Effect of dosing time of angiotensin II receptor blockade titrated by self-measured blood pressure recordings on cardiorenal protection in hypertensives: the Japan Morning Surge-Target Organ Protection (J-TOP) study

Abstract

Objectives: To study the impact of the dosing time of an angiotensin II receptor blocker (ARB) titrated by self-measured home blood pressure (HBP) on cardiorenal damage in hypertensives.

Methods: We conducted an open-label multicenter trial, the J-TOP study, that enrolled 450 hypertensives with self-measured systolic HBP more than 135 mmHg. The study patients were stratified into three groups according to the difference between their morning and evening SBPs difference: a morning hypertension group (morning and evening difference at least 15 mmHg; n = 170), a morning and evening hypertension group (0 mmHg < or = morning and evening difference <15 mmHg; n = 198), and an evening hypertension group (morning and evening difference <0 mmHg; n = 82). Individuals were then randomly allocated to receive bedtime dosing or awakening dosing of candesartan (+/- diuretic as needed) titrated to achieve a target systolic HBP less than 135 mmHg. The 6-month change in the urinary albumin/creatinine ratio (UACR) was assessed.

Results: In total patients, the UACR was more markedly reduced in the bedtime-dosing group than in the awakening-dosing group (-45.7 vs. -34.5%, P = 0.02), whereas there were no differences in the reduction of any of the HBPs including the sleep blood pressures (BPs) between the two groups. Among the three subgroups stratified by the morning and evening difference, the difference in the UACR reduction between the bedtime-dosing and awakening-dosing groups was only significant in the morning hypertension group (-50.6 vs. -31.3%, P = 0.02).

Conclusion: In HBP-guided antihypertensive treatment in hypertensives, bedtime dosing of an ARB may be superior to awakening dosing for reducing microalbuminuria.