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A Meta-analysis of Randomized Controlled Trials

John C. LaRosa, MD; Jiang He, MD, PhD; Suma Vupputuri, MPH

JAMA. 1999;282:2340-2346.

Context  Lowering low-density lipoprotein cholesterol (LDL-C) is known to reduce risk of recurrent coronary heart disease in middle-aged men. However, this effect has been uncertain in elderly people and women.

Objective  To estimate the risk reduction of coronary heart disease and total mortality associated with statin drug treatment, particularly in elderly individuals and women.

Data Sources  Trials published in English-language journals were retrieved by searching MEDLINE (1966–December 1998), bibliographies, and authors' reference files.

Study Selection  Studies in which participants were randomized to statin or control treatment for at least 4 years and clinical disease or death was the primary outcome were included in the meta-analysis (5 of 182 initially identified).

Data Extraction  Information on sample size, study drug duration, type and dosage of statin drug, participant characteristics at baseline, reduction in lipids during intervention, and outcomes was abstracted independently by 2 authors (J.H. and S.V.) using a standardized protocol. Disagreements were resolved by consensus.

Data Synthesis  Data from the 5 trials, with 30,817 participants, were included in this meta-analysis. The mean duration of treatment was 5.4 years. Statin drug treatment was associated with a 20% reduction in total cholesterol, 28% reduction in LDL-C, 13% reduction in triglycerides, and 5% increase in high-density lipoprotein cholesterol. Overall, statin drug treatment reduced risk 31% in major coronary events (95% confidence interval [CI], 26%-36%) and 21% in all-cause mortality (95% CI, 14%-28%). The risk reduction in major coronary events was similar between women (29%; 95% CI, 13%-42%) and men (31%; 95% CI, 26%-35%), and between persons aged at least 65 years (32%; 95% CI, 23%-39%) and persons younger than 65 years (31%; 95% CI, 24%-36%).

Conclusions  Our meta-analysis indicates that reduction in LDL-C associated with statin drug treatment decreases the risk of coronary heart disease and all-cause mortality. The risk reduction was similar for men and women and for elderly and middle-aged persons.

Author Affiliations: Office of the President, State University of New York Health Science Center at Brooklyn, Brooklyn, NY (Dr LaRosa); and the Department of Epidemiology, Tulane University Medical Center, New Orleans, La (Dr He and Mr Vupputuri).

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