Increased Benefit With Vorapaxar Use in Patients With a History of Myocardial Infarction and Diabetes Mellitus: What the Data Show Us.

Type 2 diabetes mellitus (T2DM) is a progressive and multifactorial metabolic disease mainly characterized by hyperglycemia and insulin resistance. Abnormal platelet reactivity associated with an increased risk of cardiovascular disease (CVD) is also a feature characteristic of patients with T2DM. Dual antiplatelet therapy consisting of aspirin and an adenosine diphosphate platelet P2Y receptor antagonist, such as clopidogrel, represents the standard antithrombotic regimen for the secondary prevention of CVD risk in T2DM. However, a high proportion of patients with T2DM exhibit high on-treatment platelet reactivity to aspirin and/or clopidogrel, associated with a greater risk of adverse cardiovascular events compared with nondiabetic patients. Consequently, novel antiplatelet therapeutic approaches may be required in order to avoid such events. Vorapaxar is a novel antiplatelet agent that targets the platelet protease-activated receptor 1 and inhibits thrombin-induced platelet activation. Vorapaxar has been studied in 2 phase III clinical trials and has been approved for use in the secondary prevention of atherothrombotic events in patients with a previous myocardial infarction (MI) or peripheral arterial disease. New data from the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-TIMI 50 trial MI cohort demonstrate that the subgroup of patients with T2DM exhibits increased benefit from vorapaxar use compared with non-T2DM patients. The aim of the present work is to critically review the current knowledge concerning vorapaxar use in patients with T2DM as well as to discuss the possible mechanism(s) underlying vorapaxar's beneficial effect in T2DM.