Add-on effect of hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension uncontrolled with losartan 50 mg and amlodipine 5 mg

• Published in: Hypertension research 2015-05, Vol.38 (5), p.329-335
• Main Authors: Rakugi, Hiromi, Tsuchihashi, Takuya, Shimada, Kazuyuki, Numaguchi, Hirotaka, Nishida, Chisato, Yamaguchi, Hiroya, Shirakawa, Masayoshi, Azuma, Kyoichi, Fujita, Kenji P
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Amlodipine - pharmacology; Amlodipine - therapeutic use; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Antihypertensives; Blood Pressure - drug effects; Clinical trials; Double-Blind Method; Drug dosages; Drug therapy; Drug Therapy, Combination; Essential Hypertension; Evidence-based medicine; Female; Humans; Hydrochlorothiazide - pharmacology; Hydrochlorothiazide - therapeutic use; Hypertension; Hypertension - drug therapy; Japan; Losartan - pharmacology; Losartan - therapeutic use; Male; Middle Aged; Single-Blind Method; Treatment Outcome; Young Adult
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1038/hr.2015.3

This study assessed the antihypertensive efficacy of a triple combination, fixed-dose therapy of losartan 50 mg (L50)/hydrochlorothiazide 12.5 mg (H12.5)/amlodipine 5 mg (A5) versus co-administration of L50 plus A5 (L50+A5) in Japanese subjects with uncontrolled essential hypertension. Initially, all subjects received single-blind treatment with L50+A5 for 8 weeks. Subjects whose blood pressure (BP) remained stable within pre-specified limits during the last 4 weeks of L50+A5 administration were randomized (n =3 27) to double-blind treatment with L50/H12.5/A5 or L50+A5 for 8 weeks. Primary and secondary efficacy endpoints were mean change from baseline to Week 8 in trough diastolic BP (DBP) and trough systolic BP (SBP), respectively. Safety was assessed throughout the study. The treatment difference for L50/H12.5/A5 versus L50+A5 in mean change from baseline in DBP at Week 8 was -1.1 mm Hg (95% confidence interval (CI) -2.7, 0.6; P = 0.205). However, the treatment difference in mean change from baseline in SBP at Week 8 was -3.2 mm Hg (95% CI: -5.7, -0.8; P=0.011). A chance imbalance in the change in DBP before randomization between groups was identified in a post-hoc analysis as a major reason for the smaller-than-expected difference in DBP between groups. The overall safety profile was generally similar between groups. In conclusion, treatment with L50/H12.5/A5 for 8 weeks did not demonstrate a significant difference in DBP reduction, but demonstrated a nominally significant difference in SBP reduction, compared with L50+A5. L50/H12.5/A5 was well tolerated. (ClinicalTrials.gov identifier NCT01302691.).