Chronotherapy of Hypertension with Angiotensin Receptor Blockers–A Meta-Analysis of Blood Pressure Measured by Ambulatory Blood Pressure Monitoring in Randomized Trials

Background: We performed this meta-analysis evaluating the efficacy of chronotherapy of hypertension with angiotensin receptor blockers (ARBs).Methods: We searched Pubmed, Web of Science, and Cochrane for all published randomized trials that compare antihypertensive effects of ARBs between bedtime dosing and awakening dosing. Blood pressure (BP) was measured by ambulatory BP monitoring in patients with mild or moderate essential hypertension.Results: The effects of ARBs on BP were assessed in 805 essential hypertensive patients included in 8 trials with a follow-up of 12 +/- 3 weeks. The sleep-time systolic and diastolic BP (SBP, DBP) with bedtime dosing greatly decreased as compared with awakening dosing (weighted mean differences [WMD] for SBP WMD -5.23 [95% confidence intervals (CI), -7.27, -3.20] mm Hg, p < 0.001; WMD for DBP -2.94 [95% CI, -4.52, -1.36] mm Hg, p < 0.001). The reduction of daytime SBP (WMD 0.98 [95% CI, -0.20, 2.17] mm Hg, p = 0.10), DBP (WMD 0.11 [95% CI, -0.68, 0.89] mm Hg, p = 0.79), 24 hour SBP (WMD -0.75 [95% CI, -1.93, 0.42] mm Hg, p = 0.21) and DBP (WMD -0. 77 [95% CI, -1.55 0.01] mm Hg, p = 0.05) with bedtime dosing was similar with awakening dosing.Conclusions: Bedtime dosing with ARBs is more effective in lowering sleep-time BP than awakening dosing in patients with essential hypertension, suggesting a utilization of chronotherapy of hypertension with ARBs to reduce sleep-time high BP. Larger multi-ethnic studies are needed to investigate the efficacy of chronotherapy of hypertension.