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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.

Abstract

AIMS:

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.

METHODS AND RESULTS:

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).

CONCLUSION:

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

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PMID:
23257948
[PubMed - indexed for MEDLINE]
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