BACKGROUND AND AIMS: This systematic review and meta-analysis aimed to compare the clinical outcomes of antihypertensive medication administration at bedtime versus morning, focusing on major adverse cardiovascular events (MACE), mortality, and secondary cardiovascular outcomes in hypertensive patients.
METHODS: We conducted a systematic search across multiple databases to identify randomized controlled trials (RCTs) comparing bedtime versus morning antihypertensive dosing. Studies were included if they evaluated MACE, all-cause mortality, or cardiovascular mortality. Myocardial infarction, stroke, and heart failure were considered secondary outcomes. Data were extracted, and statistical analysis was performed using hazard ratios and mean differences with 95% confidence intervals. A random-effects model with Hartung-Knapp correction was used to account for between-study heterogeneity. Sensitivity analyses were conducted to assess the robustness of the results.
RESULTS: Five studies with 36,477 patients (42.30% male) were included. No significant differences were found between bedtime and morning dosing for MACE (HR: 0.71, 95% CI: 0.43-1.15, = 0.11) and mortality outcomes (all-cause HR: 0.76, 95% CI: 0.50-1.16, = 0.14; cardiovascular HR: 0.54, 95% CI: 0.08-3.86, = 0.31). These findings, which showed substantial heterogeneity (I² > 90%), were consistent in sensitivity analyses. Also, for secondary outcomes, there were no significant differences observed in myocardial infarction (HR: 0.79, 95% CI: 0.49-1.29, = 0.26), stroke (HR: 0.61, 95% CI: 0.32-1.17, = 0.10), or heart failure (HR: 0.64, 95% CI: 0.37-1.08, = 0.07). p p p p p p
CONCLUSION: This meta-analysis found no significant difference in cardiovascular outcomes between bedtime and morning antihypertensive dosing. Within the limitations of the available evidence, a universal chronotherapy strategy does not appear to provide additional cardiovascular benefit. Once-daily antihypertensive medications can be taken at a time that aligns with the patient's lifestyle, with adherence being the most critical factor in ensuring treatment effectiveness.
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