# Colchicine en spironolacton bij acuut MI: voordeel-risico analyse

*geplaatst 2026-02-23 · Algemeen · Heart (British Cardiac Society) · doi 10.1136/heartjnl-2025-326218 · https://hartvaat.nl/2026/02/23/colchicine-en-spironolacton-bij-acuut-mi-voordeel-risico-analyse/*

Gezamenlijke voordeel-risico analyse van colchicine en spironolacton na acuut MI. Colchicine biedt netto voordeel, spironolacton niet. Dit informeert de post-MI farmacotherapie.

## English: Benefit-risk of colchicine and spironolactone in acute myocardial infarction: a prespecified generalised pairwise comparisons analysis of the CLEAR trial.

This prespecified generalized pairwise comparison analysis of CLEAR SYNERGY assessed the combined benefit-risk of colchicine and spironolactone after MI, providing a more nuanced evaluation than conventional composite endpoints.

## Abstract (original, from the publication)

BACKGROUND: Composite outcomes in cardiovascular trials often group events of unequal clinical importance, and conventional analyses may obscure treatment trade-offs. Generalised pairwise comparisons (GPC), expressed as a win ratio (WR), allow for hierarchical ranking of events and incorporation of recurrent outcomes, providing a potentially more intuitive assessment of benefit-risk. METHODS: In a prespecified exploratory analysis of the 2×2 factorial, randomised CLEAR (Colchicine and Spironolactone in Patients with Myocardial Infarction) trial (7062 patients within 72 hours of acute myocardial infarction (MI) and percutaneous coronary intervention), we applied both time-to-first and recurrent-event GPC to reassess low-dose colchicine (0.5 mg daily) and spironolactone (25 mg daily) versus placebo. For the colchicine comparison, the hierarchical benefit-risk outcome included all-cause death, stroke, recurrent MI, unplanned ischaemia-driven revascularisation, serious infection or diarrhoea. For the spironolactone comparison, the outcome included all-cause death, stroke, MI, new or worsening heart failure, significant ventricular arrhythmia, hyperkalaemia or gynaecomastia/gynaecodynia. GPC results were compared with Cox, logistic and Andersen-Gill models. RESULTS: For colchicine, the time-to-first event GPC showed a 12% lower proportional win rate compared with placebo (WR 0.88, 95% CI 0.79 to 0.98; win difference -2.10%, 95% CI -3.84 to -0.37), driven largely by excess diarrhoea. For spironolactone, patients experienced a 14% lower win rate (WR 0.86, 95% CI 0.75 to 0.99; win difference -1.46%, 95% CI -2.84% to -0.08%), largely attributable to gynaecomastia and hyperkalaemia. Conventional statistical approaches yielded concordant results. Across both interventions, higher-order efficacy outcomes (death, MI, stroke, heart failure) showed no benefit. CONCLUSIONS: 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.

Auteurs: Marc-André d'Entremont, Sanjit S Jolly, Faisal Alharthi, Binita Shah, David Austin, Quilong Yi, Robert F Storey, Matthias Bossard, Jan Cornel, Jeroen Jaspers Focks, Sasko Kedev, Valon Asani, Goran Stankovic, Michael Tsang, Nicholas Valettas, Jessica Tyrwhitt, Jackie Betz, Shun Fu Lee, Rajibul Mian, Johanne Silvain, Farzin Beygui, Andrew Czarnecki, Payam Dehghani, Warren Cantor, Shahar Lavi, James C Spratt, Emilie P Belley-Côté, John W Eikelboom

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Bron: Heart (British Cardiac Society), https://doi.org/10.1136/heartjnl-2025-326218. Bijgewerkt 2026-07-03T13:31:10Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.