New evidences for old concerns with oral anticoagulation in atrial fibrillation: Focus on dabigatran

Expert Opinion on Pharmacotherapy

Volumn 13, Issue 18, 2012, Pages 2649-2661

  Barrios, Vivencio ^a   Escobar, Carlos ^b  

^a HOSPITAL RAMÓN Y CAJAL   (Spain)

^b HOSPITAL UNIVERSITARIO LA PAZ   (Spain)

Author keywords

Anticoagulation; Antithrombotic therapy; Atrial fibrillation; Dabigatran; Stroke.

Indexed keywords

AMIODARONE; CARBAMAZEPINE; CLARITHROMYCIN; DABIGATRAN; KETOCONAZOLE; PHENYTOIN; QUINIDINE; RIFAMPICIN; VERAPAMIL; WARFARIN;

ANTICOAGULANT THERAPY; BLEEDING; BRAIN HEMORRHAGE; CARDIOVASCULAR RISK; CARDIOVERSION; CEREBROVASCULAR ACCIDENT; CLINICAL PRACTICE; COST EFFECTIVENESS ANALYSIS; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENCY; DRUG SAFETY; EMBOLISM; HEART ATRIUM FIBRILLATION; HEART INFARCTION; HUMAN; MAXIMUM PLASMA CONCENTRATION; META ANALYSIS (TOPIC); NONVALVULAR ATRIAL FIBRILLATION; REVIEW;

ADMINISTRATION, ORAL; ANTITHROMBINS; ATRIAL FIBRILLATION; BENZIMIDAZOLES; BETA-ALANINE; EMBOLISM; EVIDENCE-BASED MEDICINE; HEMORRHAGE; HUMANS; RISK FACTORS; STROKE;

EID: 84870233755     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2012.749860     Document Type: Review

References (78)

1. Fuster V, Ryden 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:e257-354
2. Go AS, Hylek EM, Phillips KA, et al. 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;285:2370-5
3. Furberg CD, Psaty BM, Manolio TA, et al. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol 1994;74:236-41
4. Barrios V, Calderon A, Escobar C, de la Figuera M. Patients with atrial fibrillation in a primary care setting: val-FAAP study. Rev Esp Cardiol 2012;65:47-53
5. Krahn AD, Manfreda J, Tate RB, et al. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study. Am J Med 1995;98:476-84
6. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983-8
7. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996;27:1760-4
8. Camm AJ, Kirchhof P, Lip GY, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010;31:2369-429
9. Hart RG, Pearce LA, Aguilar MI. Metaanalysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146:857-67
10. Hirsh J, O'Donnell M, Weitz JI. New Anticoagulants. Blood 2005;105:453-63
11. Escobar C, Barrios V, Jimenez D. Atrial fibrillation and dabigatran: has the time come to use new anticoagulants? Cardiovasc Ther 2010;28:295-301
12. Hylek EM, Go AS, Chang Y, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003;349:1019-26
13. Kalra L, Yu G, Perez I, et al. Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness. BMJ 2000;320:1236-9
14. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51
15. Poldermans D, Bax JJ, Boersma E, et al. Guidelines for pre-operative cardiac risk assessment and perioperative cardiac management in noncardiacsurgery: the Task Force for Preoperative Cardiac Risk Assessment and Perioperative Cardiac Management in noncardiacSurgery of the European Society of Cardiology (ESC) and endorsed by the European Society of Anaesthesiology (ESA). Eur Heart J 2009;30:2769-812
16. Stangier J, Rathgen K, Stahle 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
17. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet 2008;47:285-95
18. Blech S, Ebner T, Ludwig-Schwellinger E, et al. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 2008;36:386-99
19. Ordovas Baines JP, Climent Grana E, Jover Botella A, Valero Garcia I. Pharmacokinetics and pharmacodynamics of new oral anticoagulants. Farm Hosp 2009;33:125-33
20. European Medicines Agency (EMA). Pradaxa-, "Summary of Product Characteristics". Updated 20-March-2012. Available from: http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/ human/000829/WC500041059.pdf
21. Clemens A, Haertter S, Friedman J, et al. Twice daily dosing of dabigatran for stroke prevention in atrial fibrillation: a pharmacokinetic justification. Curr Med Res Opin 2012;28:195-201
22. U.S. Food and Drug Administration. FDA approves Pradaxa to prevent stroke in people with atrial fibrillation. 2010.Available from: http://www.fda.gov/ NewsEvents/Newsroom/PressAnnouncements/ucm230241.htm
23. Lehr T, Haertter S, Liesenfeld KH, et al. Dabigatran etexilate in atrial fibrillation patients with severe renal impairment: dose identification using pharmacokinetic modeling and simulation. J Clin Pharmacol 2011; [Epub ahead of print]
24. Mack DR, Kim JJ. Pharmacokinetic and clinical implications of dabigatran use in severe renal impairment for stroke prevention in nonvalvular atrial fibrillation (July/August). Ann Pharmacother 2012; [Epub ahead of print]
25. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Newly identified events in the RE-LY trial. N Engl J Med 2010;363:1875-6
26. Hori M, Connolly SJ, Ezekowitz MD, RE-LY Investigators. Efficacy and safety of dabigatran vs. warfarin in patients with atrial fibrillation-sub- analysis in Japanese population in RE-LY trial. Circ J 2011;75:800-5
27. Bytzer P, Connolly SJ, Yang S, et al. Analysis of upper gastrointestinal adverse events among patients given dabigatran in the RE-LY trial. Clin Gastroenterol Hepatol 2012; Epub ahead of print
28. Ferreira J, Ferreira D, Viana-Baptista M, et al. Dabigatran for stroke prevention in nonvalvular atrial fibrillation: answers to challenging "real-world" questions. Thrombosis 2012;2012:867121
29. Hoffman A, Galle PR. Gastrointestinal disorders and dabigatran. Scand J Gastroenterol 2012; Epub ahead of print
30. Oldgren J, Alings M, Darius H, et al. RE-LY Investigators. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. Ann Intern Med 2011;155:660-7
31. Pengo V, Pegoraro C, Cucchini U, Iliceto S. Worldwide management of oral anticoagulant therapy: the ISAM study. J Thromb Thrombolysis 2006;21:73-7
32. Connolly SJ, Pogue J, Eikelboom J, et al. 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;118:2029-37
33. McBride D, Bruggenjurgen B, Roll S, Willich SN. Anticoagulation treatment for the reduction of stroke in atrial fibrillation: a cohort study to examine the gap between guidelines and routine medical practice. J Thromb Thrombolysis 2007;24:65-72
34. 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;376:975-83
35. Flaker G, Ezekowitz M, Yusuf S, et al. Efficacy and safety of dabigatran compared to warfarin in patients with paroxysmal, persistent, and permanent atrial fibrillation: Results from the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) study. J Am Coll Cardiol 2012;59:854-5
36. Barrios V, Escobar C, Murga N, Quijano JJ. Clinical profile and management of patients with chronic ischemic heart disease according to age in the population daily attended by cardiologists in Spain. The ELDERCIC study. Eur J Intern Med 2010;21:180-4
37. Hughes PJ, Freeman MK. Dabigatran for the prevention of thromboembolic complications in the elderly: a RE-LY-able alternative to warfarin? Consult Pharm 2012;27:445-52
38. Eikelboom JW, Wallentin L, Connolly SJ, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation 2011;123:2363-72
39. Diener HC, Connolly SJ, Ezekowitz MD, et al. RE-LY study group. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol 2010;9:1157-63
40. Hart RG, Diener HC, Yang S, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY Trial. Stroke 2012;43:1511-17
41. Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch Intern Med 2012;172:397-402
42. Cairns J. Review: dabigatran increases MI and reduces mortality compared with warfarin, enoxaparin, or placebo. Ann Intern Med 2012;156:JC6-11
43. Eriksson BI, Dahl OE, Rosencher N, et al. RENOVATE Study Group. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007;370:949-56
44. Eriksson BI, Dahl OE, Rosencher N, et al. REMODEL Study Group. 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;5:2178-85
45. Ezekowitz MD, Reilly PA, Nehmiz G, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol 2007;100:1419-26
46. Schulman S, Kearon C, Kakkar AK, et al. RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009;361:2342-52
47. Oldgren J, Budaj A, Granger CB, et al. Dabigatran vs placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J 2011;32:2781-9
48. Eriksson BI, Dahl OE, Huo MH, et al. RE-NOVATE II Study Group. Oral dabigatran versus enoxaparina for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*): a randomised, double-blind, non-inferiority trial. Thromb Haemost 2011;105:721-9
49. Hohnloser SH, Oldgren J, Yang S, et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation 2012;125:669-76
50. Nagarakanti R, Ezekowitz MD, Oldgren J, et al. Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation 2011;123:131-6
51. You JJ, Singer DE, Howard PA, et al. American College of Chest Physicians. Antithrombotic therapy for atrial fibrillation: antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e531S-75S
52. Healey JS, Eikelboom J, Douketis J, et al. on behalf of the RE-LY Investigators. Periprocedural Bleeding and Thromboembolic Events With Dabigatran Compared With Warfarin: Results From the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Randomized Trial. Circulation 2012;126:343-8
53. Ezekowitz MD, Wallentin L, Connolly SJ, et al. RE-LY Steering Committee and Investigators. Dabigatran and warfarin in vitamin K antagonist-naive and-experienced cohorts with atrial fibrillation. Circulation 2010;122:2246-53
54. De Caterina R, Husted S, Wallentin L, et al. Coordinating Committee. New oral anticoagulants in atrial fibrillation and acute coronary syndromes: ESC Working Group on Thrombosis-Task Force on Anticoagulants in Heart Disease position paper. J Am Coll Cardiol 2012;59:1413-25
55. Kolominsky-Rabas PL, Heuschmann PU, Marschall D, et al. Lifetime cost of ischemic stroke in Germany: Results and national projections from a population-based stroke registry: the Erlangen Stroke Project. Stroke 2006;37:1179-83
56. Wolowacz SE, Samuel M, Brennan VK, et al. The cost of illness of atrial fibrillation: a systematic review of the recent literature. Europace 2011;13:1375-85
57. Stewart S, Murphy NF, Walker A, et al. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart 2004;90:286-92
58. Coyne KS, Paramore C, Grandy S, et al. Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States. Value Health 2006;9:348-56
59. Freeman JV, Zhu RP, Owens DK, et al. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med 2011;154:1-11
60. You JH, Tsui KK, Wong RS, Cheng G. Cost-Effectiveness of Dabigatran versus Genotype-Guided Management of Warfarin Therapy for Stroke Prevention in Patients with Atrial Fibrillation. PLoS One 2012;7:e39640
61. McKeage K. Dabigatran Etexilate: a Pharmacoeconomic Review of its Use in the Prevention of Stroke and Systemic Embolism in Patients with Atrial Fibrillation. Pharmacoeconomics 2012; Epub ahead of print
62. Davidson T, Husberg M, Janzon M, et al. Cost-effectiveness of dabigatran compared with warfarin for patients with atrial fibrillation in Sweden. Eur Heart J 2012; Epub ahead of print
63. Kansal AR, Sorensen SV, Gani R, et al. Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation. Heart 2012;98:573-8
64. Langkilde LK, Bergholdt Asmussen M, Overgaard M. Cost-effectiveness of dabigatran etexilate for stroke prevention in non-valvular atrial fibrillation. Applying RE-LY to clinical practice in Denmark. J Med Econ 2012;15:695-703
65. Adcock AK, Lee-Iannotti JK, Aguilar MI, et al. Is dabigatran cost effective compared with warfarin for stroke prevention in atrial fibrillation?: a critically appraised topic. Neurologist 2012;18:102-7
66. Kamel H, Johnston SC, Easton JD, Kim AS. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack. Stroke 2012;43:881-3
67. Pink J, Lane S, Pirmohamed M, Hughes DA. Dabigatran etexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses. BMJ 2011;343:d6333
68. Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation 2011;123:2562-70
69. Gonzalez-Juanatey JR, Alvarez-Sabin J, Lobos JM, et al. Cost-effectiveness of Dabigatran for Stroke Prevention in Non-valvular Atrial Fibrillation in Spain. Rev Esp Cardiol 2012;65:901-10
70. Kansal AR, Sharma M, Bradley-Kennedy C, et al. Dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in atrial fibrillation in Canada. Comparative efficacy and cost-effectiveness. Thromb Haemost 2012;108:672-82
71. Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation * Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; [Epub ahead of print]
72. Wann LS, Curtis AB, Ellenbogen KA, et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on Dabigatran): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2011;123:1144-50
73. Cairns JA, Connolly S, McMurtry S, CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society atrial fibrillation guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. Can J Cardiol 2011;27:74-90
74. Skanes AC, Healey JS, Cairns JA, et al. Canadian Cardiovascular Society Atrial Fibrillation Guidelines Committee. Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Can J Cardiol 2012;28:125-36
75. Harper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail elderly. N Engl J Med 2012;366:864-6
76. European Medicines Agency (EMA) updates patient and prescriber information for Pradaxa-on 25-May-2012. Available from: http://www.ema.europa. eu/docs/en-GB/document-library/Press-release/2012/05/WC500127771.pdf
77. FDA Drug Safety Communication: update on the risk for serious bleeding events with the anticoagulant Pradaxa. Updated 11-02-2012. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm326580.htm
78. Van de Werf F, Brueckmann M, Connolly SJ, et al. A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: the Randomized, phase II study to Evaluate the sAfety and pharmacokinetics of oraL dabIGatran etexilate in patients after heart valve replacemeNt (RE-ALIGN). Am Heart J 2012;163:931-7