LONG-TERM EFFICACY AND TOLERABILITY OF SIMVASTATIN IN A LARGE COHORT OF ELDERLY HYPERCHOLESTEROLEMIC PATIENTS

The long-term efficacy and tolerability of simvastatin, a 3-hydroxy-3- methylglutaryl-co-enzyme A (HMG-CoA) reductase inhibitor, was assessed during a 24-month follow-up period in 168 elderly hypercholesterolemi c patients. After completing a 4 week double blind dose ranging study with simvastatin, 47 males and 122 females over 62 years of age with t ype II hyperlipidemia, a total cholesterol level above 6.5 mmol/l and clinically manifest cardiovascular disease were included in this exten ded study. A total of 159 patients completed the 12-month follow-up pe riod and 141 patients were monitored over the full 24 months. All pati ents were started on 10 mg simvastatin once daily and the dosage was i ncreased until the target levels of low density lipoprotein (LDL) chol esterol between 2.3 mmol/l (90 mg/dl) and 3.6 mmol/l (140 mg/dl) were reached. Fifty percent of patients reached the targeted LDL cholestero l goal of < 3.6 mmol/l (140 mg/dl) during the study. At study completi on, 65 patients (39%) were taking 40 mg simvastatin per day, 56 patien ts (33%) 20 mg, 42 patients (25%) 10 mg and 5 patients (3%) only used 5 mg per day. Sixteen patients (9%) received concomitant lipid lowerin g therapy. Over 2 years, the mean decrease in LDL cholesterol ranged f rom 36% to 38%, the median decrease in triglycerides was 12% to 19% an d the mean increase in high density lipoprotein (HDL) cholesterol rang ed from 9% to 10%, respectively. Seven patients discontinued simvastat in because of adverse clinical or laboratory events, but only in two ( 1.1%) was this considered to be drug-related. Side-effects were mild a nd most frequently gastrointestinal in nature. Mean changes in asparat e aminotransferase (AST) were not significantly different from zero an d mean changes in alanine aminotransferase (ALT) and creatine phosphok inase (CPK) showed a small increase. We conclude that simvastatin is a n efficacious and well-tolerated treatment for hypercholesterolemia in elderly individuals for extended periods.