Benefits and risks assessment of simvastatin in familial hypercholesterolaemia

Abstract

Familial hypercholesterolaemia (FH) is a frequent inherited monogenic disorder, associated with premature coronary artery disease. Life expectancy of FH patients is reduced by 15 - 30 years unless they are adequately treated with lipid-lowering therapy. Patients with this disorder need long-term drug therapy and the selection of treatment should be strongly based on its long-term safety and tolerability. The introduction of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors has changed the treatment of FH. Simvastatin 40 - 80 mg/day effectively reduces serum low-density lipoprotein cholesterol levels, and also reduces triglycerides with a modest rise in high-density lipoprotein cholesterol levels. Other potentially important effects, such as improvement of endothelial function, reduction of LDL oxidation and vascular inflammation, have been associated with simvastatin therapy in FH. In addition, simvastatin has been shown to abolish the progression, and even facilitate the regression of existing human atherosclerotic lesions. The safety and tolerability of simvastatin is clearly highlighted by the low rate of therapy discontinuation observed in several population-based clinical trials. Asymptomatic elevations in liver transaminase levels and myopathy are uncommon. The efficacy and tolerability of simvastatin at doses up to 80 mg/day are well-established, as well as its cost-effectiveness in the management of FH patients.