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Eur Heart J. 2013 Mar;34(12):903-8. doi: 10.1093/eurheartj/ehs438. Epub 2012 Dec 19.

Evaluation of early percutaneous coronary intervention vs. standard therapy after fibrinolysis for ST-segment elevation myocardial infarction: contribution of weighting the composite endpoint.

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  • 1Division of Cardiology, 2-132 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, Alberta, Canada T6G 2E1.



The selection of optimal endpoints for cardiovascular clinical trials continues to be challenging. We examined an alternative interpretation of a series of trials when the individual event severity is considered.


We analysed three contemporary myocardial infarction (MI) trials of early percutaneous coronary intervention after fibrinolysis, using a weighted composite method. This method allows the examination of the heterogeneity in the direction and magnitude of component endpoints, and multiple events (vs. first event). We incorporated a physician-assessed severity of each component endpoint in all patients for the five-item composite in the largest study, Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), which enrolled 1059 ST-elevation MI patients. The traditional approach yielded event-free survival probabilities of 0.89 [95% confidence interval (CI) 0.86-0.91] for the early invasive arm and 0.83 (95% CI 0.79-0.86) for the standard care arm (P = 0.004). After accounting for the clinician-investigator-determined weights, the effective survival probabilities were 0.93 (95% CI 0.91-0.95) for the early invasive arm and 0.93 (95% CI 0.90-0.95) with no significant difference (P = 0.54). The same pattern was observed in the three-trial cohort using a four-item composite with an observed improvement in event-free survival outcomes (P = 0.01), which was no longer apparent after the severity weights were considered (P = 0.44).


This analysis highlights the importance of considering the relative severity and multiple events in the evaluation of a clinical trial.

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