The management of familial hypercholesterolaemia with statin-associated muscle symptoms

Hypercholesterolaemia and dyslipidaemia, marked by decreased levels of high-density lipoproteins (HDL) and elevated levels of low-density lipoprotein cholesterol (LDL-C), increase the risk of cardiovascular disease. By agreement, statin therapy constitute the agents of choice for the reduction of LDL-C. Despite being the most commonly prescribed lipid-lowering agents, with an exceptional safety profile and good tolerability, 10-25% of statin users experience muscle toxicity. This is known as the statin-associated muscle symptoms (SAMS), which range from myalgia to rare, life-threatening cases of rhabdomyolysis, in the presence of normal or elevated creatine kinase (CK). Familial hypercholesterolaemia (FH), diagnosed based on the clinical features seen in patients with a positive family history, constitutes a heritable disorder involving a single gene. FH can exist in either the heterozygous (HeFH), or the homozygous (HoFH) form, and may be differentiated based on clinical features and genetic studies. A novel drug target, namely proprotein convertase subtilisin/kexin type 9 (PCSK9), has resulted in the development and subsequent approval of new, targeted monoclonal antibodies in the treatment of hypercholesterolaemia. Targeting PCSK9 with such monoclonal antibodies (evolocumab and alirocumab) inhibits the degradation of LDL-receptors and, against a background of optimised statin therapy, increases the life expectancy of patients with hypercholesterolaemia by reducing the incidence and severity of coronary artery diseases. This article gives an overview on the management of hypercholesterolaemia in this setting.