1 Adams GL, Manson RJ, Turner I, Sindram D, Lawson JH. The balance of thrombosis and hemorrhage in surgery. Hematol Oncol Clin North Am. 2007;21(1):13-24.
2 Anderson FA Jr, Zayaruzny M, Heit JA, Fidan D, Cohen AT. Estimated annual numbers of US acute-care hospital patients at risk for venous thromboembolism. Am J Hematol. 2007;82(9):777-782.
3 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(6 suppl):160S-198S.
4 Bassand JP, Hamm CW, Ardissino D, et al; Task Force for Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of European Society of Cardiology. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J. 2007;28(13):1598-1660.
5 Cohen AT, Agnelli G, Anderson FA, et al; VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98(4):756-764.
6 Cohen AT, Tapson VF, Bergmann JF, et al; ENDORSE Investigators. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet. 2008;371(9610):387-394.
7 Colman RW, Clowes AW, George JN, Goldhaber SZ, Marder VJ. Overview of hemostasis. In: Colman RW, Clowes AW, George JN, Goldhaber SZ, Marder VJ, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 5th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2006:1-16.
8 Data on file. Turpie, 2008 EFORT Presentation RECORD4.
9 Eriksson BI, Borris LC, Friedman RJ, et al; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358(26):2765-2775.
10 Fisher WD, Turpie AG. Outpatient thromboprophylaxis after hip or knee surgery: discrepancies and concerns. CMAJ. 2008;178(12):1571-1572.
11 Fitzmaurice DA, Murray E. Thromboprophylaxis for adults in hospital. BMJ. 2007;334(7602):1017-1018.
12 Francis CW. Clinical practice. Prophylaxis for thromboembolism in hospitalized medical patients. N Engl J Med. 2007;356(14):1438-1444.
13 Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol. 2005;46(6):937-954.
14 Fuster V, Rydén LE, Cannom DS, 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(7):e257-e354.
15 Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 suppl):381S-453S.
16 Gelfand EV, Cannon CP. Acute coronary syndrome. In: Colman RW, Clowes AW, George JN, Goldhaber SZ, Marder VJ, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 5th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2006:1387-1404.
17 Goldhaber SZ, Tapson VF; DVT FREE Steering Committee. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol. 2004;93(2):259-262.
18 Guyatt GH, Cook DJ, Jaeschke R, Pauker SG, Schünemann HJ. Grades of recommendation for antithrombotic agents: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 suppl):123S-131S.
19 Haas S. New oral Xa and IIa inhibitors: updates on clinical trial results. J Thromb Thrombolysis. 2008;25(1):52-60.
20 Harkess JW. Arthroplasty of hip. In: Canale ST, ed. Campbell’s Operative Orthopedics. 10th ed. Philadelphia, PA: Mosby, Inc; 2003. www.mdconsult.com. Accessed February 12, 2008.
21 Hart RG, Halperin JL. Atrial fibrillation and thromboembolism: a decade of progress in stroke prevention. Ann Intern Med. 1999;131(9):688-695.
22 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857-867.
23 Heit JA. Venous thromboembolism: disease burden, outcomes and risk factors. J Thromb Haemost. 2005;3(8):1611-1617.
24 International Congress on Thrombosis: Rivaroxaban is first novel oral anticoagulant to significantly reduce the composite outcome of symptomatic VTE and death [press release]. Leverkusen, Germany: Bayer HealthCare AG; June 30, 2008.
25 Kakkar AK. Prevention of venous thromboembolism in general surgery. In: Colman RW, Clowes AW, George JN, Goldhaber SZ, Marder VJ, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 5th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2006:1361-1367.
26 Kakkar AK, Brenner B, Dahl OE, et al; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008;372(9632):31-39.
27 Kearon C. Natural history of venous thromboembolism. Circulation. 2003;107(23 suppl 1):I22-I30.
28 Kubitza D, Haas S. Novel factor Xa inhibitors for prevention and treatment of thromboembolic diseases. Expert Opin Investig Drugs. 2006;15(8):843-855.
29 Lapostolle F, Surget V, Borron SW, et al. Severe pulmonary embolism associated with air travel. N Engl J Med. 2001;345(11):779-783.
30 Lassen MR, Ageno W, Borris LC, et al; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358(26):2776-2786.
31 Leadley RJ Jr. Coagulation factor Xa inhibition: biological background and rationale. Curr Top Med Chem. 2001;1(2):151-159.
32 Lees M, Sengupta N. Economic impact of venous thromboembolism prophylaxis with rivaroxaban after major orthopaedic surgery. Poster P082 presented at: 20th International Congress on Thrombosis (ICT), June 25-28, 2008; Athens, Greece.
33 Lip GY, Lim HS. Atrial fibrillation and stroke prevention. Lancet Neurol. 2007;6(11):981-993.
34 Lip GY, Tse HF. Management of atrial fibrillation. Lancet. 2007;370(9587):604-618.
35 Lohrmann J, Becker RC. New anticoagulants—the path from discovery to clinical practice. N Engl J Med. 2008;358(26):2827-2829.
36 Mackman N. Triggers, targets and treatments for thrombosis. Nature. 2008;451(7181):914-918.
37 MAGELLAN - Multicenter, rAndomized, Parallel Group Efficacy and Safety for the Prevention of VTE in Hospitalized Medically iLL Patients Comparing rivaroxabAN With Enoxaparin. Available at
38 http://clinicaltrials.gov/ct2/show/NCT00571649. Accessed 13 August 2008.
39 Mann KG, Brummel K, Butenas S. What is all that thrombin for? J Thromb Haemost. 2003;1(7):1504-1514.
40 Merli GJ. Pathophysiology of venous thrombosis, thrombophilia, and the diagnosis of deep vein thrombosis-pulmonary embolism in the elderly. Clin Geriatr Med. 2006;22(1):75-92.
41 Moll S, Mackman N. Venous thromboembolism: a need for more public awareness and research into mechanisms. Arterioscler Thromb Vasc Biol. 2008;28(3):367-369.
42 Motte S, Samama CM, Guay J, Barré J, Borg JY, Rosencher N. Prevention of postoperative venous thromboembolism. Risk assessment and methods of prophylaxis. Can J Anaesth. 2006;53(6 suppl):S68-S79.
43 Nicolaides AN, Fareed J, Kakkar AK, et al. Prevention and treatment of venous thromboembolism. International Consensus Statement (guidelines according to scientific evidence). Int Angiol. 2006;25(2):101-161.
44 Once-Daily Oral Direct Factor Xa Inhibitor Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism in Patients With Symptomatic Deep-Vein Thrombosis or Pulmonary Embolism. The Einstein-Extension Study. Available at http://clinicaltrials.gov/ct2/show/NCT00439725. Accessed 13 August 2008.
45 Oral Direct Factor Xa Inhibitor Rivaroxaban In Patients With Acute Symptomatic Deep-Vein Thrombosis Without Symptomatic Pulmonary Embolism: Einstein-DVT Evaluation. Available at http://clinicaltrials.gov/ct2/show/NCT00440193. Accessed 13 August 2008.
46 Oral Direct Factor Xa Inhibitor Rivaroxaban In Patients With Acute Symptomatic Pulmonary Embolism With Or Without Symptomatic Deep-Vein Thrombosis: Einstein-PE Evaluation. Available at http://clinicaltrials.gov/ct2/show/NCT00439777. Accessed 13 August 2008.
47 Pengo V, Lensing AW, Prins MH, et al; Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004;350(22):2257-2264.
48 Prandoni P, Noventa F, Ghirarduzzi A, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica. 2007;92(2):199-205.
49 A Prospective, Randomized, Double-Blind, Double-Dummy, Parallel-Group, Multicenter, Event-Driven, Non-Inferiority Study Comparing the Efficacy and Safety of Once-Daily Oral Rivaroxaban (BAY 59-7939) With Adjusted-Dose Oral Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Subjects With Non-Valvular Atrial Fibrillation. Available at http://clinicaltrials.gov/ct2/show/NCT00403767. Accessed 13 August 2008.
50 A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Escalation and Dose-Confirmation Study to Evaluate the Safety and Efficacy of Rivaroxaban in Combination With Aspirin Alone or With Aspirin and a Thienopyridine in Subjects With Acute Coronary Syndromes. The ATLAS ACS TIMI 46 Trial (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Aspirin With or Without Thienopyridine Therapy in Subjects With Acute Coronary Syndrome). Available at http://clinicaltrials.gov/ct2/show/NCT00402597. Accessed 13 August 2008.
51 RECORD 4 Study: REgulation of Coagulation in ORthopedic Surgery to Prevent DVT and PE; a Controlled, Double-Blind, Randomized Study of BAY 59-7939 in the Prevention of VTE in Subjects Undergoing Elective Total Knee Replacement. Available at http://clinicaltrials.gov/ct2/show/NCT00362232. Accessed 13 August 2008.
52 Sandler DA. Martin JF. Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis? J R Soc Med. 1989;82(4):203-205.
53 Schulman S, Lindmarker P, Holmström M, et al. Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months. J Thromb Haemost. 2006;4(4):734-742.
54 Tilleul P, LaFuma A, Colin X, Ozier Y. Estimated annual costs of prophylaxis and treatment of venous thromboembolic events associated with major orthopedic surgery in France. Clin Appl Thromb Hemost. 2006;12(4):473-484.
55 Turpie AG. Oral, direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases. Arterioscler Thromb Vasc Biol. 2007;27(6):1238-1247.
56 Turpie AG, Chin BS, Lip GY. Venous thromboembolism: pathophysiology, clinical features, and prevention. BMJ. 2002;325(7369):887-890.
57 Waldo AL. Anticoagulation: stroke prevention in patients with atrial fibrillation. Med Clin North Am. 2008;92(1):143-159.
58 Warwick D, Friedman RJ, Agnelli G, et al. Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: findings from the Global Orthopaedic Registry. J Bone Joint Surg Br. 2007;89(6):799-807.
59 Xarelto (rivaroxaban) SPC, draft version.
60 Xarelto CCDS ficha técnica de la compañía versión 03, del 3 de junio del 2008.