Colchicine reduces cardiovascular risk in patients post-myocardial infarction and those with chronic coronary disease irrespective of history and timing of acute coronary syndrome (ACS), according to a new LoDoCo2 trial analysis. The drug is an inexpensive anti-inflammatory treatment widely used to treat gout, pericarditis and familial Mediterranean fever, the authors, led by Tjerk S.J. Opstal, MD, of Radboud University Medical Center and Northwest Clinics, the Netherlands, noted. The results of the latest analysis were published Monday online ahead of the Aug 31 issue of the Journal of the American College of Cardiology. Background Anti-inflammatory treatments are believed to have the potential to reduce cardiovascular events because inflammation drives all phases of atherosclerosis, the researchers noted – a theory first supported by data from the CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) study for canakinumab. Similarly to canakinumab, colchicine attenuates NLRP3 (nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain containing protein-3) inflammasome activation. It is also suggested that colchicine inhibits phagocytosis, neutrophil recruitment, and function. Colchicine reduced the risk of cardiovascular events by 23% in patients with very recent (<30 days) myocardial infarction compared with placebo in the 4,765-patient COLCOT (Colchicine Cardiovascular Outcomes Trial) study, with the greatest benefits seemingly related to patients who started their treatment within 3 days of the acute event. The randomized, controlled, double-blind LoDoCo2 (Low-Dose Colchicine 2) trial in 5,522 patients with chronic coronary disease demonstrated that colchicine reduced the risk of cardiovascular events by 31% compared with placebo, driven by reductions in both myocardial infarction and ischemia-driven coronary revascularization, the researchers added. However, whether reduced risk was actually related to treatment timing following ACS remained unknown. The current analysis, therefore, set out to investigate major adverse cardiovascular event (MACE) risk in relation to ACS and its timing. New analysis LoDoCo2 ran between 2014 and 2020 across 43 sites in Australia and the Netherlands, evaluating a once-daily 0.5-mg dose of colchicine compared with placebo for the prevention of cardiovascular events in chronic coronary disease patients who were clinically stable for at least 6 months prior to enrollment. They were followed up for a median of 28.6 months. In the current study, the researchers compared the rate of the composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke or ischemia-driven coronary revascularization between patients with no prior, recent (6-24 months), remote (2-7 years) or very remote (>7 years) ACS. Patients were of similar age across the groups (a median of 67.3 years, 63.7, 64.3 and 68.4 respectively), and were majority male. The trial excluded patients who had experienced an ACS within 6 months prior to randomization. Colchicine consistently reduced the primary endpoint in patients with no prior ACS (incidence: 2.8 vs 3.4 events per 100 person-years; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.52-1.27), recent ACS (incidence: 2.4 vs 3.3 events per 100 person-years; HR: 0.75; 95% CI: 0.51-1.10), remote ACS (incidence: 1.8 vs 3.2 events per 100 person-years, HR: 0.55; 95% CI: 0.37-0.82), and very remote ACS (incidence: 3.0 vs 4.3 events per 100 person-years, HR: 0.70; 95% CI: 0.51-0.96) (P for interaction = 0.59). “The benefits of colchicine are consistent irrespective of history and timing of prior ACS, thereby highlighting the importance of compliance with long-term secondary prevention therapies, including the use of anti-inflammatory therapy,” the researchers concluded. They called for future studies addressing whether patients with chronic coronary disease without a prior ACS benefit from treatment with colchicine. “Although the current subgroup analysis of LoDoCo2 was not prespecified, it contributes to the evidence supporting the efficacy and use of low-dose colchicine to reduce the risk of vascular events both in patients with a recent myocardial infarction and those with chronic coronary artery disease,” Jean-Claude Tardif, MD, and Guillaume Marquis-Gravel, MD, MSc, from the Université de Montréal, said in an accompanying editorial. “In light of the positive results from LoDoCo2, COLCOT, and meta-analyses; its good tolerability profile; and cost-effectiveness, inflammation reduction with low-dose colchicine should be considered to treat patients with coronary disease in the absence of severe renal dysfunction.” Sources Opstal TSJ, Fiolet ATL, van Broekhoven A, et al. Colchicine in Patients With Chronic Coronary Disease in Relation to Prior Acute Coronary Syndrome. J Am Coll Cardiol 2021;78:859-866. Tardif J-C, Marquis-Gravel G. Low-Dose Colchicine for the Management of Coronary Artery Disease. J Am Coll Cardiol 2021;78:867-869. Image Credit: Soni's – stock.adobe.com