Phase III trials of new oral anticoagulants in the acute treatment and secondary prevention of VTE: Comparison and critique of study methodology and results

Advances in Therapy

Volumn 31, Issue 5, 2014, Pages 473-493

  Cohen, Alexander T ^a   Imfeld, Stephan ^b,c   Rider, Thomas ^d  

^a GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

^b KING S COLLEGE HOSPITAL   (United Kingdom)

^c UNIVERSITY HOSPITAL BASEL   (Switzerland)

^d ROYAL SUSSEX COUNTY HOSPITAL   (United Kingdom)

Author keywords

Clotting factor inhibitors; Low molecular weight heparin; New oral anticoagulants; Oral anticoagulant; Venous thromboembolism

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; ANTIVITAMIN K; APIXABAN; DABIGATRAN; EDOXABAN; HEPARIN; PLACEBO; RIVAROXABAN; WARFARIN; PYRAZOLE DERIVATIVE; PYRIDINE DERIVATIVE; PYRIDONE DERIVATIVE; THIAZOLE DERIVATIVE;

ANTICOAGULANT THERAPY; ANTICOAGULATION; BLEEDING TENDENCY; CLINICAL FEATURE; COMPARATIVE STUDY; DRUG EFFICACY; DRUG SAFETY; HEALTH CARE QUALITY; HUMAN; KIDNEY FUNCTION; LONG TERM CARE; MONOTHERAPY; MORTALITY; PHASE 3 CLINICAL TRIAL (TOPIC); PREVENTION STUDY; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECURRENT DISEASE; REVIEW; SECONDARY PREVENTION; STUDY DESIGN; TREATMENT DURATION; TREATMENT OUTCOME; VENOUS THROMBOEMBOLISM; CHEMICALLY INDUCED; HEMORRHAGE; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; PATIENT ACUITY; PROCEDURES;

ANTICOAGULANTS; CLINICAL TRIALS, PHASE III AS TOPIC; DABIGATRAN; HEMORRHAGE; HUMANS; OUTCOME ASSESSMENT (HEALTH CARE); PATIENT ACUITY; PYRAZOLES; PYRIDINES; PYRIDONES; RIVAROXABAN; SECONDARY PREVENTION; THIAZOLES; VENOUS THROMBOEMBOLISM;

EID: 84903775609     PISSN: 0741238X     EISSN: 18658652     Source Type: Journal    
DOI: 10.1007/s12325-014-0119-7     Document Type: Review

References (38)

1. Cohen AT, Agnelli G, Anderson FA, et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98:756-64. (Pubitemid 47555066)
2. Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol. 2008;28:370-2.
3. Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165:1095-106. (Pubitemid 40720733)
4. Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet. 1960;1:1309-12.
5. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e419S-94S.
6. Hutten BA, Prins MH. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev 2006:CD001367.
7. Buller HR, Gallus AS, Pillion G, Prins MH, Raskob GE, Cassiopea I. Enoxaparin followed by once-weekly idrabiotaparinux versus enoxaparin plus warfarin for patients with acute symptomatic pulmonary embolism: a randomised, double-blind, double-dummy, non-inferiority trial. Lancet. 2012;379:123-9.
8. van Gogh I, Buller HR, Cohen AT, et al. Idraparinux versus standard therapy for venous thromboembolic disease. N Engl J Med. 2007;357:1094-104. (Pubitemid 47443214)
9. Simonneau G, Sors H, Charbonnier B, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine Standard: evaluations dans l'Embolie Pulmonaire. N Engl J Med. 1997;337:663-9.
10. NICE. Treating venous thromboembolism. National Clinical Guideline Centre 2012.
11. Moualla H, Garcia D. Vitamin K antagonists-current concepts and challenges. Thromb Res. 2011;128:210-5.
12. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):204S-33S. (Pubitemid 39297955)
13. NICE. Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism. NICE technology appraisal guidance 261. National Clinical Guideline Centre 2012.
14. Kahn SR, M'Lan CE, Lamping DL, et al. The influence of venous thromboembolism on quality of life and severity of chronic venous disease. J Thromb Haemost. 2004;2:2146-51. (Pubitemid 40185774)
15. Weitz JI, Eikelboom JW, Samama MM, American College of Chest. New antithrombotic drugs: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e120S-51S.
16. 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;92:199-205.
17. Prandoni P, Lensing AW, Prins MH, et al. Residual venous thrombosis as a predictive factor of recurrent venous thromboembolism. Ann Intern Med. 2002;137:955-60. (Pubitemid 35440241)
18. Eichinger S, Heinze G, Jandeck LM, Kyrle PA. Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation. 2010;121:1630-6.
19. Hansson PO, Sorbo J, Eriksson H. Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med. 2000;160:769-74. (Pubitemid 30165237)
20. Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368:699-708.
21. EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499-510.
22. EINSTEIN-PE Investigators, Buller HR, Prins MH, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287-97.
23. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361:2342-52.
24. Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368:709-18.
25. AgnelliG, BullerHR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369:799-808.
26. Hokusai-VTE Investigators, Büller HR, Décousus H, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369:1406-15.
27. Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129:764-72.
28. Raskob G, Buller H, Prins M et al. Edoxaban for the long-term treatment of venous thromboembolism: rationale and design of the Hokusai-VTE study. J Thromb Haemost 2013;11:1287-94.
29. Agnelli G, Gallus A, Goldhaber SZ, et al. Treatment of proximal deep-vein thrombosis with the oral direct factor Xa inhibitor rivaroxaban (BAY 59-7939): the ODIXa-DVT (Oral Direct Factor Xa Inhibitor BAY 59-7939 in patients with acute symptomatic deep-vein thrombosis) study. Circulation. 2007;116:180-7. (Pubitemid 47057524)
30. Fang MC, Go AS, Hylek EM, et al. Age and the risk of warfarin-associated hemorrhage: the anticoagulation and risk factors in atrial fibrillation study. J Am Geriatr Soc. 2006;54:1231-6. (Pubitemid 44166528)
31. Heit JA. Predicting the risk of venous thromboembolism recurrence. Am J Hematol. 2012;87(Suppl 1):S63-7.
32. Beyer-Westendorf J, Buller H. External and internal validity of open label or double-blind trials in oral anticoagulation: better, worse or just different? J Thromb Haemost. 2011;9:2153-8.
33. Erkens PM, ten Cate H, Buller HR, Prins MH. Benchmark for time in therapeutic range in venous thromboembolism: a systematic review and meta-analysis. PLoS ONE. 2012;7:e42269.
34. Deitelzweig SB, Lin J, Kreilick C, Hussein M, Battleman D. Warfarin therapy in patients with venous thromboembolism: patterns of use and predictors of clinical outcomes. Adv Ther. 2010;27:623-33.
35. Kimmel SE, Chen Z, Price M, et al. 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;167:229-35.
36. Shameem R, Ansell J. Disadvantages of VKA and requirements for novel anticoagulants. Best Pract Res Clin Haematol. 2013;26:103-14.
37. Gonzalez CD, Bolanos R, de Sereday M. Editorial on hypothesis and objectives in clinical trials: superiority, equivalence and non-inferiority. Thromb J. 2009;7:3.
38. Christensen E. Methodology of superiority vs. equivalence trials and non-inferiority trials. J Hepatol. 2007;46:947-54. (Pubitemid 46546604)