Anti-inflammatory treatment within 3 days after MI improves CV outcomes

Introduction and methods

Myocardial infarction (MI) is associated with an acute excessive inflammatory burst. This inflammatory burst plays a role in adverse cardiac remodeling by activation of NLRP3 inflammasomes [1-4]. Colchicine is a potent anti-inflammatory medication, that inhibits tubulin polymerization leading to effects on cellular adhesion molecules, inflammatory chemokines, and the inflammasome [5-7]. In COLCOT, a daily low dose of colchicine reduced the risk of the CV primary endpoint by 23% when initiated in the first 30 days after an MI compared to placebo [8].

This subanalysis of COLCOT assessed whether time-to-treatment initiation (TTI) of colchicine therapy had a clinical impact on CV outcomes in patients with an MI.

COLCOT was an international, multicenter, randomized, double-blind trial. Patients with a recent MI (<30 days) were included and randomized (1:1) to colchicine 0.5 mg once daily (n=2322) or matching placebo (n=2339). Patients were subdivided into three TTI groups: day 0-3 (in-hospital management; n=1193), day 4-7 (early post-discharge period; n=720), and day 8-30 (late post-discharge period; n=2748). The primary efficacy endpoint was a composite of CV death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. Secondary endpoints included the components of the primary outcome, all-cause death, and a composite of CV death, resuscitated cardiac arrest, MI, or stroke. Exploratory endpoints were all coronary revascularizations, which included elective and urgent coronary revascularizations. Median follow-up was 22.7 months.

Main results

• There was a 48% risk reduction for the primary composite endpoint in patients treated between day 0 and 3 with colchicine compared to patients receiving placebo (4.3% vs. 8.3%, respectively, HR 0.52, 95% CI: 0.32-0.84, P=0.007).

• No significant differences for the primary endpoint were observed between the colchicine and placebo treated groups when TTI was between days 4 and 7 (6.0% vs. 5.9% respectively, HR 0.96, 95% CI: 0.53-1.75), and days 8 and 30 (5.7% vs. 7.1%, respectively, HR 0.82, 95% CI; 0.61-1.11).

• Colchicine treatment after MI initiated between day 0 and 3 reduced urgent hospitalizations for angina requiring coronary revascularization compared to patients with placebo treatment (1.0% vs. 2.9%, respectively, HR 0.35, 95% CI: 0.14-0.88, P=0.026).

• The secondary endpoint, a composite of CV death, resuscitated cardiac arrest, MI, or stroke was reduced by 45% in the colchicine group when TTI was between day 0 and 3 compared to the placebo group (HR 0.55, 95% CI: 0.32-0.95, P=0.031).

• The number of deaths due to all-causes was similar in colchicine and placebo treated patients for the different TTI groups.

• All coronary revascularization events were reduced in patients treated within 3 days with colchicine compared to those on placebo (HR 0.63, 95% CI: 0.40-0.97, P=0.037).

Conclusion

References

Find this article online at Eur Heart J