Bedtime Dosing of Antihypertensive Medications Improves Nocturnal Blood Pressure: A Meta-Analysis of Randomized Trials

Objective: To determine whether bedtime administration of antihypertensive medication provides superior ambulatory blood pressure (BP) control and improved clinical outcomes compared to morning dosing.Design and method: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing bedtime versus morning dosing in hypertensive adults. Primary outcomes were changes in ambulatory BP parameters. Results: Sixty-nine RCTs were included. In the overall population, evening dosing provided significantly greater reductions in 24-hour (SBP WMD: 2.06 mmHg; DBP WMD: 0.69 mmHg), daytime (SBP WMD: 0.99 mmHg; DBP WMD: 0.68 mmHg), and nighttime BP (SBP WMD: 4.87 mmHg; DBP WMD: 2.80 mmHg) compared to morning dosing. In non-dipper patients, evening dosing significantly improved only nighttime BP (SBP WMD: 7.57 mmHg; DBP WMD: 3.77 mmHg). For clinical events, evening dosing was associated with significantly lower risks of all-cause mortality (OR=1.50), cardiovascular mortality (OR=2.32) and MACE (OR=1.72). Subgroup analyses revealed that the BP-lowering efficacy of evening dosing was significantly influenced by the type of ambulatory BP monitoring device used, with attenuated effects observed in studies utilizing a unified model. Furthermore, a higher baseline prevalence of non-dipper status was a key modifier, associated with a markedly greater reduction in nighttime BP with evening dosing. Conclusions: Evening dosing provides superior ambulatory BP control, particularly for nighttime BP in non-dippers, and is associated with reduced cardiovascular risk. The effect is modified by technical factors and patient characteristics, highlighting the importance of personalized therapy.