title: Safety of atorvastatin derived from analysis of 44 completed trials in 9,416 patients.
abstract: This analysis assessed the safety of atorvastatin in the 10- to 80-mg dose range using pooled data from 44 completed trials comprising 16,495 dyslipidemic patients treated with atorvastatin (n = 9,416), placebo (n = 1,789), and other statins (n = 5,290). A retrospective analysis was conducted and included treatment-associated adverse events, serious adverse events, and musculoskeletal and hepatic adverse events. Only 3% (n = 241) of atorvastatin-treated patients withdrew from studies due to treatment-associated adverse events, compared with 1% of those (n = 16) on placebo and 4% of those (n = 188) receiving other statins; the most frequently reported treatment-associated adverse events were related to the digestive system. Serious adverse events were rare and seldom led to withdrawal. Persistent elevations in hepatic transaminases to >3 times the upper limit of normal (ULN) were experienced by 0.5% (n = 47) of atorvastatin-treated patients. A persistent elevation in creatine phosphokinase (CPK) (>10 x ULN) was observed in only 1 atorvastatin-treated patient and was not associated with myopathy. The incidence of treatment-associated myalgia was low in the atorvastatin (1.9% [n = 181]), placebo (0.8% [n = 14]), and other statin (2.0% [n = 105]) groups, and was not related to the atorvastatin dose. No cases of rhabdomyolysis or myopathy were reported. Thus, the overall incidence of treatment-associated adverse events observed with atorvastatin did not increase in the 10- to 80-mg dose range, and was similar to that observed with placebo and in patients treated with other statins. Specific analysis of musculoskeletal and hepatic adverse events showed that these occurred infrequently and rarely resulted in treatment discontinuation.
authors.affiliation: Pfizer Global Pharmaceuticals, 235 East 42nd Street, New York, NY 10017-5755, USA. connie.newman@pfizer.com
authors.forename: Connie B
authors.initials: CB
authors.lastname: Newman
authors.forename: Gary
authors.initials: G
authors.lastname: Palmer
authors.forename: Halit
authors.initials: H
authors.lastname: Silbershatz
authors.forename: Michael
authors.initials: M
authors.lastname: Szarek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin