The full content of Annals is available to subscribers

Subscribe/Learn More  >
Ideas and Opinions |

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, Author, and Disclosure 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
Text Size: A A A

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.


Grahic Jump Location
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.

Grahic Jump Location
Grahic Jump Location
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.

Grahic Jump Location




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment/Letter
Submit a Comment/Letter

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now for $32.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Related Articles
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.