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Atherosclerosis has long been hypothesized to be an inflammatory disease; recent data from the CANTOS trial demonstrating that canakinumab, an antibody that inhibits interleukin-1β, can reduce inflammation as well as cardiovascular events (NEJM JW Cardiol Oct 2017 and N Engl J Med 2017; 377:1119), support this theory.
To further test the inflammatory hypothesis of atherosclerosis, the CANTOS authors conducted the CIRT trial (NCT01594333). A total of 4786 patients with stable cardiovascular disease and either type 2 diabetes or the metabolic syndrome were randomized to receive low-dose methotrexate (15 to 20 mg weekly) or placebo. The primary endpoint was a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death,…