Benefits and Risks of Simvastatin in Patients with Familial Hypercholesterolaemia
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REVIEW ARTICLE
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Benefits and Risks of Simvastatin in Patients with Familial Hypercholesterolaemia Pedro Mata,1 Rodrigo Alonso1 and Juan J. Badim´on2 1 2
´ Jim´enez D´iaz, Madrid, Spain Lipid Clinic, Internal Medicine Department, Fundacion Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New York, New York, USA
Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 769 1. Current Management of Familial Hypercholesterolaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 770 2. Pharmacological Properties of Simvastatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772 3. General Cardiovascular Benefits of Simvastatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772 4. Efficacy of Simvastatin in Familial Hypercholesterolaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773 4.1 Homozygous Familial Hypercholesterolaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773 4.2 Heterozygous Familial Hypercholesterolaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 774 4.2.1 Short-Term Effects on Lipid Levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 774 4.2.2 Long-Term Effects on Lipid Levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 774 4.2.3 Comparison of Simvastatin with Other HMG-CoA Reductase Inhibitors on Lipid Levels 774 4.2.4 Effects on Lipid Levels in Children and Adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 776 4.2.5 Effects on Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 776 4.2.6 Genetic Determinants of Simvastatin Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 778 4.2.7 Pleiotropic Effects of Simvastatin Related to Cardiovascular Benefit . . . . . . . . . . . . . . . . . 778 5. Tolerability and Safety of Simvastatin in Familial Hypercholesterolaemia . . . . . . . . . . . . . . . . . . . . . . . 780 5.1 Elevation of Transaminase Levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 780 5.2 Myotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 781 6. Economic Considerations of Treating Familial Hypercholesterolaemia . . . . . . . . . . . . . . . . . . . . . . . . . 782 7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 782
Abstract
Familial hypercho
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