Published online before print December 11, 2006, doi: 10.1161/CIRCULATIONAHA.106.624890
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(Circulation. 2006;114:2788-2797.)
© 2006 American Heart Association, Inc.
Epidemiology |
Risks Associated With Statin Therapy
A Systematic Overview of Randomized Clinical Trials
From the Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Conn (A.K., J.M.F., Y.W., H.M.K.); Department of General Internal Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio (C.O.P.); VA Connecticut Healthcare System, West Haven, Conn (J.M.F.); Ambulatory Health Clinic, United States Navy, Groton, Conn (S.M.); Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada (D.T.K.); and Section of Health Policy and Administration, Department of Epidemiology and Public Health, and the Robert Wood Johnson Clinical Scholars Program, Department of Medicine, Yale University School of Medicine, and Center for Outcomes Research and Evaluation, Yale–New Haven Hospital, New Haven, Conn (H.M.K.).
Correspondence to Harlan M. Krumholz, MD, SM, 333 Cedar St, Room I-456 SHM, PO Box 208088, New Haven, CT 06520-8088. E-mail harlan.krumholz{at}yale.edu
Received March 9, 2006; revision received October 20, 2006; accepted October 25, 2006.
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.
Methods and 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 
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.
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