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Vorapaxar in the secondary prevention of atherothrombosis.

Publication ,  Journal Article
Tantry, US; Liu, F; Chen, G; Gurbel, PA
Published in: Expert Rev Cardiovasc Ther
December 2015

Dual antiplatelet therapy with aspirin, a platelet cyclooxygenase-1 inhibitor and P2Y12 receptor blockers, remains the major drug strategy to prevent ischemic event occurrence in patients with acute coronary syndromes and in patients undergoing coronary stenting, but there some limitations that can be overcome by targeting novel targets. Unlike direct thrombin inhibitors that bind directly to thrombin, targeting the platelet thrombin receptor, protease activated receptor (PAR)-1, may offer a better choice for the attenuation of atherosclerosis progression, thrombus-mediated ischemic events and restenosis without interfering with primary hemostasis. Vorapaxar - a synthetic analogue of himbacine, is a high affinity and highly selective PAR-1 antagonist that can effectively inhibit thrombin-induced platelet aggregation. In the TRACER trial, the addition of vorapaxar to standard therapy in patients with non-stent thrombosis-elevation- acute coronary syndromes did not significantly reduce the primary composite end point occurrence of cardiovascular (CV) death, myocardial infarction (MI), stroke, hospitalization for ischemia, or urgent revascularization, but significantly increased the GUSTO moderate and severe bleeding (p < 0.001) and intracranial hemorrhage (ICH). In the TRA 2°P-TIMI 50 trial, in patients with a history of MI and peripheral arterial disease (PAD) (67% of the total population), the end point of CV death, MI, or stroke was significantly (20%) reduced with vorapaxar whereas GUSTO moderate or severe bleeding was increased (1.5-fold), but not ICH or fatal bleeding and the net clinical outcome favoring the vorapaxar therapy. Based on these favorable results, the FDA approved vorapaxar for the reduction of thrombotic cardiovascular events in patients with prior MI or with PAD for long term therapy. A careful patient selection is needed to balance efficacy versus safety. At this time, patients with high risk for recurrent ischemic event occurrence such as patients with diabetes mellitus and previous MI can be safely treated with vorapaxar for long-term therapy.

Duke Scholars

Published In

Expert Rev Cardiovasc Ther

DOI

EISSN

1744-8344

Publication Date

December 2015

Volume

13

Issue

12

Start / End Page

1293 / 1305

Location

England

Related Subject Headings

  • Thrombosis
  • Stroke
  • Secondary Prevention
  • Risk Assessment
  • Receptor, PAR-1
  • Pyridines
  • Platelet Aggregation Inhibitors
  • Patient Selection
  • Outcome and Process Assessment, Health Care
  • Myocardial Ischemia
 

Citation

APA
Chicago
ICMJE
MLA
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Tantry, U. S., Liu, F., Chen, G., & Gurbel, P. A. (2015). Vorapaxar in the secondary prevention of atherothrombosis. Expert Rev Cardiovasc Ther, 13(12), 1293–1305. https://doi.org/10.1586/14779072.2015.1109447
Tantry, Udaya S., Fang Liu, Gailing Chen, and Paul A. Gurbel. “Vorapaxar in the secondary prevention of atherothrombosis.Expert Rev Cardiovasc Ther 13, no. 12 (December 2015): 1293–1305. https://doi.org/10.1586/14779072.2015.1109447.
Tantry US, Liu F, Chen G, Gurbel PA. Vorapaxar in the secondary prevention of atherothrombosis. Expert Rev Cardiovasc Ther. 2015 Dec;13(12):1293–305.
Tantry, Udaya S., et al. “Vorapaxar in the secondary prevention of atherothrombosis.Expert Rev Cardiovasc Ther, vol. 13, no. 12, Dec. 2015, pp. 1293–305. Pubmed, doi:10.1586/14779072.2015.1109447.
Tantry US, Liu F, Chen G, Gurbel PA. Vorapaxar in the secondary prevention of atherothrombosis. Expert Rev Cardiovasc Ther. 2015 Dec;13(12):1293–1305.
Journal cover image

Published In

Expert Rev Cardiovasc Ther

DOI

EISSN

1744-8344

Publication Date

December 2015

Volume

13

Issue

12

Start / End Page

1293 / 1305

Location

England

Related Subject Headings

  • Thrombosis
  • Stroke
  • Secondary Prevention
  • Risk Assessment
  • Receptor, PAR-1
  • Pyridines
  • Platelet Aggregation Inhibitors
  • Patient Selection
  • Outcome and Process Assessment, Health Care
  • Myocardial Ischemia