title: Sustained reduction of serum cholesterol in low-dose 6-year simvastatin treatment with minimum side effects in 51,321 Japanese hypercholesterolemic patients.
abstract: The Japan Lipid Intervention Trial (J-LIT) study, a nationwide cohort study utilizing the clinical practice of general physicians, was designed to clarify the relationship between the incidence of coronary heart disease and serum lipid concentrations during simvastatin therapy, as well as the safety of the therapy, in a large number of Japanese hypercholesterolemic patients. All the enrolled patients were treated with simvastatin. The current study analyzed the lipid lowering effect and safety of the low-dose simvastatin therapy used in the J-LIT study. Open-labeled simvastatin was given to 51,321 patients at an initial dose of mostly 5 mg/day. After 6 months of the treatment, the average serum total cholesterol (TC) and low density lipoprotein-cholesterol concentrations in all the patients followed up were reduced by 18.3% and 26.0%, respectively, and that of high density lipoprotein-cholesterol increased 2.3% on average. These concentrations were well maintained throughout the 6-year treatment period. A minority of patients (1.4%) unexpectedly had a remarkable reduction in TC concentration by more than 40%. Hyper-responders, even to low-dose statin, were found for the first time in this large-scale and long-term investigation. Overall adverse drug reactions occurred in 3.3% of subjects during the 6-year treatment, the major events being hepatic and musculoskeletal disorders, of which the incidence was less than 1%. Low-dose simvastatin therapy of 5 mg/day effectively controlled the serum TC concentration by reducing it by approximately 20% on average in hypercholesterolemic Japanese patients, a reduction that corresponds to the effect of simvastatin 20 mg/day in Western studies. In addition, the low incidence of drug-related adverse events in this study may be also related to the low dosage of simvastatin.
authors.affiliation: Osaka University Graduate School of Medicine, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mabuchi
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nakaya
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oikawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Jun
authors.initials: J
authors.lastname: Sasaki
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Itakura
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury; D002784:Cholesterol / Q000097:blood*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000139:chemically induced; D009994:Osmolar Concentration; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000924:Anticholesteremic Agents; D002784:Cholesterol; D019821:Simvastatin