Benefit of colchicine independent of timing of prior ACS

Colchicine in Patients With Chronic Coronary Disease in Relation to Prior Acute Coronary Syndrome

Literature - Opstal TSJ, Fiolet ATL, van Broekhoven A, et al. - JACC 2021;78:8590866, doi:10.1016/jacc.2021.06.037

Introduction and methods

In the COLCOT trial, the anti-inflammatory drug colchicine reduced CV events by 23% compared to placebo in patients with a very recent history of myocardial infarction (< 30 days) [1]. Benefit appeared to be greatest in those starting colchicine within 3 days of MI [2]. In the LoDoCo2 trial colchicine reduced risk of CV events by 31% compared to placebo in patients with chronic coronary disease. The benefit was driven by reductions in MI and ischemia-driven coronary revascularization [3]. In the LoDoCo2 trial, patients who had experience an acute coronary syndrome (ACS) within 6 months were excluded. The findings in these two trials raised questions about the benefit of colchicine with regard to timing of treatment following an episode of ACS.

Therefore, it was examined whether the effects of colchicine on CV events compared to placebo were consistent in patients with no prior, recent, remote or very remote ACS, using data of the LoDoCo2 trial.

LoDoCo2 was a randomized, controlled, double-blind trial in which 5522 patients were enrolled in Australia and the Netherlands, with a median follow-up of 28.6 months. Patients were required to have had a stable condition ≥6 months before enrollment. Primary endpoint was the composite of CV death, MI, ischemic stroke or ischemia-driven revascularization. Subgroups were as follows: no prior ACS (n=864, 16%), recent ACS (6-24 months at randomization) (n=1479, 27%), remote ACS (2-7 years at randomization) (n=1582, 29%), and very remote ACS (>7 years at randomization) (n1597, 29%).

Main results

  • There was no difference in incidence of the primary endpoint between patients with prior ACS and those with no prior ACS.
  • Also, patients with remote ACS had similar risk of the primary endpoint compared with patients with recent ACS. Patients with very remote ACS had a slightly higher incidence of primary endpoint compared with patients with recent ACS, but this difference was not statistically significant.
  • Benefit of colchicine on risk of the primary endpoint was consistent in patients with no prior ACS (HR 0.81, 95%CI: 0.52-1.27) and in those with prior ACS (HR 0.67, 95%CI: 0.54-0.82) (Pinteraction=0.43).
  • Benefit of colchicine was also consistent across subgroups of patients with prior ACS; recent ACS (HR 0.75, 95%CI: 0.51-1.10), remote ACS (HR 0.55, 95%CI: 0.37-0.82) and very remote ACS (HR 0.70, 95%CI:0.51-0.96) (Pinteraction=0.59).


Efficacy of colchicine in patients with chronic coronary disease enrolled in the LoDoCo2 trial is independent of history and timing of prior ACS. ‘These findings highlight the importance of compliance with long-term secondary prevention therapies, including the use of anti-inflammatory therapy’, the authors conclude.


1. Tardif J-CC, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019;381:2497–2505.

2. Bouabdallaoui N, Tardif JC, Waters DD, et al. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Eur Heart J. 2020;41:4092–4099.

3. Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020;383:1838–184

Find this article online at JACC

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