Anti-inflammatory treatment within 3 days after MI improves CV outcomes
Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)
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 .
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.
- 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).
Early initiation of low-dose colchicine between day 0 and 3 in patients who suffered from a MI reduced the risk of the primary composite endpoint by 48% compared to patients receiving placebo. Most prominent effect of early colchicine treatment initiation was observed for urgent hospitalization due to angina leading to coronary revascularization. Also, the secondary composite endpoint and all coronary revascularization events were significantly reduced in the early initiated colchicine treated group compared to placebo.