Assessing the Impact of Colchicine on Coronary Plaque Phenotype After Myocardial Infarction with Optical Coherence Tomography: Rationale and Design of the COCOMO-ACS Study

Abstract

Introduction Recurrent event rates after myocardial infarction (MI) remain unacceptably high, in part because of the continued growth and destabilization of residual coronary atherosclerotic plaques, which may occur despite lipid-lowering therapy. Inflammation is an important contributor to this ongoing risk. Recent studies have shown that the broad-acting anti-inflammatory agent, colchicine, may reduce adverse cardiovascular events in patients post-MI, although the mechanistic basis for this remains unclear. Advances in endovascular arterial wall imaging have allowed detailed characterization of the burden and compositional phenotype of coronary plaque, along with its natural history and responsiveness to treatment. One such example has been the use of optical coherence tomography (OCT) to demonstrate the plaque-stabilizing effects of statins on both fibrous cap thickness and the size of lipid pools within plaque. Methods The Phase 2, multi-centre, double-blind colchicine for coronary plaque modification in acute coronary syndrome (COCOMO-ACS) study will evaluate the effect of colchicine 0.5 mg daily on coronary plaque features using serial OCT imaging in patients following MI. Recruitment for the trial has been completed with 64 participants with non-ST elevation MI randomized 1:1 to colchicine or placebo in addition to guideline recommended therapies, including high-intensity statins. The primary endpoint is the effect of colchicine on the minimal fibrous cap thickness of non-culprit plaque over an 18-month period. Summary The COCOMO-ACS study will determine whether addition of colchicine 0.5 mg daily to standard post-MI treatment has incremental benefits on high-risk features of coronary artery plaques. If confirmed, this will provide new mechanistic insights into how colchicine may confer clinical benefits in patients with atherosclerotic cardiovascular disease. Trial Registration ANZCTR trial registration number: ACTRN12618000809235. Date of trial registration: 11th of May 2018.

Coronary Computed Tomography Angiography for the Assessment of Sirolimus-Eluting Resorbable Magnesium Scaffold

“…This goal cannot be achieved by the implantation of metallic platforms, but only by aggressive lipid lowering and anti-remodeling treatments. In the same direction, the development of anti-inflammatory drugs aims to reduce the inflammatory burden on atherosclerotic plaques and to reduce their recurrence [ 15 , 16 ]. Finally, it is important to note that most of the patients in the present analysis were admitted to hospital for MI (82%, 95% CI 63–94%).…”

Intracoronary Imaging of Coronary Atherosclerotic Plaque: From Assessment of Pathophysiological Mechanisms to Therapeutic Implication

“…The COCOMO-ACS trial is a phase 2, multi-center, double-blind study testing colchicine for coronary plaque modification in ACS. The study evaluated the effect of colchicine 0.5 mg daily on coronary plaque features using serial OCT imaging in patients following MI with the aim of providing new insights into the mechanisms underlying the clinical benefit of colchicine therapy in patients with atherosclerotic cardiovascular disease [ 118 ]. As of today, the use of colchicine may be considered in the secondary prevention of CVD in cases of the suboptimal control of the other risk factors or recurrent events under optimal therapy, according to the 2021 ESC Guidelines on CVD prevention in clinical practice [ 119 ].…”

Role of plaque imaging for identification of vulnerable patients beyond the stage of myocardial ischemia

“…During the 2-year follow-up, the colchicine group showed a 23% reduction in cardiovascular events. These clinical trials provided evidence for the addition of anti-inflammatory therapy to standard medical regimens, and suggested the importance of imaging techniques to assess vascular inflammation and plaque stabilization (10,126,127).…”