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

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.

Effect of low‐dose colchicine in acute and chronic coronary syndromes: A systematic review and meta‐analysis

“…LD colchicine may then allow to combat the residual cardiovascular risk after full implementation of strategies for secondary cardiovascular prevention, 12 thus yielding an additional prognostic benefit in patients with CCS or ACS. While the prognostic benefit of colchicine in CCS has emerged quite clearly from LoDoCo 4 and LoDoCo2, 5 the improvement in prognosis seems less evident in studies on the heterogeneous ACS setting, with the greatest benefit observed in patients with MI from <3 days, 6 followed by a borderline significant benefit in patients with ACS in the smaller COPS study 7 . These findings seem to point to a greater benefit of colchicine in the most acute settings, reasonably because of greater inflammatory activation, but evidence is currently too limited to allow this conclusion.…”

Repurposing Colchicine to Combat Residual Cardiovascular Risk: The LoDoCo2 Trial

“…Similarly, the COLCOT trial found reduced rates of ischaemic CV events among patients with a recent history of myocardial infarction (MI) receiving colchicine at a median of 30 days post‐MI 9 . Notably, protective effects were more pronounced in patients in whom treatment was initiated shortly after the event, suggesting that patients with MI benefit from early colchicine initiation when inflammation is most pronounced 12 . Importantly, the role of specific pro‐inflammatory pathways in atherothrombosis was reinforced by CANTOS in which superior CV outcomes were found in patients with a history of MI on the interleukin‐1‐β targeting antibody canakinumab as compared to placebo 2 …”

“…9 Notably, protective effects were more pronounced in patients in whom treatment was initiated shortly after the event, suggesting that patients with MI benefit from early colchicine initiation when inflammation is most pronounced. 12 Importantly, the role of specific pro-inflammatory pathways in atherothrombosis was reinforced by CANTOS in which superior CV outcomes were found in patients with a history of MI on the interleukin-1-β targeting antibody canakinumab as compared to placebo. 2 Despite the striking relative risk reduction of the primary endpoint by roughly 30% observed in LoDoCo2, 8 major practical concerns that limit the widespread use of colchicine remain.…”

Lo mejor del 2020: Estudios que marcarán nuestra práctica clínica

“…COLCOT (20) del COLCOT demostraron que el beneficio mayor se da cuando se inicia la colchicina en los tres primeros días del IM, con una ↓ RR 48%, p<0,05 en el evento primario antes mencionado, a diferencia de iniciarlo días después del IM (21) . Asimismo, en el subanálisis en población diabética se observó una ↓ RR 35%, p<0,05 en el evento primario (22) .…”