Risks associated with statin therapy: a systematic overview of randomized clinical trials.
BACKGROUND
Although statins reduce the risk of cardiovascular events, concerns about adverse effects may deter physicians from prescribing these agents. We performed a systematic overview of randomized statin trials to quantify the risks of musculoskeletal, renal, and hepatic complications associated with therapy.


RESULTS
Major statin trials were identified by electronic search of the MEDLINE database from 1966 to December 2005. We included English language reports of adults with documented hyperlipidemia; double-blind, random allocation of > or = 100 patients to statin monotherapy versus placebo; and reports of myalgia, creatine kinase elevations, rhabdomyolysis, transaminase elevations, and discontinuation due to adverse events. Among 74,102 subjects enrolled in 35 trials (follow-up range, 1 to 65 months), statin therapy (excluding cerivastatin) did not result in significant absolute increases in risks of myalgias (risk difference/1000 patients [RD], 2.7; 95% CI, -3.2 to 8.7), creatine kinase elevations (RD, 0.2; 95% CI, -0.6 to 0.9), rhabdomyolysis (RD, 0.4; 95% CI, -0.1 to 0.9), or discontinuation due to any adverse event (RD, -0.5; 95% CI, -4.3 to 3.3). The absolute risk of transaminase elevations was significantly higher with statin therapy (RD, 4.2; 95% CI, 1.5 to 6.9).


CONCLUSIONS
On the basis of data available from published clinical trials, statin therapy is associated with a small excess risk of transaminase elevations, but not of myalgias, creatine kinase elevations, rhabdomyolysis, or withdrawal of therapy compared with placebo. Further study is necessary to determine whether the results from these published clinical trials are similar to what occurs in routine practice, particularly among patients who are older, have more severe comorbid conditions, or receive higher statin doses than most patients in these clinical trials.
Kashani
Amir
A
Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Conn, USA.
Phillips
Christopher O
CO
Foody
JoAnne M
JM
Wang
Yongfei
Y
Mangalmurti
Sandeep
S
Ko
Dennis T
DT
Krumholz
Harlan M
HM
D000328:Adult; D004282:Documentation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D009135:Muscular Diseases / Q000139:chemically induced / Q000453:epidemiology; D010146:Pain / Q000139:chemically induced / Q000453:epidemiology; D018579:Patient Selection; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D018570:Risk Assessment; D014481:United States; D014486:United States Food and Drug Administration
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos