Inflammation and Atherosclerosis

oes inflammation matter in coronary artery disease?Is it a driving force in atherosclerosis or merely an epiphenomenon?Is there space for novel therapies besides those targeting cholesterol?The CANTOS trial (Canakinumab Anti-inflammatory Thrombosis Outcomes Study), which was presented at the European Society of Cardiology meeting in Barcelona a few weeks ago, provides answers to these important questions.Indeed, the results of this trial open up a new avenue for cardiovascular prevention.Atherosclerosis, the underlying pathology in most cases of myocardial infarction, ischemic stroke, and ischemic gangrene, is a disease of complex genesis that has remained controversial for decades.Clinical and experimental studies have provided unequivocal evidence for an etiologic role of cholesterol and also offered strong support for a pathogenic role of inflammation. 1 By targeting cholesterol, blood pressure, and cigarette smoking, cardiovascular prevention has become one of the great success stories in medicine.We have witnessed a reduction in the incidence of myocardial infarction by ≈40% in large parts of the world during the past 2 decades, and a substantial part of this decrease can be ascribed to preventive medicine. 1Cholesterol-lowering statin therapy reduces the incidence of major adverse cardiovascular events by 25% to 50% in individuals with elevated low-density lipoprotein cholesterol and has become standard therapy for a large segment of the population in the Western world.The success of statins made us wonder whether we could realistically expect any further improvement in cardiovascular prevention.This attitude gained further support when it was found that statins also have anti-inflammatory properties.Although residual risk after myocardial infarction remains high, many clinicians and investigators did not see any reason for further development of cardiovascular prevention.The results of the CANTOS study demand a reassessment of the situation. 2ANTOS is a randomized, double-blind secondary prevention trial in 10 061 patients with prior myocardial infarction and elevated levels of the inflammation marker, high-sensitive C-reactive protein (>2 mg/L). 2 In all, 80% of the study participants were treated for hypertension, 40% had diabetes mellitus, and >90% were on statin therapy.They were randomized into 4 groups that received canakinumab, a human monoclonal antibody to the inflammatory cytokine, interleukin (IL)-1β at 3 different dosages, or placebo.Canakinumab is currently used clinically in some rare autoinflammatory conditions and as a second line of treatment in rheumatoid diseases.As expected, canakinumab reduced high-sensitive C-reactive protein levels; it had no substantial effect on plasma lipids. 2 The primary end point of the study was the first occurrence of myocardial infarction, stroke, or cardiovascular death.Canakinumab reduced this end point significantly, from 4.5 per 100 person-years in the placebo group to 3.9 in the groups receiving ≥150 mg antibody per dose. 2 This translated to a 15% relative reduction Inflammation and AtherosclerosisThe End of a Controversy