Applying novel methods to assess clinical outcomes: insights from the TRILOGY ACS trial
Abstract
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.
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- Authors
- Bakal, J. A., Roe, M. T., Ohman, E. M., Goodman, S. G., Fox, K. A. A., Zheng, Y., Westerhout, C. M., Hochman, J. S., Lokhnygina, Y., Brown, E. B., & Armstrong, P. W.
- Affiliations
- University of Alberta (CA)
- Duke University (US)
- St. Michael's Hospital (CA)
- British Heart Foundation (GB)
- NYU Langone Health (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Armstrong, P. W.
- ORCID
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-07-10
- Volume
- 36
- Issue
- 6
- Pages
- 385-392
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W1985541943
- Cited by
- 59
- References
- 13
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 9 · 2015: 7 · 2014: 2
- FWCI
- 7.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- University of Toronto
- Daiichi Sankyo Europe
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Keywords
- acute coronary syndrome, prasugrel, clopidogrel, composite endpoints, win ratio, recurrent event analysis, time to first event, event weighting, clinical trial outcome assessment, antiplatelet therapy
- MeSH terms
- Prasugrel Hydrochloride, Clopidogrel, Aged, Angina, Unstable, Humans, Middle Aged, Myocardial Infarction, Platelet Aggregation Inhibitors, Recurrence, Ticlopidine, Survival Analysis, Treatment Outcome, Stroke, Endpoint Determination, Purinergic P2Y Receptor Antagonists
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