Familial hypercholesterolaemia is a frequent, inherited, monogenic disorder, associated with accelerated development of atherosclerotic disease leading to
coronary artery disease. Life expectancy of patients with familial hypercholesterolaemia is reduced by 15-30 years unless they are adequately treated with
lipid-lowering
therapy. Given the chronic nature of this disease, the selection of a therapeutic approach should be strongly based on its long-term safety and tolerability. The introduction of
HMG-CoA reductase inhibitors has revolutionised the treatment of familial hypercholesterolaemia.
Simvastatin 40-80 mg/day effectively reduces serum
low density lipoprotein (
LDL)-cholesterol levels. Furthermore,
simvastatin reduces
triglycerides and mildly raises
high density lipoprotein-cholesterol levels. In addition to the hypolipidaemic effect, other potentially important effects, such as improvement of endothelial function and reduction of
LDL oxidation and vascular
inflammation, have been associated with
HMG-CoA reductase inhibitor therapy.
Simvastatin has also been shown to abolish the progression, and even facilitate the regression, of existing human atherosclerotic lesions. The good safety and tolerability profile of
simvastatin is clearly highlighted by the low rate of
therapy discontinuation observed in several population-based clinical trials. The most common adverse events leading to the discontinuation of
therapy are gastrointestinal upset and
headache. Asymptomatic elevations in liver
transaminase levels and
myopathy are uncommon. The overwhelming clinical evidence regarding the long-term use of
HMG-CoA reductase inhibitor therapy in patients with familial hypercholesterolaemia together with the long-term safety data (particularly relating to
simvastatin) provide support for the use of this
drug as a first-line agent when pharmacological treatment is indicated. Early intervention with
simvastatin treatment can be successfully implemented with favourable economic benefits.