Is Atherosclerosis Amenable to Anti-Inflammatory Compounds?

Abstract

The hypothesis of an inflammatory component in the pathogenesis of atherosclerosis has been under investigation for a long time but the data have not been conclusive. No clinical trial of anti-inflammatory, anti-oxidant, or anti-bacterial agents has ever proven efficacious. However, the recent announcement and publication of the CANTOS trial has raised expectations. This pivotal trial showed for the first time that anti-inflammatory therapy targeting the interleukin-1β innate immunity pathway with subcutaneous injections of canakinumab every 3 months conferred significantly, albeit modestly (15%), lower rate of the composite end-point of nonfatal MI, nonfatal stroke and cardiovascular (CV) death than placebo, independent of lipid-level lowering, in patients with prior myocardial infarction (MI). An unexpected corollary of this investigation revealed significant concomitant reduction in lung cancer mortality. Despite the initial enthusiasm about the trial results, sceptics point to that fact that CV mortality was not affected, while the incidence of fatal infections was much higher with the drug compared with placebo, and the cost of this therapy remains currently prohibitive for wider use. Ongoing and future trials with similar or more convenient and less expensive anti-inflammatory agents may provide more data whether such results are reproducible and/or supportive or evidential of the inflammatory hypothesis of atherosclerosis. Rhythmos 2017; 12(4):63-68.