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Cited by 473

The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.

Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials

Open access
Ferreira-González, Ignacio, Permanyer-Miralda, Gaiet, Domingo-Salvany, Antònia, Busse, Jason W, Heels-Ansdell, Diane, Montori, Victor M, Akl, Elie A, Bryant, Dianne M, Alonso-Coello, Pablo, Alonso, Jordi, Worster, Andrew, Upadhye, Suneel, Jaeschke, Roman, Schünemann, Holger J, Pacheco-Huergo, Valeria, Wu, Ping, Mills, Edward J, Guyatt, Gordon H·2007·BMJ

Abstract

OBJECTIVE: To explore the extent to which components of composite end points in randomised controlled trials vary in importance to patients, the frequency of events in the more and less important components, and the extent of variability in the relative risk reductions across components. DESIGN: Systematic review of randomised controlled trials. DATA SOURCES: Cardiovascular randomised controlled trials published in the Lancet, Annals of Internal Medicine, Circulation, European Heart Journal, JAMA, and New England Journal of Medicine, from 1 January 2002 to 30 June 2003. Component end points of composite end points were categorised according to importance to patients as fatal, critical, major, moderate, or minor. RESULTS: Of 114 identified randomised controlled trials that included a composite end point of importance to patients, 68% (n=77) reported complete component data for the primary composite end point; almost all (98%; n=112) primary composite end points included a fatal end point. Of 84 composite end points for which component data were available, 54% (n=45) showed large or moderate gradients in both importance to patients and magnitude of effect across components. When analysed by categories of importance to patients, the most important components were associated with lower event rates in the control group (medians of 3.3-3.7% for fatal, critical, and major outcomes; 12.3% for moderate outcomes; and 8.0% for minor outcomes). Components of greater importance to patients were associated with smaller treatment effects than less important ones (relative risk reduction of 8% for death and 33% for components of minor importance to patients). CONCLUSION: The use of composite end points in cardiovascular trials is frequently complicated by large gradients in importance to patients and in magnitude of the effect of treatment across component end points. Higher event rates and larger treatment effects associated with less important components may result in misleading impressions of the impact of treatment.

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Metadata

Authors
Ferreira-González, I., Permanyer-Miralda, G., Domingo-Salvany, A., Busse, J. W., Heels-Ansdell, D., Montori, V. M., Akl, E. A., Bryant, D. M., Alonso-Coello, P., Alonso, J., Worster, A., Upadhye, S., Jaeschke, R., Schünemann, H. J., Pacheco-Huergo, V., Wu, P., Mills, E. J., & Guyatt, G. H.
Venue
BMJ
Publisher
BMJ
Published
2007-04-02
Volume
334
Issue
7597
Pages
786
ISSN
  • 0007-1447 (ISSN-L)
  • 0959-8138
  • 1468-5833
OpenAlex
W2042805913
Cited by
473
References
15
FWCI
4.77
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials. https://app.cochat.ai/papers/10.1136/bmj.39136.682083.ae
The paper
Ferreira-González, I., Permanyer-Miralda, G., Domingo-Salvany, A., Busse, J. W., Heels-Ansdell, D., Montori, V. M., Akl, E. A., Bryant, D. M., Alonso-Coello, P., Alonso, J., Worster, A., Upadhye, S., Jaeschke, R., Schünemann, H. J., Pacheco-Huergo, V., Wu, P., Mills, E. J., & Guyatt, G. H. (2007). Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials. BMJ. https://doi.org/10.1136/bmj.39136.682083.ae

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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