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Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by OCT
TAKE-HOME MESSAGE
- This moderate-sized, double-blind, placebo-controlled randomized trial evaluated the effects of colchicine on coronary artery plaque stabilization and found that colchicine use significantly increased minimal fibrous cap thickness — a positive measure of plaque stability — compared with placebo (an increase of 87.2 vs 51.9 μm). In addition, the colchicine arm also had expected decreases in the levels of inflammatory markers, such as C-reactive protein and interleukin-6.
- This study provides further evidence of the efficacy of colchicine in preventing coronary artery disease by suggesting a mechanism that includes the stabilization of coronary artery plaques. Providers should consider colchicine therapy in patients with coronary artery disease in accordance with current guidelines.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine-Optical Coherence Tomography Trial) and LoDoCo2 studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques.
METHODS
This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up.
RESULTS
Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] μm versus 87.2 [95% CI, 69.9 to 104.5] μm; difference, 34.2 [95% CI, 9.7 to 58.6] μm; P=0.006), and reduced average lipid arc (-25.2° [95% CI, -30.6° to -19.9°] versus -35.7° [95% CI, -40.5° to -30.8°]; difference, -10.5° [95% CI, -17.7° to -3.4°]; P=0.004), mean angular extension of macrophages (-8.9° [95% CI, -13.3° to -4.6°] versus -14.0° [95% CI, -18.0° to -10.0°]; difference, -6.0° [95% CI, -11.8° to -0.2°]; P=0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P=0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P=0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P=0.047).
CONCLUSIONS
Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome.
Additional Info
Disclosure statements are available on the authors' profiles:
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;[EPub Ahead of Print], M Yu, Y Yang, SL Dong, C Zhao, F Yang, YF Yuan, YH Liao, SL He, K Liu, F Wei, HB Jia, B Yu, X ChengFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Is colchicine making plaques more stable?
We have learned that plaque inflammation can increase the risk of cardiovascular events. Reducing inflammation with colchicine had benefits as shown in the COLCOT (Colchicine Cardiovascular Outcome Trial) and LoDoCo2 studies. However, colchicine's mechanism of action was always in question. Does it reduce inflammation and, therefore, plaque rupture? Or does it reduce inflammation and affect plaque growth?
The only way to figure this out was to examine the plaque with optical coherence tomography (OCT) over 12 months. So, instead of using ultrasound waves to examine the interior of the coronary artery, OCT uses light waves to examine the wall of the artery and it can see deep into the plaque. OCT can determine how much cholesterol is in the arterial wall, and it is reported in degrees of arc — the whole circumference of the artery is 360o; so, if the reading is 30o, then you know how far the cholesterol plaque has gone around the artery wall. You can also measure the fibrous cap thickness over the plaque. A plaque with a thicker fibrous cap is less likely to rupture. OCT can also detect the location of macrophages — the more macrophages, the more likely there will be inflammation and rupture.
This study examined 104 patients, with half on colchicine and half on placebo. After 12 months, the fibrous cap thickness was increased by 34.2 μm (95% CI, 9.7–58.6; P = .006) in favor of colchicine. The lipid arc was reduced by –10.5° (95% CI, –17.7° to –3.4°; P = .004) from 35° to 25°. The angular extension of macrophages was reduced by 6.0° (95% CI, –11.8° to –0.2°; P = .044) from 14.0° to 8.9°. Basically, the plaque was getting smaller and becoming more stable. The levels of all inflammatory markers in the blood samples were also reduced. High-sensitivity C-reactive protein, interleukin-6, and myeloperoxidase levels were all lower in the colchicine group.
These findings suggest that inflammation is part of the daily plaque progression, and, by blocking inflammation with colchicine, we can not only help reduce plaque growth but we can also get some plaque regression as well.
Not all things that reduce inflammation are useful as we remember the cyclooxygenase-2 inhibitors such as rofecoxib, which increase the risk of cardiovascular events. In this case, colchicine is blocking the NLRP3 inflammasome. This helps stop the inflammation associated with gout and now it seems it is also helpful for reducing inflammation and plaque growth within the coronary arteries. An inexpensive drug with multiple benefits — what a refreshing change.