Residual risk for secondary ischemic events in patients with atherothrombotic disease: Opportunity for future improvements in patient care

Atherothrombotic disease is highly prevalent in Western countries and is associated with morbidity, mortality, and a significant economic burden. The primary pathophysiological mechanism of acute ischemic events in patients with atherothrombotic disease is complex but involves thrombotic occlusion in response to rupture or erosion of atherosclerotic lesions. Current treatments for long-term secondary prevention in patients with established atherothrombotic disease, such as those with prior myocardial infarction, ischemic stroke/transient ischemic attack, or symptomatic peripheral artery disease, include therapies aimed at preventing rupture/erosion of atherosclerotic lesions (life-style modification and blood pressure reduction, in addition to statins and angiotensin II-active agents) and thrombus formation (primarily antiplatelet agents, such as aspirin, thienopyridines (clopidogrel, prasugrel, ticlopidine), and, to a lesser degree, anticoagulants). Despite the proven benefits and broad use of these therapies, the long-term rates of mortality and recurrent ischemic events remain high. This residual risk can be attributed to the fact that atherothrombosis continues in the presence of current treatments; because these agents each inhibit relatively specific pathways, atherosclerosis, thrombus formation, and other processes may progress. These considerations suggest that novel therapies with a different mechanism of action may provide additional reductions in morbidity and mortality beyond those observed with current agents.