Abstract 4366476: Chronotherapy in Hypertension: A Meta-analysis on Comparative Effectiveness of Evening Versus Morning Dosing on Systolic Blood Pressure Control

Abstract

Background: Blood pressure follows a circadian pattern, typically dipping at night and rising in the early morning. The timing of antihypertensive medication administration—known as chronotherapy—may influence blood pressure control and cardiovascular outcomes. Objectives: To compare the effects of evening versus morning dosing of antihypertensives on systolic blood pressure control. Methods: A comprehensive literature search was conducted across PubMed, Cochrane, Embase and Scopus between 2010 and May 2025. Randomised controlled trials (RCTs) comparing the evening versus morning dosing were included in the meta-analysis. Results: Thirty-three studies were included in the systematic review, with 12 RCTs (n = 2,350; 1,182 evening dosing, 1,168 morning dosing) being eligible for the meta-analysis. Antihypertensive classes studied included angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs) and beta-blockers. Evening dosing was associated with a statistically significant greater reduction in 24-hour systolic blood pressure (SBP) compared to morning dosing (mean difference: 2.16 mmHg; 95% CI: 0.65 to 3.67; p = 0.009). Subgroup analyses showed that evening dosage led to a statistically non-significant drop in night-time SBP (mean difference: 4.73 mmHg; 95% CI: -6.26 to 15.71; p = 0.21) and morning SBP (mean difference: 5.15 mmHg; 95% CI: -0.50 to 10.80; p = 0.06), favouring evening dosing over the morning one. Safety outcomes were not consistently reported. In some studies, no differences in adverse events or any cardiovascular events were notable. However, some of the trials, such as Hermida et al. (2011), found significantly fewer cardiovascular events with evening dosing (HR 0.33; p < 0.001), while Hermida et al. (2008) noted a reduction in edema incidence. Pigazzani et al. observed fewer hospitalisations for non-fatal myocardial infarction with evening dosing but no significant differences in stroke rates. Conclusion: Despite the heterogeneity, the studies support the clinical relevance of chronotherapy in optimising 24-hour blood pressure control. The results show the potential of evening-time dosing strategies to improve both efficacy and safety in hypertension management. Current evidence is favouring the consideration of evening dosing as a viable and potentially better dosing strategy, yet further larger trials are needed to validate these findings and explore the population-specific effects.