Familial hypercholesterolaemia: optimum treatment strategies

Familial hypercholesterolaemia (FH) is a hereditary metabolic disorder characterised by defects in the low-density lipoprotein (LDL) receptor, elevated LDL cholesterol (LDL-C) levels and an extremely high risk for premature cardiovascular disease. Heterozygous FH occurs in about one of every 500 individuals in the United States and Europe. The high prevalence of FH and associated morbidity and mortality strongly support aggressive screening and treatment. There are two major barriers to effective management of FH: 1) the failure to screen for this disease in people who may be at increased risk for it; and 2) the inability of most available therapies to enable achievement of LDL-C goals. More aggressive screening, coupled with new genetic screening techniques, and more powerful 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have the potential to overcome these limitations. Automated genetic assays are now available for detection of common LDL receptor mutations in individuals at risk for FH, and they have been used effectively to identify patients with this condition. Recent clinical trial results with the new synthetic statin rosuvastatin (Crestor; AstraZeneca, Alderley Park, Macclesfield, Cheshire, UK; licensed from Shionogi & Co, Ltd, Osaka, Japan) in patients with heterozygous FH have shown that it decreased LDL-C by 58% and increased high-density lipoprotein cholesterol (HDL-C) by 12%. Rosuvastatin was significantly superior to high-dose atorvastatin in improving these lipid parameters as well as total cholesterol, apolipoprotein (apo) B, apo A-I, and the LDL-C/HDL-C ratio. Thus, new screening tools and medical therapies have the potential to significantly improve management and reduce cardiovascular disease risk for patients with FH.