OBJECTIVE: The aim of this study was to compare the safety profile of atorvastatin calcium at 4 doses with that of placebo in elderly patients (age, > or =65 years). METHODS: A single pooled database (Pfizer Atorvastatin Clinical Program Database) of 50 published and unpublished completed clinical trials was analyzed retrospectively. Tolerability data from male and female study participants aged > or =65 years at the time of study enrollment were extracted from this database and grouped based on treatment: atorvastatin 10, 20, 40, or 80 mg/d, or placebo. Analyses included comparisons of treatment-related and serious adverse events (AEs) of the musculoskeletal, hepatic, and renal systems. Descriptive statistics were employed. No inferential statistical analyses were performed. RESULTS:A total of 5924 patients were included in the pooled analysis (range of mean age, 71-74 years; white race, 5437 [91.8%]; female sex, 2506 [42.3%]; treatment withatorvastatin10 mg/d, n = 2042; atorvastatin 20 mg/d, n = 667; atorvastatin 40 mg/d, n = 522; atorvastatin 80 mg/d, n = 1698; and placebo, n = 995). The overall AE profiles appeared similar with all atorvastatin doses and placebo. The proportions of patients experiencing at least 1 treatment-related AE were 16.1%, 10.2%, 11.3%, 15.0%, and 15.3% in the atorvastatin 10-, 20-, 40-, and 80-mg/d, and placebo groups, respectively. The rates of discontinuation due to treatment-associated AEs appeared comparable between all doses of atorvastatin and placebo (2.1% vs 1.7%). Serious AEs were rare (< or =1.0%) and seldom led to withdrawal. The prevalence of treatment-associated myalgia was low in all treatment groups (< or =1.8%). None of the patients experienced persistent creatine kinase elevations >10-fold the upper limit of normal (x ULN), and no cases of myopathy or rhabdomyolysis were reported. The rates of patients with persistent elevation >3 x ULN) of hepatic aminotransferases were 0.1%, 0%, 0.2%, 0.5%, and 0.2% in the atorvastatin 10-, 20-, 40-, and 80-mg/d, and placebo groups, respectively. Although the prevalences of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations appeared slightly higher in the 80-mg/d group (3.2% vs < or =0.9% in all other groups), specific musculoskeletal and hepatic AEs were rare (< or =3.0%). CONCLUSIONS: This pooled analysis of 50 published and unpublished studies in elderly patients found that the overall prevalences of AEs did not appear to increase with dose and appeared comparable to that observed with placebo. Although the prevalences of ALT/AST elevations appeared slightly higher in the 80-mg/d group (3.2% vs < or =0.9% in all other groups), specific musculoskeletal and hepatic AEs were rare (< or =3.0%). The rates of discontinuation appeared comparable between all 4 doses of atorvastatin and placebo. The results of this analysis support the favorable safety profile of atorvastatin across the full dose range in patients aged > or =65 years.
RCT Entities:
OBJECTIVE: The aim of this study was to compare the safety profile of atorvastatin calcium at 4 doses with that of placebo in elderly patients (age, > or =65 years). METHODS: A single pooled database (Pfizer Atorvastatin Clinical Program Database) of 50 published and unpublished completed clinical trials was analyzed retrospectively. Tolerability data from male and female study participants aged > or =65 years at the time of study enrollment were extracted from this database and grouped based on treatment: atorvastatin 10, 20, 40, or 80 mg/d, or placebo. Analyses included comparisons of treatment-related and serious adverse events (AEs) of the musculoskeletal, hepatic, and renal systems. Descriptive statistics were employed. No inferential statistical analyses were performed. RESULTS: A total of 5924 patients were included in the pooled analysis (range of mean age, 71-74 years; white race, 5437 [91.8%]; female sex, 2506 [42.3%]; treatment with atorvastatin 10 mg/d, n = 2042; atorvastatin 20 mg/d, n = 667; atorvastatin 40 mg/d, n = 522; atorvastatin 80 mg/d, n = 1698; and placebo, n = 995). The overall AE profiles appeared similar with all atorvastatin doses and placebo. The proportions of patients experiencing at least 1 treatment-related AE were 16.1%, 10.2%, 11.3%, 15.0%, and 15.3% in the atorvastatin 10-, 20-, 40-, and 80-mg/d, and placebo groups, respectively. The rates of discontinuation due to treatment-associated AEs appeared comparable between all doses of atorvastatin and placebo (2.1% vs 1.7%). Serious AEs were rare (< or =1.0%) and seldom led to withdrawal. The prevalence of treatment-associated myalgia was low in all treatment groups (< or =1.8%). None of the patients experienced persistent creatine kinase elevations >10-fold the upper limit of normal (x ULN), and no cases of myopathy or rhabdomyolysis were reported. The rates of patients with persistent elevation >3 x ULN) of hepatic aminotransferases were 0.1%, 0%, 0.2%, 0.5%, and 0.2% in the atorvastatin 10-, 20-, 40-, and 80-mg/d, and placebo groups, respectively. Although the prevalences of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations appeared slightly higher in the 80-mg/d group (3.2% vs < or =0.9% in all other groups), specific musculoskeletal and hepatic AEs were rare (< or =3.0%). CONCLUSIONS: This pooled analysis of 50 published and unpublished studies in elderly patients found that the overall prevalences of AEs did not appear to increase with dose and appeared comparable to that observed with placebo. Although the prevalences of ALT/AST elevations appeared slightly higher in the 80-mg/d group (3.2% vs < or =0.9% in all other groups), specific musculoskeletal and hepatic AEs were rare (< or =3.0%). The rates of discontinuation appeared comparable between all 4 doses of atorvastatin and placebo. The results of this analysis support the favorable safety profile of atorvastatin across the full dose range in patients aged > or =65 years.