Vorapaxar: A novel protease-activated receptor-1 inhibitor

Paul A. Gurbel, Young Hoon Jeong, Udaya S. Tantry

Research output: Contribution to journalReview article

Abstract

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 P2Y12 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 thrombinprotease-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.

Original languageEnglish (US)
Pages (from-to)1445-1453
Number of pages9
JournalExpert Opinion on Investigational Drugs
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2011

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Keywords

  • PAR-1 receptor
  • Platelet
  • Thrombosis
  • Vorapaxar

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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