Effects of Acute Colchicine Administration Prior to Percutaneous Coronary Intervention: COLCHICINE-PCI Randomized Trial

Abstract

Background: Vascular injury and inflammation during percutaneous coronary intervention (PCI) are associated with increased risk of post-PCI adverse outcomes. Colchicine decreases neutrophil recruitment to sites of vascular injury. The anti-inflammatory effects of acute colchicine administration before PCI on subsequent myocardial injury are unknown.

Methods: In a prospective, single-site trial, subjects referred for possible PCI (n=714) were randomized to acute preprocedural oral administration of colchicine 1.8 mg or placebo.

Results: Among the 400 subjects who underwent PCI, the primary outcome of PCI-related myocardial injury did not differ between colchicine (n=206) and placebo (n=194) groups (57.3% versus 64.2%, P=0.19). The composite outcome of death, nonfatal myocardial infarction, and target vessel revascularization at 30 days (11.7% versus 12.9%, P=0.82), and the outcome of PCI-related myocardial infarction defined by the Society for Cardiovascular Angiography and Interventions (2.9% versus 4.7%, P=0.49) did not differ between colchicine and placebo groups. Among 280 PCI subjects in a nested inflammatory biomarker substudy, the primary biomarker end point, change in interleukin-6 concentrations did not differ between groups 1-hour post-PCI but increased less 24 hours post-PCI in the colchicine (n=141) versus placebo group (n=139; 76% [-6 to 898] versus 338% [27 to 1264], P=0.02). High-sensitivity C-reactive protein concentration also increased less after 24 hours in the colchicine versus placebo groups (11% [-14 to 80] versus 66% [1 to 172], P=0.001).

Conclusions: Acute preprocedural administration of colchicine attenuated the increase in interleukin-6 and high-sensitivity C-reactive protein concentrations after PCI when compared with placebo but did not lower the risk of PCI-related myocardial injury. Registration: URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT02594111, NCT01709981.

Keywords: biomarker; colchicine; inflammation; myocardial infarction; percutaneous coronary intervention.

Figures

Figure 1.

Screening, enrollment, and randomization of study population

Figure 2.

Percent change in interleukin (IL)-6 concentration (A) and IL-1β concentration (B) from baseline to one hour, baseline to 6 to 8 hours, and baseline to 22 to 24 hours post-PCI in the colchicine versus placebo groups; and percent change in high sensitivity C-reactive protein (hsCRP) concentration (C) from baseline to 22 to 24 hours post-PCI in the colchicine versus placebo groups. Data are shown as median [interquartile range] of the percent changes, and percent changes in inflammatory marker concentrations from baseline to one hour, from baseline to 6 to 8 hours, and from baseline to 22 to 24 hours were compared between the colchicine and placebo groups using Mann-Whitney test.