Faculty Bibliography

An improved understanding of the pathogenesis of acute coronary syndromes and its relationship to atherosclerotic plaque rupture and thrombosis has contributed to the investigation of novel therapies for prevention and treatment. New data ascribe an increasingly important role of active inflammation in contributing to thinning of the atherosclerotic fibrous cap and plaque instability. Despite this understanding, there are currently no therapeutic approaches to specifically target the unstable plaque. Multiple randomized trials investigating treatment strategies have recently been completed or are currently being conducted, using anti-inflammatory medications, such as methotrexate, colchicine, darapladib, varespladib, losmapimod, and canakinumab, to reduce the incidence of cardiovascular events including acute coronary syndromes. These anti-inflammatory medications differ in their mechanism of action from having widespread targets (as is the case for methotrexate and colchicine) to having specific targets (as is the case for darapladib, varespladib, losmapimod, and canakinumab). The trials investigating the efficacy of darapladib in reducing cardiovascular events revealed no significant benefit when compared with the current standard of care. The varespladib studies were terminated early because of adverse outcomes. However, the outcomes of the remaining drug studies may still contribute to novel therapeutic approaches in the treatment of patients with unstable coronary artery disease.