Antithrombotic effects of DX-9065a, a direct factor Xa inhibitor: a comparative study in humans versus low molecular weight heparin.
BACKGROUND
Recent evidence suggests that TF may play a causal role in acute coronary syndromes, and may be an important therapeutic target. Several inhibitors of TF, coagulation factors VIIa and Xa are under investigation as novel antithrombotic approaches. We compared the antithrombotic effects of DX-9065a, a new FXa inhibitor, vs. enoxaparin.


RESULTS
The protocol was an open-label crossover study. Subjects (n = 6) participated in 3 consecutive study-arms: a) enoxaparin + ASA (1 mg/Kg s. c + 162 mg/day x 3 days), b) three escalating doses of DX-9065a (1 mg bolus + 0.25 mg/h x 2 h, followed by an additional 1 mg bolus + 0.625 mg/h x 2 h and, a final 1 mg bolus + 1.25 mg/h x 2 h), and c) the same doses of DX-9065a in Arm 2 plus ASA pre-treatment. The antithrombotic effects were assessed using the Badimon perfusion chamber at each dose level. The administration of DX-9065a whether alone or combined with ASA significantly inhibited thrombus formation at high and low shear rate conditions while enoxaparin did not have a significant effect. Furthermore, these antithrombotic effects were obtained without significant prolongations of the standard coagulation parameters as those induced by enoxaparin.


CONCLUSIONS
The direct inhibition of FXa by DX-9065a appears to be a safe and effective new approach for preventing the thrombotic complications of atherosclerotic disease. The clinical effectiveness of the direct FXa inhibitors should be further investigated.
Shimbo
Daichi
D
Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New York, NY 10029, USA.
Osende
Julio
J
Chen
Julie
J
Robbins
Jonathan
J
Shimoto
Yoshimasa
Y
Kunitada
Satoshi
S
Fuster
Valentin
V
Badimon
Juan Jose
JJ
D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D001780:Blood Coagulation Tests; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D017984:Enoxaparin / Q000008:administration & dosage / Q000494:pharmacology; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018056:Hemorheology; D006487:Hemostasis / Q000187:drug effects; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D011422:Propionates / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D013314:Stress, Mechanical
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D009281:Naphthalenes; D011422:Propionates; D001241:Aspirin