Potent arterial antithrombotic effect of direct factor-Xa inhibition with ZK-807834 administered to coronary artery disease patients

Thromb Haemost. 2007 Mar;97(3):487-92.


It was the objective of this study to evaluate the anti-thrombotic potency of direct factor-Xa inhibition with ZK-807834 in stable coronary patients, using an ex-vivo model of arterial thrombus formation. Tissue factor pathway is important in atherothrombosis. Direct factor-Xa blockade may more potently reduce thrombosis and prevent coronary events. Badimon Perfusion Chamber 5-minute quantitative studies have shown 40-55% arterial thrombus reduction with abciximab, 23% with clopidogrel, but none with heparin. Coronary patients (n = 18, 59 +/- 9 years, 55% males) were blindly randomized to four groups receiving 24-hour infusion of a low, medium or high dose of direct factor- Xa inhibitor ZK-807834, or placebo. Arterial thrombus formation was measured in Badimon Chamber at baseline, end-of-infusion [EoI], and four hours and eight hours after EoI, and factor-X activity, prothrombin time [PT] ratio and plasma drug levels were measured simultaneously. For the low-, medium- and high-dose ZK-807834 groups, mean percent-reduction in thrombus size from baseline to EoI were 29%, 34% and 68%, respectively (p < 0.001), and at 8-h post EoI were 11%, 19% and 27%, respectively (p < 0.01). Mean PT-ratio prolongation showed a strong linear relationship (Pearson's r = 0.93) with ZK-807834 plasma concentration. Mean percent-reduction in factor-X activity from baseline was 13%, 42% and 58%, respectively. Placebo had no effect on thrombus size or factor-X activity. In conclusion, direct factor-Xa inhibition with ZK-807834 markedly reduces ex-vivo arterial thrombus formation and factor-X activity in a dose-dependent manner. Plasma levels of ZK-807834 show a strong linear correlation with PT ratio. This direct factor-Xa inhibitor may reduce the need for additional potent glycoprotein IIbIIIa inhibition.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines / administration & dosage
  • Amidines / pharmacokinetics
  • Amidines / therapeutic use*
  • Animals
  • Aorta / drug effects*
  • Aorta / pathology
  • Blood Coagulation / drug effects*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Factor Xa Inhibitors*
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / pharmacokinetics
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Infusions, Intravenous
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Perfusion
  • Prothrombin Time
  • Pyridines / administration & dosage
  • Pyridines / pharmacokinetics
  • Pyridines / therapeutic use*
  • Swine
  • Thrombosis / blood
  • Thrombosis / etiology
  • Thrombosis / pathology
  • Thrombosis / prevention & control*
  • Time Factors
  • Treatment Outcome


  • Amidines
  • Factor Xa Inhibitors
  • Fibrinolytic Agents
  • Pyridines
  • Fidexaban