Targeting Inflammation to Reduce Residual Cardiovascular Risk.

Recent trials of anti-inflammatory agents have specifically tested the hypothesis that inflammation reduction reduces residual cardiovascular risk. Most prominent among these are the CANTOS, COLCOT, and CIRT trials. CANTOS enrolled patients with prior myocardial infarction (MI) and a high-sensitivity C-reactive protein ≥ 2 mg/L and reported a 15% reduction in major adverse cardiovascular events (MACE; HR 0.85, 95% CI 0.74-0.98) with the interleukin-1β inhibitor canakinumab. In COLCOT, colchicine 0.5 mg daily led to a 23% relative risk reduction (HR 0.77, 95% CI 0.61-0.96) in major vascular events in patients with recent acute coronary syndrome. By contrast, CIRT was stopped early for lack of benefit of low-dose methotrexate in preventing MACE in patients with coronary artery disease and either type 2 diabetes or the metabolic syndrome. Ongoing subclinical inflammation is an important marker of risk in patients with established cardiovascular disease, and novel therapies targeted at specific inflammatory pathways now demonstrate efficacy for the prevention of major adverse cardiovascular events.