Novel Oral Anticoagulants in the Treatment of Acute Coronary Syndromes: Is there any Room for New Anticoagulants?

Spyridon      Deftereos; Georgios      Bouras; Georgios      Giannopoulos; Charalambos      Kossyvakis; Vasiliki      Panagopoulou; Vlasios      Pyrgakis; Christodoulos      Stefanadis

Abstract

Thrombosis plays a key role in the pathophysiology of acute coronary syndromes (ACS). The management of patients with ACS includes interventional procedures and use of antithrombotic agents acutely, and dual antiplatelet therapy (aspirin and a P2Y12 receptor antagonist) for secondary prevention. However, patients with recent ACS remain at a substantial residual risk for recurrent ischemic events or death. The idea of follow-up treatment with an oral anticoagulant on top of standard therapy seems promising. Warfarin was the first oral anticoagulant thoroughly investigated in this direction, but the widespread long-term use of warfarin in ACS has been limited by challenges associated with pharmacodynamic/pharmacokinetic deficiencies of the drug and the risk of bleeding. Novel oral anticoagulants, such as direct thrombin inhibitors (DTIs) and FXa inhibitors overcome the downsides of VKAs. Ximelagatran was the first DTI, investigated and proven to be effective in prevention of recurrent ischemic events in ACS patients, but the drug association with hepatotoxicity prompted its withdrawal. Dabigatran etexilate, apixaban, darexaban (YM150) and TAK-442 were studied in phase II dose-escalation trials in order to determine the balance between clinical effectiveness and bleeding risk in daily use with dual antiplatelet therapy, with both positive and negative results. Rivaroxaban is the only agent that completed a phase III trial, showing reduction in recurrent ischemic events rate and death from cardiovascular causes as well as all-cause death. This review summarizes the data from completed and ongoing clinical trials of the new oral anticoagulants in patients with ACS.

Keywords: Acute coronary syndromes, apixaban, dabigatran, direct thrombin inhibitors, Factor Xa inhibitors, oral anticoagulants, rivaroxaban, XIMELEGATRAN, DABIGATRAN ETEXILATE, gastrointestinal hemorrhage