Applying novel methods to assess clinical outcomes: insights from the TRILOGY ACS trial

Eur Heart J. 2015 Feb 7;36(6):385-92a. doi: 10.1093/eurheartj/ehu262. Epub 2014 Jul 10.


Aims: Several methods provide new insights into understanding clinical trial composite endpoints, using both conventional and novel methods. The TRILOGY ACS trial is used as a contemporary example to prospectively compare these methods side by side.

Methods and results: The traditional time-to-first-event, Andersen-Gill recurrent events method, win ratio, and a weighted composite endpoint (WCE) are compared using the randomized, active-control TRILOGY ACS trial. This trial had a neutral result and randomized 9326 patients managed without coronary revascularization within 10 days of their acute coronary syndrome to receive either prasugrel or clopidogrel and followed them for up to 30 months. The traditional composite, win ratio, and WCE demonstrated no significant survival advantage for prasugrel, whereas the Andersen-Gill method demonstrated a statistical advantage for prasugrel [hazard ratio (HR), 0.86 (95% CI, 0.72-0.97)]. The traditional composite used 73% of total patient events; 40% of these were derived from the death events. The win ratio used 66% of total events; deaths comprised 57% of these. Both Andersen-Gill and WCE methods used all events in all participants; however, with the Andersen-Gill method, death comprised 41% of the proportion of events, whereas with the WCE method, death comprised 64% of events.

Conclusion: This study addresses the relative efficiency of various methods for assessing clinical trial events comprising the composite endpoint. The methods accounting for all events, in particular those incorporating their clinical relevance, appear most advantageous, and may be useful in interpreting future trials. This clinical and statistical advantage is especially evident with long-term follow-up where multiple non-fatal events are more common.

Clinical trial registration: NCT00699998.

Keywords: Acute coronary syndromes; Clinical trial; Composite endpoints.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angina, Unstable / drug therapy*
  • Angina, Unstable / mortality
  • Clopidogrel
  • Endpoint Determination
  • Humans
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prasugrel Hydrochloride / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Recurrence
  • Stroke / etiology
  • Stroke / mortality
  • Survival Analysis
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine

Associated data