What can ongoing clinical trials of anticoagulants demonstrate?

Journal of Cardiovascular Medicine

Volumn 10, Issue 8, 2009, Pages 610-615

  Halperin, Jonathan L ^a  

^a MOUNT SINAI MEDICAL CENTER   (United States)

Author keywords

Atrial fibrillation; Clinical trials; Idraparinux; Novel anticoagulants; Ximelagatran

Indexed keywords

ACENOCOUMAROL; ANTICOAGULANT AGENT; ANTIVITAMIN K; AVIDIN; BLOOD CLOTTING FACTOR 10A INHIBITOR; DABIGATRAN; HEPARIN; IDRABIOTAPARINUX; IDRAPARINUX; LOW MOLECULAR WEIGHT HEPARIN; SSR 126517E; THROMBIN INHIBITOR; UNCLASSIFIED DRUG; WARFARIN; XIMELAGATRAN;

ANTICOAGULATION; BLEEDING; CLINICAL TRIAL; DRUG EFFECT; DRUG EFFICACY; DRUG INDICATION; EMBOLISM; EVIDENCE BASED PRACTICE; HEART ATRIUM FIBRILLATION; HUMAN; LIVER TOXICITY; METHODOLOGY; PATIENT SELECTION; PROPHYLAXIS; REVIEW; STROKE; THROMBOEMBOLISM; VENOUS THROMBOEMBOLISM;

ANTICOAGULANTS; AZETIDINES; BENZIMIDAZOLES; BENZYLAMINES; CLINICAL TRIALS AS TOPIC; DRUGS, INVESTIGATIONAL; HUMANS; OLIGOSACCHARIDES; PYRIDINES; THROMBOEMBOLISM; UNITED STATES;

EID: 68349130617     PISSN: 15582027     EISSN: None     Source Type: Journal    
DOI: 10.2459/JCM.0b013e32832e496b     Document Type: Review

References (43)

1. Heeringa J, van der Kuip DAM, Hofman A, Kors JA, van Herpen G, Stricker BHC, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J 2006; 27:949-953.
2. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006; 114:119-125.
3. 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.
4. Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:546S-592S.
5. Hylek EM. The need for new oral anticoagulants in clinical practice. J Cardiovasc Med 2009; 10:605-609.
6. Friberg L, Hammar N, Ringh M, Pettersson H, Rosenqvist M. Stroke prophylaxis in atrial fibrillation: who gets it and who does not? Report from the Stockholm Cohort-study on Atrial Fibrillation (SCAF-study). Eur Heart J 2006; 27:1954-1964.
7. Waldo AL, Becker RC, Tapson VF, NABOR Steering Committee. Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. J Am Coll Cardiol 2005; 46:1729-1736.
8. White RH, McBurnie MA, Manolio T, Furberg CD, Gardin JM, Kittner SJ, et al. Oral anticoagulation in patients with atrial fibrillation: adherence with guidelines in an elderly cohort. Am J Med 1999; 106:165-171. (Pubitemid 29115956)
9. Hylek EM, Evans-Molina C, Shea C, Henault LE, 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. (Pubitemid 46842784)
10. Nieuwlaat R, Olsson SB, Lip GY, Camm AJ, Breithardt G, Capucci A, et al. Guideline-adherent antithrombotic treatment is associated with improved outcomes compared with undertreatment in high-risk patients with atrial fibrillation. The Euro Heart Survey on Atrial Fibrillation. Am Heart J 2007; 153:1006-1012.
11. Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, et al., ACC/AHA/ESC 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 and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22:1852-1923.
12. De Caterina R, Husted S, Wallentin L, Agnelli G, Bachmann F, Baigent C, et al. Anticoagulants in heart disease: current status and perspectives. Eur Heart J 2007; 28:880-913. (Pubitemid 47343588)
13. Dahl OE, Borris LC, Bergqvist D, Schnack RM, Eriksson BI, Kakkar AK, et al. Major joint replacement. A model for antithrombotic drug development: from proof-of-concept to clinical use. Int Angiol 2008; 27:60-67.
14. Committee for Medicinal Products for Human Use. Guideline on clinical investigation of medicinal products for the prophylaxis of venous thromboembolic risk in nonsurgical patients. 2006. http:// www.emea.europa.eu/pdfs/human/ewp/ 623504en.pdf. [Accessed 13 May 2009].
15. Committee for Medicinal Products for Human Use. Guideline on clinical investigation of medicinal products for prophylaxis of high intra- and postoperative venous thromboembolic risk. 2008. http:// www.emea.europa.eu/pdfs/ human/ewp/70798en-fin.pdf. [Accessed 13 May 2009].
16. EMEA. European Medicines Agency. 2009. http://www.emea.europa.eu. [Accessed 13 May 2009].
17. FDA. Center for Drug Evaluation and Research. 2009. http://www.fda.gov/ cder/index.html. [Accessed 13 May 2009].
18. Gomberg-Maitland M, Frison L, Halperin JL. Active-control clinical trials to establish equivalence or noninferiority: methodological and statistical concepts linked to quality. Am Heart J 2003; 146:398-403. (Pubitemid 37083073)
19. Piaggio G, Elbourne DR, Altman DG, Pocock SJ, Evans SJ, CONSORT Group. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA 2006; 295:1152-1160. (Pubitemid 43352345)
20. Buller HR, Halperin JL, Bounameaux H, Prins M. Double-blind studies are not always optimum for evaluation of a novel therapy: the case of new anticoagulants. J Thromb Haemost 2008; 6:227-229.
21. Casteels M, Flamion B. Open-label trials and drug registration: a European regulator's view. J Thromb Haemost 2008; 6:232-234.
22. Furberg CD, Soliman EZ. Double-blindness protects scientific validity. J Thromb Haemost 2008; 6:230-231.
23. Steffel J, Lüscher TF. Novel anticoagulants in development: clinical perspectives. J Cardiovasc Med 2009; 10:616-623.
24. Bredberg E, Andersson TB, Frison L, Thuresson A, Johansson S, Eriksson-Lepkowska M, et al. Ximelagatran, an oral direct thrombin inhibitor, has a low potential for cytochrome P450-mediated drug-drug interactions. Clin Pharmacokinet 2003; 42:765-777. (Pubitemid 36976123)
25. Eriksson UG, Johansson L, Taure K, Frison L, Bredberg U, Gustafsson D. Pharmacokinetics and pharmacodynamics of melagatran, the active form of the oral, direct thrombin inhibitor H 376/95, in healthy male subjects. Haemostasis 2000; 30 (Suppl):164.
26. 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. (Pubitemid 36702757)
27. Johansson LC, Frison L, Logren U, Fager G, Gustafsson D, Eriksson UG. Influence of age on the pharmacokinetics and pharmacodynamics of ximelagatran, an oral direct thrombin inhibitor. Clin Pharmacokinet 2003; 42:381-392. (Pubitemid 36433878)
28. Sarich TC, Wolzt M, Eriksson UG, Mattsson C, Schmidt A, Elg S, et al. Effects of ximelagatran, an oral direct thrombin inhibitor, r-hirudin and enoxaparin on thrombin generation and platelet activation in healthy male subjects. J Am Coll Cardiol 2003; 41:557-564. (Pubitemid 36223319)
29. Eriksson BI, Bergqvist D, Kalebo P, Dahl OE, Lindbratt S, Bylock A, et al. Ximelagatran and melagatran compared with dalteparin for prevention of venous thromboembolism after total hip or knee replacement: the METHRO II randomised trial. Lancet 2002; 360:1441-1447. (Pubitemid 35356320)
30. Eriksson BI, Agnelli G, Cohen AT, Dahl OE, Mouret P, Rosencher N, et al. Direct thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement. Thromb Haemost 2003; 89:288-296. (Pubitemid 36227281)
31. Francis CW, Davidson BL, Berkowitz SD, Lotke PA, Ginsberg JS, Lieberman JR, et al. Ximelagatran versus warfarin for the prevention of venous thromboembolism after total knee arthroplasty. A randomized, double-blind trial. Ann Intern Med 2002; 137:648-655.
32. Heit JA, Colwell CW, Francis CW, Ginsberg JS, Berkowitz SD, Whipple J, et al. Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: a phase 2 dose-finding study. Arch Intern Med 2001; 161:2215-2221. (Pubitemid 32905002)
33. Fiessinger JN, Huisman MV, Davidson BL, Bounameaux H, Francis CW, Eriksson H, et al. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial. JAMA 2005; 293:681-689. (Pubitemid 40216038)
34. Halperin JL, Executive Steering Committee SIaVSI. Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V). Am Heart J 2003; 146:431-438.
35. Diener HC, Executive Steering Committee of the SPORTIFF III and V Investigators. Stroke prevention using the oral direct thrombin inhibitor ximelagatran in patients with nonvalvular atrial fibrillation. Pooled analysis from the SPORTIF III and V studies. Cerebrovasc Dis 2006; 21:279-293.
36. Boehringer Ingelheim Pharmaceuticals. Randomized evaluation of long term anticoagulant therapy (RE-LY) With dabigatran etexilate. 2008. http:// clinicaltrials.gov/ct2/show/NCT00262600. [Accessed 13 May 2009].
37. Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost 2005; 3:1843-1853.
38. Herbert JM, Herault JP, Bernat A, Van Amsterdam RG, Lormeau JC, Petitou M, et al. Biochemical and pharmacological properties of SANORG 34006, a potent and long-acting synthetic pentasaccharide. Blood 1998; 91:4197-4205. (Pubitemid 28261983)
39. PERSIST investigators. A novel long-acting synthetic factor Xa inhibitor (SanOrg34006) to replace warfarin for secondary prevention in deep vein thrombosis. A Phase II evaluation. J Thromb Haemost 2004; 2:47-53.
40. Amadeus Investigators, Bousser MG, Bouthier J, Buller HR, Cohen AT, Crijns H, et al. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, noninferiority trial. Lancet 2008; 371:315-321.
41. Sanofi-Aventis. Evaluation of weekly subcutaneous biotinylated idraparinux versus oral adjusted-dose warfarin to prevent stroke and systemic thromboembolic events in patients with atrial fibrillation (BOREALIS-AF). 2008. http://www.clinicaltrials.gov/ct2/show/ NCT00580216. [Accessed 13 May 2009].
42. Savi P, Herault JP, Duchaussoy P, Millet L, Schaeffer P, Petitou M, et al. Reversible biotinylated oligosaccharides: a new approach for a better management of anticoagulant therapy. J Thromb Haemost 2008; 6:1697-1706.
43. Buller HR, Destors J-M, Gallus AS, Prins MH, Raskob GE. Idrabiotaparinux, a biotinylated long-acting anticoagulant, in the treatment of deep venous thrombosis (EQUINOX study): safety, efficacy, and reversibility by avidin [abstract #32]. Blood 2008; 112.