Cited by 1,140Meta-analysis and systematic reviewsAcute Myocardial Infarction ResearchStatistical Methods in Clinical Trials

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Cumulative Meta-Analysis of Therapeutic Trials for Myocardial Infarction

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Lau, Joseph, Antman, Elliott M., Jimenez-Silva, Jeanette, Kupelnick, Bruce, Mosteller, Frederick, Chalmers, Thomas C.·1992·New England Journal of Medicine

DOI 10.1056/nejm199207233270406

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Abstract

BACKGROUND: The large volume of published randomized, controlled trials has led to a need for meta-analyses to track therapeutic advances. Performing a new meta-analysis whenever the results of a new trial of a particular therapy are published permits the study of trends in efficacy and makes it possible to determine when a new treatment appears to be significantly effective or deleterious. We describe the use of such a procedure, cumulative meta-analysis, to assess therapeutic trials among patients with myocardial infarction. METHODS: We performed cumulative meta-analyses of clinical trials that evaluated 15 treatments and preventive measures for acute myocardial infarction. RESULTS: An example of this method is its application to the use of intravenous streptokinase as thrombolytic therapy for acute infarction. Thirty-three trials evaluating this therapy were performed between 1959 and 1988. We found that a consistent, statistically significant reduction in total mortality (odds ratios, 0.74; 95 percent confidence interval, 0.59 to 0.92) was achieved in 1973, after only eight trials involving 2432 patients had been completed. The results of the 25 subsequent trials, which enrolled an additional 34,542 patients through 1988, had little or no effect on the odds ratio establishing efficacy, but simply narrowed the 95 percent confidence interval. In particular, two very large trials, the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial in 1986 (11,712 patients) and the Second International Study of Infarct Survival trial in 1988 (17,187 patients) did not modify the already established evidence of efficacy. We used a similar approach to study the accumulating evidence of efficacy (or lack of efficacy) of 14 other therapies and preventive measures for myocardial infarction. CONCLUSIONS: Cumulative meta-analysis of therapeutic trials facilitates the determination of clinical efficacy and harm and may be helpful in tracking trials, planning future trials, and making clinical recommendations for therapy.

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Authors: Lau, J., Antman, E. M., Jimenez-Silva, J., Kupelnick, B., Mosteller, F., & Chalmers, T. C.
Affiliations: Tufts University (US)
Brigham and Women's Hospital (US)
United States Department of Veterans Affairs (US)
Harvard University (US)
ORCID: Lau, Joseph
Antman, Elliott M.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 1992-07-23
Volume: 327
Issue: 4
Pages: 248-254
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejm199207233270406
OpenAlex: W2320350515
Cited by: 1,140
References: 54
Citations by year: 2026: 17 · 2025: 14 · 2024: 17 · 2023: 25 · 2022: 28 · 2021: 25 · 2020: 25 · 2019: 21 · 2018: 28 · 2017: 19 · 2016: 38 · 2015: 36 · 2014: 61 · 2013: 32 · 2012: 49
FWCI: 11.59
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: Agency for Healthcare Research and Quality (R01 HS-05936, P0RT-1-PO1-HS 06341-02)
Topics: Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Keywords: myocardial infarction, acute myocardial infarction treatment, streptokinase, thrombolysis, mortality reduction, prophylaxis
MeSH terms: Humans, Myocardial Infarction, Streptokinase, Meta-Analysis as Topic, Thrombolytic Therapy, Confidence Intervals, Odds Ratio, Randomized Controlled Trials as Topic

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Cumulative Meta-Analysis of Therapeutic Trials for Myocardial Infarction

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