PMID- 16860258
OWN - NLM
STAT- MEDLINE
DCOM- 20061114
LR  - 20181201
IS  - 1543-5946 (Print)
IS  - 1876-7761 (Linking)
VI  - 4
IP  - 2
DP  - 2006 Jun
TI  - Tolerability of atorvastatin in a population aged > or =65 years: a retrospective 
      pooled analysis of results from fifty randomized clinical trials.
PG  - 112-22
AB  - 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      Program Database) of 50 published and unpublished completed clinical trials was 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.
FAU - Hey-Hadavi, Judith H
AU  - Hey-Hadavi JH
AD  - Pfizer Human Health, Pfizer Inc., New York, NY 10017, USA. 
      judith.h.hadavi@pfizer.com
FAU - Kuntze, Erik
AU  - Kuntze E
FAU - Luo, Don
AU  - Luo D
FAU - Silverman, Paul
AU  - Silverman P
FAU - Pittman, Donald
AU  - Pittman D
FAU - Lepetri, Barbara
AU  - Lepetri B
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PL  - United States
TA  - Am J Geriatr Pharmacother
JT  - The American journal of geriatric pharmacotherapy
JID - 101190325
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Pyrroles)
RN  - A0JWA85V8F (Atorvastatin)
SB  - IM
MH  - Aged
MH  - Anticholesteremic Agents/*adverse effects/therapeutic use
MH  - Atorvastatin
MH  - Chemical and Drug Induced Liver Injury
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Heptanoic Acids/*adverse effects/therapeutic use
MH  - Humans
MH  - Hypercholesterolemia/drug therapy
MH  - Kidney Diseases/chemically induced
MH  - Male
MH  - Musculoskeletal Diseases/chemically induced
MH  - Pyrroles/*adverse effects/therapeutic use
MH  - Randomized Controlled Trials as Topic
MH  - Retrospective Studies
EDAT- 2006/07/25 09:00
MHDA- 2006/11/15 09:00
CRDT- 2006/07/25 09:00
PHST- 2006/02/06 00:00 [accepted]
PHST- 2006/07/25 09:00 [pubmed]
PHST- 2006/11/15 09:00 [medline]
PHST- 2006/07/25 09:00 [entrez]
AID - S1543-5946(06)00023-7 [pii]
AID - 10.1016/j.amjopharm.2006.06.001 [doi]
PST - ppublish
SO  - Am J Geriatr Pharmacother. 2006 Jun;4(2):112-22. doi: 
      10.1016/j.amjopharm.2006.06.001.