Questions and answers on the use of dabigatran and perpectives on the use of other new oral anticoagulants in patients with atrial fibrillation.

Vittorio Pengo; Luciano Crippa; Anna Falanga; Guido Finazzi; Francesco Marongiu; Gualtiero Palareti; Daniela Poli; Sophie Testa; Eros Tiraferri; Alberto Tosetto; Armando Tripodi; Cesare Manotti

doi:10.1160/TH11-05-0358

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2011; 106(05): 868-876
DOI: 10.1160/TH11-05-0358

Consensus Document

Schattauer GmbH

Questions and answers on the use of dabigatran and perpectives on the use of other new oral anticoagulants in patients with atrial fibrillation.

A consensus document of the Italian Federation of Thrombosis Centers (FCSA)

Vittorio Pengo

¹Clinical Cardiology, Thrombosis Centre, University of Padova, Padova, Italy

,

Luciano Crippa

²Thrombosis Research Unit, IRCCS H S.Raffaele, Milan, Italy

,

Anna Falanga

³Division of Immunohematology and Transfusion Medicine, Ospedali Riuniti, Bergamo, Italy

,

Guido Finazzi

⁴Division of Hematology, Ospedali Riuniti, Bergamo, Italy

,

Francesco Marongiu

⁵Department of Medical Sciences, University Hospital, Cagliari, Italy

,

Gualtiero Palareti

⁶Department of Angiology and Blood Coagulation ″Marino Golinelli″, University Hospital, Bologna, Italy

,

Daniela Poli

⁷Department of Heart and Vessels, Thrombosis Center, Careggi University Hospital, Firenze, Italy

,

Sophie Testa

⁸Thrombosis Centre, District Hospital, Cremona, Italy

,

Eros Tiraferri

⁹Haemostasis and Thrombosis Centre, City Hospital, Rimini, Italy

,

Alberto Tosetto

¹⁰Department of Hematology, San Bortolo Hospital, Vicenza, Italy

,

Armando Tripodi

¹¹Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Cà Granda Maggiore Hospital Foundation and Università degli Studi di Milano, Milan, Italy

,

Cesare Manotti

¹²Anticoagulation Service, Fidenza, Italy

› Institutsangaben

Abstract

als PDF herunterladen

Summary

Dabigatran and other new oral anticoagulants (OAC) represent a step forward in stroke prevention in patients with atrial fibrillation (AF). They indeed have been shown to be an alternative to vitamin K antagonists (VKAs) without the burden of laboratory control. However, these new drugs compete with an effective and well-established therapy, thus bringing about a series of questions and doubts. In this report members of the board of the Italian Federation of Thrombosis Centers (FCSA) answer some questions every clinician might be confronted with.

Keywords

Clinical trials - oral anticoagulants - heart - prevention

PDF (196 kb)

Referenzen

References
1 Connolly SJ, Ezekowitz MD, Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
2 Boehringer Ingelheim. Boehringer Ingelheim's Pradaxa available in US pharmacies starting Wednesday, November 3 [press release]. November 1, 2010 Available at: http://www.prnewswire.com/news-releases/boehringer-ingelheims-pradaxa-available-in-us-pharmacies-starting-wednesday-november-3-106474818.html
3 Results of Rivaroxaban on AF: Presentation to AHA - November 15, 2010 Chicago - (ROCKET AF t trial).
4 Connolly SJ, Eikelboom J, Joyner C. et al. AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364: 806-817.
5 Weitz JI, Connolly SJ, Patel I. et al. Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation. Thromb Haemost 2010; 104: 633-646.
6 Harbour R, Miller J. for the Scottish Intercollegiate Guidelines Network Grading Review Group. A new system for grading recommendations in evidence based guidelines. Br Med J 2001; 323: 334-336.
7 Wallentin L, Yusuf S, Ezekowitz MD. et al. RE-LY investigators. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010; 376: 975-983.
8 Pengo V, Legnani C, Noventa F. et al. ISCOAT Study Group.(Italian Study on Complications of Oral Anticoagulant Therapy).Oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and risk of bleeding. A Multicenter Inception Cohort Study. Thromb Haemost 2001; 85: 418-422.
9 Burnier M. Medication Adherence and Persistence as the Cornerstone of Effective Antihypertensive Therapy. Am J Hypert 2006; 19: 1190-1196.
10 Newby LK, LaPointe NM, Chen AY. et al. Long-term adherence to evidence-based secondary prevention therapies in coronary artery disease. Circulation 2006; 113: 203-212.
11 Ho PM, Bryson CL, Rumsfeld JS. Medication Adherence: Its Importance in Cardiovascular Outcomes. Circulation 2009; 119: 3028-3035.
12 Doggrell SA. Adherence to medicines in the older-aged with chronic conditions: does intervention by an allied health professional help?. Drugs Aging 2010; 27: 239-254.
13 Stangier J, Rathgen K, Stähle H. et al. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol 2007; 64: 292-303.
14 Samama MM, Martinoli JL, LeFlem L. et al. Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa inhibitor. Thromb Haemost 2010; 103: 815-825.
15 Tripodi A, Chantarangkul V, Guinet C. et al. The International Normalized Ratio calibrated for rivaroxaban has the potential to normalize prothrombin time results for rivaroxaban-treated patients: results of an in vitro study. J Thromb Haemost 2011; 9: 226-228.
16 Tripodi A. Measuring the anticoagulant effect of direct factor Xa inhibitors. Is the anti-Xa assay preferable to the prothrombin time test?. Thromb Haemost 2011; 105: 735-736.
17 Palareti G Hirsh J, Legnani C. et al. Oral anticoagulation treatment in the elderly: a nested, prospective, case-control study. Arch Intern Med 2000; 160: 470-478.
18 Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998; 105: 91-99.
19 Mant J, Hobbs FD, Fletcher K. et al. BAFTA investigators. 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.
20 Singer DE, Chang Y, Fang MC. et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009; 151: 297-305.
21 Poli D, Antonucci E, Testa S, et al.. On behalf of FCSA ( Italian Federation of Anticoagulation Clinics). Bleeding risk in very old patients on VKAs treatment: results of a prospective collaborative study. Circulation. 2011. in press
22 Ufer M. Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost 2010; 103: 572-585.
23 Stangier J, Rathgen K, Stähle H. et al. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet 2010; 49: 259-268.
24 European Medicines Agency (EMEA). European public assessment report: Pradaxa Available at: http://www.emea.europa.eu/humandocs/PDFs/EPAR/pradaxa/H-829-PI-en.pdf.AccessedNov3,2009.
25 Healey JS. Effect of age and renal function on the risks of stroke and major bleeding with dabigatran compared with warfarin. J Am Coll Cardiol 2010; 55: A4 E37
26 Ansell J. Warfarin versus new agents: interpreting the data. Hematology / the Education Program of the American Society of Hematology American Society of Hematology 2010; 221-228.
27 Walenga JM, Adiguzel C. Drug and dietary interactions of the new and emerging oral anticoagulants. Int J Clin Pract 2010; 64: 956-967.
28 Garcia D, Libby E, Crowther MA. The new oral anticoagulants. Blood 2010; 115: 15-20.
29 Baglin TP, Keeling DM, Watson HG. Guidelines on oral anticoagulation (Warfarin): third edition -2005 update. Br J Haematol 2005; 132: 277-285.
30 Schulman S., Beyth RJ, Kearon C. et al. Hemorrhagic complications of Anticoagulant and Thrombolytic Treatment American College of Chest physicians evidence based clinical practice guidelines (8th edition). Chest 2008; 133: 257S-98S.
31 Dentali F, Ageno W, Crowther M. Treatment of coumarin-associated coagulopathy: a systematic review and proposed treatment algorithms. J Thromb Haemost 2006; 4: 1853-1863.
32 Crowther MA, Warkentin TE. Managing bleeding in anticoagulated patients with a focus on novel therapeutic agents.J. Thromb Haemost 2009; 7 (Suppl) 107-110.
33 Eriksson BI, Quinlan DJ, Weitz JL. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factorXa inhibitors in depelopment. Clin Pharmacokinet 2009; 48: 1-22.
34 Dabigatran medication Guide Available at: http//bidocs.boehringer-ingelheim.com. Accessed January 3, 2011.
35 Levi M, Levy JH, Andersen HF. et al. Safety of Recombinant Activated Factor VII in randomized Clinical Trials. N Eng J Med 2010; 363: 1791-1800.
36 Ibbotson SH, Grant PJ, Kerry R. et al. The influence of infusion of 1-desamino-8D-arginine vasopressin (DDAVP) in vivo on the anticoagulant effect of recombinant Hirudin (CGP39393) in vitro. Thromb Haemost 1991; 65: 64-66.
37 Lu G, De Guzman F, Lakothia S. et al. Recombinant Antidote for Reversal of Anticoagulation by afctor Xa Inhibitors. Blood 2008; 112: 983 (Abstract)
38 Wan Y, Heneghan C, Perera R. et al. Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Circ Cardiovasc Qual Outcomes 2008; 1: 84-91.
39 Connolly SJ, Pogue J, Eikelboom J. et al. ACTIVE W Investigators. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 2008; 118: 2029-2037.
40 Freeman JV, Turakhia MP. Dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med 2011; 154: 570-571.
41 Wallentin L, Yusuf S, Ezekowitz MD. et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010; 376: 975-983.
42 Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation 2011; 123: 2562-2570.