Benefit–risk of colchicine and spironolactone in acute myocardial infarction: a prespecified generalised pairwise comparisons analysis of the CLEAR trial
Authors' conclusion
In patients with post-MI, both low-dose colchicine and spironolactone demonstrated disadvantageous benefit-risk profiles, reinforcing that neither agent should be used routinely. This prespecified application of GPC provided results consistent with traditional methods but offered a clinically intuitive framework for interpreting composite outcomes.
Study context
- Population
- Patients within 72 hours of acute myocardial infarction (MI) and percutaneous coronary intervention
- Participants
- 7,062 patients
- Comparison
- Low-dose colchicine and spironolactone versus placebo
Methodological detailsgeneralised pairwise comparisons, time-to-first and recurrent-event generalised pairwise comparisons (GPC)
- Generalised pairwise comparisons
- Time-to-first and recurrent-event GPC
Primary result
As reported in the abstract
Hierarchical benefit-risk outcome:
- All-cause death
- Stroke
- Recurrent MI
- Unplanned ischaemia-driven revascularisation
- Serious infection
- Diarrhoea
colchicine vs placeboWin ratio (95% CI)
12% lower proportional win rate
0.88(0.79–0.98)
colchicine vs placeboWin difference (95% CI)
Hierarchical benefit-risk outcome (all-cause death, stroke, recurrent MI, unplanned ischaemia-driven revascularisation, serious infection or diarrhoea), time-to-first event GPC
−2.10%(−3.84 to −0.37)
Further findings
| Outcome | WR (95% CI) | |
|---|---|---|
| Hierarchical benefit-risk outcome (all-cause death, stroke, MI, new or worsening heart failure, significant ventricular arrhythmia, hyperkalaemia or gynaecomastia/gynaecodynia)Spironolactonevs placebo14% lower win rate · largely attributable to gynaecomastia and hyperkalaemia | 0.86 (0.75–0.99) | |
| 0.512Win ratio (log scale) |
| Outcome | Win difference (95% CI) | |
|---|---|---|
| Hierarchical benefit-risk outcome (all-cause death, stroke, MI, new or worsening heart failure, significant ventricular arrhythmia, hyperkalaemia or gynaecomastia/gynaecodynia)Spironolactonevs placeboLargely attributable to gynaecomastia and hyperkalaemia | −1.46% (−2.84% to −0.08%) | |
| −4−202Difference (linear scale) |
Conventional statistical approaches (Cox, logistic and Andersen-Gill models)
- Conventional statistical approaches yielded concordant results
Higher-order efficacy outcomes (death, MI, stroke, heart failure)
- No benefit across both interventions
Original publication
Benefit–risk of colchicine and spironolactone in acute myocardial infarction: a prespecified generalised pairwise comparisons analysis of the CLEAR trial. Heart. Published 4 September 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →