Morning Versus Nighttime Antihypertensive Drug Dosing and Major Cardiovascular Outcomes

Background: The optimal timing of antihypertensive therapy remains uncertain despite recent large randomized trials. We conducted an updated systematic review and meta-analysis to compare morning versus nighttime dosing on cardiovascular outcomes. Methods: We systematically searched PubMed, Embase, and Web of Science for randomized controlled trials enrolling patients with hypertension assigned to morning or nighttime dosing. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models, and heterogeneity was assessed using the I 2 statistic. Sensitivity analyses were performed using a leave-one-out approach. Results: Five randomized controlled trials including 42,075 participants were analyzed. No significant differences were observed between morning and nighttime dosing for all-cause mortality (RR 0.99; 95% CI 0.91-1.08; I 2 =0%), myocardial infarction (RR 1.14; 95% CI 0.98-1.33; I 2 =0%), major adverse cardiovascular events (RR 1.04; 95% CI 0.92-1.19; I 2 =0%), or stroke (RR 0.95; 95% CI 0.75-1.20; I 2 =49.9%). Sensitivity analyses confirmed the robustness of these findings, with consistent results across leave-one-out evaluations. Conclusions: Morning and nighttime antihypertensive dosing strategies were associated with similar cardiovascular outcomes. Dosing time was not associated with differences in major cardiovascular events and does not appear to be a key determinant of cardiovascular risk reduction.