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Effect of the novel direct factor Xa inhibitor DX-9065a on thrombin generation and inhibition among patients with stable atherosclerotic coronary artery disease.

Publication ,  Journal Article
Becker, RC; Alexander, JH; Dyke, C; Huang, Y; Saint-Jacques, H; Hasselblad, V; Harrington, RA; Bovill, EG; XaNADU-1B Investigators,
Published in: Thromb Res
2006

INTRODUCTION: Thrombin, a pluripotential effector enzyme with prothrombotic, proinflammatory, and mitogenic properties, plays a pivotal role in the pathobiology and clinical expression of atherothrombotic coronary artery disease. Existing anticoagulant drugs have not been shown to attenuate thrombin generation or activity consistently. We sought to investigate the effect of DX-9065a on thrombin generation and inhibition in patients with stable CAD. DX-9065a is a small-molecule, synthetic, direct inhibitor of factor Xa. MATERIALS AND METHODS: Peripheral venous blood samples were collected serially during and after administration of either placebo or 1 of 4 weight-adjusted regimens of DX-9065a, in 73 patients with stable CAD participating in the XaNADU-1B study. RESULTS AND CONCLUSIONS: At baseline, the median (25th, 75th) prothrombin activation fragment 1.2 (F1.2) level was 2.56 (2.05, 3.20) nmol/L, and the median d-dimer level was 0.26 (0.19, 0.38) microg FEU/L. There were significant relationships between measured plasma DX-9065a concentrations and both F1.2 (4.9% decrease for each doubling of DX-9065a) (P<0.0001) and d-dimer (5.5% decrease for each doubling of DX-9065a) (P=0.001). F1.2 was suppressed (below baseline) at 96 h after administration of DX-9065a. Coronary thrombotic events did not occur during or after study drug administration. DX-9065a, the first in a class of small-molecule, direct, selective and reversible factor Xa inhibitors, reduces thrombin generation and fibrin formation among patients with stable CAD. The effect is concentration-dependent and persists for at least 96 h following drug cessation, without biochemical or clinical evidence of rebound.

Duke Scholars

Published In

Thromb Res

DOI

EISSN

1879-2472

Publication Date

2006

Volume

117

Issue

4

Start / End Page

439 / 446

Location

United States

Related Subject Headings

  • Thrombin
  • Propionates
  • Naphthalenes
  • Middle Aged
  • Male
  • Humans
  • Female
  • Coronary Artery Disease
  • Cardiovascular System & Hematology
  • Antithrombin III
 

Citation

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Chicago
ICMJE
MLA
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Becker, R. C., Alexander, J. H., Dyke, C., Huang, Y., Saint-Jacques, H., Hasselblad, V., … XaNADU-1B Investigators, . (2006). Effect of the novel direct factor Xa inhibitor DX-9065a on thrombin generation and inhibition among patients with stable atherosclerotic coronary artery disease. Thromb Res, 117(4), 439–446. https://doi.org/10.1016/j.thromres.2005.03.017
Becker, Richard C., John H. Alexander, Christopher Dyke, Yao Huang, Henock Saint-Jacques, Vic Hasselblad, Robert A. Harrington, Edwin G. Bovill, and Edwin G. XaNADU-1B Investigators. “Effect of the novel direct factor Xa inhibitor DX-9065a on thrombin generation and inhibition among patients with stable atherosclerotic coronary artery disease.Thromb Res 117, no. 4 (2006): 439–46. https://doi.org/10.1016/j.thromres.2005.03.017.
Becker RC, Alexander JH, Dyke C, Huang Y, Saint-Jacques H, Hasselblad V, et al. Effect of the novel direct factor Xa inhibitor DX-9065a on thrombin generation and inhibition among patients with stable atherosclerotic coronary artery disease. Thromb Res. 2006;117(4):439–46.
Becker, Richard C., et al. “Effect of the novel direct factor Xa inhibitor DX-9065a on thrombin generation and inhibition among patients with stable atherosclerotic coronary artery disease.Thromb Res, vol. 117, no. 4, 2006, pp. 439–46. Pubmed, doi:10.1016/j.thromres.2005.03.017.
Becker RC, Alexander JH, Dyke C, Huang Y, Saint-Jacques H, Hasselblad V, Harrington RA, Bovill EG, XaNADU-1B Investigators. Effect of the novel direct factor Xa inhibitor DX-9065a on thrombin generation and inhibition among patients with stable atherosclerotic coronary artery disease. Thromb Res. 2006;117(4):439–446.
Journal cover image

Published In

Thromb Res

DOI

EISSN

1879-2472

Publication Date

2006

Volume

117

Issue

4

Start / End Page

439 / 446

Location

United States

Related Subject Headings

  • Thrombin
  • Propionates
  • Naphthalenes
  • Middle Aged
  • Male
  • Humans
  • Female
  • Coronary Artery Disease
  • Cardiovascular System & Hematology
  • Antithrombin III