New antithrombotic agents--insights from clinical trials

Antithrombotic agents are the cornerstones of therapy for thrombosis. The compositions of arterial and venous clots differ, rendering antiplatelet agents more effective for arterial thrombosis and anticoagulants more effective for venous disease. Despite taking acetylsalicylic acid, some patients with arterial disease experience thrombotic events. The addition of the ADP-receptor antagonist clopidogrel to therapeutic regimens containing acetylsalicylic acid improves outcomes in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. However, clopidogrel has several limitations, including variable absorption, drug-drug interactions and genetic factors that lead to reduced generation of the active metabolite, and a delayed onset and offset of action. A search for new ADP-receptor inhibitors has yielded drugs such as prasugrel, ticagrelor, and cangrelor. For patients with venous thrombosis, the coumarins have been the only available oral anticoagulants for more than 60 years. Despite their effectiveness in preventing and treating thromboembolism, coumarins have well-documented limitations, including drug-drug and drug-dietary interactions, a narrow therapeutic range, and inconvenience and cost of monitoring therapy. A search for new oral anticoagulants has yielded drugs such as dabigatran etexilate, rivaroxaban, and apixaban. In this article, we review these new antithrombotic agents and provide plausible explanations for the results of phase III randomized controlled trials of these drugs.