Long Term Experience with Simvastatin

Summary

Simvastatin is a potent lipid-lowering agent that has proven highly effective in the treatment of primary hypercholesterolaemia. This report extends the data on controlled clinical trials, involving 2423 patients receiving simvastatin. The mean duration of treatment was 1.5 years, and some patients were followed up for a period of up to 4.3 years. This cohort had a mean age of 50 years, with males comprising 61% of the population. Because of the severity of lipid abnormalities treated in this population, simvastatin was titrated to the maximum daily dose of 40mg each evening in over half the population. An evaluation of long term efficacy indicates that improvements in the lipid/lipoprotein profile observed initially in patients were maintained over 3 years of treatment with chronic administration. The improvements in plasma levels included reductions in total and low-density lipoprotein cholesterol, decreases in triglyceride and increases in high-density lipoprotein cholesterol plasma levels. The profile of adverse events remained unchanged since the initial controlled clinical studies, with no reports of new or unexpected adverse effects. The most commonly reported drug-related clinical adverse experiences were gastrointestinal in nature, including constipation (in 2.5% of the patient population), abdominal pain (2.5%), flatulence (2.0%) and nausea (1.2%). Persistent elevations in levels of serum transaminases > 3 times the upper limit of normal were observed in 1.2% of the population, but rarely required discontinuation of therapy. Elevations in levels of creatine Phosphokinase (CPK) > 10 times the upper limit of normal were infrequent (0.7%), and reports of myopathy were rare (0.08%). Elderly patients (aged ⩾ 65 years) had a clinical and laboratory tolerability profile comparable to the nonelderly population. The long term clinical experience with simvastatin confirms its efficacy and tolerability profile for the treatment of hypercholesterolaemia.