Marjet J A M Braamskamp1, Gisle Langslet2, Brian W McCrindle3, David Cassiman4, Gordon A Francis5, Claude Gagné6, Daniel Gaudet7, Katherine M Morrison8, Albert Wiegman9, Traci Turner10, D Meeike Kusters11, Elinor Miller12, Joel S Raichlen12, Jenny Wissmar13, Paul D Martin14, Evan A Stein10, John J P Kastelein15. 1. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: J.A.Braamskamp@amc.uva.nl. 2. Lipid Clinic, Oslo University Hospital, Oslo, Norway. Electronic address: glangsle@ous-hf.no. 3. Department of Pediatrics, Labatt Family Health Center, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. 4. Department of Hepatology and Metabolic Center, University Hospitals Leuven, Leuven, Belgium. 5. Department of Medicine, Healthy Heart Program Prevention Clinic, University of British Columbia, Vancouver, BC, Canada. 6. Clinique des Maladies Lipidiques de Québec, Québec, QC, Canada. 7. Department of Medicine, Université de Montréal, Chicoutimi, QC, Canada. 8. Department of Pediatrics, McMaster University, Hamilton, ON, Canada. 9. Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands. 10. Metabolic & Atherosclerosis Research Center, Cincinnati, OH, USA. 11. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands. 12. Department of Research and Development, AstraZeneca LP, Wilmington, DE, USA. 13. Department of Biometrics and Information Sciences, AstraZeneca, Mölndal, Sweden. 14. Department of Pharmacology, AstraZeneca, Macclesfield, Cheshire, UK. 15. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Abstract
OBJECTIVE: Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Guidelines recommend initiating statins early to reduce low-density lipoprotein cholesterol (LDL-C). Studies have evaluated rosuvastatin in children aged ≥10 years, but its efficacy and safety in younger children is unknown. METHODS: Children with HeFH and fasting LDL-C >4.92 mmol/L (190 mg/dL) or >4.10 mmol/L (>158 mg/dL) with other cardiovascular risk factors received rosuvastatin 5 mg daily. Based on LDL-C targets (<2.85 mmol/L [<110 mg/dL]), rosuvastatin could be uptitrated to 10 mg (aged 6-9 years) or 20 mg (aged 10-17 years). Treatment lasted 2 years. Changes in lipid values, growth, sexual maturation, and adverse events (AEs) were assessed. RESULTS: The intention-to-treat analysis included 197 patients. At 24 months, LDL-C was reduced by 43, 45, and 35% vs baseline in patients aged 6-9, 10-13, and 14-17 years, respectively (P < .001 for all groups). Most AEs were mild. Intermittent myalgia was reported in 11 (6%) patients and did not lead to discontinuation of rosuvastatin treatment. Serious AEs were reported by 9 (5%) patients, all considered unrelated to treatment by the investigators. No clinically important changes in hepatic biochemistry were reported. Rosuvastatin treatment did not appear to adversely affect height, weight, or sexual maturation. CONCLUSIONS: In HeFH patients aged 6-17 years, rosuvastatin 5-20 mg over 2 years significantly reduced LDL-C compared with baseline. Treatment was well tolerated, with no adverse effects on growth or sexual maturation.
OBJECTIVE: Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Guidelines recommend initiating statins early to reduce low-density lipoprotein cholesterol (LDL-C). Studies have evaluated rosuvastatin in children aged ≥10 years, but its efficacy and safety in younger children is unknown. METHODS:Children with HeFH and fasting LDL-C >4.92 mmol/L (190 mg/dL) or >4.10 mmol/L (>158 mg/dL) with other cardiovascular risk factors received rosuvastatin 5 mg daily. Based on LDL-C targets (<2.85 mmol/L [<110 mg/dL]), rosuvastatin could be uptitrated to 10 mg (aged 6-9 years) or 20 mg (aged 10-17 years). Treatment lasted 2 years. Changes in lipid values, growth, sexual maturation, and adverse events (AEs) were assessed. RESULTS: The intention-to-treat analysis included 197 patients. At 24 months, LDL-C was reduced by 43, 45, and 35% vs baseline in patients aged 6-9, 10-13, and 14-17 years, respectively (P < .001 for all groups). Most AEs were mild. Intermittent myalgia was reported in 11 (6%) patients and did not lead to discontinuation of rosuvastatin treatment. Serious AEs were reported by 9 (5%) patients, all considered unrelated to treatment by the investigators. No clinically important changes in hepatic biochemistry were reported. Rosuvastatin treatment did not appear to adversely affect height, weight, or sexual maturation. CONCLUSIONS: In HeFH patients aged 6-17 years, rosuvastatin 5-20 mg over 2 years significantly reduced LDL-C compared with baseline. Treatment was well tolerated, with no adverse effects on growth or sexual maturation.
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