Anti-inflammatory therapy in ischaemic heart disease: from canakinumab to colchicine

Four large trials have recently evaluated the effects of anti-inflammatory drugs in the secondary prevention of major cardiovascular events (MACE) in over 25 000 patients followed for 1.9-3.7 years. CANTOS tested subcutaneous canakinumab [an anti-interleukin (IL) 1 beta antibody] 300 mg every 3 months against placebo in patients with a history of myocardial infarction (MI) and serum C-reactive protein (CRP) >2 mg/L, demonstrating efficacy in preventing MACE but increased rates of fatal infections. COLCOT (in patients with recent MI) and LoDoCo2 (in patients with chronic coronary syndromes) tested oral colchicine (an NLRP3 inflammasome inhibitor) 0.5mg daily vs. placebo, demonstrating prevention of MACE with a slightly increased risk of pneumonia in COLCOT (0.9 vs. 0.4%) but not in LoDoCo2. CIRT tested oral methotrexate (an anti-rheumatic anti-nuclear factor-kB) 15-20 mg per week against placebo in ischaemic heart disease patients with diabetes or metabolic syndrome, without significant reduction in MACE rates or in circulating IL6 or CRP levels, and with increased risk of skin cancers. In summary, canakinumab and colchicine have shown efficacy in preventing MACE in ischaemic heart disease patients, but only colchicine has acceptable safety (and cost) for use in secondary cardiovascular prevention. Clinical results are expected with the anti-IL6 ziltivekimab.