Addressing Acute Coronary Syndromes
New Challenges and Opportunities After the CANTOS Trial (Canakinumab Anti-inflammatory Thrombosis Outcomes Study)
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In the mid-1980s, it became clear that plaque quality rather than plaque quantity explained coronary instability, as suggested by data deriving from retrospective angiographic studies, and, in 1985, M.J. Davies proposed that plaque fissure was the link between atherosclerosis and thrombosis. In 1994, we found that patients with acute coronary syndrome (ACS) and high levels of C-reactive protein (CRP), a prototypic marker of inflammation, had a worse outcome than patients with normal levels of CRP, and proposed that plaque inflammation was responsible for plaque fissure.1 Several other studies then confirmed an association between activation of inflammatory cells and ACS but without proving the causality. The recent publication of the CANTOS trial (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) has convincingly proved the inflammatory hypothesis of ACS we proposed 23 years ago.2
Indeed, CANTOS showed that interleukin-1β inhibition by canakinumab administration added to current optimal treatment in patients with a history of myocardial infarction and levels of high-sensitivity CRP >2 mg/L resulted in a 39% reduction of high-sensitivity CRP levels from baseline without any effect on lipids, and in a 15% reduction in the risk of the primary composite efficacy end point of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death, in comparison with placebo-treated patients.2
Yet, the benefit of canakinumab administration on ischemic events was rather modest and …