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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

Kario, Kazuomia; Hoshide, Satoshia; Shimizu, Motohiroa; Yano, Yuichiroa; Eguchi, Kazuoa; Ishikawa, Jojia; Ishikawa, Shizukiyob; Shimada, Kazuyukia

doi: 10.1097/HJH.0b013e3283395267
Original papers: Therapeutic aspects

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 ≤ 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.

aDivision of Cardiovascular Medicine, Department of Medicine, Japan

bDivision of Community and Family Medicine, Jichi Medical School, Tochigi, Japan

Received 1 October, 2009

Revised 11 February, 2010

Accepted 27 February, 2010

Correspondence to Kazuomi Kario, MD, FACC, FACP, FAHA, Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, 3311-1, Yakushiji, Shimotsuke, Tochigi 329-0498, Japan Tel: +81 285 58 7344; fax: +81 285 44 2132; e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.