Oral load of colchicine prior to PCI prevents a rise of inflammatory biomarkers in acute injury

AHA 2019 Pre-procedural administration of colchicine vs. placebo did not reduce PCI-related myocardial injury or MACE at 30 days, but attenuated increase in IL-6 and hsCRP at 24 hours post-PCI.

Presented during the AHA Scientific Sessions 2019 by Binita Shah (VA New York Harbor Healthcare System, Manhattan Campus, NYU School of Medicine New York, NY).

Introduction and methods

Colchicine is extracted from a flower and used in medicine for its properties to inhibit neutrophil chemotaxis and activity in response to vascular injury. It inhibits inflammasome signaling and reduces the production of active IL-1β, as well as neutrophil-platelet interaction and aggregation. Its current indication is for gout, since the standard regimen for gout flares (1.2 mg PO followed by 0.6 mg PO administered over an hour) has rapid onset of anti-inflammatory effects.

That is the rationale for testing the hypothesis that an acute, pre-procedural oral administration of 1.8 mg of colchicine reduces biomarker evidence of PCI-related inflammation and myocardial injury when compared with placebo. The COLCHICINE-PCI tested this in adults with suspected ischemic heart disease or acute coronary syndromes referred for clinically-indicated coronary angiography with possible PCI. Patients were given 1.2 mg colchicine, and 0.6 mg an hour later, or matching placebo’s, 1-2 hours prior to catheterization.

Inflammatory biomarkers were measured 1 hour post-PCI, 6-8 hours and 22-24 hours post-PIC. Troponin was measured at 6-8 hours and 22-24 hours post-PCI, and clinical assessment for MACE was done at 30-days follow-up. Patients will be followed for up to 5 years. The primary endpoint was PCI-related myocardial injury. Of the inflammatory biomarker substudy endpoints, the primary endpoint was between group difference in the change in plasma IL-6 concentration from baseline to 1 hour post-PCI.

714 Patients were randomized, of whom 206 randomized to colchicine underwent PCI and 194 in the placebo group.

Main results

• The primary outcome of PCI-related myocardial injury was non-significantly lower in the group assigned to colchicine (57.3% vs. 64.2%, P=0.19).
• Major adverse CV events at 30 days were not significantly altered by colchicine (11.7% vs. 12.9%, P=0.82).
• Percent change in IL-6 concentration compared to baseline was only statistically significantly lower at 22-24 hours post-PCI (P=0.02), but not at 1 (P=0.31) and 6-8 (P=0.18) hours post-PCI.
• Percent change in IL-1β concentration compared to baseline was very similar between treatment groups and at all timepoints.
• Percent change in hsCRP concentration compared to baseline was significantly smaller in the colchicine group at 22-24 hours post-PCI (P=0.001).
• Subgroup analyses based on indication, intra-procedural complications and new or stable statin therapy did not reveal differential treatment effects.

Conclusion

This investigator-initiated, single-site prospective randomized double-blind study is the first to evaluate the effects of an acute pre-procedural administration of colchicine vs. placebo on markers of myocardial injury and inflammation in patients undergoing PCI. Compared with placebo, short-term pre-procedural colchicine did not reduce PCI-related myocardial injury or MACE at 30 days. It did attenuate PCI-related increase in IL-6 and hsCRP concentration at 24 hours post-PCI.

This is the first study to demonstrate that an oral load of colchicine prevents a rise of inflammatory biomarkers in acute injury.

Limitations of the study include that the study enrolled mostly men, as the study was conducted in the Veteran’s Affair system. This limits the interpretation for women undergoing PCI.

- Our reporting is based on the information provided during AHA Scientific Sessions 2019 -