New parenteral anticoagulants: Focus on factor xa and thrombin inhibitors

Current Drug Discovery Technologies

Volumn 9, Issue 2, 2012, Pages 129-136

  Ahrens, Ingo ^a   Bode, Christoph ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

Author keywords

ACS; Aptamer; Factor Xa; Otamixaban; Parenteral anticoagulants; Thrombin

Indexed keywords

ARGATROBAN; BLOOD CLOTTING FACTOR 10A INHIBITOR; ENOXAPARIN; EPTIFIBATIDE; FIDEXABAN; FLOVAGATRAN; FONDAPARINUX; HD 122; HEPARIN; HIRULOG; IDRABIOTAPARINUX; LOW MOLECULAR WEIGHT HEPARIN; NU 172; OTAMIXABAN; PEGNIVACOGIN; RO 14; SEMULOPARIN; THROMBIN INHIBITOR; UNCLASSIFIED DRUG;

ACUTE CORONARY SYNDROME; ANTICOAGULANT THERAPY; BLEEDING; DNA STRUCTURE; DRUG HALF LIFE; DRUG RESEARCH; HUMAN; PRIORITY JOURNAL; REVIEW; RNA STRUCTURE;

EID: 84860517509     PISSN: 15701638     EISSN: 18756220     Source Type: Journal    
DOI: 10.2174/1570163811209020129     Document Type: Review

References (51)

1. Schulz S, Mehilli J, Neumann FJ, et al. ISAR-REACT 3A: a study of reduced dose of unfractionated heparin in biomarker negative patients undergoing percutaneous coronary intervention. Eur Heart J 2010; 31(20): 2482-91.
2. Montalescot G, White HD, Gallo R, et al. Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N Engl J Med 2006; 355(10): 1006-17. (Pubitemid 44343544)
3. Sheikh IR, Ahmed SH, Mori N, et al. Comparison of safety and efficacy of bivalirudin versus unfractionated heparin in percutaneous peripheral intervention: a single-center experience. JACC Cardiovasc Interv 2009; 2(9): 871-6.
4. Douketis JD, Berger PB, Dunn AS, et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133(6 Suppl): 299S-339S. (Pubitemid 351894915)
5. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004; 126(3 Suppl): 188S-203S. (Pubitemid 39297954)
6. De Luca G, Marino P. Adjunctive benefits from low-molecularweight heparins as compared to unfractionated heparin among patients with ST-segment elevation myocardial infarction treated with thrombolysis. A meta-analysis of the randomized trials. Am Heart J 2007; 154(6): 1085 e1-6.
7. Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133(6 Suppl): 340S-80S. (Pubitemid 351892970)
8. Kaatz S, Paje D. Update in bridging anticoagulation. J Thromb Thrombolysis 2011; 31(3): 259-64.
9. Gomez-Outes A, Suarez-Gea ML, Lecumberri R, Rocha E, Pozo- Hernandez C, Vargas-Castrillon E. New parenteral anticoagulants in development. Ther Adv Cardiovasc Dis 2011; 5(1): 33-59.
10. Ahrens I, Lip GY, Peter K. New oral anticoagulant drugs in cardiovascular disease. Thromb Haemost 2010; 104(1): 49-60.
11. Cohen MG, Purdy DA, Rossi JS, et al. First clinical application of an actively reversible direct factor IXa inhibitor as an anticoagulation strategy in patients undergoing percutaneous coronary intervention. Circulation 2010; 122(6): 614-22.
12. Sabatine MS, Antman EM, Widimsky P, et al. Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-ACS1 TIMI 42): a randomised, double-blind, active-controlled, phase 2 trial. Lancet 2009; 374(9692): 787-95.
13. Cohen M, Bhatt DL, Alexander JH, et al. Randomized, doubleblind, dose-ranging study of otamixaban, a novel, parenteral, shortacting direct factor Xa inhibitor, in percutaneous coronary intervention: the SEPIA-PCI trial. Circulation 2007; 115(20): 2642-51. (Pubitemid 46791363)
14. Zafar MU, Farkouh ME, Osende J, et al. Potent arterial antithrombotic effect of direct factor-Xa inhibition with ZK- 807834 administered to coronary artery disease patients. Thromb Haemost 2007; 97(3): 487-92. (Pubitemid 46437813)
15. Chi L, Pen YW, Potoczak R, et al. Assessment of ex vivo pharmacodynamic markers during inhibition of thrombosis by CI-1031 (ZK-807834), a novel direct factor Xa inhibitor. Pharmacology 2002; 64(2): 76-83. (Pubitemid 34114193)
16. Guertin KR, Choi YM. The discovery of the Factor Xa inhibitor otamixaban: from lead identification to clinical development. Curr Med Chem 2007; 14(23): 2471-81. (Pubitemid 47618035)
17. Hinder M, Frick A, Jordaan P, et al. Direct and rapid inhibition of factor Xa by otamixaban: a pharmacokinetic and pharmacodynamic investigation in patients with coronary artery disease. Clin Pharmacol Ther 2006; 80(6): 691-702. (Pubitemid 44920219)
18. Paccaly A, Frick A, Rohatagi S, et al. Pharmacokinetics of otamixaban, a direct factor Xa inhibitor, in healthy male subjects: pharmacokinetic model development for phase 2/3 simulation of exposure. J Clin Pharmacol 2006; 46(1): 37-44. (Pubitemid 43021712)
19. Paramo JA. Prothrombin fragments in cardiovascular disease. Adv Clin Chem 2010; 51: 1-23.
20. Jolly SS, Faxon DP, Fox KA, et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors or thienopyridines: results from the OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial. J Am Coll Cardiol 2009; 54(5): 468-76.
21. Mehta SR, Boden WE, et al. Antithrombotic therapy with fondaparinux in relation to interventional management strategy in patients with ST- and non-ST-segment elevation acute coronary syndromes: an individual patient-level combined analysis of the Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) randomized trials. Circulation 2008; 118(20): 2038-46.
22. Montalescot G, Walenga JM. Catheter-related thrombosis: biological and clinical evidence for risk with currently available anticoagulants. Clin Appl Thromb Hemost 2009; 15(2): 183-96.
23. Steg PG, Mehta S, Jolly S, et al. Fondaparinux with UnfracTionated heparin dUring Revascularization in Acute coronary syndromes (FUTURA/OASIS 8): a randomized trial of intravenous unfractionated heparin during percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux. Am Heart J 2010; 160(6): 1029-34, 1034. e1.
24. Steg PG, Jolly SS, Mehta SR, et al. Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux: the FUTURA/OASIS-8 randomized trial. JAMA 2010; 304(12): 1339-49.
25. Harenberg J. Development of idraparinux and idrabiotaparinux for anticoagulant therapy. Thromb Haemost 2009; 102(5): 811-5.
26. Bousser MG, Bouthier J, Buller HR, et al. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet 2008; 371(9609): 315-21.
27. Veyrat-Follet C, Vivier N, Trellu M, Dubruc C, Sanderink GJ. The pharmacokinetics of idraparinux, a long-acting indirect factor Xa inhibitor: population pharmacokinetic analysis from Phase III clinical trials. J Thromb Haemost 2009; 7(4): 559-65.
28. Paty I, Trellu M, Destors JM, Cortez P, Boelle E, Sanderink G. Reversibility of the anti-FXa activity of idrabiotaparinux (biotinylated idraparinux) by intravenous avidin infusion. J Thromb Haemost 2010; 8(4): 722-9.
29. Büller H. Efficacy and safety of once weekly subcutaneous idrabiotaparinux in the treatment of patients with symptomatic deep venous thrombosis. J Thromb Haemost 2010; 9(1): 92-9.
30. Jeske WP, Hoppensteadt D, Gray A, et al. A common standard is inappropriate for determining the potency of ultra low molecular weight heparins such as semuloparin and bemiparin. Thromb Res 2011; 128(4): 361-7.
31. Viskov C, Just M, Laux V, Mourier P, Lorenz M. Description of the chemical and pharmacological characteristics of a new hemisynthetic ultra-low-molecular-weight heparin, AVE5026. J Thromb Haemost 2009; 7(7): 1143-51.
32. Lassen MR, Dahl OE, Mismetti P, Destree D, Turpie AG. AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery-TREK: a dose-ranging study. J Thromb Haemost 2009; 7(4): 566-72.
33. Agnelli G, George D, Fisher W, et al. The ultra-low molecular weight heparin (ULMWH) semuloparin for prevention of venous thromboembolism (VTE) in patients with cancer receiving chemotherapy: SAVE ONCO study. J Clin Oncol 2011; 29(supp.l): LBA9014.
34. Rico S, Antonijoan RM, Gich I, et al. Safety Assessment and Pharmacodynamics of a Novel Ultra Low Molecular Weight Heparin (RO-14) in Healthy Volunteers - A First-Time-In-Human Single Ascending Dose Study. Thromb Res 2011; 127(4): 292-8.
35. Greinacher A, Warkentin TE. The direct thrombin inhibitor hirudin. Thromb Haemost 2008; 99(5): 819-29. (Pubitemid 351705298)
36. Lee CJ, Ansell JE. Direct Thrombin Inhibitors. Br J Clin Pharmacol 2011; 72(4): 581-92.
37. Lincoff AM, Bittl JA, Harrington RA, et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA 2003; 289(7): 853-63. (Pubitemid 37430344)
38. Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006; 355(21): 2203-16. (Pubitemid 44791162)
39. Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358(21): 2218-30. (Pubitemid 351724451)
40. Ahrens I, Smith BK, Bode C, Peter K. Direct thrombin inhibition with bivalirudin as an antithrombotic strategy in general and interventional cardiology. Expert Opin Drug Metab Toxicol 2007; 3(4): 609-20. (Pubitemid 351324968)
41. Keefe AD, Pai S, Ellington A. Aptamers as therapeutics. Nat Rev Drug Discov 2010; 9(7): 537-50.
42. Muller J, Freitag D, Mayer G, Potzsch B. Anticoagulant characteristics of HD1-22, a bivalent aptamer that specifically inhibits thrombin and prothrombinase. J Thromb Haemost 2008; 6(12): 2105-12.
43. Bock LC, Griffin LC, Latham JA, Vermaas EH, Toole JJ. Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 1992; 355(6360): 564-6.
44. Tasset DM, Kubik MF, Steiner W. Oligonucleotide inhibitors of human thrombin that bind distinct epitopes. J Mol Biol 1997; 272(5): 688-98. (Pubitemid 27448187)
45. Lowe GD. Factor IX and thrombosis. Br J Haematol 2001; 115(3): 507-13. (Pubitemid 34015639)
46. McGraw RA, Davis LM, Lundblad RL, Stafford DW, Roberts HR. Structure and function of factor IX: defects in haemophilia B. Clin Haematol 1985; 14(2): 359-83. (Pubitemid 15038456)
47. Povsic TJ, Cohen MG, Mehran R, et al. A randomized, partially blinded, multicenter, active-controlled, dose-ranging study assessing the safety, efficacy, and pharmacodynamics of the REG1 anticoagulation system in patients with acute coronary syndromes: design and rationale of the RADAR Phase IIb trial. Am Heart J 2011; 161(2): 261-8 e1-2.
48. Povsic TJ, Cohen MG, Chan MY, et al. Dose Selection for a Direct and Selective Factor IXa Inhibitor and its Complementary Reversal Agent: Translating Pharmacokinetic and Pharmacodynamic Properties of the REG1 System to Clinical Trial Design. J Thromb Thrombolysis 2011; 32(1): 21-31.
49. Chan MY, Rusconi CP, Alexander JH, Tonkens RM, Harrington RA, Becker RC. A randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor IXa inhibitor. J Thromb Haemost 2008; 6(5): 789-96. (Pubitemid 351524539)
50. Chan MY, Cohen MG, Dyke CK, et al. Phase 1b randomized study of antidote-controlled modulation of factor IXa activity in patients with stable coronary artery disease. Circulation 2008; 117(22): 2865-74. (Pubitemid 351787073)
51. Dyke CK, Steinhubl SR, Kleiman NS, et al. First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology: a phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity. Circulation 2006; 114(23): 2490-7 (Pubitemid 44901522)