Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)

Nadia Bouabdallaoui (1) , Jean-Claude Tardif (1) , David D Waters , Fausto J Pinto (2) , Aldo Pietro Maggioni (3) , Rafael Diaz , Colin Berry , Wolfgang Koenig (4) , José Lopez-Sendon , Habib Gamra (5) , Ghassan Kiwan , Lucie Blondeau , Andreas Orfanos , Reda Ibrahim (1) , Jean C. Grégoire (1) , Marie-Pierre Dubé (1) , Michelle Samuel (1) , Olivier Morel (6) , Pascal Lim (7, 8) , Olivier F. Bertrand , Simon Kouz , Marie-Claude Guertin , Philippe L'Allier (1) , François Roubille (9, 10)

1 Montreal Heart Institute - Institut de Cardiologie de Montréal
2 ULISBOA - Universidade de Lisboa = University of Lisbon
3 ANMCO Research Center, Firenze,Italy
4 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
5 UM - Université de Monastir - University of Monastir
6 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
7 Hôpital Henri Mondor
8 IMRB - Institut Mondor de Recherche Biomédicale
9 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
10 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]

Aims: The COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine. Methods and results: In COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (<3, 4–7 and >8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated < Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32–0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53–1.75) or > Day 8 (HR = 0.82, 95% CI 0.61–1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P < 0.05). Conclusion: Patients benefit from early, in-hospital initiation of colchicine after MI. Trial Registration: COLCOT ClinicalTrials.gov number, NCT02551094.

Mots clés: Cardiovascular inflammation; Time-to-treatment initiation; Colchicine; COLCOT; Inflammasome

Domaines: Cardiologie et système cardiovasculaire; Pharmacologie

Nadia Bouabdallaoui, Jean-Claude Tardif, David D Waters, Fausto J Pinto, Aldo Pietro Maggioni, et al.. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). European Heart Journal, 2020, 41 (42), pp.4092-4099. ⟨10.1093/eurheartj/ehaa659⟩. ⟨hal-02925336⟩