EFFICACY AND 6-MONTH SAFETY OF SIMVASTATIN 80 MG DAY - RESULTS FROM THE WORLDWIDE SIMVASTATIN EXPANDED DOSE PROGRAM (WSEDP)/

Background and Aim: This I randomised multinational, double-blind stud y evaluated the lipid-altering efficacy and safety of simvastatin 80 m g/day as compared to 40 mg/day. Methods and Results: Men and women wit h hypercholesterolaemia were recruited at 29 centres in 19 countries a nd randomised to receive simvastatin 40 (n=229) or 80 mg/day (n=355) i n conjunction with a lipid-lowering diet. After 24 weeks, low-density lipoprotein cholesterol levels were reduced by 42.6% and 48.4%, in the groups respectively (p<0.001). Simvastatin 80 mg/day also reduced tot al cholesterol, triglycerides, and the ratio of low-density to high-de nsity lipoprotein cholesterol by 37%, 24%, and 52%, respectively. Redu ction of triglycerides appeared to be a function of their baseline lev els. No new or unexpected adverse effects were observed, and there wer e no significant between-group differences in adverse events ol discon tinuations. There was a slight trend toward higher muscle and hepatic enzyme elevations with the 80 mg/day dose; 3 patients with myopathy an d 6 with liver enzyme elevations (all in the 80 mg/day group) were dis continued from treatment. However, such clinical and laboratory abnorm alities reversed promptly after drug discontinuation. Conclusions: Sim vastatin 80 mg/day offers significant additional lipid-lowering effica cy over the 40 mg/day nose. Given the improved efficacy and the excell ent safety and tolerability profile, simvastatin 80 mg/day may be bene ficial for those patients requiring greater reductions of low-density lipoprotein cholesterol and triglycerides. (C) 1998, Medikal Press.