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Dimitrios A Vrachatis, Georgios V Giannopoulos, Spyridon G Deftereos, Colchicine administered early in acute myocardial infarction: ready, set … go?, European Heart Journal, Volume 42, Issue 28, 21 July 2021, Page 2802, https://doi.org/10.1093/eurheartj/ehab010
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This commentary refers to ‘Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)’, by N. Bouabdallaoui et al., doi:10.1093/eurheartj/ehaa659; ‘Colchicine and coronary artery disease: a virtuous adoption’, by F. Angelini et al., doi:10.1093/eurheartj/ehab008; ‘Lessons from COLCOTand LoDoCo2: colchicine for secondary prevention in coronary artery disease’, by N. Bouabdallaoui et al., doi:10.1093/eurheartj/ehab020; and ‘Initiation of low-dose colchicine early after myocardial infarction’, by N. Bouabdallaoui and J-C Tardif, doi:10.1093/eurheartj/ehab038.
The involvement of inflammatory pathways in the course of atherosclerosis from the subclinical level to overt clinical syndrome are well recognized. Indeed, the role of potential pharmaceutical interventions targeting inflammation has lately been in the focus of clinical research. Remarkably, Prof. Eugene Braunwald, in the European Heart Journal Dialogues for the 400th anniversary of cardiology,1 underlined the importance of recent landmark trials—such as COLCOT2—in introducing anti-inflammatory agents as a new class of drugs in coronary artery disease; a class which shall be explored regarding the right drug and proper dose, in the way diuretics were explored in the past.
We read with great interest a post hoc analysis of COLCOT trial3 regarding the differential effect of early vs. late administration of colchicine in the course of acute (type 1) myocardial infarction (MI). The authors of the main COLCOT results paper reported a mean time of almost 2 weeks (13.5 days) between the index MI and colchicine or placebo administration. This means that some patients were started on colchicine while still in the acute phase of their MI, whereas others had well entered the post-MI recovery phase. Starting early has a certain pathophysiological appeal, considering that inflammatory mechanisms may play an important part in the processes of reperfusion, functional recovery of stunned myocardium and necrosis.2 The findings of this post hoc analysis appear to confirm the advantages of early initiation of colchicine in this setting: patients who were enrolled in the first 3 days showed greater benefit in terms of cardiovascular outcomes compared to those who were started later on the study drug.
In support of this point of view, we found in a pilot study of 151 patients that acute (within the first 12 h) colchicine administration in ST-elevation MI (STEMI) resulted in smaller infarct size, as assessed by myocardial necrosis biomarkers and magnetic resonance imaging (60 patients sub-study).4 It would thus be very interesting to further analyse the 1193 patients that comprised the subgroup of COLCOT in whom treatment was initiated 0–3 days post-MI and investigate whether an even earlier initiation of treatment was associated with better outcomes or a smaller biomarker-defined infarct size (if these data are available)—provided that there was an adequate number of patients who were enrolled as early as less than 24 h after the MI.
Taking all this into account, there is an obvious need for clinical trials adequately designed to evaluate the effects of acute colchicine administration in STEMI. There is definitely at least a signal of benefit,5 but we still need firm ground to stand on.
Conflict of interest: none declared.
References
EHJ Dialogues: 400th anniversary of cardiology. https://www.youtube.com/watch?v=hm_zLeZ7rnE&feature=emb_logo (2 December