PP.35.28

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Objective: Many prospective trials have documented the safety and effects on the 24 h blood pressure (BP) pattern of several classes of hypertension medications are greatly improved when ingested at bedtime rather than upon awakening. Recent findings further indicate reduction of asleep BP by bedtime hypertension treatment significantly reduces the risk of cardiovascular events. We evaluated the potential differential administration-time-dependent effects on the risk of chronic kidney disease (CKD) of the various classes of hypertension 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. 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). Patients in the bedtime-treatment regimen evidenced a significantly lower risk of CKD than those ingesting all medications upon awakening, independent of class. Greater benefits were observed for bedtime compared to awakening treatment with ACEIs (adjusted hazard ratio: 0.20 [95%CI: 0.10–0.38]; P < 0.001) and ARBs (0.47 [0.32–0.69], P < 0.001). There were no differences in the risk of CKD between the six classes of tested medications in patients randomized to ingest them upon awakening. Treatment at bedtime with ACEIs, however, was associated with significantly lower hazard ratio of new-onset CKD than ingestion of other classes of medications also at bedtime. Conclusions: Bedtime hypertension treatment significantly reduces the risk of developing CKD compared to conventional morning dosing independent of the class of BP-lowering medication used for treatment. There is no advantage of any particular class of medication when ingested upon awakening. Renin-angiotensin blockade, however, is significantly superior to any other BP-lowering strategy for reducing the risk of CKD when the medications are dosed at bedtime.