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Discordance between Meta-analyses and Large-Scale Randomized, Controlled Trials: Examples from the Management of Acute Myocardial Infarction

Steven Borzak, MD; and Paul M. Ridker, MD
[+] Article and Author Information

From Henry Ford Hospital, Detroit, Michigan; and Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Acknowledgments: The authors thank Lori Douthat for assistance in figure and manuscript preparation and Dr. Elliott Antman for reviewing the manuscript. Grant Support: Dr. Ridker is a Clinician Scientist of the American Heart Association. Requests for Reprints: Steven Borzak, MD, Cardiovascular Division, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI, 48202. Current Author Addresses: Dr. Borzak: Cardiovascular Division, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI, 48202.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1995;123(11):873-877. doi:10.7326/0003-4819-123-11-199512010-00010
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Clinicians making treatment decisions are faced with ever-growing numbers of therapies, each supported by different types of clinical data. By bringing together large amounts of data, meta-analysis has emerged as a useful tool for generating hypotheses with which to plan definitive trials, and it has also been recommended as a basis for decision making in the absence of definitive trials. In several instances, early meta-analyses have provided evidence of efficacy that was subsequently confirmed. However, in other instances, the results of initial meta-analyses have disagreed with the results of subsequent large-scale trials.

Nitrate and magnesium therapy for acute myocardial infarction are two contemporary examples of treatments about which hypothesis-generating meta-analyses and subsequent large trials have disagreed. We review the issues surrounding the interpretation of meta-analyses in these cases, and we suggest that the appropriate use of meta-analyses in clinical decision making be carefully placed in the context of a review of pathophysiologic principles and the results of basic laboratory research and individual trials.

Figures

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Figure 1.
Concordance and discordance between meta-analyses and megatrials.

Comparison of the odds ratios and 95% Cls for the given treatments. The first published meta-analysis is shown by the solid bars; the first published megatrial is shown by the open bars. Years of publication are given on the left; the numbers of patients included in each trial or meta-analysis are given on the right. Data on thrombolytic therapy is from references 8 and 12; data on early β-blocker therapy is from references 9 and 13; data on nitrate therapy is from references 10 and 14; and data on magnesium therapy is from references 11 and 15.

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Figure 2.
Magnesium therapy for acute myocardial infarction: trials and meta-analyses.[11][20][15][25][15, 25]

The odds ratios of death and 95% Cls from seven smaller trials of magnesium therapy and the LIMIT-2 and ISIS-4 trials . The two open bars are the results of the meta-analyses done using the random-effects model and the fixed-effects model ; they illustrate the discrepancy between these two forms of meta-analysis.

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