Lee, Sang Eun; Kim, Yong-Jin; Lee, Hae-Young; Yang, Han-Mo; Park, Chang-Gyu; Kim, Jae-Joong; Kim, Soon-Kil; Rhee, Moo-Yong; Oh, Byung-Hee
Clinical therapeutics
2012Mar ; 34 ( 3 ) :552-568, 568.e1-9.
PMID : 22381711
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Lee, Sang Eun -
Kim, Yong-Jin -
Lee, Hae-Young -
Yang, Han-Mo -
Park, Chang-Gyu -
Kim, Jae-Joong -
Kim, Soon-Kil -
Rhee, Moo-Yong -
Oh, Byung-Hee -
ABSTRACT
BACKGROUND: Angiotensin receptor blockers (ARBs) is an effective and well tolerated first-line antihypertensive drug. Fimasartan is a newly developed ARB that has not been compared with other ARBs with regard to its efficacy and tolerability. OBJECTIVE: The goal of this study was to determine the noninferiority of fimasartan to losartan with regard to its efficacy and tolerability in adult Korean patients with mild-to-moderate hypertension.
METHODS: This was a randomized, multicenter, double-blind, parallel group, dose escalation, Phase III, noninferiority clinical trial. Patients aged 18 to 70 years with mild-to-moderate hypertension were randomized to receive either fimasartan 60/120 mg daily or losartan 50/100 mg daily with optional titration. Antihypertensive efficacy and tolerability were evaluated for 12 weeks. The primary end point was noninferiority of improvement in mean siDBP from baseline to week 12 for fimasartan compared with losartan. The incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs) were evaluated to assess their tolerability. In addition, some patients whose blood pressure reached goal levels participated in a 24-week extension study for additional assessment of tolerability and efficacy.
RESULTS: Five hundred six patients were randomly allocated to receive fimasartan (n = 256) or losartan (n = 250). There was no significant difference in baseline demographic characteristics between the 2 treatment groups (fimasartan-treated group-mean age, 53.96 [8.79] years; mean weight, 70.58 [11.73] kg; male, 68.02%; losartan-treated group-mean age, 53.58 [9.61] years; mean weight, 69.80 [11.08] kg; male, 70.17%). At week 12, siDBP was significantly decreased from baseline in both groups (-11.26 [7.53] mm Hg in the fimasartan group and -8.56 [7.72] mm Hg in the losartan group [P < 0.0001]). The between-group difference was 2.70 mm Hg (P = 0.0002), and the lower limit of the 2-sided 95% CI (1.27 mm Hg) was higher than the prespecified noninferiority margin (-2.5 mm Hg). The incidence of ADRs were 7.84% and 10.40% in the fimasartan and losartan groups, respectively (?(2) test, P = 0.3181). The efficacy of fimasartan was maintained over 24 weeks, and its tolerability was comparable with losartan in the extension study.
CONCLUSIONS: In this study with eligible adult Korean patients who had mild-to-moderate hypertension, the reduction of siDBP after 12 weeks of treatment with fimasartan 60/120 mg was noninferior to that of losartan 50/100 mg. By post hoc comparison, between-group differences in siDBP were significant in favor of fimasartan, suggesting superiority to losartan. There was no statistically significant difference in tolerability between the groups. This efficacy and tolerability were maintained throughout the additional 12-week extension study. CI - Copyright A??2012 Elsevier HS Journals, Inc. All rights reserved.
active- control equivalence trial, angiotension receptor blocker, fimasartan, hypertension, losartan
MESH
Adolescent, Adult, Aged, Angiotensin Receptor Antagonists/administration & dosage/adverse, Antihypertensive Agents/administration & dosage/adverse, Biphenyl Compounds/adverse effects/pharmacology/*therapeutic use, Blood Pressure/drug effects, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Hypertension/diagnosis/*drug therapy, Losartan/administration & dosage/adverse effects/pharmacology/*therapeutic use, Male, Middle Aged, Prospective Studies, Pyrimidines/adverse effects/pharmacology/*therapeutic use, Republic of Korea, Severity of Illness Index, Tetrazoles/adverse effects/pharmacology/*therapeutic use, Treatment Outcome, Young Adult
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