Anticoagulation in the elderly

Pharmaceuticals

Volumn 3, Issue 12, 2010, Pages 3543-3569

  Robert Ebadi, Helia ^a   Righini, Marc ^a  

^a GENEVA UNIVERSITY HOSPITALS   (Switzerland)

Author keywords

Anticoagulation; Elderly patient; Factor xa inhibitor; Hemorrhagic risk; Thrombin inhibitors; Vitamin K antagonist

Indexed keywords

ACETYLSALICYLIC ACID; ANTIVITAMIN K; APIXABAN; ARGATROBAN; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 10A INHIBITOR; DABIGATRAN; DABIGATRAN ETEXILATE; DALTEPARIN; EDOXABAN; ENOXAPARIN; FONDAPARINUX; HEPARIN; HIRUDIN; IDRAPARINUX; LOW MOLECULAR WEIGHT HEPARIN; NADROPARIN; PLACEBO; RIVAROXABAN; TINZAPARIN; WARFARIN; XIMELAGATRAN;

AGED; ANTICOAGULATION; BLEEDING; BRAIN HEMORRHAGE; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CHRONIC DRUG ADMINISTRATION; COMORBIDITY; DEEP VEIN THROMBOSIS; DOSE RESPONSE; DRUG ABSORPTION; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG WITHDRAWAL; DYSPEPSIA; ELDERLY CARE; EVIDENCE BASED MEDICINE; FALL RISK ASSESSMENT; HEART ATRIUM FIBRILLATION; HIGH RISK PATIENT; HUMAN; INTERMETHOD COMPARISON; LIVER TOXICITY; LOW DRUG DOSE; LUNG EMBOLISM; RECOMMENDED DRUG DOSE; REVIEW; RISK BENEFIT ANALYSIS; RISK REDUCTION; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT INDICATION; UNSPECIFIED SIDE EFFECT; VALVULAR HEART DISEASE; VENOUS THROMBOEMBOLISM;

EID: 78651247324     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph3123543     Document Type: Review

References (95)

1. Go, A.S.; Hylek, E.M.; Phillips, K.A.; Chang, Y.; Henault, L.E.; Selby, J.V.; Singer, D.E. 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. Naess, I.A.; Christiansen, S.C.; Romundstad, P.; Cannegieter, S.C.; Rosendaal, F.R.; Hammerstrom, J. Incidence and mortality of venous thrombosis: a population-based study. J. Thromb. Haemost. 2007, 5, 692-699.
3. Di Minno, G.; Tufano, A. Challenges in the prevention of venous thromboembolism in the elderly. J. Thromb. Haemost. 2004, 2, 1292-1298.
4. Brotman, D.J.; Jaffer, A.K. Prevention of venous thromboembolism in the geriatric patient. Cardiol. Clin. 2008, 26, 22-234.
5. Weill-Engerer, S.; Meaume, S.; Lahlou, A.; Piette, F.; Saint-Jean, O.; Sachet, A.; Beinis, J.Y.; Gallinari, C.; Grancher, A.S.; Vincent, J.P.; Naga, H.; Belmin, J.; Salvatore, R.; Kazes, M.; Pautas, E.; Boiffin, A.; Piera, J.B.; Duviquet, M.; Knafo, D.; Piau, A.; Miric, D.; Jean, A.; Bellamy, V.; Tissandier, O.; Le Blanche, A.F. Risk factors for deep vein thrombosis in inpatients aged 65 and older: a case-control multicenter study. J. Am. Geriatr. Soc. 2004, 52, 1299-1304.
6. Bosson, J.L.; Labarere, J.; Sevestre, M.A.; Belmin, J.; Beyssier, L.; Elias, A.; Franco, A.; Le Roux, P. Deep vein thrombosis in elderly patients hospitalized in subacute care facilities: a multicenter cross-sectional study of risk factors, prophylaxis, and prevalence. Arch. Intern. Med. 2003, 163, 2613-2618.
7. White, R.H.; Zhou, H.; Gage, B.F. Effect of age on the incidence of venous thromboembolism after major surgery. J. Thromb. Haemost. 2004, 2, 1327-1333.
8. Geerts, W.H.; Bergqvist, D.; Pineo, G.F.; Heit, J.A.; Samama, C.M.; Lassen, M.R.; Colwell, C.W. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008, 133, 381S-453S.
9. Kearon, C.; Kahn, S.R.; Agnelli, G.; Goldhaber, S.; Raskob, G.E.; Comerota, A.J. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians EvidenceBased Clinical Practice Guidelines (8th Edition). Chest 2008, 133, 454S-545S.
10. Monreal, M.; Lopez-Jimenez, L. Pulmonary embolism in patients over 90 years of age. Curr. Opin. Pulm. Med. 2010, 16, 432-436.
11. Levine, M.N.; Hirsh, J.; Gent, M.; Turpie, A.G.; Weitz, J.; Ginsberg, J.; Geerts, W.; LeClerc, J.; Neemeh, J.; Powers, P.; et al. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis. Thromb. Haemost. 1995, 74, 606-611.
12. Schulman, S.; Rhedin, A.S.; Lindmarker, P.; Carlsson, A.; Larfars, G.; Nicol, P.; Loogna, E.; Svensson, E.; Ljungberg, B.; Walter, H. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. N. Engl. J. Med. 1995, 332, 1661-1665.
13. Lee, A.Y.; Levine, M.N.; Baker, R.I.; Bowden, C.; Kakkar, A.K.; Prins, M.; Rickles, F.R.; Julian, J.A.; Haley, S.; Kovacs, M.J.; Gent, M. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N. Engl. J. Med. 2003, 349, 146-153.
14. Schulman, S.; Granqvist, S.; Holmstrom, M.; Carlsson, A.; Lindmarker, P.; Nicol, P.; Eklund, S.G.; Nordlander, S.; Larfars, G.; Leijd, B.; Linder, O.; Loogna, E. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. The Duration of Anticoagulation Trial Study Group. N. Engl. J. Med. 1997, 336, 393-398.
15. Kearon, C.; Gent, M.; Hirsh, J.; Weitz, J.; Kovacs, M.J.; Anderson, D.R.; Turpie, A.G.; Green, D.; Ginsberg, J.S.; Wells, P.; MacKinnon, B.; Julian, J.A. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N. Engl. J. Med. 1999, 340, 901-907.
16. Kearon, C.; Ginsberg, J.S.; Kovacs, M.J.; Anderson, D.R.; Wells, P.; Julian, J.A.; MacKinnon, B.; Weitz, J.I.; Crowther, M.A.; Dolan, S.; Turpie, A.G.; Geerts, W.; Solymoss, S.; van Nguyen, P.; Demers, C.; Kahn, S.R.; Kassis, J.; Rodger, M.; Hambleton, J.; Gent, M. Comparison of low- intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N. Engl. J. Med. 2003, 349, 631-639.
17. Ridker, P.M. Long-term low-dose warfarin use is effective in the prevention of recurrent venous thromboembolism: yes. J. Thromb. Haemost. 2004, 2, 1034-1037.
18. Wolf, P.A.; Abbott, R.D.; Kannel, W.B. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991, 22, 983-988.
19. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch. Intern. Med. 1994, 154, 1449-1457.
20. Fang, M.C.; Go, A.S.; Chang, Y.; Borowsky, L.; Pomernacki, N.K.; Singer, D.E. Comparison of risk stratification schemes to predict thromboembolism in people with nonvalvular atrial fibrillation. J. Am. Coll. Cardiol. 2008, 51, 810-815.
21. Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation. Stroke 2008, 39, 1901-1910.
22. Gage, B.F.; Waterman, A.D.; Shannon, W.; Boechler, M.; Rich, M.W.; Radford, M.J. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001, 285, 2864-2870.
23. Lip, G.Y.; Nieuwlaat, R.; Pisters, R.; Lane, D.A.; Crijns, H.J. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010, 137, 263-272.
24. Singer, D.E.; Albers, G.W.; Dalen, J.E.; Fang, M.C.; Go, A.S.; Halperin, J.L.; Lip, G.Y.; Manning, W.J. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008, 133, 546S-592S.
25. Mant, J.; Hobbs, F.D.; Fletcher, K.; Roalfe, A.; Fitzmaurice, D.; Lip, G.Y.; Murray, E. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007, 370, 493-503.
26. Zimetbaum, P.J.; Thosani, A.; Yu, H.T.; Xiong, Y.; Lin, J.; Kothawala, P.; Emons, M. Are atrial fibrillation patients receiving warfarin in accordance with stroke risk? Am. J. Med. 2010, 123, 446-453.
27. Ogilvie, I.M.; Newton, N.; Welner, S.A.; Cowell, W.; Lip, G.Y. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am. J. Med. 2010, 123, 638-645, e4.
28. Tulner, L.R.; Van Campen, J.P.; Kuper, I.M.; Gijsen, G.J.; Koks, C.H.; Mac Gillavry, M.R.; van Tinteren, H.; Beijnen, J.H.; Brandjes, D.P. Reasons for undertreatment with oral anticoagulants in frail geriatric outpatients with atrial fibrillation: a prospective, descriptive study. Drugs Aging 2010, 27, 39-50.
29. Baudet, E.M.; Puel, V.; McBride, J.T.; Grimaud, J.P.; Roques, F.; Clerc, F.; Roques, X.; Laborde, N. Long-term results of valve replacement with the St. Jude Medical prosthesis. J. Thorac. Cardiovasc. Surg. 1995, 109, 858-70.
30. Salem, D.N.; O'Gara, P.T.; Madias, C.; Pauker, S.G. Valvular and structural heart disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008, 133, 593S-629S.
31. Mangoni, A.A.; Jackson, S.H. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br. J. Clin. Pharmacol. 2004, 57, 6-14.
32. Aymanns, C.; Keller, F.; Maus, S.; Hartmann, B.; Czock, D. Review on pharmacokinetics and pharmacodynamics and the aging kidney. Clin. J. Am. Soc. Nephrol. 2010, 5, 314-327.
33. Lindeman, R.D.; Tobin, J.; Shock, N.W. Longitudinal studies on the rate of decline in renal function with age. J. Am. Geriatr. Soc. 1985, 33, 278-285.
34. Schwartz, J.B. The current state of knowledge on age, sex, and their interactions on clinical pharmacology. Clin. Pharmacol. Ther. 2007, 82, 87-96.
35. Spruill, W.J.; Wade, W.E.; Cobb, H.H., 3rd. Continuing the use of the Cockcroft-Gault equation for drug dosing in patients with impaired renal function. Clin. Pharmacol. Ther. 2009, 86, 468-470.
36. Pautas, E.; Moreau, C.; Gouin-Thibault, I.; Golmard, J.L.; Mahe, I.; Legendre, C.; Taillandier- Heriche, E.; Durand-Gasselin, B.; Houllier, A.M.; Verrier, P.; Beaune, P.; Loriot, M.A.; Siguret, V. Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients. Clin. Pharmacol. Ther. 2010, 87, 57-64.
37. Mallet, L.; Spinewine, A.; Huang, A. The challenge of managing drug interactions in elderly people. Lancet 2007, 370, 185-191.
38. Hirsh, J.; Bauer, K.A.; Donati, M.B.; Gould, M.; Samama, M.M.; Weitz, J.I. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008, 133, 141S-159S.
39. Jacobs, L.G. Warfarin pharmacology, clinical management, and evaluation of hemorrhagic risk for the elderly. Cardiol. Clin. 2008, 26, 157-167, v.
40. Gage, B.F.; Birman-Deych, E.; Kerzner, R.; Radford, M.J.; Nilasena, D.S.; Rich, M.W. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am. J. Med. 2005, 118, 612-617.
41. Schulman, S.; Beyth, R.J.; Kearon, C.; Levine, M.N. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008, 133, 257S-298S.
42. Ruiz-Gimenez, N.; Suarez, C.; Gonzalez, R.; Nieto, J.A.; Todoli, J.A.; Samperiz, A.L.; Monreal, M. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb. Haemost. 2008, 100, 26-31.
43. Gage, B.F.; Yan, Y.; Milligan, P.E.; Waterman, A.D.; Culverhouse, R.; Rich, M.W.; Radford, M.J. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am. Heart J. 2006, 151, 713-719.
44. Kagansky, N.; Knobler, H.; Rimon, E.; Ozer, Z.; Levy, S. Safety of anticoagulation therapy in well-informed older patients. Arch. Intern. Med. 2004, 164, 2044-2050.
45. Bounameaux, H. The novel anticoagulants: entering a new era. Swiss Med. Wkly. 2009, 139, 60-64.
46. Hirsh, J. Heparin. N. Engl. J. Med. 1991, 324, 1565-1574.
47. Greinacher, A., Heparin-induced thrombocytopenia. J. Thromb. Haemost. 2009, 7 (Suppl. 1), 9-12.
48. Kleber, F.X.; Witt, C.; Vogel, G.; Koppenhagen, K.; Schomaker, U.; Flosbach, C.W. Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease. Am. Heart J. 2003, 145, 614-621.
49. Campbell, N.R.; Hull, R.D.; Brant, R.; Hogan, D.B.; Pineo, G.F.; Raskob, G.E. Aging and heparin-related bleeding. Arch. Intern. Med. 1996, 156, 857-860.
50. Samama, M.M.; Cohen, A.T.; Darmon, J.Y.; Desjardins, L.; Eldor, A.; Janbon, C.; Leizorovicz, A.; Nguyen, H.; Olsson, C.G.; Turpie, A.G.; Weisslinger, N. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N. Engl. J. Med. 1999, 341, 793-800.
51. Alikhan, R.; Cohen, A.T.; Combe, S.; Samama, M.M.; Desjardins, L.; Eldor, A.; Janbon, C.; Leizorovicz, A.; Olsson, C.G.; Turpie, A.G. Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study. Blood Coagul. Fibrinolysis 2003, 14, 341-346.
52. Kucher, N.; Leizorovicz, A.; Vaitkus, P.T.; Cohen, A.T.; Turpie, A.G.; Olsson, C.G.; Goldhaber, S.Z. Efficacy and safety of fixed low-dose dalteparin in preventing venous thromboembolism among obese or elderly hospitalized patients: a subgroup analysis of the PREVENT trial. Arch. Intern. Med. 2005, 165, 341-345.
53. van Dongen, C.J.; van den Belt, A.G.; Prins, M.H.; Lensing, A.W. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst. Rev. 2004, CD001100.
54. Mismetti, P.; Laporte-Simitsidis, S.; Navarro, C.; Sie, P.; d'Azemar, P.; Necciari, J.; Duret, J.P.; Gaud, C.; Decousus, H.; Boneu, B. Aging and venous thromboembolism influence the pharmacodynamics of the anti-factor Xa and anti-thrombin activities of a low molecular weight heparin (nadroparin). Thromb. Haemost. 1998, 79, 1162-1165.
55. Nagge, J.; Crowther, M.; Hirsh, J. Is impaired renal function a contraindication to the use of low- molecular-weight heparin? Arch. Intern. Med. 2002, 162, 2605-2609.
56. Lim, W.; Dentali, F.; Eikelboom, J.W.; Crowther, M.A. Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann. Intern. Med. 2006, 144, 673-684.
57. Mahe, I.; Gouin-Thibault, I.; Drouet, L.; Simoneau, G.; Di Castillo, H.; Siguret, V.; Bergmann, J.F.; Pautas, E. Elderly medical patients treated with prophylactic dosages of enoxaparin: influence of renal function on anti-Xa activity level. Drugs Aging 2007, 24, 63-71.
58. Mahe, I.; Aghassarian, M.; Drouet, L.; Bal Dit-Sollier, C.; Lacut, K.; Heilmann, J.J.; Mottier, D.; Bergmann, J.F. Tinzaparin and enoxaparin given at prophylactic dose for eight days in medical elderly patients with impaired renal function: a comparative pharmacokinetic study. Thromb. Haemost. 2007, 97, 581-586.
59. Samama, M.M.; Gerotziafas, G.T. Evaluation of the pharmacological properties and clinical results of the synthetic pentasaccharide (fondaparinux). Thromb. Res. 2003, 109, 1-11.
60. Bijsterveld, N.R.; Moons, A.H.; Boekholdt, S.M.; van Aken, B.E.; Fennema, H.; Peters, R.J.; Meijers, J.C.; Buller, H.R.; Levi, M. Ability of recombinant factor VIIa to reverse the anticoagulant effect of the pentasaccharide fondaparinux in healthy volunteers. Circulation 2002, 106, 2550-2554.
61. Cohen, A.T.; Davidson, B.L.; Gallus, A.S.; Lassen, M.R.; Prins, M.H.; Tomkowski, W.; Turpie, A.G.; Egberts, J.F.; Lensing, A.W. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006, 332, 325-329.
62. Lassen, M.R.; Bauer, K.A.; Eriksson, B.I.; Turpie, A.G. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet 2002, 359, 1715-1720.
63. Turpie, A.G.; Bauer, K.A.; Eriksson, B.I.; Lassen, M.R. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet 2002, 359, 1721-1726.
64. Turpie, A.G.; Bauer, K.A.; Eriksson, B.I.; Lassen, M.R. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch. Intern. Med. 2002, 162, 1833-1840.
65. Turpie, A.G.; Lensing, A.W.; Fuji, T.; Boyle, D.A. Pharmacokinetic and clinical data supporting the use of fondaparinux 1.5 mg once daily in the prevention of venous thromboembolism in renally impaired patients. Blood Coagul. Fibrinolysis 2009, 20, 114-121.
66. Buller, H.R.; Davidson, B.L.; Decousus, H.; Gallus, A.; Gent, M.; Piovella, F.; Prins, M.H.; Raskob, G.; Segers, A.E.; Cariou, R.; Leeuwenkamp, O.; Lensing, A.W. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann. Intern. Med. 2004, 140, 867-873.
67. Buller, H.R.; Davidson, B.L.; Decousus, H.; Gallus, A.; Gent, M.; Piovella, F.; Prins, M.H.; Raskob, G.; van den Berg-Segers, A.E.; Cariou, R.; Leeuwenkamp, O.; Lensing, A.W. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N. Engl. J. Med. 2003, 349, 1695-1702.
68. Buller, H.R.; Cohen, A.T.; Davidson, B.; Decousus, H.; Gallus, A.S.; Gent, M.; Pillion, G.; Piovella, F.; Prins, M.H.; Raskob, G.E. Idraparinux versus standard therapy for venous thromboembolic disease. N. Engl. J. Med. 2007, 357, 1094-1104.
69. Bousser, M.G.; Bouthier, J.; Buller, H.R.; Cohen, A.T.; Crijns, H.; Davidson, B.L.; Halperin, J.; Hankey, G.; Levy, S.; Pengo, V.; Prandoni, P.; Prins, M.H.; Tomkowski, W.; Torp-Pedersen, C.; Wyse, D.G. 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, 315-321.
70. Paty, I.; Trellu, M.; Destors, J.M.; 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, 722-729.
71. Ansell, J.; Hirsh, J.; Hylek, E.; Jacobson, A.; Crowther, M.; Palareti, G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008, 133, 160S-198S.
72. Siguret, V.; Gouin, I.; Debray, M.; Perret-Guillaume, C.; Boddaert, J.; Mahe, I.; Donval, V.; Seux, M.L.; Romain-Pilotaz, M.; Gisselbrecht, M.; Verny, M.; Pautas, E. Initiation of warfarin therapy in elderly medical inpatients: a safe and accurate regimen. Am. J. Med. 2005, 118, 137-142.
73. Fang, M.C.; Go, A.S.; Hylek, E.M.; Chang, Y.; Henault, L.E.; Jensvold, N.G.; Singer, D.E. Age and the risk of warfarin-associated hemorrhage: the anticoagulation and risk factors in atrial fibrillation study. J. Am. Geriatr. Soc. 2006, 54, 1231-1236.
74. Palareti, G.; Hirsh, J.; Legnani, C.; Manotti, C.; D'Angelo, A.; Pengo, V.; Moia, M.; Guazzaloca, G.; Musolesi, S.; Coccheri, S. Oral anticoagulation treatment in the elderly: a nested, prospective, case-control study. Arch. Intern. Med. 2000, 160, 470-478.
75. Hylek, E.M.; Evans-Molina, C.; Shea, C.; Henault, L.E.; Regan, S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007, 115, 2689-2696.
76. Shireman, T.I.; Mahnken, J.D.; Howard, P.A.; Kresowik, T.F.; Hou, Q.; Ellerbeck, E.F. Development of a contemporary bleeding risk model for elderly warfarin recipients. Chest 2006, 130, 1390-1396.
77. Pisters, R.; Lane, D.A.; Nieuwlaat, R.; de Vos, C.B.; Crijns, H.J.; Lip, G.Y. A novel user-friendly score (HAS-BLED) to assess one-year risk of major bleeding in atrial fibrillation patients: The Euro Heart Survey. Chest 2010, 138, 1093-1100.
78. Fang, M.C.; Chang, Y.; Hylek, E.M.; Rosand, J.; Greenberg, S.M.; Go, A.S.; Singer, D.E. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann. Intern. Med. 2004, 141, 745-752.
79. Kimmel, S.E.; Chen, Z.; Price, M.; Parker, C.S.; Metlay, J.P.; Christie, J.D.; Brensinger, C.M.; Newcomb, C.W.; Samaha, F.F.; Gross, R. The influence of patient adherence on anticoagulation control with warfarin: results from the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study. Arch. Intern. Med. 2007, 167, 229-235.
80. Connolly, S.J.; Ezekowitz, M.D.; Yusuf, S.; Eikelboom, J.; Oldgren, J.; Parekh, A.; Pogue, J.; Reilly, P.A.; Themeles, E.; Varrone, J.; Wang, S.; Alings, M.; Xavier, D.; Zhu, J.; Diaz, R.; Lewis, B.S.; Darius, H.; Diener, H.C.; Joyner, C.D.; Wallentin, L. Dabigatran versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 2009, 361, 1139-1151.
81. Man-Son-Hing, M.; Laupacis, A. Anticoagulant-related bleeding in older persons with atrial fibrillation: physicians' fears often unfounded. Arch. Intern. Med. 2003, 163, 1580-1586.
82. Fiessinger, J.N.; Huisman, M.V.; Davidson, B.L.; Bounameaux, H.; Francis, C.W.; Eriksson, H.; Lundstrom, T.; Berkowitz, S.D.; Nystrom, P.; Thorsen, M.; Ginsberg, J.S. Ximelagatran vs low- molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial. JAMA 2005, 293, 681-689.
83. Testa, L.; Andreotti, F.; Biondi Zoccai, G.G.; Burzotta, F.; Bellocci, F.; Crea, F. Ximelagatran/melagatran against conventional anticoagulation: a meta-analysis based on 22,639 patients. Int. J. Cardiol. 2007, 122, 117-124.
84. Mismetti, P.; Laporte, S. Dabigatran: clinical pharmacology. Ann. Fr. Anesth. Reanim. 2009, 28, S8-S14.
85. Gross, P.L.; Weitz, J.I. New antithrombotic drugs. Clin. Pharmacol. Ther. 2009, 86, 139-146.
86. Wolzt, M.; Levi, M.; Sarich, T.C.; Bostrom, S.L.; Eriksson, U.G.; Eriksson-Lepkowska, M.; Svensson, M.; Weitz, J.I.; Elg, M.; Wahlander, K. Effect of recombinant factor VIIa on melagatran-induced inhibition of thrombin generation and platelet activation in healthy volunteers. Thromb. Haemost. 2004, 91, 1090-1096.
87. Eriksson, B.I.; Dahl, O.E.; Rosencher, N.; Kurth, A.A.; van Dijk, C.N.; Frostick, S.P.; Kalebo, P.; Christiansen, A.V.; Hantel, S.; Hettiarachchi, R.; Schnee, J.; Buller, H.R. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J. Thromb. Haemost. 2007, 5, 2178-2185.
88. Eriksson, B.I.; Dahl, O.E.; Rosencher, N.; Kurth, A.A.; van Dijk, C.N.; Frostick, S.P.; Prins, M.H.; Hettiarachchi, R.; Hantel, S.; Schnee, J.; Buller, H.R. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007, 370, 949-956.
89. Ginsberg, J.S.; Davidson, B.L.; Comp, P.C.; Francis, C.W.; Friedman, R.J.; Huo, M.H.; Lieberman, J.R.; Muntz, J.E.; Raskob, G.E.; Clements, M.L.; Hantel, S.; Schnee, J.M.; Caprini, J.A. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J. Arthroplasty 2009, 24, 1-9.
90. Friedman, R.J.; Dahl, O.E.; Rosencher, N.; Caprini, J.A.; Kurth, A.A.; Francis, C.W.; Clemens, A.; Hantel, S.; Schnee, J.M.; Eriksson, B.I. Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: a pooled analysis of three trials. Thromb. Res. 2010, 126, 175-182.
91. Schulman, S.; Kearon, C.; Kakkar, A.K.; Mismetti, P.; Schellong, S.; Eriksson, H.; Baanstra, D.; Schnee, J.; Goldhaber, S.Z. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N. Engl. J. Med. 2009, 361, 2342-2352.
92. Stangier, J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin. Pharmacokinet. 2008, 47, 285-295.
93. Eriksson, B.I.; Borris, L.C.; Friedman, R.J.; Haas, S.; Huisman, M.V.; Kakkar, A.K.; Bandel, T.J.; Beckmann, H.; Muehlhofer, E.; Misselwitz, F.; Geerts, W. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N. Engl. J. Med. 2008, 358, 2765-2775.
94. Lassen, M.R.; Ageno, W.; Borris, L.C.; Lieberman, J.R.; Rosencher, N.; Bandel, T.J.; Misselwitz, F.; Turpie, A.G. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N. Engl. J. Med. 2008, 358, 2776-2786.
95. Turpie, A.G.; Lassen, M.R.; Davidson, B.L.; Bauer, K.A.; Gent, M.; Kwong, L.M.; Cushner, F.D.; Lotke, P.A.; Berkowitz, S.D.; Bandel, T.J.; Benson, A.; Misselwitz, F.; Fisher, W.D. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009, 373, 1673-1680.