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Interpreting apparent differences among the major colchicine trials for cardiovascular prevention: A descriptive
Thomas C Scheier1, Hertzel C Gerstein2, Arend Mosterd3
1Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
American Heart Journal
|July 11, 2026
Summary
The outlier status of colchicine trials for cardiovascular prevention depends on the assumed treatment effect. CLEAR SYNERGY is not necessarily the outlier, as its status shifts with different assumed benefits.
Area of Science:
- Cardiology
- Clinical Trials
- Pharmacology
Background:
- Colchicine trials (COLCOT, LoDoCo2, CLEAR SYNERGY) show varying results for cardiovascular prevention.
- CLEAR SYNERGY's neutral outcome has led to its designation as a potential outlier.
- This analysis re-evaluates outlier status based on assumed treatment effects.
Purpose of the Study:
- To examine how the trial least reconciled with assumed treatment effects changes.
- To assess the impact of assumed colchicine benefits on trial outlier designation.
Main Methods:
- Descriptive analysis using published hazard ratios (HRs) and confidence intervals from COLCOT, LoDoCo2, and CLEAR SYNERGY.
- Calculated probabilities of trial repeat outcomes under various assumed true treatment effects.
- Analyzed primary composite outcomes and exploratory outcomes (cardiovascular death, myocardial infarction, stroke).
Main Results:
- Observed primary composite HRs: COLCOT (0.77), LoDoCo2 (0.69), CLEAR SYNERGY (0.99).
- Outlier status shifted: CLEAR SYNERGY for larger assumed benefits, LoDoCo2 for smaller assumed benefits (HRs 0.65-1.00).
- Component analyses revealed divergent patterns for myocardial infarction and stroke outcomes.
Conclusions:
- The trial least reconciled with evidence depends on the assumed true treatment effect.
- CLEAR SYNERGY's neutral result does not automatically designate it as the outlier.
- Differences in trial design, conduct, or population may explain divergent results.
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