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

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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  • Existing tools to accelerate systematic reviews are not capable of full automation with human-level accuracy.

    “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]

    The paper describes techniques for conducting cumulative meta-analyses (Introduction, p. 1) and says they can simplify digesting clinical-trial literature (Future Applications, p. 6). Neither passage assesses tools for accelerating systematic reviews or their capacity for full automation with human-level accuracy. Searches for those terms and for automated review software found no passage addressing that claim. (LLM, conf=0.73)

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  • Lau et al. 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.

    “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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Research works printed but not linked: 6

  1. [2]2. Sacks HS, Berrier J, Reitman D, Ancona-Berk VA, Chalmers TC. Metaanalyses of randomized controlled trials. N Engl J Med 1987;316:450-5.
  2. [24]24. Long-term and short-term beta-blockade after myocardial infarction. Lancet 1982;1:1159-61.
  3. [28]28. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349-60.
  4. [43]43. Aspirin after myocardial infarction. Lancet 1980;1:1172-3.
  5. [44]44. Canner PL. Aspirin in coronary heart disease: comparison of six clinical trials. Isr J Med Sci 1983;19:413-23.
  6. [53]53. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;1:397-402.

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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
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
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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