COLCHICINE-PCI

Purpose: To evaluate whether pre-procedure colchicine would reduce PCI-related myocardial injury.

Trial Design: Phase 4 trial N=714. Double blinded. Follow-up 6 years. Randomized to pre-procedure colchicine 1.8 mg PO over 1 hour versus placebo.

Primary Endpoints: PCI-related myocardial injury

Results: Pre-PCI colchicine compared to placebo reduced post-PCI inflammation biomarkers but not PCI-related myocardial injury or MACE at 30 days.

Primary Endpoints Results

• Myocardial injury (400 subjects): Peri-procedural myocardial injury using troponin I, as defined by the Universal Definition of myocardial infarction
  • Colchicine 118 (57.3%) vs. placebo 122 (64.2%); P=.19

Secondary Endpoints Results

• Peri-procedural myocardial injury using CKMB & the SCAI definition of clinically relevant myocardial infarction (MI) after coronary revascularization
  • Colchicine 6 (2.9%) vs. placebo 9 (4.7%); P=.49
• Occurrence of major adverse cardiac events (MACE) with composite of the earliest occurrence of death from any cause, non-fatal MI (defined by the Universal Definition), or target vessel revascularization (bypass surgery or repeat PCI of the target vessel) at 30 days: Colchicine 23 (11.2%) vs. placebo 25 (12.9%); P=.71
  • Type 4a MI (Universal): 23 (11.2%) vs. 23 (12.1%); P=.89
  • Type I MI (Universal): 0 vs. 1 (0.5%); P=.49
  • Target vessel revascularization: 0 vs. 0
  • All-cause mortality: 0 vs. 1 (0.5%); P=.49

Inflammatory Biomarker Sub-study

• Primary Outcome (280 subjects):
  • There was no significant difference in the change in soluble IL-6 levels, from baseline to 1 hour post-PCI, when comparing colchicine (n=141) and placebo (n=139) groups.
• Other Key Findings:
  • IL-6 changes at 24 hrs post-PCI: increased less 24 hours post-PCI in the colchicine vs. placebo groups (76% [-6, 898] vs. 338% [27, 1264]; p=0.02)
  • High sensitivity C-reactive protein (hsCRP) concentration increased less 24 hours after PCI in the colchicine vs. placebo groups (7% [-13, 70] vs. 57% [0, 145]; p=0.001) 

Key Findings: Among 400 subjects who underwent PCI, there was no significant difference in the probability of PCI-related myocardial injury between the colchicine (n=206) and placebo (n=194) groups (57.3% vs. 64.2%; P=.19). There was also no significant difference in inflammatory biomarker changes within 1 hour post-PCI, though at 24 hours post-PCI, two inflammatory markers, IL-6 (76% vs. 338%; P=.02) and hsCRP (7% vs. 57%; p=.001), had increased less in the colchicine group compared to placebo.

Impression: While colchicine appears to attenuate increases in inflammatory biomarkers over the first 24 hours after PCI, there was no significant difference in peri-procedural myocardial injury or major adverse cardiovascular events at 30 days post-PCI.

Recommended

• COLCHICINE-PCI Abstract
• Binita Shah's presentation slides (PDF)
• Discussant slides (PDF)

Related Science

• Jneid H, Anderson JL, Wright RS et al. 2012 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction (Updating the 2007 Guideline and Replacing the 2011 Focused Update). Circulation 2012;126:875-910.
• O’Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. Circulation 2013;127:e362-e425.
• Martínez GJ, Robertson S, Barraclough J et al. Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome. Journal of the American Heart Association 2015;4:e002128.
• Deftereos S, Giannopoulos G, Angelidis C et al. Anti-Inflammatory Treatment With Colchicine in Acute Myocardial Infarction. Circulation 2015;132:1395-1403.
   

Trial Design — Randomized, double blind, placebo-controlled, single-site trial with parallel assignment to either colchicine (1.2 mg prior to PCI and 0.6 mg within 1 hr post-PCI) or placebo of the same dose

Trial Population: — 714 were enrolled, 400 adult (>18 yrs) patients undergoing PCI were studied; 280 were part of a pre-specified inflammatory marker sub-study

• Key Inclusion Criteria:
  • Adult men & women >18 years of age
  • Referred for coronary angiography with possible PCI
     
• Key exclusion criteria:
  • Colchicine use within 1 month
  • History of colchicine intolerance
  • Glomerular filtration rate <30 mL/min or on dialysis (due to need for adjusted dosing
  • Active malignancy or infection
  • History of myelodysplasia
  • High-dose statin load <24 hours prior to procedure (major confounder that is known to reduce inflammatory levels in 12 to 24 hours)
  • Use of anti-inflammatory agents (except aspirin) within 5 half-lives of the individual drug
  • Use of strong Cytochrome P450, Family 3, Subfamily A, Polypeptide 4 (CYP3A4) and/or P-glycoprotein inhibitors (e.g. ritonavir, ketoconazole, clarithromycin, cyclosporine, diltiazem and verapamil, again due to drug interactions)
  • Unable to consent
  • Participating in a competing study
  • Any significant condition or situation that may put the subject at higher risk, confound the study results or interfere with adherence to study procedures

Primary Endpoint:

• Peri-procedural myocardial necrosis within 24 hours, based on troponin I concentration above the upper limit of normal

Secondary Endpoints:

• All-cause mortality, non-fatal MI, or target vessel revascularization within 30 days
  • Non-fatal MI was defined as PCI-related (type 4a) or type I MI per the 3rd Universal Definition of MI
• Periprocedural myocardial infarction within 24 hrs based on SCAI definition

Biomarker Sub-study 

• Primary Outcome:
  • Change in plasma IL-6 concentration between baseline and 1 hour post-PCI
• Secondary Outcomes:
  • Change in plasma IL-6 concentration between baseline and other timepoints post-PCI
  • Change in plasma IL-1ß concentration between baseline and post-PCI
  • Change in hsCRP concentration between baseline and 22 to 24 hours post-PCI 

Sponsor(s)/Collaborator(s): VA Office of Research and Development; NYU Langone Health

Keywords: Keywords: American Heart Association Scientific Sessions; AHA2019; inflammation; percutaneous coronary intervention; coronary artery disease; colchicine; myocardial necrosis; myocardial infarction; biomarker; troponin