title: Efficacy and safety of losartan 100 mg/hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension: two randomized, controlled trials.
abstract: Two randomized studies were designed to assess the safety, tolerability and efficacy of losartan 100 mg (L100) plus hydrochlorothiazide 12.5 mg (H12.5) in a single fixed-dose combination. In one study, subjects received losartan 50 mg (L50) plus H12.5 during an 8-week filter period. They were then randomized to either L100/H12.5 or L50/H12.5 for another 8 weeks, followed by L100/H12.5 for 44 weeks. The primary end point was safety of L100/H12.5 for 52 weeks. In the second study, subjects received L100 during an 8-week filter period. Subjects were then randomized to receive either L100/H12.5 or L100 for a further 8 weeks. The primary end point was change from baseline in sitting diastolic blood pressure (SiDBP) at week 8. Safety was assessed throughout both studies. L100/H12.5 reduced SiDBP and sitting systolic blood pressure (SiSBP) at 8 weeks, and when compared with L100, the differences were statistically significant for both measures (P<0.001). L100/H12.5 reductions SiDBP for 8 weeks were comparable to L50/H12.5. The efficacy of L100/H12.5 was maintained to week 52. Drug-related adverse events with an incidence ⩾ 2% in the L100/H12.5 group during the 52-week extension period were an increase in aspartate aminotransferase and in blood uric acid. Additionally, mean uric acid levels were reduced by 0.57 mg dl(-1) from baseline with long-term treatment with L100/H12.5 in subjects whose baseline uric acid level was >7.0 mg dl(-1). In conclusion, L100/H12.5 was shown to be more effective than L100 at reducing SiDBP and SiSBP and showed good tolerability in Japanese patients with essential hypertension.
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: Steel Memorial Yawata Hospital, Fukuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsuchihashi
authors.affiliation: Department of Internal Medicine, Shin-Oyama City Hospital, Tochigi, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimada
authors.affiliation: MSD KK, Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Numaguchi
authors.affiliation: MSD KK, Tokyo, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Nishida
authors.affiliation: MSD KK, Tokyo, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: MSD KK, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Fujimoto
authors.affiliation: MSD KK, Tokyo, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Azuma
authors.affiliation: MSD KK, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shirakawa
authors.affiliation: Merck, Whitehouse Station, NJ, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Hanson
authors.affiliation: Merck, Whitehouse Station, NJ, USA.
authors.forename: Kenji P
authors.initials: KP
authors.lastname: Fujita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D023381:Endpoint Determination; D000075222:Essential Hypertension; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D019808:Losartan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D004232:Diuretics; D004338:Drug Combinations; D006852:Hydrochlorothiazide; D019808:Losartan