The effect of bedtime versus morning dosing of antihypertensive drugs on the cardiovascular outcomes: a systematic review and meta-analysis of randomized controlled trials

Background and objective:Antihypertensive drugs are one of the most effective strategies to prevent disability and mortality; however, there have been contradictory findings about the best dosing time for antihypertensive drugs. Therefore, we aim to evaluate the effect of bedtime versus morning dosing of antihypertensive drugs on cardiovascular outcomes.Methods:We synthesized randomized controlled studies (RCTs) from the Web of Science, SCOPUS, EMBASE, PubMed, and CENTRAL until 13 October 2022. The risk ratio (RR) for dichotomous outcomes with the corresponding 95% confidence interval (CI) was used. The study protocol was registered in PROSPERO with ID: CRD42022368612.Results:Five RCTs with 59 200 participants were included. Bedtime dosing was significantly associated with less incidence of myocardial infarction (MI) [RR: 0.80 with 95% CI (0.70-0.91), P = 0.0007] compared with morning dosing; however, there was no statistically significant difference between bedtime and morning dosing, regarding all-cause mortality [RR: 0.77 with 95% CI (0.51-1.16), P = 0.21], cardiovascular mortality [RR: 0.65 with 95% CI (0.35-1.21), P = 0.17], major adverse cardiac events (MACE) [RR: 0.79 with 95% CI (0.56-1.10), P = 0.16], heart failure [RR: 0.68 with 95% CI (0.42-1.09), P = 0.11], cerebrovascular accidents [RR: 0.80 with 95% CI (0.53-1.22), P = 0.30], coronary revascularization [RR: 0.79 with 95% CI (0.50-1.24), P = 0.30}, and angina [RR: 0.91 with 95% CI (0.55-1.50), P = 0.70].Conclusion:Evidence about the comparative efficacy of bedtime versus morning dosing of antihypertensives is still uncertain. However, bedtime dosing significantly reduced MI, which warrants more robust RCTs to validate.