Effect of amlodipine, efonidipine, and trichlormethiazide on home blood pressure and upper-normal microalbuminuria assessed by casual spot urine test in essential hypertensive patients

ABSTRACT

The aim of this study was to assess the effects of irbesartan alone and combined with amlodipine, efonidipine, or trichlormethiazide on blood pressure (BP) and urinary albumin (UA) excretion in hypertensive patients with microalbuminuria (30≤UA/creatinine (Cr) ratio [UACR] <300 mg/g Cr) and upper-normal microalbuminuria (10≤UACR<30 mg/g Cr). This randomized controlled trial enrolled 175 newly diagnosed and untreated hypertensive patients (home systolic blood pressure [SBP]≥135 mmHg; 10≤UACR<300 mg/g Cr of casual spot urine at the first visit to clinic). All patients were treated with irbesartan (week 0). Patients who failed to achieve home SBP ≤125 mmHg on 8-week irbesartan monotherapy (nonresponders, n = 115) were randomized into three additional drug treatment groups: trichlormethiazide (n = 42), efonidipine (n = 39), or amlodipine (n = 34). Irbesartan monotherapy decreased home SBP and first morning urine samples (morning UACR) for 8 weeks (p < 0.0001). At 8 weeks after randomization, all three additional drugs decreased home SBP (p < 0.0002) and trichlormethiazide significantly decreased morning UACR (p = 0.03). Amlodipine decreased morning UACR in patients with microalbuminuria based on casual spot urine samples (p = 0.048). However, multivariate analysis showed that only higher home SBP and UACR at week 8, but not any additional treatments, were significantly associated with UACR reduction between week 8 and week 16. In conclusion, crucial points of the effects of combination therapy on UACR were basal UACR and SBP levels. The effect of trichlormethiazide or amlodipine treatment in combination with irbesartan treatment on microalbuminuria needs to be reexamined based on a larger sample size after considering basal UACR and SBP levels.

KEYWORDS:

• Home blood pressure
• microalbuminuria
• irbesartan
• amlodipine
• efonidipine
• trichlormethiazide

Acknowledgments

The study was designed, conducted, and interpreted by the investigators, independent of the sponsors. This study was conducted by the J-HOME-ALB study group.

Declaration of interest

TH, who is a full-time employee of GlaxoSmithKline, contributed to this study independently.

Supplemental data

Supplemental data for this article can be accessed on the publisher’s website.

Funding

This work was supported by Nouvelle Place Inc., Japan, with an unrestricted grant from the Miyagi Kidney Foundation; Grants for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (23249036, 23390171, 24390084, 24591060, 24790654, 25253059, 25461205, 25461083, 25860156, and 26860093); a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) fellows (25*9328 and 25*7756); and a Health Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare, Japan (H23-Junkankitou [Seishuu]-Ippan-005).

Members of the J-HOME-ALB study group

Principal investigator: Y. Imai.

Coordinating and data management center: M. Hosaka M, R. Inoue,M. Satoh, T. Ohkubo, M. Kikuya, K. Asayama, H. Metoki, T. Obara, T. Hirose.

Participating practitioners: Y. Imai, Y. Emura, N. Tamaki, M. Miyataka, Y. Kimura, K. Ninomiya, T. Oishi, Y. Arai, T. Nakayama, N. Yagi, M. Yanagisawa, T. Yabuki, K. Matsuo, N. Hiwatari, S. Shibayama, Y. Tanno, Y. Suzuki, K. Iwasaki, H. Yamamoto, H. Akimoto, T. Katsuya, Y. Yamamoto, T. Hayashi, S. Watanabe, S. Suzuki, S. Sato, T. Ito, T. Furuki, G. Tashima, M. Miyakawa, J.H. Kim, M. Tosaka, K. Yoshida, T. Iwaoka, K. Okamoto, J. Komiya, O. Minami, S. Wakamatsu, and T. Shinagawa.

Additional information

Funding

This work was supported by Nouvelle Place Inc., Japan, with an unrestricted grant from the Miyagi Kidney Foundation; Grants for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (23249036, 23390171, 24390084, 24591060, 24790654, 25253059, 25461205, 25461083, 25860156, and 26860093); a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) fellows (25*9328 and 25*7756); and a Health Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare, Japan (H23-Junkankitou [Seishuu]-Ippan-005).

Notes on contributors

Miki Hosaka

M. Hosaka drafted the manuscript. All authors commented on the manuscript and approved the final version for submission.