Adjunctive therapies to reduce thrombotic events in patients with a history of myocardial infarction: role of vorapaxar

Acute myocardial infarction (AMI) is generally attributed to coronary atherothrombotic disease. Platelet activation is essential for thrombus formation and is thus an important target for pharmacological intervention to prevent and treat AMI. Despite contemporary treatment with dual antiplatelet therapy, including acetylsalicylic acid and adenosine diphosphate receptor antagonists, patients with prior AMI remain at increased risk of future thrombotic events. This has stimulated the search for more potent antithrombotic agents. Among these is the oral protease-activated receptor-1 antagonist vorapaxar, which represents a new oral antiplatelet agent to reduce thrombotic risk in patients with atherothrombotic disease. The TRACER and the TRA 2°P-TIMI 50 trials concluded that vorapaxar in addition to standard therapy reduced ischemic adverse cardiac events. A remarkable benefit was observed in patients with stable atherosclerotic disease, particularly those with a previous history of AMI. Although favorable effects were seen in reduction of adverse cardiac events, this was associated with excess major and intracranial bleeding, particularly in patients at high risk of bleeding and those with a history of stroke or transient ischemic attack. Currently, the lack of a reliable individualized risk stratification tool to assess patients for thrombotic and bleeding tendencies in order to identify those who might gain most net clinical benefit has led to limited use of vorapaxar in clinical practice. Vorapaxar may find a niche as an adjunct to standard care in patients at high risk of thrombotic events and who are at low risk of bleeding.