Impact of selective platelet inhibition in reducing cardiovascular risk – role of vorapaxar

This article reviews the pharmacology, clinical efficacy, and safety of vorapaxar in reducing cardiovascular risk. Vorapaxar is a tricyclic himbacine-derived reversible inhibitor of platelet surface protease activator receptor-1, which prevents thrombin from activating platelets. Two Phase III clinical trials and multiple subanalyses from the two trials with vorapaxar have been published. In patients with recent acute coronary syndrome, vorapaxar, when added to standard therapy, did not reduce the composite cardiovascular end point. In contrary, in a study of secondary prevention for patients with cardiovascular diseases, vorapaxar reduced the risk of cardiovascular death or ischemic events (myocardial infarction, stroke) in patients with stable atherosclerosis who were receiving standard therapy. Vorapaxar is approved in the US for use with aspirin and/or clopidogrel in the secondary prevention of thrombogenic cardiovascular events in stable patients with peripheral arterial disease or a history of myocardial infarction. Vorapaxar increases risk of bleeding and is contraindicated in patients with previous cerebrovascular events. It is essential to balance individual patient’s bleeding risk to any further cardiovascular benefits that they may get. Future investigation is also needed to evaluate use of vorapaxar with newer antiplatelet agents such as ticagrelor and cangrelor, as well as its role as monotherapy.