Thromb Haemost 2002; 88(05): 733-738
DOI: 10.1055/s-0037-1613294
Review Article
Schattauer GmbH

Antithrombotic Effects of DX-9065a, a Direct Factor Xa Inhibitor

A Comparative Study in Humans versus Low Molecular Weight Heparin
Daichi Shimbo
1   Cardiovascular Biology Research Laboratory
,
Julio Osende
1   Cardiovascular Biology Research Laboratory
,
Julie Chen
1   Cardiovascular Biology Research Laboratory
,
Jonathan Robbins
1   Cardiovascular Biology Research Laboratory
,
Yoshimasa Shimoto
3   Daiichi Pharmaceutical Co., Ltd, Japan
,
Satoshi Kunitada
3   Daiichi Pharmaceutical Co., Ltd, Japan
,
Valentin Fuster
2   Cardiovascular Institute, Mount Sinai School of Medicine New York
,
Juan Jose Badimon
1   Cardiovascular Biology Research Laboratory
› Institutsangaben
This work was supported by Daiichi Pharmaceutical Co, Ltd, Japan and the followings NIH grants P50-HL54469 to JJB and 5-MO1-RR-00071 to the Mount Sinai General Clinical Research Center.
Weitere Informationen

Publikationsverlauf

Received 13. Mai 2002

Accepted after resubmission 11. Juli 2002

Publikationsdatum:
08. Dezember 2017 (online)

Summary

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.

Methods and 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.

 
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