CANTOS: A Gigantic Proof-of-Concept Trial

Cumulative evidence links inflammation with atherothrombotic disease. Conversely, the role of modulating the inflammatory process as a therapeutic target has remain an unproven hypothesis until the execution of the CANTOS trial (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study). On the one hand, this trial provides robust evidence that interleukin-1β (IL-1β) inhibition by canakinumab reduces the incidence of repetitive atherothrombotic events in patients with postmyocardial infarction already on state-of-the-art treatment but with a residual inflammatory risk. On the other hand, the absolute antiatherothrombotic effect size of this intervention seems small (189 patients had to be intervened during 1 year to prevent 1 myocardial infarction episode) and associated with a mild increase in the incidence of serious adverse events (≈1 in 750 patients intervened during 1 year developed a fatal infection or sepsis). Beyond all these considerations, CANTOS represents a gigantic (10 000 patients) proof-of-concept trial.