With the publication of CANTOS (the Canakinumab Anti-inflammatory Thrombosis Outcomes Study) in 2017, the cardiovascular community received proof of principle that therapeutic targeting of interleukin-1 and interleukin-6 to the C-reactive protein (CRP) pathway of innate immunity can significantly reduce major adverse cardiovascular event rates (1). Although the benefits of interleukin-1b inhibition in CANTOS were observed in the absence of any effects on lowdensity lipoprotein cholesterol (LDLC), the cardiovascular protection from canakinumab was identical in magnitude to that observed in major trials of PCSK9 inhibition. Furthermore, on-treatment levels of the inflammatory biomarkers interleukin-6 and highsensitivity CRP (hsCRP) were powerful predictors of efficacy after inflammation-lowering therapy in a manner fully parallel to that of on-treatment levels of LDLC following lipid-lowering therapy (2, 3). CANTOS thus provided the first hard evidence in 40 years of an effective therapy for atherosclerosis not directly related to cholesterol reduction, blood pressure, or coagulation.

Although CANTOS was a secondary prevention trial, there is considerable interest in addressing residual inflammatory risk in the setting of acute coronary ischemia. From a biomarker perspective, both interleukin-6 and hsCRP have repeatedly proven effective for risk prediction, not only in primary prevention and stable coronary disease, but also in acute coronary syndromes (4). By contrast, comparatively little is known about plasma levels of interleukin-1b itself, in part because its measurement is more complex and less well suited for epidemiologic investigation. Nonetheless, information about circulating interleukin-1b could provide important insights into the pathophysiology of acute plaque rupture and, by extension, atherosclerotic progression. In one recent example, interleukin-1b levels were associated with increased mortality in the setting of heart failure (5), an endpoint also reduced by interleukin-1b inhibition in CANTOS (6).