Colchicine for secondary prevention in coronary disease

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Colchicine in Stable Coronary Artery Disease

Contains fulltext : 215196.pdf (publisher's version ) (Closed access)PURPOSE: Disease management of stable coronary artery disease consists of controlling hemostasis and lipid regulation. No treatment strategies preventing plaque erosion or rupture are yet available. Cholesterol crystal-induced inflammation leading to plaque destabilization is believed to be an important factor contributing to plaque instability and might well be amenable to treatment with anti-inflammatory drugs. Colchicine has anti-inflammatory properties with the potential to address both the direct and indirect inflammatory mechanisms in the plaque. METHODS: A literature search was performed in MEDLINE (PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials, as well as in the clinical trial registries, to identify finished and ongoing clinical studies on colchicine in stable coronary artery disease. FINDINGS: Preclinical findings of colchicine in stable coronary artery disease have shown protective effects on surrogate outcomes, such as myocardial infarction size and postangioplasty restenosis. Retrospective cohort studies in patients with gout report a lower incidence of combined cardiovascular outcomes in those treated with colchicine. Thus far, one prospective, randomized clinical trial has provided evidence on a possible protective effect of colchicine in stable coronary artery disease. Meta-analysis of trials of colchicine in multiple cardiovascular diseases revealed a decrease in myocardial infarction with varying levels of evidence. Currently, 5 major clinical trials involving >10,000 patients are recruiting patients, all focusing on major cardiovascular outcomes. IMPLICATIONS: The body and quality of evidence regarding the efficacy of colchicine for secondary prevention of stable and acute phases of coronary artery disease will be greatly expanded in the upcoming years, providing less biased and more accurate effect estimates. If colchicine's anti-inflammatory characteristics translate to improved event-free cardiovascular survival, this relatively safe, low-cost, and well-known drug may become the third pillar (next to lipid regulation and platelet inhibition) in the medical management of stable coronary artery disease

Emerging evidence for the use of colchicine for secondary prevention of coronary heart disease

Cardiovascular disease imposes a major burden on Australians and the Australian health care system. Due to campaigns to reduce smoking and the widespread use of effective lipid-lowering therapy, there has been a significant decline in the death rate from cardiovascular disease over several decades.1 However, nearly 600 000 patients are hospitalised each year with cardiovascular disease, at a cost to the community of over $4 billion in 2018 – 19.1 Patients with coronary heart disease face an ongoing risk of cardiovascular events even when their lipid-lowering and antithrombotic therapy is optimal. Thus, to reduce morbidity in these patients, there is a need for doctors to employ additional therapies that are effective, safe, readily available and cost-efficient for this purpose. In the past decade, increasing evidence has accrued suggesting that there are cardiovascular benefits associated with adding colchicine 0.5 mg daily to lipid-lowering and antithrombotic therapy for secondary prevention of coronary heart disease.Stefan M Nidorf, Jamie Layland, Philip C Robinson, Sanjay Patel, Peter J Psaltis, Peter L Thompso

The Effect of Years-Long Exposure to Low-Dose Colchicine on Renal and Liver Function and Blood Creatine Kinase Levels: Safety Insights from the Low-Dose Colchicine 2 (LoDoCo2) Trial

BACKGROUND AND OBJECTIVE: The Low-Dose Colchicine-2 (LoDoCo2) trial showed that 2-4 years exposure to colchicine 0.5 mg once daily reduced the risk of cardiovascular events in patients with chronic coronary artery disease. The potential effect of years-long exposure to colchicine on renal or liver function and creatine kinase (CK) has not been systematically evaluated and was investigated in this LoDoCo2 substudy. METHODS: Blood samples drawn from 1776 participants at the close-out visit of the LoDoCo2 trial were used to measure markers of renal function (creatinine, blood urea nitrogen [BUN]), liver function (alanine aminotransferase [ALT], γ-glutamyl transferase [GGT], bilirubin and albumin), and CK. Renal and liver function as well as hyperCKemia (elevated CK) were categorized to the degree of elevation biomarkers as mild, mild/moderate, moderate/severe, and marked elevations. RESULTS: In total, 1776 participants (mean age 66.5 years, 72% male) contributed to this analysis, with a median exposure to trial medication of 32.7 months. Compared with placebo, colchicine was not associated with changes in creatinine and BUN but was associated with elevations in ALT (30 U/L vs. 26 U/L; p  5-10 × upper limit of normal [ULN]) in both treatment groups, and 6 (0.7%) colchicine-treated vs. 2 (0.2%) placebo-treated participants had moderate to marked CK elevations (> 5-10 × ULN). CONCLUSION: In chronic coronary artery disease, 2-4 years of exposure to colchicine 0.5 mg once daily was associated with small elevations in ALT and CK, but was not associated with changes in renal function. TRIAL REGISTRATION: https://www.anzctr.org.au ; ACTRN12614000093684, 24 January 2014

Assessing the impact of colchicine on coronary plaque phenotype after myocardial infarction with optical coherence tomography: rationale and design of the COCOMO-ACS study

Published: 25 August 2021 OnlinePublIntroduction 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.Nicholas J. Montarello, Kuljit Singh, Ajay Sinhal, Dennis T. L. Wong, Richard Alcock, Sharmalar Rajendran ... et al