Letter by Brown and Ezekowitz Regarding Article, “Development and Evolution of a Hierarchical Clinical Composite End Point for the Evaluation of Drugs and Devices for Acute and Chronic Heart Failure: A 20-Year Perspective”
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To the Editor:
We read with great interest the historical perspective of what is termed a hierarchical composite end point (HCE). A number of issues should be considered before adoption of this end point not fully elucidated by Packer.1 Not surprisingly, almost all the trials quoted have been neutral in the primary HCE outcome, and one needs to look at the actual components to understand the totality of the effect. An inherent attraction exists to capture the totality of effect in 1 place, but the HCE may not be it.
First, the construction of the HCE can inadvertently place more emphasis on some outcomes over others (Figure). For example, a slight change to the definition of the HCE can impact the extent to which the mortality effect is represented in the overall result: when the mortality assessment time window is short, the influence or contribution of mortality on the composite is diminished relative to dyspnea, despite its obvious importance. The authors’ previous publication, which used an HCE as the primary end point, overwhelmed …