Na, Sang-Hoon; Lee, Hae-Young; Hong Baek, Sang; Jeon, Hui-Kyung; Kang, Jin-Ho; Kim, Yoon-Nyun; Park, Chang-Gyu; Ryu, Jae-Kean; Rhee, Moo-Yong; Kim, Moo-Hyun; Hong, Taek-Jong; Choi, Dong-Ju; Cho, Seong-Wook; Cha, Dong-Hun; Jeon, Eun-Seok; Kim, Jae-Joong; Shin, Joon-Han; Park, Sung-Ha; Lee, Seung-Hwan; John, Sung-Hee; Shin, Eun-Seok; Kim, Nam-Ho; Lee, Sung-Yun; Kwan, Jun; Jeong, Myung-Ho; Kim, Sang-Wook; Jeong, Jin-Ok; Kim, Dong-Woon; Lee, Nam-Ho; Park, Woo-Jung; Ahn, Jeong-Cheon; Won, Kyung-Heon; Uk Lee, Seung; Cho, Jang-Hyun; Kim, Soon-Kil; Ahn, Taehoon; Hong, Sukkeun; Yoo, Sang-Yong; Kim, Song-Yi; Kim, Byung-Soo; Juhn, Jae-Hyeon; Kim, Sun-Young; Lee, Yu-Jeong; Oh, Byung-Hee
Clinical therapeutics
2015Aug ; 37 ( 8 ) :1726-39.
PMID : 26164786
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Na, Sang-Hoon - Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
Lee, Hae-Young - Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
Hong Baek, Sang - St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Jeon, Hui-Kyung - Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Kang, Jin-Ho - Kangbuk Samsung Hospital, Seoul, Korea.
Kim, Yoon-Nyun - Keimyung University, Dongsan Medical Center, Seoul, Korea.
Park, Chang-Gyu - Korea University Guro Hospital, Seoul, Korea.
Ryu, Jae-Kean - Daegu Catholic University Medical Center, Seoul, Korea.
Rhee, Moo-Yong - Dongguk University Ilsan Hospital, Seoul, Korea.
Kim, Moo-Hyun - Dong-A University Hospital, Seoul, Korea.
Hong, Taek-Jong - Pusan National University Hospital, Seoul, Korea.
Choi, Dong-Ju - Seoul National University Bundang Hospital, Seoul, Korea.
Cho, Seong-Wook - Bundang Jesaeng Hospital, Seoul, Korea.
Cha, Dong-Hun - CHA University Bundang CHA Hospital, Seoul, Korea.
Jeon, Eun-Seok - Samsung Medical Center, Seoul, Korea.
Kim, Jae-Joong - Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea.
Shin, Joon-Han - Ajou University Hospital, Seoul, Korea.
Park, Sung-Ha - Yonsei University College of Medicine Severance Hospital, Seoul, Korea.
Lee, Seung-Hwan - Wonju Severance Christian Hospital, Seoul, Korea.
John, Sung-Hee - Presbyterian Medical Center, Seoul, Korea.
Shin, Eun-Seok - Ulsan University Hospital, Seoul, Korea.
Kim, Nam-Ho - Wonkwang University Hospital, Seoul, Korea.
Lee, Sung-Yun - Inje University Ilsan-Paik Hospital, Seoul, Korea.
Kwan, Jun - Inha University Hospital, Seoul, Korea.
Jeong, Myung-Ho - Chonnam National University Hospital, Seoul, Korea.
Kim, Sang-Wook - Chung-Ang University Hospital, Seoul, Korea.
Jeong, Jin-Ok - Chungnam National University Hospital, Seoul, Korea.
Kim, Dong-Woon - Chungbuk National University Hospital, Seoul, Korea.
Lee, Nam-Ho - Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea.
Park, Woo-Jung - Hallym University Sacred Heart Hospital, Seoul, Korea.
Ahn, Jeong-Cheon - Korea University Ansan Hospital, Seoul, Korea.
Won, Kyung-Heon - Seoul Medical Center, Seoul, Korea.
Uk Lee, Seung - Kwangju Christian Hospital, Seoul, Korea.
Cho, Jang-Hyun - St. Carollo Hospital, Seoul, Korea.
Kim, Soon-Kil - Hanyang University Guri Hospital, Seoul, Korea.
Ahn, Taehoon - Gachon University Gil Hospital, Seoul, Korea.
Hong, Sukkeun - Sejong General Hospital, Seoul, Korea.
Yoo, Sang-Yong - Gangneng Asan Hospital, Seoul, Korea.
Kim, Song-Yi - Jeju National University Hospital, Seoul, Korea.
Kim, Byung-Soo - Dae Dong Hospital, Seoul, Korea. Electronic address ohbhmed@snu.ac.kr.
Juhn, Jae-Hyeon - LG Life Sciences Ltd, Seoul, Korea.
Kim, Sun-Young - LG Life Sciences Ltd, Seoul, Korea.
Lee, Yu-Jeong - LG Life Sciences Ltd, Seoul, Korea.
Oh, Byung-Hee - Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
ABSTRACT
PURPOSE: The objective of this study was to evaluate the efficacy and safety of the lercanidipine/valsartan combination compared with lercanidipine monotherapy in patients with hypertension.
METHODS: Part 1 of this study was the randomized, multicenter, double-blind, parallel group, Phase III, 8-week clinical trial to compare superiority of lercanidipine 10 mg/valsartan 80 mg (L10/V80) and lercanidipine 10 mg/valsartan 160 mg (L10/V160) combinations with lercanidipine 10 mg (L10) monotherapy. At screening, hypertensive patients, whose diastolic blood pressure (DBP) was >90 mm Hg after 4 weeks with L10, were randomized to 3 groups of L10, L10/V80, and L10/V160. The primary end point was the change in the mean sitting DBP from baseline (week 0) after 8 weeks of therapy. Patients who were randomly assigned to L10/V160 and whose mean DBP was still ??90 mm Hg in part 1 were enrolled to the up-titration extension study with lercanidipine 20 mg/valsartan 160 mg (L20/V160) (part 2). FINDINGS: Of 772 patients screened, 497 were randomized to 3 groups (166 in the L10 group, 168 in the L10/V80 group, and 163 in the L10/V160 group). Mean (SD) age was 55 (9.9) years, and male patients comprised 69%. The mean (SD) baseline systolic blood pressure (SBP)/DBP were 148.4 (15.1)/94.3 (9.5) mm Hg. No significant differences were found between groups in baseline characteristics except the percentages of previous history of antihypertensive medication. The primary end points, the changes of mean (SD) DBP at week 8 from the baseline were -2.0 (8.8) mm Hg in the L10 group, -6.7 (8.5) mm Hg in L10/V80 group, and -8.1 (8.4) mm Hg in L10/V160 group. The adjusted mean difference between the combination groups and the L10 monotherapy group was -4.6 mm Hg (95% CI, -6.5 to -2.6; P < 0.001) in the L10/V80 group and -5.9 mm Hg (95% CI, -7.9 to -4.0, P < 0.001) in the L10/V160 group, which had significantly greater efficacy in BP lowering. A total of 74 patients were enrolled in the part 2 extension study. Changes of mean (SD) DBP and SBP from week 8 to week 12 and week 16 were -5.6 (7.9)/-8.0 (12.0) mm Hg and -5.5 (7.0)/-8.5 (11.3) mm Hg, respectively. For evaluation of the safety profile, the frequencies of adverse events between groups were also not significantly different. The most frequently reported adverse events were headache (6 cases, 20.7%) in the L10 group, dizziness (8 cases, 16.3%) in L10/V80 group, and nasopharyngitis (3 cases, 9.4%) in L10/V160 group, and the incidences of adverse events were not different between groups. IMPLICATIONS: Treatment of L10/V80 or L10/V160 combination therapy resulted in significantly greater BP lowering compared with L10 monotherapy. Moreover, the L20/V160 high dose combination had additional BP lowering effect compared with nonresponders with the L10/V160 combination. ClinicalTrials.gov: NCT01928628. CI - Copyright ??2015 Elsevier HS Journals, Inc. All rights reserved.
keyword
combination; hypertension; lercanidipine; valsartan
MESH
Adult, Aged, Antihypertensive Agents/administration & dosage/adverse effects/*therapeutic use, Blood Pressure/drug effects, Dihydropyridines/adverse effects/*therapeutic use, Dizziness/chemically induced, Dose-Response Relationship, Drug, Double-Blind Method, Drug Combinations, Female, Headache/chemically induced, Humans, Hypertension/*drug therapy/physiopathology, Male, Middle Aged, Treatment Outcome, Valsartan/administration & dosage/adverse effects/*therapeutic use, Young Adult
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