of 63,333 patients were included. Subgroup analysis showed reductions in cardiovascular outcomes associated with bedtime dosing, primarily driven by trials under the Hermida subgroup. Contrarily, large-scale trials under the non-Hermida subgroup reported no significant difference between bedtime and morning administration, resulting in substantial heterogeneity between subgroups. Our pooled analysis exhibits no statistically significant variation between bedtime and morning dosing in myocardial infarction (RR: 0.86; 95% CI: 0.71–1.04), heart failure (RR: 0.72; 95% CI: 0.50–1.06), stroke (RR: 0.78; 95% CI: 0.55–1.11), major adverse cardiovascular events (RR: 0.84; 95% CI: 0.65–1.11), or all-cause mortality (RR: 0.82; 95% CI: 0.61–1.09). Conclusion: The overall evidence suggests that the timing of antihypertensive medication has no consequential impact on improving major adverse cardiovascular outcomes and all-cause mortality, and hence, bedtime dosing does not confer any consistent clinical advantages over morning administration. These findings underscore the importance of personalized treatment approaches and advocate for a more patient-centered treatment model, rather than uniform medication timing strategies.