Abstract Body (Do not enter title and authors here): Background:
The timing of antihypertensive medication may influence cardiovascular outcomes and blood pressure control, yet the evidence remains inconclusive. Hence, we conducted a meta-analysis to compare the effects of bedtime versus morning dosing of antihypertensives on mortality, cardiovascular events, and ambulatory blood pressure.
Methods:
We searched PubMed, Scopus, Web of Science, and CENTRAL for Randomized controlled trials comparing bedtime and morning administration of antihypertensive therapy. We calculated pooled risk ratios (RR) for categorical variables and mean differences (MD) for continuous variables. Analysis was performed using R.4.3.3.
Results:
A pooled analysis of five randomized controlled trials comprising a total of 49,983 patients was conducted. The mean age of the participants was 67 years, and 44.3% were female. Bedtime dose of anti-hypertensive medications resulted in lower incidence of heart failure (1.3% vs. 2.0%; RR 0.63, p = 0.0024) but not myocardial infarction (1.4% vs. 1.6%; RR 0.87, p = 0.3494), stroke or transient ischemic attack (0.9% vs. 1.3%; RR 0.71, p = 0.0852) all-cause mortality (2.6% vs. 3.1%; RR 0.75, p = 0.1047) or cardiovascular mortality (1.0% vs. 1.5%; RR 0.52, p = 0.1286). For blood pressure, bedtime dosing significantly reduced evening systolic blood pressure (MD –4.71 mmHg, p < 0.0001) and diastolic blood pressure (MD –1.66 mmHg, p < 0.0001), with no significant differences observed in morning readings.
Conclusion:
Bedtime administration of antihypertensive medications resulted in a statistically significant reduction in heart failure, although the absolute differences were small. No significant reduction observed in mortality, myocardial infarction, or stroke.