title: Comparative safety of atorvastatin 80 mg versus 10 mg derived from analysis of 49 completed trials in 14,236 patients.
abstract: Atorvastatin has been shown to reduce coronary events and revascularization procedures in patients with multiple risk factors for coronary heart disease. Recent studies with atorvastatin 80 mg support the overall safety of this dose during long-term treatment. However, physicians appear reluctant to use high doses of statins. A retrospective analysis of pooled data from 49 clinical trials of atorvastatin in 14,236 patients treated for an average period of 2 weeks to 52 months was conducted. The study compared the safety of atorvastatin 10 mg (n = 7,258), atorvastatin 80 mg (n = 4,798), and placebo (n = 2,180) and included analyses on treatment-associated adverse events; nonserious and serious adverse events related to the musculoskeletal, hepatic, and renal systems; the incidence of elevations of creatine kinase >10 times the upper limit of normal (ULN); and hepatic transaminases >3 times ULN. Percentages of patients experiencing > or =1 adverse event were similar across all 3 groups. Withdrawals due to treatment-related adverse events were observed in 2.4%, 1.8%, and 1.2% of patients in the atorvastatin 10 mg, atorvastatin 80 mg, and placebo groups, respectively. Serious adverse events were rare and seldom led to treatment withdrawal with any dose. Treatment-associated myalgia was observed in 1.4%, 1.5%, and 0.7% of patients in the atorvastatin 10 mg, atorvastatin 80 mg, and placebo groups, respectively. No cases of rhabdomyolysis were reported in any group. Persistent elevations in hepatic transaminases >3 times ULN were observed in 0.1%, 0.6%, and 0.2% of patients in the atorvastatin 10 mg, atorvastatin 80 mg, and placebo groups, respectively. The incidence of treatment-associated adverse events for atorvastatin 80 mg was similar to that of atorvastatin 10 mg and placebo. In conclusion, the results of this analysis support the positive safety profile of atorvastatin at the highest dose.
authors.affiliation: Pfizer Global Pharmaceuticals, New York, New York, USA. connie.newman@pfizer.com
authors.forename: Connie
authors.initials: C
authors.lastname: Newman
authors.forename: John
authors.initials: J
authors.lastname: Tsai
authors.forename: Michael
authors.initials: M
authors.lastname: Szarek
authors.forename: Don
authors.initials: D
authors.lastname: Luo
authors.forename: Eric
authors.initials: E
authors.lastname: Gibson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000419:Albuminuria / Q000139:chemically induced; D001219:Aspartate Aminotransferases / Q000097:blood; D000069059:Atorvastatin; D056486:Chemical and Drug Induced Liver Injury; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004363:Drug Utilization / Q000639:trends; D005260:Female; D006417:Hematuria / Q000139:chemically induced; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced; D010146:Pain / Q000139:chemically induced; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase