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

Thrombosis Research

Volumn 117, Issue 4, 2006, Pages 439-446

  Becker, Richard C ^a,b   Alexander, John H ^a,b   Dyke, Christopher ^b   Huang, Yao ^b   Saint Jacques, Henock ^c   Hasselblad, Vic ^b   Harrington, Robert A ^a,b   Bovill, Edwin G ^d  

^a DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b DUKE CLINICAL RESEARCH INSTITUTE   (United States)

^c E203 Given Building ^*  (United States)

^d UNIVERSITY OF VERMONT COLLEGE OF MEDICINE   (United States)

Author keywords

CAD; DX 9065a; Factor Xa inhibitors; Thrombin

Indexed keywords

2 [4 [(1 ACETIMIDOYL 3 PYRROLIDINYL)OXY]PHENYL] 3 (7 AMIDINO 2 NAPHTHYL)PROPIONIC ACID; BIOLOGICAL MARKER; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 10A INHIBITOR; PLACEBO; THROMBIN;

ADULT; AGED; ARTICLE; ATHEROSCLEROSIS; BLOOD CLOTTING TEST; BLOOD SAMPLING; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CORONARY ARTERY DISEASE; DRUG BLOOD LEVEL; FIBRIN FORMATION; HUMAN; LIQUID CHROMATOGRAPHY; MAJOR CLINICAL STUDY; MASS SPECTROMETRY; PARTIAL THROMBOPLASTIN TIME; PRIORITY JOURNAL; PROTHROMBIN TIME; STATISTICAL ANALYSIS; THROMBIN TIME; THROMBOSIS;

AGED; ANTICOAGULANTS; ANTITHROMBIN III; CORONARY ARTERY DISEASE; FEMALE; HUMANS; MALE; MIDDLE AGED; NAPHTHALENES; PROPIONIC ACIDS; THROMBIN;

EID: 32044434887     PISSN: 00493848     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.thromres.2005.03.017     Document Type: Article

References (41)

1. E. Falk Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion Circulation 71 1985 699 708
2. P.L. Giesen, U. Rauch, B. Bohrmann, D. Kling, M. Roque, and J.T. Fallon Blood-borne tissue factor: another view of thrombosis Proc Natl Acad Sci U S A 96 1999 2311 2315
3. U. Rauch, and Y. Nemerson Circulating tissue factor and thrombosis Curr Opin Hematol 7 2000 273 277
4. P.R. Eisenberg, J.E. Siegel, D.R. Abendschein, and J.P. Miletich Importance of factor Xa in determining the procoagulant activity of whole-blood clots J Clin Invest 91 1993 1877 1883
5. R. Rho, R.P. Tracy, E.G. Bovill, S.P. Ball, and R.C. Becker Plasma markers of procoagulant activity among individuals with coronary artery disease J Thromb Thrombolysis 2 1995 239 243
6. R.C. Becker, R.P. Tracy, E.G. Bovill, J.M. Corrao, S. Baker, and S.P. Ball Surface 12-lead electrocardiographic findings and plasma markers of thrombin activity and generation in patients with myocardial ischemia at rest J Thromb Thrombolysis 1 1994 101 107
7. P.A. Merlini, K.A. Bauer, L. Oltrona, D. Ardissino, M. Cattaneo, and C. Belli Persistent activation of coagulation mechanism in unstable angina and myocardial infarction Circulation 90 1994 61 68
8. R. Bar-Shavit, A. Eldor, and I. Vlodavsky Binding of thrombin to subendothelial extracellular matrix. Protection and expression of functional properties J Clin Invest 84 1989 1096 1104
9. N.A. Nelken, S.J. Soifer, J. O'Keefe, T.K. Vu, I.F. Charo, and S.R. Coughlin Thrombin receptor expression in normal and atherosclerotic human arteries J Clin Invest 90 1992 1614 1621
10. T.K. Vu, V.I. Wheaton, D.T. Hung, I. Charo, and S.R. Coughlin Domains specifying thrombin-receptor interaction Nature 353 1991 674 677
11. M. Hoffman, and D.M. Monroe III A cell-based model of hemostasis Thromb Haemost 85 2001 958 965
12. B.A. Bouchard, C.S. Catcher, B.R. Thrash, C. Adida, and P.B. Tracy Effector cell protease receptor-1, a platelet activation-dependent membrane protein, regulates prothrombinase-catalyzed thrombin generation J Biol Chem 272 1997 9244 9251
13. R. Kumar, S. Beguin, and H.C. Hemker The effect of fibrin clots and clot-bound thrombin on the development of platelet procoagulant activity Thromb Haemost 74 1995 962 968
14. K.E. Brummel, S.G. Paradis, R.F. Branda, and K.G. Mann Oral anticoagulation thresholds Circulation 104 2001 2311 2317
15. D. Lasne, M. Krenn, V. Pingault, E. Arnaud, J.N. Fiessinger, and M. Aiach Interdonor variability of platelet response to thrombin receptor activation: influence of P1A2 polymorphism Br J Haematol 99 1997 801 807
16. T. Hara, A. Yokoyama, H. Ishihara, Y. Yokoyama, T. Nagahara, and M. Iwamoto DX-9065a, a new synthetic, potent anticoagulant and selective inhibitor for factor Xa Thromb Haemost 71 1994 314 319
17. S. Katakura, T. Nagahara, T. Hara, S. Kunitada, and M. Iwamoto Molecular model of an interaction between factor Xa and DX-9065a, a novel factor Xa inhibitor: contribution of the acetimidoylpyrrolidine moiety of the inhibitor to potency and selectivity for serine proteases Eur J Med Chem 30 1995 387 394
18. S.I. Katakura, T. Nagahara, T. Hara, and M. Iwamoto A novel factor Xa inhibitor: structure-activity relationships and selectivity between factor Xa and thrombin Biochem Biophys Res Commun 197 1993 965 972
19. H. Ishihara, T. Hara, and S. Kunitada Antithrombin III independent mechanism of factor C inhibition on prothrombinase with DX-9065a Haemostas 26 1996 580
20. J.P. Hërault, A. Bernat, A.M. Pflieger, J.C. Lormeau, and J.M. Herbert Comparative effects of two direct and indirect factor Xa inhibitors on free and clot-bound prothrombinase J Pharmacol Exp Ther 283 1997 16 22
21. A.R. Rezaie DX-9065a inhibition of factor Xa and the prothrombinase complex: mechanism of inhibition and comparison with therapeutic heparins Thromb Haemost 89 2003 112 121
22. C.K. Dyke, R.C. Becker, N.S. Kleiman, J.S. Hochman, E.G. Bovill, and A.M. Lincoff First experience with direct factor Xa inhibition in patients with stable coronary artery disease: a pharmacokinetic and pharmacodynamic evaluation Circulation 105 2002 2385 2391
23. G. Pejler, C. Lunderius, and B. Tomasini-Johansson Macrophages synthesize factor X and secrete factor X/Xa-containing prothrombinase activity into the surrounding medium Thromb Haemost 84 2000 429 435
24. J. Herbert, F. Bono, J. Herault, C. Avril, F. Dol, and A. Mares Effector protease receptor 1 mediates the mitogenic activity of factor Xa for vascular smooth muscle cells in vitro and in vivo J Clin Invest 101 1998 993 1000
25. P. Schaeffer, A.M. Mares, F. Dol, F. Bono, and J.M. Herbert Coagulation factor Xa induces endothelium-dependent relaxations in rat aorta Circ Res 81 1997 824 828
26. M.S. Goel, and S.L. Diamond Neutrophil enhancement of fibrin deposition under flow through platelet-dependent and -independent mechanisms Arterioscler Thromb Vasc Biol 21 2001 2093 2098
27. K.E. Brummel, S.G. Paradis, S. Butenas, and K.G. Mann Thrombin functions during tissue factor-induced blood coagulation Blood 100 2002 148 152
28. K.A. Bauer, L.M. Weiss, D. Sparrow, P.S. Vokonas, and R.D. Rosenberg Aging-associated changes in indices of thrombin generation and protein C activation in humans. Normative aging study J Clin Invest 80 1987 1527 1534
29. M. Cushman, B.M. Psaty, E. Macy, E.G. Bovill, E.S. Cornell, and L.H. Kuller Correlates of thrombin markers in an elderly cohort free of clinical cardiovascular disease Arterioscler Thromb Vasc Biol 16 1996 1163 1169
30. W.T. Sumner, D.M. Monroe, and M. Hoffman Variability in platelet procoagulant activity in healthy volunteers Thromb Res 81 1996 533 543
31. P.B. Tracy, M.E. Nesheim, and K.G. Mann Platelet factor Xa receptor Methods Enzymol 215 1992 329 360
32. J.P. Herault, F. Bono, C. Avril, P. Schaeffer, and J.M. Herbert Activation of human vascular endothelial cells by factor Xa: effect of specific inhibitors Biochem Pharmacol 57 1999 603 610
33. F. Depasse, and M.M. Samama Measurement of anti-Xa activity of direct factor Xa inhibitors: inter-assay variability for DX9065a [abstract] Thromb Haemost 2001 P687 [Suppl]
34. E.G. Bovill, R.C. Becker, C.K. Dyke, V. Hasselblad, M.M. Samama, and E. Golden Functional anti-Xa assay correlates highly with direct measurement of a novel factor Xa inhibitor, DX-9065a, in the XaNADU phase 1b dose finding study [abstract] Thromb Haemost 2001 P3097 [Suppl]
35. D. Shimbo, J. Osende, J. Chen, J. Robbins, Y. Shimoto, and S. Kunitada Antithrombotic effects of DX-9065a, a direct factor Xa inhibitor. A comparative study in humans versus low molecular weight heparin Thromb Haemost 88 2002 733 738
36. P. Theroux, D. Waters, J. Lam, M. Juneau, and J. McCans Reactivation of unstable angina after the discontinuation of heparin N Engl J Med 327 1992 141 145
37. A.J. Smith, R.E. Holt, J.B. Fitzpatrick, I.F. Palacios, H.K. Gold, and W. Werner Transient thrombotic state after abrupt discontinuation of heparin in percutaneous coronary angioplasty Am Heart J 131 1996 434 439
38. H.K. Gold, F. Torres, H. Garabedian, W. Werner, I.K. Jang, and A. Khan Evidence for a rebound coagulation phenomenon after cessation of a 4-hour infusion of a specific thrombin inhibitor in patients with unstable angina pectoris J Am Coll Cardiol 21 1993 1039 1047
39. H.D. Garabedian, H.K. Gold, J.B. Newell, D. Collen, J.N. Hagstrom, and E.G. Bovill Accelerated thrombin generation during anticoagulation in patients with unstable angina pectoris [correspondence] Blood 83 1994 1155a
40. P. Zoldhelyi, J. Bichler, W.G. Owen, D.E. Grill, V. Fuster, and J.S. Mruk Persistent thrombin generation in humans during specific thrombin inhibition with hirudin Circulation 90 1994 2671 2678
41. R.C. Becker, F.A. Spencer, Y. Li, S.P. Ball, Y. Ma, and T. Hurley Thrombin generation after the abrupt cessation of intravenous unfractionated heparin among patients with acute coronary syndromes: potential mechanisms for heightened prothrombotic potential J Am Coll Cardiol 34 1999 1020 1027