Mariko Harada-Shiba1, John J P Kastelein2, G Kees Hovingh2, Kausik K Ray3, Akira Ohtake4, Osamu Arisaka5, Takao Ohta6, Tomoo Okada7, Hideki Suganami8, Albert Wiegman9. 1. Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute. 2. Department of Vascular Medicine, Academic Medical Center, University of Amsterdam. 3. Department of Primary Care and Public Health, School of Public Health, Imperial College London. 4. Department of Pediatrics, Faculty of Medicine, Saitama Medical University. 5. Department of Pediatrics, Dokkyo Medical University School of Medicine. 6. Department of Child Health and Welfare (Pediatrics), Faculty of Medicine, University of the Ryukyu. 7. Department of Pediatrics and Child Health, Nihon University School of Medicine. 8. Clinical Data Science Department, Kowa Company, Ltd. 9. Department of Pediatrics, Academic Medical Center, University of Amsterdam.
Abstract
AIM: Children with Familial Hypercholesterolemia (FH) are widely prescribed statins, and it has been suggested that the effects of statins differ among ethnicities. We compared the efficacy and safety of pitavastatin in children and adolescents with FH in clinical trials conducted in Japan and Europe. METHODS:Low-density lipoprotein cholesterol (LDL-C) reductions, adjusted for confounding factors, and safety were compared between the studies in Japan and Europe. In the Japanese study, 14 males with heterozygous FH, aged 11.8±1.6 years, were randomized to 52-week double-blind treatment with 1 or 2 mg/day pitavastatin. In the European study, 106 children and adolescents with high risk hyperlipidemia (103 heterozygous FH), aged 10.6±2.9 years, were randomized to 12-week double-blind treatment with 1, 2 or 4 mg/day pitavastatin or placebo; 84 of these patients and 29 new patients participated in a 52-week open-label extension study. RESULTS: Age, body weight and baseline LDL-C were identified as factors influencing LDL-C reduction. There were no significant differences in the adjusted mean percentage reduction in LDL-C in Japanese and European children by pitavastatin (24.5% and 23.6%, respectively at 1 mg/day and 33.5% and 30.8%, respectively at 2 mg/day). Pitavastatin was well tolerated without any difference in the frequency or nature of adverse events between the treatment groups, or between the studies. CONCLUSION: There were no significant differences between the efficacy or safety of pitavastatin in Japanese and European children and adolescents with FH, suggesting no relevant ethnic differences in the safety or efficacy of pitavastatin.
RCT Entities:
AIM: Children with Familial Hypercholesterolemia (FH) are widely prescribed statins, and it has been suggested that the effects of statins differ among ethnicities. We compared the efficacy and safety of pitavastatin in children and adolescents with FH in clinical trials conducted in Japan and Europe. METHODS: Low-density lipoprotein cholesterol (LDL-C) reductions, adjusted for confounding factors, and safety were compared between the studies in Japan and Europe. In the Japanese study, 14 males with heterozygous FH, aged 11.8±1.6 years, were randomized to 52-week double-blind treatment with 1 or 2 mg/day pitavastatin. In the European study, 106 children and adolescents with high risk hyperlipidemia (103 heterozygous FH), aged 10.6±2.9 years, were randomized to 12-week double-blind treatment with 1, 2 or 4 mg/day pitavastatin or placebo; 84 of these patients and 29 new patients participated in a 52-week open-label extension study. RESULTS: Age, body weight and baseline LDL-C were identified as factors influencing LDL-C reduction. There were no significant differences in the adjusted mean percentage reduction in LDL-C in Japanese and European children by pitavastatin (24.5% and 23.6%, respectively at 1 mg/day and 33.5% and 30.8%, respectively at 2 mg/day). Pitavastatin was well tolerated without any difference in the frequency or nature of adverse events between the treatment groups, or between the studies. CONCLUSION: There were no significant differences between the efficacy or safety of pitavastatin in Japanese and European children and adolescents with FH, suggesting no relevant ethnic differences in the safety or efficacy of pitavastatin.
Authors: Gerald F Watts; Samuel Gidding; Anthony S Wierzbicki; Peter P Toth; Rodrigo Alonso; W Virgil Brown; Eric Bruckert; Joep Defesche; Khoo Kah Lin; Michael Livingston; Pedro Mata; Klaus G Parhofer; Frederick J Raal; Raul D Santos; Eric J G Sijbrands; William G Simpson; David R Sullivan; Andrey V Susekov; Brian Tomlinson; Albert Wiegman; Shizuya Yamashita; John J P Kastelein Journal: Int J Cardiol Date: 2013-11-20 Impact factor: 4.164
Authors: Albert Wiegman; Samuel S Gidding; Gerald F Watts; M John Chapman; Henry N Ginsberg; Marina Cuchel; Leiv Ose; Maurizio Averna; Catherine Boileau; Jan Borén; Eric Bruckert; Alberico L Catapano; Joep C Defesche; Olivier S Descamps; Robert A Hegele; G Kees Hovingh; Steve E Humphries; Petri T Kovanen; Jan Albert Kuivenhoven; Luis Masana; Børge G Nordestgaard; Päivi Pajukanta; Klaus G Parhofer; Frederick J Raal; Kausik K Ray; Raul D Santos; Anton F H Stalenhoef; Elisabeth Steinhagen-Thiessen; Erik S Stroes; Marja-Riitta Taskinen; Anne Tybjærg-Hansen; Olov Wiklund Journal: Eur Heart J Date: 2015-05-25 Impact factor: 29.983
Authors: Børge G Nordestgaard; M John Chapman; Steve E Humphries; Henry N Ginsberg; Luis Masana; Olivier S Descamps; Olov Wiklund; Robert A Hegele; Frederick J Raal; Joep C Defesche; Albert Wiegman; Raul D Santos; Gerald F Watts; Klaus G Parhofer; G Kees Hovingh; Petri T Kovanen; Catherine Boileau; Maurizio Averna; Jan Borén; Eric Bruckert; Alberico L Catapano; Jan Albert Kuivenhoven; Päivi Pajukanta; Kausik Ray; Anton F H Stalenhoef; Erik Stroes; Marja-Riitta Taskinen; Anne Tybjærg-Hansen Journal: Eur Heart J Date: 2013-08-15 Impact factor: 29.983
Authors: Gerald F Watts; Samuel S Gidding; Pedro Mata; Jing Pang; David R Sullivan; Shizuya Yamashita; Frederick J Raal; Raul D Santos; Kausik K Ray Journal: Nat Rev Cardiol Date: 2020-01-23 Impact factor: 32.419
Authors: Alpo Vuorio; Jaana Kuoppala; Petri T Kovanen; Steve E Humphries; Serena Tonstad; Albert Wiegman; Euridiki Drogari; Uma Ramaswami Journal: Cochrane Database Syst Rev Date: 2019-11-07