N Engl J Med 2019;381:2497-2505Background: Inflammation increases the risk of atherosclerosis, and reducing inflammation with canakinumab, a monoclonal antibody that neutralizes interleukin-1β, reduced plasma markers of inflammation and the risk of future myocardial infarctions but was associated with small yet statistically significant increased risk of fatal infections. Methotrexate, in the CIRT trial, did not reduce plasma markers of inflammation or cardiovascular events.Cardiology Trial’s Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.Colchicine, extracted from the plant autumn crocus, is a potent inexpressive anti-inflammatory medication that has been used for centuries, and is used for conditions like gout, familial Mediterranean fever and pericarditis.The Colchicine Cardiovascular Outcomes Trial (COLCOT) sought to test the hypothesis that colchicine is superior to placebo in reducing cardiovascular events in patients with recent myocardial infarction.Patients: Eligible patients were adults who had myocardial infarction within 30 days of enrollment, had any planned revascularization completed, and were on guidelines recommended treatment. Exclusion criteria included severe heart failure, left ventricular ejection fraction <35%, stroke within 3 months, CABG within the previous 3 years or planned, inflammatory bowel disease or chronic diarrhea, clinically significant non-transient hematologic abnormalities, severe renal disease, long-term systemic glucocorticoid therapy, plus a few others.Baseline characteristics: The trial randomized 2,366 patients to colchicine and 2,379 patients to placebo. The average age of patients was 61 years with 81% being men. The average body mass index was 28 kg/m2. About 30% were current smokers, 51% had hypertension, 20% had diabetes, 16% had prior myocardial infarction, 2% had history of heart failure, and 3% had history of stroke or TIA. Percutaneous coronary intervention for the index myocardial infarction was performed in 93% of the patients. The average time from index event to randomization was 13 days. Aspirin was prescribed in 99% of the patients, other antiplatelets in 98%, and statins in 99%.Procedures: Patients were randomized 1:1 to receive colchicine 0.5mg oral daily or placebo, in a double-blind fashion. Follow up visits or phone assessments were performed at 1, 3, and 6 months and every 3 months thereafter.Endpoints: The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. Secondary endpoints included components of the primary endpoint as well as death from any cause.Statistical analysis was performed based on the intention-to-treat principle. The trial was event driven. It was estimated that a total of 4,500 patients and 301 primary endpoint events would give the trial 80% power to detect 27% relative reduction of the primary endpoint with colchicine compared to placebo. The assumed event rate in the placebo arm was 7% at 2 years.Results: After a median follow up time of 22.6 months, colchicine reduced the primary composite endpoint compared to placebo (5.5% vs 7.1%, HR: 0.77, 95% CI: 0.61 - 0.96; p=0.02). The reduction in the composite primary endpoint was primarily driven by significant reduction in urgent hospitalization for angina leading to coronary revascularization (1.1% vs 2.1%, HR: 0.50, 95% CI: 0.31 - 0.81) and stroke (0.2% vs 0.8%, HR: 0.26, 95% CI: 0.10 - 0.70). There was no significant reduction in death from cardiovascular causes (0.8% vs 1.0%), resuscitated cardiac arrest (0.2% vs 0.3%), myocardial infarction (3.8% vs 4.1%) or death from any cause (1.8% in both arms).Data on Hs-CRP at baseline and 6 months were available from 207 patients. At baseline, geometric mean of hs-CRP was 4.27 mg/L in the colchicine group and 5.