Novel direct-acting anticoagulants for risk reduction in ACS

Acute coronary syndrome (ACS) is a devastating adverse cardiovascular event with a massive burden on patient morbility and mortality, as well as the economy. Approximately 1.2 million people are hospitalized annually for ACS in the United States, with direct medical costs estimated at $150 billion in 2009. Rehospitalization is common, often as the result of recurrence of the initial event or complications of ACS or its therapy. Thrombosis is central to the pathogenesis of ACS. The current standard of care includes dual antiplatelet therapy, which reduces platelet activation and aggregation, integral steps for forming a thrombus. However, antiplatelet therapy does not prevent continued thrombin generation or the deposition of fibrin in the clot and residual risk of a recurrent event remains high. New oral anticoagulants offer a mechanism of action that is different from and complementary to that of antiplatelet agents. The ATLAS ACS-TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51) trial, using rivaroxaban, is the first trial of the new oral anticoagulants to show a benefit when added to antiplatelet therapy in reducing ACS events and mortality. While there was more major bleeding with the addition of rivaroxaban, fatal bleeding was not increased. These agents, if added to the current standard of care, might substantially reduce the high clinical and economic consequences of ACS.