Colchicine Therapy and Plaque Stabilization in Patients With Acute Coronary Syndrome: A CT Coronary Angiography Study

JACC Cardiovasc Imaging. 2018 Feb;11(2 Pt 2):305-316. doi: 10.1016/j.jcmg.2017.08.013. Epub 2017 Oct 18.

Abstract

Objectives: The authors sought to evaluate the plaque-modifying effects of low-dose colchicine therapy plus optimal medical therapy (OMT) in patients post-acute coronary syndrome (ACS), as assessed by coronary computed tomography angiography (coronary CTA).

Background: Colchicine therapy has been postulated to have beneficial anti-inflammatory effects in patients with ACS, translating into reduction in future adverse cardiovascular events. However, whether favorable plaque modification underpins this is yet unproven.

Methods: In this prospective nonrandomized observational study of 80 patients with recent ACS (<1 month), patients received either 0.5 mg/day colchicine plus OMT or OMT alone and were followed for 1 year. Our primary outcome was change in low attenuation plaque volume (LAPV), a marker of plaque instability on coronary CTA and robust predictor of adverse cardiovascular events. Secondary outcomes were changes in other coronary CTA measures and in high-sensitivity C-reactive protein (hsCRP).

Results: Mean duration of follow-up was 12.6 months; mean age was 57.4 years. Colchicine therapy significantly reduced LAPV (mean 15.9 mm3 [-40.9%] vs. 6.6 mm3 [-17.0%]; p = 0.008) and hsCRP (mean 1.10 mg/l [-37.3%] vs. 0.38 mg/l [-14.6%]; p < 0.001) versus controls. Reductions in total atheroma volume (mean 42.3 mm3 vs. 26.4 mm3; p = 0.28) and low-density lipoprotein levels (mean 0.44 mmol/l vs. 0.49 mmol/l; p = 0.21) were comparable in both groups. With multivariate linear regression, colchicine therapy remained significantly associated with greater reduction in LAPV (p = 0.039) and hsCRP (p = 0.004). There was also a significant linear association (p < 0.001) and strong positive correlation (r = 0.578) between change in LAPV and hsCRP.

Conclusions: Our findings suggest, for the first time, that low-dose colchicine therapy favorably modifies coronary plaque, independent of high-dose statin intensification therapy and substantial low-density lipoprotein reduction. The improvements in plaque morphology are likely driven by the anti-inflammatory properties of colchicine, as demonstrated by reductions in hsCRP, rather than changes in lipoproteins. Colchicine may be beneficial as an additional secondary prevention agent in patients post-ACS if validated in future studies.

Keywords: CT coronary angiography; acute coronary syndrome; atherosclerosis; colchicine; coronary artery disease; inflammation.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / diagnostic imaging*
  • Acute Coronary Syndrome / drug therapy*
  • Adult
  • Aged
  • Anti-Inflammatory Agents / administration & dosage*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Colchicine / administration & dosage*
  • Computed Tomography Angiography*
  • Coronary Angiography / methods*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnostic imaging*
  • Coronary Artery Disease / drug therapy*
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Lipids / blood
  • Male
  • Middle Aged
  • Pilot Projects
  • Plaque, Atherosclerotic*
  • Predictive Value of Tests
  • Prospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Inflammation Mediators
  • Lipids
  • C-Reactive Protein
  • Colchicine