PP.35.29

Abstract

Objective: In hypertension, ingesting blood pressure (BP)-lowering medications at bedtime, compared to ingesting them upon awakening, is associated with significant improved reduction of sleep-time BP mean, a sensitive prognostic marker of cardiovascular disease (CVD) risk, also identified as a predictor of the risk of developing chronic kidney disease (CKD). This randomized trial investigated if bedtime therapy with the entire daily dose of at least one hypertension medication exerts greater reduction in the risk for developing CKD than morning-time therapy with all medications. Design and method: We conducted a prospective, randomized, open-label, blinded endpoint trial on 2078 hypertensive patients without CKD, 1017 men/1061 women, 53.6 ± 13.7 years of age. Patients were randomized to ingest all their prescribed hypertension medications upon awakening or the entire daily dose of at least one of them at bedtime. At baseline and annually (or more frequently if hypertension treatment was adjusted based on ambulatory BP) thereafter, BP and physical activity (wrist actigraphy) were simultaneously monitored for 48 h to accurately derive the awake and asleep BP means. Results: During a 5.9-year median follow-up, 368 patients developed CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2, albuminuria, or both, at least twice within 3 months). Participants ingesting at least one BP-lowering medications at bedtime showed a significantly lower hazard ratio (HR) of new-onset CKD (adjusted by the significant influential characteristics of age, waist perimeter, diabetes, sleep-time systolic BP mean, and sleep-time relative systolic BP decline) than those ingesting all medications upon awakening (0.28 [95%CI: 0.22–0.36]; event-rate 8.3 vs. 27.1%; P < 0.001). There was an even further benefit in preventing CKD among patients ingesting not just one but all BP-lowering medications at bedtime (event-rate 3.8 vs. 13.5% in patients ingesting medications both upon awakening and at bedtime; P < 0.001). Conclusions: In hypertensive patients without CKD, ingestion of at least one, preferably all, BP-lowering medication at bedtime, compared to ingestion of all medications upon-awakening, resulted in improved ambulatory BP control (significant further reduction of asleep BP and enhanced sleep-time relative BP decline) and markedly reduced prevalence of new-onset CKD.