Cardiology trials often adopt composite endpoints that combine several events of clinical interest as the primary efficacy outcome.
Time-to-first-event approaches follow the recommendations of regulatory agencies. But composite outcomes that only consider the first event are suboptimal for a chronic disease such as heart failure (HF), which is characterized by recurrent HF hospitalizations since repeat events within individuals are ignored in analyses.
Recurrent HF hospitalizations indicate a worsening condition and disease progression, so considering all HF hospitalizations in analysis more accurately assesses the effect of treatment on the true disease burden. Currently, there is no recommendation as to the preferred approach. The CHARM-Preserved trial shows the impact of analyzing only the time-to-first event and ignoring repeat hospitalizations.1