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Cumulative Meta-Analysis of Therapeutic Trials for Myocardial Infarction
Open accessAbstract
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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“While several tools have been developed to accelerate SRs 4,5 , none are capable of full automation with human-level accuracy.”
From Automation of Systematic Reviews with Large Language Models (2025) · cites this paper as [5]
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“Lau and colleagues demonstrated that, had a cumulative meta-analysis been regularly updated, the beneficial effect of streptokinase in patients who had experienced an acute myocardial infarction would have been established by 1973”
From Commentary: Two-sample Mendelian randomization: opportunities and challenges (2016) · cites this paper as [22]
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Metadata
- 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)
- 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
- 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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