The Sooner, the Better: Anti-inflammation in Acutemyocardial Infarction

Thomas F. Lüscher


Eur Heart J. 2020;41(42):4100-4102. 

In This Article

Anti-inflammatory Therapy as a New Strategy

Based on these data and insights into the molecular mechanisms of ACS, inflammation became the new therapeutic frontier. After a few smaller proof-of-concept studies, the CANTOS trial using the interleukin-1β (IL-β) antagonist canakinumab proved the causal association of inflammation with MACE after ACS.[17] Indeed, after 4 years, canakinumab reduced MACE (i.e. non-fatal myocardial infarction or stroke and cardiovascular death) overall by ~15%[17] and by 26% in those with an on-treatment CRP level <2 mg/L.[18] Interestingly, canakinumab also reduced the occurrence of cancer, and in particular lung cancer, in these patients.[19] The latter finding led the sponsor Novartis to decide to develop canakinumab for this indication rather than in cardiac patients.

Thus, at this point, the clinical implementation of anti-inflammation came to a halt until recently when the results of the COLCOT trial were published. In this trial, patients who had survived an ACS were randomized within 30 days after the event to either placebo or colchicine at a low dose of 0.5 mg daily and were followed-up for a median of 2 years.[20] Impressively, colchicine led to a 23% reduction of the primary endpoint of death, rescucitated cardiac arrest, ACS, stroke, and urgent hospitalization for angina requiring revascularization (however with the latter beiing the primary driver of the effect). Given the early inflammatory burst at the time of ACS, it remained unclear—as has been the case in CANTOS—whether very early anti-inflammation might be even more advantageous or possibly rather dangerous. This question has now been addressed in the manuscript by Bouabdallaoui et al. in the current issue of the European Heart Journal.[21] They grouped the patients enrolled in COLCOT into three groups that had received investigational drugs (i.e. colchicine or placebo) within the first 3, 4–7, or 8 or more days. Importantly, after a mean follow-up of 23 months, there was an amazing significant reduction of 48% in the primary endpoint in those receiving colchicine within 3 days or less, but only of 4–18% in those receiving the drug at a later timepoint. Thus, anti-inflammatory therapy seems to work best the sooner it is provided after ACS. Given the fact that inflammation is most pronounced in the very early phase of an acute myocardial infarction, these results make a lot of sense.