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Randomized Controlled Trial
. 2020 Nov 7;41(42):4092-4099.
doi: 10.1093/eurheartj/ehaa659.

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  2 , Fausto J Pinto  3 , Aldo P Maggioni  4 , Rafael Diaz  5 , Colin Berry  6 , Wolfgang Koenig  7   8   9 , Jose Lopez-Sendon  10 , Habib Gamra  11 , Ghassan S Kiwan  12 , Lucie Blondeau  13 , Andreas Orfanos  13 , Reda Ibrahim  1 , Jean C Grégoire  1 , Marie-Pierre Dubé  1 , Michelle Samuel  1 , Olivier Morel  14   15 , Pascal Lim  16 , Olivier F Bertrand  17 , Simon Kouz  18 , Marie-Claude Guertin  13 , Philippe L L'Allier  1 , Francois Roubille  19
Affiliations
Randomized Controlled Trial

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

Nadia Bouabdallaoui et al. Eur Heart J. .

Abstract

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.

Keywords: COLCOT; Cardiovascular inflammation; Colchicine; Inflammasome; Time-to-treatment initiation.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Subject disposition, flow chart diagram.
Figure 2
Figure 2
Associations between time-to-treatment initiation and the risk of occurrence of the primary composite endpoint. The adjusted hazard ratio and 95% confidence intervals come from a quadratic multivariable Cox regression model.
Figure 3
Figure 3
Kaplan–Meier event curves for the primary and secondary efficacy composite endpoints in the colchicine group and the placebo group according to time-to-treatment initiation. The inset shows the same data on an enlarged y-axis. (A) Cumulative incidence of the primary composite endpoint in patients with time-to-treatment initiation ≤ 3 days; (B) Cumulative incidence of the secondary composite endpoint in patients with time-to-treatment initiation ≤ 3 days.
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Comment in

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