THE EFFECTS OF OLMESARTAN/AMLODIPINE ADMINISTERED IN THE MORNING OR AT NIGHT ON NOCTURNAL BLOOD PRESSURE IN CHINESE PATIENTS WITH MILD-MODERATE ESSENTIAL HYPERTENSION (OMAN TRIAL)

Abstract

Objective: The clinical evidence of antihypertensive chronotherapy remains controversial. This study aimed to compare the effects of morning and bedtime antihypertensive administration on the nocturnal blood pressure (BP) reduction and the circadian rhythm of hypertensives. Design and method: A randomized, multicenter, open-label clinical trial was conducted in China from March, 2022. Patients aged 18-75, not taking or stopped using antihypertensive drugs for 2 weeks, were recruited. At baseline, all patients received 24-h ambulatory BP measurement (ABPM) and office BP measurement (OBPM), and were randomized to the morning (06:00-10:00 AM, group 1) or the bedtime dosing group (6:00-10:00 PM, group 2). Each patient received one tablet of olmesartan/amlodipine (OA) (20/5 mg) daily for 4 weeks, and then followed up every 4 weeks for 12 weeks. The OA dosage was adjusted based on the ABPM and OBPM. Patients with uncontrolled BP at the first follow-up received an increased dosage to 1.5 tablets, and increased to 2 tablets if BP was uncontrolled after 4 weeks of dosage increase. Results: 700 patients were recruited (mean age 56.54±10.52 years; 45.5% female), with 382 finished the 12-week follow-up and were included in the analysis (follow-ups are continuing). At week 4, the mean BP differences of ABPM and OBPM did not differ significantly between groups. At week 12, compared with group 1, patients in group 2 showed significantly greater reductions from baseline in nighttime systolic BP (SBP) (between-group difference -5.04mmHg, 95% confidence interval (CI): -8.38 to -1.70), and diastolic BP (DBP) (-3.03mmHg, 95% CI -5.08 to -0.97); with better nocturnal SBP control (67.4% vs. 76.7%, P=0.04), and decrease in nocturnal BP load. The proportion of non-dipper or reverse dipper increased from 52.3% to 54.4% in group 1 (P=0.64), and dropped from 57.9% to 45.5% in group 2 (P<0.01). The incidence of nocturnal hypotension (SBP/DBP<100/90mmHg) did not differ. Conclusions: Compared with morning dosing, bedtime dosing can better control nocturnal BP, and improve the circadian rhythm without increasing the risk of nocturnal hypotension. It represents a reasonable strategy to optimize BP control, especially nocturnal BP control.