title: Long-term efficacy and tolerability of simvastatin in a large cohort of elderly hypercholesterolemic patients.
abstract: 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 hypercholesterolemic patients. After completing a 4 week double blind dose ranging study with simvastatin, 47 males and 122 females over 62 years of age with type II hyperlipidemia, a total cholesterol level above 6.5 mmol/l and clinically manifest cardiovascular disease were included in this extended study. A total of 159 patients completed the 12-month follow-up period and 141 patients were monitored over the full 24 months. All patients were started on 10 mg simvastatin once daily and the dosage was increased until the target levels of low density lipoprotein (LDL) cholesterol 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 cholesterol goal of < 3.6 mmol/l (140 mg/dl) during the study. At study completion, 65 patients (39%) were taking 40 mg simvastatin per day, 56 patients (33%) 20 mg, 42 patients (25%) 10 mg and 5 patients (3%) only used 5 mg per day. Sixteen patients (9%) received concomitant lipid lowering therapy. Over 2 years, the mean decrease in LDL cholesterol ranged from 36% to 38%, the median decrease in triglycerides was 12% to 19% and the mean increase in high density lipoprotein (HDL) cholesterol ranged from 9% to 10%, respectively. Seven patients discontinued simvastatin because of adverse clinical or laboratory events, but only in two (1.1%) was this considered to be drug-related. Side-effects were mild and most frequently gastrointestinal in nature. Mean changes in asparate aminotransferase (AST) were not significantly different from zero and mean changes in alanine aminotransferase (ALT) and creatine phosphokinase (CPK) showed a small increase. We conclude that simvastatin is an efficacious and well-tolerated treatment for hypercholesterolemia in elderly individuals for extended periods.
authors.affiliation: Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Lansberg
authors.forename: Y B
authors.initials: YB
authors.lastname: Mitchel
authors.forename: D
authors.initials: D
authors.lastname: Shapiro
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: R
authors.initials: R
authors.lastname: Altman
authors.forename: G
authors.initials: G
authors.lastname: Jerums
authors.forename: K
authors.initials: K
authors.lastname: Bolzano
authors.forename: S
authors.initials: S
authors.lastname: Giannini
authors.forename: J
authors.initials: J
authors.lastname: Davignon
authors.forename: P
authors.initials: P
authors.lastname: DeWailly
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008148:Lovastatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019821:Simvastatin
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin