Vorapaxar: a novel protease-activated receptor-1 inhibitor.


Journal Article (Review)

INTRODUCTION: Platelet activation and reactivity are pivotal for both acute and chronic atherothrombotic event occurrences. AREAS COVERED: Only 20% relative risk (∼ 2% absolute risk) reduction associated with newer P2Y(12) receptor blocker therapy such as prasugrel and ticagrelor compared with clopidogrel indicates that dual antiplatelet therapy may be associated with a ceiling effect in attenuating platelet-mediated ischemic event occurrence and that residual ischemic event occurrences are mediated by other pathways that are unblocked by current antiplatelet therapy. Therefore, inhibition of the thrombin-protease-activated receptor (PAR)-1 interaction may provide additional benefits in attenuating ischemic event occurrence in selected patients. There are two major PAR-1 blockers are under investigations - vorapaxar and atopaxar. In preclinical and Phase I - II studies, inhibition of thrombin-mediated platelet activation by a PAR-1 inhibitor, in general, has added to the antithrombotic efficacy of aspirin and clopidogrel without increasing bleeding. However, intracranial hemorrhage in patients with a history of stroke associated with vorapaxar and hepatic toxicity associated with atopaxar are important concerns. EXPERT OPINION: At this time, the specific role of PAR-1 inhibitor in the settings of percutaneous coronary intervention and acute coronary syndrome, both during the acute setting and as a long-term therapeutic agent, is not clear. Although the PAR-1 inhibitors are associated with less bleeding, its effectiveness as an antithrombotic agent and also side effects are major concerns. Future large-scale trials with goals addressing these concerns are needed to define the specific role of PAR-1 receptor inhibitor.

Full Text

Duke Authors

Cited Authors

  • Gurbel, PA; Jeong, Y-H; Tantry, US

Published Date

  • October 2011

Published In

Volume / Issue

  • 20 / 10

Start / End Page

  • 1445 - 1453

PubMed ID

  • 21819272

Pubmed Central ID

  • 21819272

Electronic International Standard Serial Number (EISSN)

  • 1744-7658

Digital Object Identifier (DOI)

  • 10.1517/13543784.2011.606809


  • eng

Conference Location

  • England