Physicians' Academy for Cardiovascular Education

Anti-inflammatory agent favorably modifies vulnerable coronary plaque

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

Literature - Vaidya K, Arnott C, Martínez GJ et al. - JACC Cardiovasc Imaging. 2017 Oct 14. doi: 10.1016/j.jcmg.2017.08.013

Main results


This study shows that low-dose colchicine treatment has greater coronary plaque-stabilizing effects than optimal medical therapy, as is evident from a reduction of LAPV and hsCRP. The modest positive correlation between change in LDL and change in LAP volume suggests that LDL reduction may have contributed to plaque stabilization, but the similar LDL reduction in both groups indicates that the changes in plaque morphology are not solely driven by changes in LDL. The larger reduction in hsCRP in the colchicine group suggests that its anti-inflammatory properties play a role.

Editorial comment

Over the past twenty years, various lines of evidence have demonstrated the link between CRP and inflammation and future CV risk. Studies had also suggested that lowering hsCRP, just like LDL-c, is beneficial, but the proof that inflammation is causal in atherosclerosis came from the recent randomized CANTOS trial in which inflammation was lowered in the absence of lipid lowering. Indeed, treatment with the interleukin-1β antibody canakinumab reduced the primary endpoint of MI, stroke or CV death without changing LDL-c. Another large-scale randomized trial, CIRT, evaluating low-dose methotrexate is still underway. Colchicine has shown promise for secondary prevention in preliminary trials.

Various surrogate imaging markers for atherosclerosis and vascular inflammation have been examined. Ridker and Narula [5] call the finding of reduced LAP volume provocative, because LAP is considered an imaging marker for instability and a predictor of adverse CV events. They note ‘Vaidya et al report little if any effect of colchicine on total atheroma volume, a finding suggesting plaque modification and stabilization.’

They point out several limitations of the current study, including the lack of randomization, thus it being subject to confounding and bias. Moreover, control patients were derived from a general cardiology clinic, thus they were likely to differ from the ACS patients in the intervention group. Ridker and Narula are critical of surrogate imaging markers: ‘Although imaging-verified change in plaque composition (including LAP or inflammation) should be intuitively more informative than the interval change in the percentage of atheroma volume in response to therapeutic intervention, it is likely that no imaging modality would succeed as a validated surrogate for hard clinical events.’ They name various examples, including a recent MRI study of the carotid arteries and aorta that did not demonstrate significant effects of canakinumab on measures of vascular structure and function, despite evidence of hsCRP lowering.

Still, they conclude that imaging can likely serve as a useful tool to understand the pathogenesis of atherosclerosis and the effects of drugs on these mechanisms. The authors anticipate that, after presentation of the CANTOS results, the search for valid imaging surrogate predictive of drug effects will likely accelerate.


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