Colchicine in Coronary Plaque Stabilization: Results According to OCT

Cardiovascular inflammation has been globally recognized and accepted in recent years as a key factor in the progression of coronary artery disease (CAD). Inflammation can lead to arterial plaque instability, which in turn can trigger acute coronary syndromes (ACS). Recently, three major randomized studies (CANTOS, COLCOT, and LoDoCo2) have demonstrated that by focusing on inflammation as a therapeutic target, it is possible to reduce cardiovascular events.

While colchicine has historically been used to treat gout and pericarditis, in recent years, its use has also been approved to reduce cardiovascular risk in adult patients with CAD.

The objective of this study, called COLOCT, was to assess the effects of colchicine on coronary plaque characterization using optical coherence tomography (OCT).

Yu et al. conducted a randomized, single-center study at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. They included patients over 18 years of age who had been hospitalized for ACS in the last month, with at least one non-culprit lesion with 30-70% stenosis by visual estimation, after completing planned revascularization, and with an OCT image showing a lipid-rich plaque (lipid arc >90°).

Exclusion criteria included patients allergic to colchicine, with baseline hepatic or renal impairment, thrombocytopenia, known immunological disease, a history of coronary artery bypass surgery, or left main coronary artery disease.

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Patients were randomized 1:1 to receive colchicine 0.5 mg daily or a placebo for 12 months. OCT (2.7F Dragonfly OPTIS) was performed at baseline, identifying non-culprit intermediate lesions, and again at 12 months of follow-up to assess treatment impact.

The primary endpoint was the change in fibrous cap thickness (FCT) at 12 months compared to baseline. Secondary endpoints included changes in lipid arc, macrophage accumulation, incidence of high-risk atheroma (thin-cap fibroatheroma, TCFA), minimum luminal area, changes in serum inflammatory biomarker levels, and the occurrence of major adverse cardiovascular events (MACE).

A total of 128 patients were included and randomized to colchicine or placebo, in addition to standard-of-care treatment according to national clinical guidelines. The average age was 58.0 ± 9.8 years, 25% of subjects were women, 25% were diabetic, and 31.3% had a history of CAD (10.1% had undergone prior coronary angioplasty). The average time from ACS to randomization was 12.1 ± 7.7 days.

Baseline OCT parameters showed no significant differences between the placebo and colchicine groups. The primary endpoint, absolute change in FCT at 12 months, was 51.9 μm (95% confidence interval [CI], 32.8 to 71.0) in the placebo group and 87.2 μm (95% CI, 69.9 to 104.5) in the colchicine group, with a difference of 34.2 μm (95% CI, 9.7 to 58.6); P = 0.006. Regarding secondary parameters, colchicine therapy significantly reduced changes in the mean lipid arc (difference of –10.5° [95% CI, –17.7° to –3.4°]; P = 0.004) and the angular extent of macrophages (difference –6.0° [95% CI, –11.8° to –0.2°]; P = 0.044).

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The difference in the incidence of TCFA during follow-up was not significant (odds ratio [OR], 0.8 [95% CI, 0.5 to 1.3]; P = 0.367). However, in laboratory parameters, colchicine significantly reduced C-reactive protein levels (difference 0.5 [95% CI, 0.3 to 1.0]; P = 0.046), IL-1 (difference 0.7 [95% CI, 0.6 to 0.9]; P = 0.003), and other markers such as IL-18 and AZU1.

As for major adverse cardiovascular events (MACE), they were reported in 17.3% of patients in the placebo group and 11.5% of those treated with colchicine (P = 0.402).

Conclusions

This study showed that plaque stabilization improved with colchicine treatment, reflected in a greater increase in fibrous cap thickness (FCT), a decrease in the lipid arc, and a reduction in macrophage infiltration.

Original Title: Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial. 

Reference: Yu M, Yang Y, Dong SL, Zhao C, Yang F, Yuan YF, Liao YH, He SL, Liu K, Wei F, Jia HB, Yu B, Cheng X. Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial. Circulation. 2024 Aug 21. doi: 10.1161/CIRCULATIONAHA.124.069808. Epub ahead of print. PMID: 39166327.