Evening versus morning administration of drug therapy for hypertension: A meta-analysis of randomized controlled trials

Studies have suggested that different administration times may lead to different antihypertensive effects. This systematic review was designed to evaluate the effectiveness of evening versus morning drug administration for hypertension. Eight databases were searched to identify randomized controlled trials (RCTs) from database inception to August 2021. The RCTs compared the effects of evening and morning dosing on cardiovascular disease events, adverse events and reduction of blood pressure (BP) in hypertensive. Two reviewers independently extracted data and assessed trial quality. Meta-analysis was performed using Stata 12.0 software. A total of 36 RCTs were included and analysed. The results showed that, compared with the morning administration, evening administration of hypertensives could decrease cardiovascular disease events (risk ratio=0.39, 95% confidence interval (CI)=0.25 to 0.60), 24 h/48 h mean systolic BP (SBP) (mean differences (MD) =-3.39, 95% CI=-4.57 to -2.22), 24 h/48 h mean diastolic BP (DBP) (MD=-1.12, 95% CI=-1.70 to -0.53), nocturnal mean SBP (MD=-6.70, 95% CI=-8.35 to -5.05) and nocturnal mean DBP (MD=-3.54, 95% CI= -4.46 to -2.63), while diurnal mean SBP (MD=-0.53, 95% CI=-1.72 to 0.65) and diurnal mean DBP (MD=-0.31, 95% CI=-1.04– 0.42) showed no difference between two groups. This meta-analysis indicated that evening administration was superior to morning administration in reducing asleep BP and the risk of cardiovascular disease events, especially for patients with essential hypertension, patients with renal hypertension and the non-dipper hypertensive patients. More evidence is needed to support this conclusion.