New pharmacologic approaches to prevent thromboembolism in patients with atrial fibrillation

Current Vascular Pharmacology

Volumn 5, Issue 3, 2007, Pages 211-219

  Hammwöhner, Matthias ^a   D'Alessandro, Alessandra ^a   Wolfram, Oliver ^a   Goette, Andreas ^a  

^a UNIVERSITY HOSPITAL MAGDEBURG   (Germany)

Author keywords

Anticoagulation; Atrial fibrillation; Pharmacology; Stroke; Thrombin inhibitors

Indexed keywords

2 [4 [(1 ACETIMIDOYL 3 PYRROLIDINYL)OXY]PHENYL] 3 (7 AMIDINO 2 NAPHTHYL)PROPIONIC ACID; ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; ANTIVITAMIN K; APIXABAN; ARGATROBAN; BLOOD CLOTTING FACTOR 10A INHIBITOR; CLOPIDOGREL; DABIGATRAN; DABIGATRAN ETEXILATE; ENALAPRIL; ENOXAPARIN; FONDAPARINUX; HEPARIN; HEPARINOID; HIRULOG; IDRAPARINUX; LEPIRUDIN; LOW MOLECULAR WEIGHT HEPARIN; MELAGATRAN; N [2 [4 (1 METHYL 4 PIPERIDINYL) 1 PIPERAZINYL] 2 OXO 1 PHENYLETHYL] 1H INDOLE 6 CARBOXAMIDE; ODIPARCIL; PHENPROCOUMON; RIVAROXABAN; THROMBOCYTE SLOWING FACTOR; TICLOPIDINE; TTP 889; UNCLASSIFIED DRUG; UNINDEXED DRUG; WARFARIN; XIMELAGATRAN; ANTITHROMBOCYTIC AGENT; BLOOD CLOTTING FACTOR 10; THROMBIN; VITAMIN K GROUP;

ACUTE CORONARY SYNDROME; AMINOTRANSFERASE BLOOD LEVEL; ANTIBIOTIC THERAPY; ANTICOAGULATION; BLEEDING; BLOOD CLOTTING; CLINICAL TRIAL; CORONARY ARTERY DISEASE; DEEP VEIN THROMBOSIS; DRESSLER SYNDROME; DRUG BIOAVAILABILITY; DRUG CONTRAINDICATION; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG ELIMINATION; DRUG ELUTING STENT; DRUG FATALITY; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG METABOLISM; DRUG MONITORING; HEART ATRIUM FIBRILLATION; HEART ATRIUM FLUTTER; HEPARIN INDUCED THROMBOCYTOPENIA; HUMAN; INTERNATIONAL NORMALIZED RATIO; LIVER TOXICITY; LOADING DRUG DOSE; MOLECULAR MECHANICS; MONOTHERAPY; NONHUMAN; OXIDATIVE STRESS; PATIENT MONITORING; PERCUTANEOUS CORONARY INTERVENTION; PROTEIN SYNTHESIS; REPEATED DRUG DOSE; REVIEW; RISK FACTOR; RISK REDUCTION; SIDE EFFECT; SINGLE DRUG DOSE; STUNNED HEART MUSCLE; THROMBOEMBOLISM; VENOUS THROMBOEMBOLISM; CEREBROVASCULAR ACCIDENT; CHEMICALLY INDUCED DISORDER; DRUG ANTAGONISM; METABOLISM; PRACTICE GUIDELINE; RISK ASSESSMENT;

ANTICOAGULANTS; ATRIAL FIBRILLATION; CEREBROVASCULAR ACCIDENT; FACTOR X; HEMORRHAGE; HUMANS; PLATELET AGGREGATION INHIBITORS; PRACTICE GUIDELINES; RISK ASSESSMENT; RISK FACTORS; THROMBIN; THROMBOEMBOLISM; VITAMIN K;

EID: 34547595448     PISSN: 15701611     EISSN: None     Source Type: Journal    
DOI: 10.2174/157016107781024118     Document Type: Review

References (103)

1. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285: 2370-2375.
2. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998; 82: 2N-9N.
3. Stewart S, Hart CL, Hole DJ, McMurray JJ. A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study. Am J Med 2002; 113: 359-364.
4. Wolf PA, Dawber TR, Thomas HE, Jr., Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology 1978; 28: 973-977.
5. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham Study. Arch Intern Med 1987; 147: 1561-1564.
6. Blackshear JL, Safford RE. AFFIRM and RACE trials: implications for the management of atrial fibrillation. Card Electrophysiol Rev. 2003; 7: 366-369.
7. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347: 1825-1833.
8. Jorgensen HS, Nakayama H, Reith J, Raaschou HO, Olsen TS. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. Stroke 1996; 27: 1765-1769.
9. Lin HJ, Wolf PA, Benjamin EJ, Belanger AJ, D'Agostino RB. Newly diagnosed atrial fibrillation and acute stroke. The Framingham Study. Stroke 1995; 26: 1527-1530.
10. Lin HJ, Wolf PA, Kelly-Hayes M, Beiser AS, Kase CS, Benjamin EJ, et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996; 27: 1760-1764.
11. Bogousslavsky J, Garazi S, Jeanrenaud X, Aebischer N, Van Melle G. Stroke recurrence in patients with patent foramen ovale: the Lausanne Study. Lausanne Stroke with Paradoxal Embolism Study Group. Neurology 1996; 46: 1301-1305.
12. Fatkin D, Kuchar DL, Thorburn CW, Feneley MP. Transesophageal echocardiography before and during direct current cardioversion of atrial fibrillation: evidence for "atrial stunning" as a mechanism of thromboembolic complications. J Am Coll Cardiol 1994; 23: 307-316.
13. Manning WJ, Silverman DI, Katz SE, Riley MF, Come PC, Doherty RM, et al. Impaired left atrial mechanical function after cardioversion: relation to the duration of atrial fibrillation. J Am Coll Cardiol 1994; 23: 1535-1540.
14. Cai H, Li Z, Goette A, Mera F, Honeycutt C, Feterik K, et al. Downregulatipn of endocardial nitric oxide synthase expression and nitric oxide production in atrial fibrillation: potential mechanisms for atrial thrombosis and stroke. Circulation 2002; 106: 2854-2858.
15. Arndt M, Lendeckel U, Rocken C, Nepple K, Wolke C, Spiess A, et al. Altered expression of ADAMs (A Disintegrin And Metalloproteinase) in fibrillating human atria. Circulation 2002; 105: 720-725.
16. Bukowska A, Lendeckel U, Hirte D, Wolke C, Striggow F, Rohnert P, et al. Activation of the calcineurin signaling pathway induces atrial hypertrophy during atrial fibrillation. Cell Mol Life Sci 2006; 63: 333-342.
17. Goette A, Honeycutt C, Langberg JJ. Electrical remodeling in atrial fibrillation. Time course and mechanisms. Circulation 1996; 94: 2968-2974.
18. Cheng W, Xiao YB, Wang XF, Chen L, Zhong QJ. Expressions of L-type calcium channel and potassium channel Kv4.3 in rapid paced primary cultured atrial myocytes. Zhonghua Xin Xue Guan Bing Za Zhi 2006; 34: 312-315.
19. Dobrev D. Electrical remodeling in atrial fibrillation. Herz 2006; 31: 108-112.
20. Goette A, Staack T, Rocken C, Arndt M, Geller JC, Huth C, et al. Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation. J Am Coll Cardiol 2000; 35: 1669-1677.
21. Goette A, Lendeckel U, Klein HU. Signal transduction systems and atrial fibrillation. Cardiovasc Res 2002; 54: 247-258.
22. Hammwohner M, D'Alessandro A, Dobrev D, Kirchhof P, Goette A. New antiarrhythmic drugs for therapy of atrial fibrillation: II. Non-ion channel blockers. Herzschrittmacherther Elektrophysiol 2006; 17: 73-80.
23. Goette A, Lendeckel U, Klein HU. Molecular biology of the heart atrium. New insights into the pathophysiology of atrial fibrillation as well as its clinical implications. Z Kardiol 2004; 93: 864-877.
24. Yamashita T, Sekiguchi A, Iwasaki YK, Sagara K, Hatano S, Iinuma H, et al. Thrombomodulin and tissue factor pathway inhibitor in endocardium of rapidly paced rat atria. Circulation 2003; 108: 2450-2452.
25. Goette A, Ittenson A, Hoffmanns P, Reek S, Hartung W, Klein H, et al. Increased expression of P-selectin in patients with chronic atrial fibrillation. Pacing Clin Electrophysiol 2000; 23: 1872-1875.
26. Conway DS, Pearce LA, Chin BS, Hart RG, Lip GY. Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation. Circulation 2003; 107: 3141-3145.
27. Kamath S, Chin BS, Blann AD, Lip GY. A study of platelet activation in paroxysmal, persistent and permanent atrial fibrillation. Blood Coagul Fibrinolysis 2002; 13: 627-636.
28. Kamath S, Blann AD, Chin BS, Lip GY. A prospective randomized trial of aspirin-clopidogrel combination therapy and dose-adjusted warfarin on indices of thrombogenesis and platelet activation in atrial fibrillation. J Am Coll Cardiol 2002; 40: 484-490.
29. Sohara H, Amitani S, Kurose M, Miyahara K. Atrial fibrillation activates platelets and coagulation in a time-dependent manner: a study in patients with paroxysmal atrial fibrillation. J Am Coll Cardiol 1997; 29: 106-112.
30. Kumagai K, Fukunami M, Ohmori M, Kitabatake A, Kamada T, Hoki N. Increased intracardiovascular clotting in patients with chronic atrial fibrillation. J Am Coll Cardiol 1990; 16: 377-380.
31. Conway DS, Buggins P, Hughes E, Lip GY. Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation. J Am Coll Cardiol 2004; 43: 2075-2082.
32. Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G, et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591-594.
33. Inwald DP, McDowall A, Peters MJ, Callard RE, Klein NJ. CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation. Circ Res 2003; 92: 1041-1048.
34. Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999; 131: 492-501.
35. Go AS, Hylek EM, Chang Y, Phillips KA, Henault LE, Capra AM, et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? JAMA 2003; 290: 2685-2692.
36. Hylek EM, Skates SJ, Sheehan MA, Singer DE. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 1996; 335: 540-546.
37. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285: 2864-2870.
38. Wittkowsky AK. Warfarin and other coumarin derivatives: pharmacokinetics, pharmacodynamics, and drug interactions. Semin Vasc Med 2003; 3: 221-230.
39. Demirkan K, Stephens MA, Newman KP, Self TH. Response to warfarin and other oral anticoagulants: effects of disease states. South Med J 2000; 93: 448-454.
40. Yuan HY, Chen JJ, Lee MT, Wung JC, Chen YF, Chang MJ, et al. A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Hum Mol Genet 2005; 14: 1745-1751.
41. Ezbianski AA. Warfarin and herbal supplements. A volatile combination. Adv Nurse Pract 2003; 11: 77-80.
42. Martin LA and Mehta SD. Diminished anticoagulant effects of warfarin with concomitant mercaptopurine therapy. Pharmacotherapy 2003; 23: 260-264.
43. Parkman CA. Polypharmacy, herbal therapies, and elders. Case Manager 2001; 12: 32-34.
44. Trilli LE, Kelley CL, Aspinall SL, Kroner BA. Potential interaction between warfarin and fluvastatin. Ann Pharmacother 1996; 30: 1399-1402.
45. Angaran DM, Dias VC, Arom KV, Northrup WF, Kersten TE, Lindsay WG, et al. The influence of prophylactic antibiotics on the warfarin anticoagulation response in the postoperative prosthetic cardiac valve patient. Cefamandole versus vancomycin. Ann Surg 1984; 199: 107-111.
46. Caraco Y and Rubinow A. Enhanced anticoagulant effect of coumarin derivatives induced by doxycycline coadministration. Ann Pharmacother 1992; 26: 1084-1086.
47. Casner PR. Inability to attain oral anticoagulation: warfarin-rifampin interaction revisited. South Med J 1996; 89: 1200-1203.
48. Taylor AT, Pritchard DC, Goldstein AO, Fletcher JL, Jr. Continuation of warfarin-nafcillin interaction during dicloxacillin therapy. J Fam Pract 1994; 39: 182-185.
49. Sieradzan RR, Bottner WA, Fasco MJ, Bertino JS, Jr. Comparative effects of cefoxitin and cefotetan on vitamin K metabolism. Antimicrob Agents Chemother 1988; 32: 1446-1449.
50. Tibbitts JS, Lipsky JJ. Effect of biliary diversion on the ability of cefamandole to inhibit vitamin K metabolism. Drug Metabol Drug Interact 1989; 7: 149-160.
51. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114: e257-e354.
52. Ezekowitz MD, Netrebko PI. Anticoagulation in management of atrial fibrillation. Curr Opin Cardiol 2003; 18: 26-31.
53. Go AS, Hylek EM, Borowsky LH, Phillips KA, Selby JV, Singer DE. Warfarin use among ambulatory patients with nonvalvular atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Ann Intern Med 1999; 131: 927-934.
54. McCormick D, Gurwitz JH, Goldberg RJ, Becker R, Tate JP, Elwell A, et al. Prevalence and quality of warfarin use for patients with atrial fibrillation in the long-term care setting. Arch Intern Med 2001; 161: 2458-2463.
55. Gras-Champel V, Voyer A, Lematte C, Pakula P, Roussel B, Lefrere JJ, et al. Assessment of the quality of oral anticoagulation management in patients admitted to Amiens University Hospital. Therapie 2005; 60: 149-157.
56. Turk A, Sidler P, Buhler H, Christen S. Quality of long-term oral anticoagulation: an observation study. Schweiz Rundsch Med Prax 2003; 92: 1769-1773.
57. Ederhy S, Meuleman C, Hammoudi N, Janower S, Boccara F, Cohen A.. Preventing cerebrovascular accidents during atrial fibrillation. Presse Med 2005; 34: 1315-1324.
58. Economides MC, Singh BN. Antithrombotic therapies for stroke prevention in atrial fibrillation. Minerva Cardioangiol 2004; 52: 125-139.
59. Taylor FC, Cohen H, Ebrahim S. Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation. BMJ 2001; 322: 321-326.
60. Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation 1991; 84: 527-539.
61. Hohnloser SH, Connolly SJ. Combined antiplatelet therapy in atrial fibrillation: review of the literature and future avenues. J Cardiovasc Electrophysiol 2003; 14: S60-S63.
62. Smith SC, Jr., Feldman TE, Hirshfeld JW, Jr., Jacobs AK, Kern MJ, King SB, III, et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention). Circulation 2006; 113: e166-e286.
63. Lehto M, Snapinn S, Dickstein K, Swedberg K, Nieminen MS. Prognostic risk of atrial fibrillation in acute myocardial infarction complicated by left ventricular dysfunction: the OPTIMAAL experience. Eur Heart J 2005; 26: 350-356.
64. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 2004; 110: e82-292.
65. Kushner FG and Antman EM. Oral anticoagulation for atrial fibrillation after ST-elevation myocardial infarction: new evidence to guide clinical practice. Circulation 2005; 112: 3212-3214.
66. Bauer KA. New anticoagulants: anti IIa vs. anti Xa - is one better? J Thromb Thrombolysis 2006; 21: 67-72.
67. Hirsh J. Heparin. N Engl J Med 1991; 324: 1565-1574.
68. Tollefsen DM. Insight into the mechanism of action of heparin cofactor II. Thromb Haemost 1995; 74: 1209-1214.
69. Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost 2005; 3: 1843-1853.
70. Markwardt F, Nowak G, Sturzebecher U, Walsmann P. Studies on the pharmacokinetics of hirudin. Biomed Biochim Acta 1987; 46: 237-244.
71. Kleinschmidt S, Stephan B, Pindur G, Bauer C. Argatroban: Pharmacological properties and anaesthesiological aspects. Anaesthesist 2006; 55: 443-450.
72. McKeage K, Plosker GL. Argatroban. Drugs 2001; 61: 515-522.
73. Walenga JM. An overview of the direct thrombin inhibitor argatroban. Pathophysiol Haemost Thromb 2002; 32 Suppl 3: 9-14.
74. Swan SK, Hursting MJ. The pharmacokinetics and pharmacodynamics of argatroban: effects of age, gender, and hepatic or renal dysfunction. Pharmacotherapy 2000; 20: 318-329.
75. Yeh RW, Jang IK. Argatroban: update. Am Heart J 2006; 151: 1131-1138.
76. Gladwell TD. Bivalirudin: a direct thrombin inhibitor. Clin Ther 2002; 24: 38-58.
77. Robson R, White H, Aylward P, Frampton C. Bivalirudin pharmacokinetics and pharmacodynamics: effect of renal function, dose, and gender. Clin Pharmacol Ther 2002; 71: 433-439.
78. Lincoff AM, Kleiman NS, Kereiakes DJ, Feit F, Bittl JA, Jackman JD, et al. Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs. heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial. JAMA 2004; 292: 696-703.
79. Agnelli G. Current issues in anticoagulation. Pathophysiol. Haemost Thromb 2005; 34 Suppl 1: 2-9.
80. Eriksson UG, Bredberg U, Gislen K, Johansson LC, Frison L, Ahnoff M, et al. Pharmacokinetics and pharmacodynamics of ximelagatran, a novel oral direct thrombin inhibitor, in young healthy male subjects. Eur J Clin Pharmacol 2003; 59: 35-43.
81. Fager G, Cullberg M, Eriksson-Lepkowska M, Frison L, Eriksson UG. Pharmacokinetics and pharmacodynamics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, are not influenced by acetylsalicylic acid. Eur J Clin Pharmacol 2003; 59: 283-289.
82. Wolzt M, Wollbratt M, Svensson M, Wahlander K, Grind M, Eriksson UG. Consistent pharmacokinetics of the oral direct thrombin inhibitor ximelagatran in patients with nonvalvular atrial fibrillation and in healthy subjects. Eur J Clin Pharmacol 2003; 59: 537-543.
83. Francis CW. Direct thrombin inhibitors for treatment of heparin induced thrombocytopenia, deep vein thrombosis and atrial fibrillation. Curr Pharm Des 2005; 11: 3931-3941.
84. Katira R, Chauhan A, More RS. Direct thrombin inhibitors: novel antithrombotics on the horizon in the thromboprophylactic management of atrial fibrillation. Postgrad Med J 2005; 81: 370-375.
85. Olsson SB. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with nonvalvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 2003; 362: 1691-1698.
86. Jorg I, Harenberg J, Fenyvesi T, Gladisch R. Atrial fibrillation and thromboprophylaxis in elderly patients. Z Kardiol 2005; 94: 87-94.
87. Olsson SB, Halperin JL. Prevention of stroke in patients with atrial fibrillation. Semin Vasc Med 2005; 5: 285-292.
88. Boos CJ, Hinton A, Lip GY. Ximelagatran: a clinical perspective. Eun J Intern Med 2005; 16: 267-278.
89. Kim HJ, Arora R. Emerging role of direct thrombin inhibitors in nonvalvular atrial fibrillation: potential and peril. J Cardiovasc Pharmacol Ther 2005; 10: 11-21.
90. Kwok L, Molckovsky D, Boucher M. Ximelagatran: a new type of oral anticoagulant. Int. J. Technol. Assess Health Care 2005; 21: 480-486.
91. Hauel NH, Nar H, Priepke H, Ries U, Stassen JM, Wienen W. Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem 2002; 45: 1757-1766.
92. Preparing for the post-warfarin generation of antithrombotics. Am J Manag Care 2004; 10: S318-S323.
93. Donat F, Duret JP, Santoni A, Cariou R, Necciari J, Magnani H, et al. The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clin Pharmacokinet 2002; 41 Suppl 2: 1-9.
94. Petitou M, Lormeau JC, Choay J. Chemical synthesis of glycosaminoglycans: new approaches to antithrombotic drugs. Nature 1991; 350: 30-33.
95. Eriksson BI, Quinlan DJ. Oral anticoagulants in development: focus on thromboprophylaxis in patients undergoing orthopaedic surgery. Drugs 2006; 66: 1411-1429.
96. Abraham E, Reinhart K, Svoboda P, Seibert A, Olthoff D, Dal Nogare A, et al. Assessment of the safety of recombinant tissue factor pathway inhibitor in patients with severe sepsis: a multicenter, randomized, placebo-controlled, single-blind, dose escalation study. Crit Care Med 2001; 29: 2081-2089.
97. Lee A, Agnelli G, Buller H, Ginsberg J, Heit J, Rote W, et al. Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement. Circulation 2001; 104: 74-78.
98. Goette A, Lendeckel U. Nonchannel drug targets in atrial fibrillation. Pharmacol Ther 2004; 102: 17-36.
99. Eto K, Isshiki T, Yamamoto H, Takeshita S, Ochiai M, Yokoyama N, et al. AJvW-2, an anti-vWF monoclonal antibody, inhibits enhanced platelet aggregation induced by high shear stress in platelet-rich plasma from patients with acute coronary syndromes. Arterioscler Thromb Vasc Biol 1999; 19: 877-882.
100. Kageyama S, Yamamoto H, Nagano M, Arisaka H, Kayahara T, Yoshimoto R. Anti-thrombotic effects and bleeding risk of AJvW-2, a monoclonal antibody against human von Willebrand factor. Br J Pharmacol 1997; 122: 165-171.
101. Wu D, Vanhoorelbeke K, Cauwenberghs N, Meiring M, Depraetere H, Kotze HF, et al. Inhibition of the von Willebrand (VWF)-collagen interaction by an antihuman VWF monoclonal antibody results in abolition of in vivo arterial platelet thrombus formation in baboons. Blood 2002; 99: 3623-3628.
102. Goette A, Schotten U. Inhibition of angiotensin II type 1 receptors reduces atrial stunning and spontaneous echo contrast after electrical cardioversion of atrial fibrillation. Eur Heart J 2006; 27: 2034-2035.
103. Hammwöhner M, Ittenson A. Dierkes J, Bukowska A, Klein H, Lendeckel U, Goette A. Increased Levels of Platelet CD40/CD40L and Atrial Adhesion Molecules During Persistent Atrial Fibrillation. Pace 2006; 29(Suppl 1): 18(34).