Bedtime vs. morning aspirin intake on the diurnal variability of blood pressure and platelet aggregation for the prevention of coronary artery diseases: a systematic review and meta-analysis

Low-dose aspirin had been widely used for secondary prevention of cardiovascular disease. Chronopharmacology of arterial hypertension and platelet aggregation impacts the long-term thromboembolic risk in patients with cardiovascular disease. Therefore, clinical studies have proposed optimising aspirin dosing time. Therefore, the aim of this study is to investigate the effect of timing of administration of low dose aspirin on the mean blood pressure profile and platelet aggregation for primary and secondary prevention of cardiovascular disease. The literature search included PubMed, Scopus, Web of Science, and Cochrane CENTRAL. The identification of included randomised controlled trials (RCTs) followed a systematic literature review (SLR) in accordance with the guidelines and recommendations of The Cochrane Collaboration. RCTs on the effect of aspirin intake at different times of the day on blood pressure and platelet aggregation in adults with coronary arterial disease or arterial hypertension for primary or secondary prevention were included. Meta-analysis included 11 RCTs out of 6495 studies. In terms of patients' characteristics, the overall mean age was 52.7, and 65% of the patients were men. The pooled mean differences of systolic and diastolic blood pressure were significant in the bedtime group in 'prehypertension and untreated hypertension' subgroup (MD = -8.20, 95% CI [-9.80, -6.61], MD = -4.02, 95% CI [-5.94, -2.11]; respectively) while no significant difference was seen in the 'treated hypertension and CVD' subgroup in both SBP and DBP (MD = -0.08, 95% CI [-2.65, 2.5], MD = -0.46, 95% CI [-2.20, 1.28]; respectively). The included studies demonstrating the effect of bedtime aspirin on platelet aggregation showed a significant reduction in platelet aggregation favouring the bedtime group with a mean difference of -21.15, 95% Cl [-32.78, -9.53]. The study shows an additional antihypertensive benefit of bedtime aspirin intake in the prehypertension and untreated hypertension groups, which may provide a positive long-term impact on cardiovascular risk in hypertensive patients. Moreover, the study revealed an additional benefit of bedtime aspirin intake on platelet aggregation, particularly in the morning hours when most thromboembolic events were found to occur.