Anti-Inflammatory Therapy for Acute Coronary Syndromes: Is It Time for a Shift in the Treatment Paradigm?

The intense inflammatory response triggered by myocardial infarction (MI) is a part of the cardiac repair process: infiltrating leukocytes, by releasing proteases and reactive oxygen species, and clear the wound from dead cells and debris. Wound cleansing establishes, in turn, an environment which favors healing. Nevertheless, the close spatial relation between leukocytes and nearby viable cardiomyocytes in the border zone of ischemic damage has been deemed responsible for leukocyte-mediated cardiomyocyte injury. During diapedesis, the white blood cells interact with the endothelium and transmigrate across the vascular wall to reach the infarct zone where they adhere to the viable cardiomyocytes; the result of this proximity and of leukocyte cytotoxic effects is the worsening of ischemic injury. Furthermore, the activation of inflammatory pathways is partly accountable for postinfarction dilative and fibrotic remodeling which impairs cardiac function through changes in geometry, mass, composition, and volume of the left ventricle. As a consequence, targeting inflammatory signals has been considered for a long time a promising therapeutic approach to prevent heart failure and reduce mortality in patients with MI.