New targets for atherothrombosis.

Abstract

Atherosclerotic plaques contain a variety of highly thrombogenic material, such as the platelet activator collagen and the procoagulant protein tissue factor. Atherothrombosis describes the formation of a thrombus after rupture or erosion of an atherosclerotic plaque. An occlusive thrombus in coronary and carotid arteries induces myocardial infarction and stroke, respectively. Arterial clots are platelet rich, so patients with cardiovascular disease are treated prophylactically with antiplatelets drugs, such as aspirin and clopidogrel. Importantly, the recent clinical trial (ATLAS ACS 2-TIMI 51 [The Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome]) showed that addition of low doses of the direct oral antifactor Xa drug rivaroxaban to standard antiplatelet therapy in patients with recent acute coronary syndrome reduced death from cardiovascular causes, myocardial infarction, or stroke.1 However, the addition of the anticoagulant was associated with increased rates of major bleeding and intracranial hemorrhage. An earlier trial (APPRAISE-2 [The Apixaban for Prevention of Acute Ischemic Events 2]) with the factor Xa inhibitor apixaban was terminated prematurely because of an increase in major bleeding events.2 Therefore, there is a need for a safer anticoagulant that reduces atherothrombosis without increasing bleeding. See accompanying articles on pages 1668 and 1674 Anticoagulant drugs that are used to treat …