Phenotype-Dependent Effect of Bedtime Antihypertensive Dosing on Nocturnal Blood Pressure: A Meta-Analysis Guided by...

Bedtime dosing of antihypertensive medications is associated with a reduction in nocturnal blood pressure (BP), but whether this effect is modified at the study level remains uncertain. We conducted an updated meta-analysis of randomized controlled trials comparing bedtime versus morning antihypertensive administration, evaluating the overall treatment effect and its potential modification by baseline non-dipper prevalence. PubMed, EMBASE, and the Cochrane Library were searched, with nighttime ambulatory systolic BP (SBP) and diastolic BP (DBP) as primary outcomes. Subgroup analyses were performed based on baseline non-dipper proportion (< 60% vs. ≥ 60%). Sixty-six RCTs involving 29,654 participants were included. In the overall hypertensive population, bedtime dosing significantly reduced nighttime SBP (WMD: 4.87 mmHg; 95% CI: 3.75-6.00) and DBP (WMD: 2.80 mmHg; 95% CI: 2.23-3.37), with modest reductions in 24 h SBP (WMD: 2.06 mmHg) and daytime SBP (WMD: 0.99 mmHg). In trials restricted to non-dippers, a more pronounced reduction in nighttime BP was observed (SBP WMD: 7.57 mmHg; DBP WMD: 3.77 mmHg). Similarly, study populations with a higher baseline proportion of non-dippers (≥ 60%) experienced approximately two-fold higher nighttime SBP reductions versus those with lower prevalence (< 60%) (WMD: ∼9.7 vs. 4.4 mmHg; p < 0.01), with a consistent pattern for nighttime DBP (5.1 vs. 2.6 mmHg; between-group p < 0.05). Bedtime antihypertensive dosing reduces nocturnal BP across the general hypertensive population; however, the magnitude of effect appears to be modified at the study level by baseline non-dipper prevalence. These findings suggest that chronotherapy effects are heterogeneous across trial populations rather than uniform across all hypertensive individuals.