CardioBrief: Imaging Offers Insight Into Inflammation in CV Disease
Preliminary evidence that colchicine may reduce coronary plaque
Interest in inflammation has risen considerably in the cardiology community as a result of the recent CANTOS trial. The 10,000-patient trial validated the role of inflammation by demonstrating the efficacy of canakinumab (Ilaris) -- a monoclonal antibody that targets interleukin-1beta -- in reducing cardiovascular events in people with heart disease and elevated high-sensitivity C-reactive protein (hs-CRP) levels.
The positive results of CANTOS have led many to wonder if other anti-inflammatory agents may be effective in the cardiovascular setting. Two imaging studies published in JACC: Cardiovascular Imaging offer further information about the role of inflammation in cardiovascular disease. One study offers early evidence that another agent -- older and presumably far less expensive than a monoclonal antibody -- may also prove effective.
In the first paper, Kaivan Vaidya (Royal Prince Alfred Hospital, Sydney, Australia) and colleagues performed a non-randomized observational study on 80 post-acute coronary syndrome (ACS) patients who received the anti-inflammatory agent colchicine (Colcrys, Mitigare), which is most often used to treat gout, and optimal medical therapy or optimal medical therapy alone.
After a year of follow-up, CT angiography found a much larger reduction in low attenuation plaque volume in the colchicine group. That measure, according to the authors, is a "marker of plaque instability" and a "robust predictor of adverse cardiovascular events."
Colchicine was also associated with a significant reduction in hs-CRP. There was a similar reduction in both groups in total atheroma volume and LDL cholesterol. The authors observed that "the comparable LDL reduction in both groups suggests that improvements in plaque morphology are not driven solely by changes in LDL, but also by the anti-inflammatory properties of colchicine. This is supported by the substantially larger reduction in hsCRP in the treatment group compared to controls."
"Our findings suggest, for the first time, that low-dose colchicine therapy favourably modifies coronary plaque, independent of high-dose statin intensification therapy and substantial LDL reduction. ... Colchicine may be beneficial as an additional secondary prevention agent in patients post-ACS if validated in future studies," the authors concluded.
In an accompanying editorial, Paul Ridker (Brigham and Women's Hospital), the principal investigator of the CANTOS trial and a pioneer of the inflammation hypothesis in cardiovascular disease, and Jagat Narula (Mt. Sinai), wrote that the results are "provocative" but pointed out that the observational nature of the study limits its significance.
Further, they noted, "it is likely that no imaging modality would succeed as a validated surrogate for hard clinical events."
Ridker and Jarula noted that two large outcome studies with colchicine are now underway, the 3,000-patient LoDoCo2 trial and the 4,500-patient COLCOT trial. Ridker is also the principal investigator of a third large ongoing trial, the 7,000-patient Cardiovascular Inflammation Reduction Trial (CIRT) studying methotrexate.
In the second paper, Joshua Rivers (NHLBI) and colleagues used PET imaging to analyze the relationship between visceral adiposity volume and vascular inflammation in 77 patients with psoriasis, which is a chronic inflammatory disease that is known to increase the risk of atherosclerosis and cardiovascular disease. They found that visceral adiposity was significantly associated with cardiovascular risk, psoriasis severity, and arterial inflammation. In a subset of 16 patients with severe psoriasis who received immune-suppressive treatment, there was a decrease in both visceral adiposity and arterial inflammation.
In an accompanying editorial, Thomas Schindler (Johns Hopkins) and Pal Pacher (NIH) wrote that the study provides the "first evidence suggesting that visceral adiposity is a novel critical player in fueling arterial inflammation in psoriasis that is likely to account for an increased prevalence of an inflammatory atherosclerotic process and increased cardiovascular risk." They called for more large clinical trials with immune-suppressive treatments.
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