Preventing cardioembolic stroke in atrial fibrillation with dabigatran

Current Neurology and Neuroscience Reports

Volumn 12, Issue 1, 2012, Pages 17-23

  Weimar, Christian ^a   Hohnloser, Stefan H ^b   Eikelboom, John W ^c   Diener, Hans Christoph ^a  

^a UNIVERSITY OF DUISBURG ESSEN   (Germany)

^b GOETHE UNIVERSITY   (Germany)

^c MCMASTER UNIVERSITY   (Canada)

Author keywords

Anticoagulants; Atrial fibrillation; Dabigatran; Prevention; Stroke

Indexed keywords

ACETYLSALICYLIC ACID; AMIODARONE; CARBAMAZEPINE; CLARITHROMYCIN; CYCLOSPORIN A; DABIGATRAN ETEXILATE; DRONEDARONE; FRESH FROZEN PLASMA; HYPERICUM PERFORATUM EXTRACT; ITRACONAZOLE; KETOCONAZOLE; PROTEINASE INHIBITOR; PROTHROMBIN; QUINIDINE; RECOMBINANT BLOOD CLOTTING FACTOR 7A; RITONAVIR; TACROLIMUS; THROMBIN; THROMBOPLASTIN; VERAPAMIL; WARFARIN; XIMELAGATRAN;

ABDOMINAL PAIN; BLEEDING; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CLINICAL PRACTICE; DEEP VEIN THROMBOSIS; DIARRHEA; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CONTRAINDICATION; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG EXCRETION; DRUG SUBSTITUTION; DRUG WITHDRAWAL; DYSPEPSIA; GASTROINTESTINAL HEMORRHAGE; HEART ATRIUM FIBRILLATION; HEART INFARCTION; HUMAN; INTERNATIONAL NORMALIZED RATIO; KIDNEY FAILURE; LUNG EMBOLISM; NAUSEA; PARTIAL THROMBOPLASTIN TIME; PATIENT COMPLIANCE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECOMMENDED DRUG DOSE; REVIEW; RISK ASSESSMENT; THROMBIN TIME; TREATMENT OUTCOME; VOMITING;

ANTICOAGULANTS; ANTITHROMBINS; ATRIAL FIBRILLATION; BENZIMIDAZOLES; BETA-ALANINE; CLINICAL TRIALS AS TOPIC; EMBOLISM; HEMORRHAGE; HUMANS; MYOCARDIAL INFARCTION; STROKE; WARFARIN;

EID: 84857635879     PISSN: 15284042     EISSN: 15346293     Source Type: Journal    
DOI: 10.1007/s11910-011-0229-4     Document Type: Review

References (28)

1. SH Hohnloser D Pajitnev J Pogue, et al. 2007 Incidence of stroke in paroxysmal versus sustained atrial fibrillation in patients taking oral anticoagulation or combined antiplatelet therapy: an ACTIVE W Substudy J Am Coll Cardiol 50 22 2156 61 18036454 10.1016/j.jacc.2007.07.076 1:CAS:528: DC%2BD2sXhtlGiu7vP (Pubitemid 350123679)
2. PA Wolf JB Mitchell CS Baker, et al. 1998 Impact of atrial fibrillation on mortality, stroke, and medical costs Arch Intern Med. 158 3 229 34 9472202 10.1001/archinte.158.3.229 1:STN:280:DyaK1c7jt1OrtQ%3D%3D (Pubitemid 28123885)
3. GY Lip R Nieuwlaat R Pisters, et al. 2010 Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation Chest 137 2 263 72 19762550 10.1378/chest.09-1584
4. RG Hart LA Pearce MI Aguilar 2007 Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation Ann Intern Med. 146 12 857 67 17577005 (Pubitemid 351650486)
5. C Weimar J Benemann Z Katsarava, et al. 2008 Adherence and quality of oral anticoagulation in cerebrovascular disease patients with atrial fibrillation Eur Neurol 60 3 142 8 18628633 10.1159/000144085 1:STN:280:DC%2BD1crks12ltQ%3D%3D
6. M Nabauer A Gerth T Limbourg, et al. 2009 The registry of the German competence NETwork on Atrial Fibrillation: patient characteristics and initial management Europace 11 4 423 34 19153087 10.1093/europace/eun369
7. SJ Connolly J Pogue J Eikelboom, et al. 2008 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 118 20 2029 37 18955670 10.1161/CIRCULATIONAHA.107.750000 1:CAS:528:DC%2BD1cXhtlags7bK
8. MD Ezekowitz S Connolly A Parekh, et al. 2009 Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran Am Heart J 157 5 805 10 19376304 10.1016/j.ahj.2009.02. 005 1:CAS:528:DC%2BD1MXkslGnsrc%3D 10 e1-2
9. •• Connolly SJ, Ezekowitz MD, Yusuf S, et al.: Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51. This is the main publication of the RE-LY trial which showed that dabigatran is more effective or safer compared with warfarin.
10. • Connolly SJ, Ezekowitz MD, Yusuf S, et al.: Newly identified events in the RE-LY trial. N Engl J Med. 2010;363(19):1875-6. After publication of the main results, additional outcome events were identified after an FDA-mandated search for silent myocardial infarctions.
11. • 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(9745):975-83. The benefits of 150 mg of dabigatran at reducing stroke, 110 mg of dabigatran at reducing bleeding, and both doses at reducing intracranial bleeding versus warfarin were consistent irrespective of centers' quality of INR control. For all vascular events, nonhemorrhagic events, and mortality, advantages of dabigatran were greater at sites with poor INR control than at those with good INR control.
12. MD Ezekowitz L Wallentin SJ Connolly, et al. 2010 Dabigatran and warfarin in vitamin K antagonist-naive and -experienced cohorts with atrial fibrillation Circulation 122 22 2246 53 21147728 10.1161/CIRCULATIONAHA.110.973735 1:CAS:528:DC%2BC3cXhsFSmtrfM
13. • Diener HC, Connolly SJ, Ezekowitz MD, et al.: 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(12):1157-63. Most effects of both dabigatran doses were consistent in patients with versus those without previous stroke or TIA.
14. ML Hansen R Sorensen MT Clausen, et al. 2010 Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation Arch Intern Med. 170 16 1433 41 20837828 10.1001/archinternmed.2010.271 1:CAS:528:DC%2BC3cXht1aqu7%2FI
15. Adjusted-dose warfarin versus low-intensity 1996 fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: stroke prevention in atrial fibrillation III randomised clinical trial Lancet 348 9028 633 8 10.1016/S0140-6736(96)03487-3 (Pubitemid 26293807)
16. AL Gullov BG Koefoed P Petersen 1999 Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation: the AFASAK 2 study. Atrial Fibrillation Aspirin and Anticoagulation Arch Intern Med 159 12 1322 8 10386508 10.1001/archinte.159.12.1322 1:STN:280:DyaK1MzhtlSkuw%3D%3D (Pubitemid 29293594)
17. P Lechat H Lardoux A Mallet, et al. 2001 Anticoagulant (fluindione)-aspirin combination in patients with high-risk atrial fibrillation. A randomized trial (Fluindione, Fibrillation Auriculaire, Aspirin et Contraste Spontane; FFAACS) Cerebrovasc Dis 12 3 245 52 11641591 10.1159/000047711 1:CAS:528:DC%2BD3MXns1aisLk%3D (Pubitemid 32973957)
18. PT Akins HA Feldman RG Zoble, et al. 2007 Secondary stroke prevention with ximelagatran versus warfarin in patients with atrial fibrillation: pooled analysis of SPORTIF III and V clinical trials Stroke 38 3 874 80 17255547 10.1161/01.STR.0000258004.64840.0b 1:CAS:528:DC%2BD2sXhslygtbc%3D (Pubitemid 46568446)
19. • 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(21):2363-72. Both doses of dabigatran compared with warfarin have lower risks of both intracranial and extracranial bleeding in patients ages less than 75 years. In those ages >75 years, intracranial bleeding risk is lower but extracranial bleeding risk is similar or higher with both doses of dabigatran compared with warfarin. Therefore, the lower dose might be considered a means to reduce the risk of bleeding.
20. DR Holmes Jr DJ Kereiakes NS Kleiman, et al. 2009 Combining antiplatelet and anticoagulant therapies J Am Coll Cardiol 54 2 95 109 19573725 10.1016/j.jacc.2009.03.044 1:CAS:528:DC%2BD1MXpslOku7o%3D
21. GY Lip K Huber F Andreotti, et al. 2010 Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/ stenting Thromb Haemost 103 1 13 28 20062939 10.1160/TH09-08-0580 1:CAS:528:DC%2BC3cXhs1CqurY%3D
22. BI Eriksson OE Dahl N Rosencher, et al. 2007 Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial Lancet 370 9591 949 56 17869635 10.1016/S0140-6736(07)61445-7 1:CAS:528:DC%2BD2sXhtVeqsL7F (Pubitemid 47393577)
23. JS Ginsberg BL Davidson PC Comp, et al. 2009 Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery J Arthroplasty. 24 1 1 9 18534438 10.1016/j.arth.2008.01.132
24. BI Eriksson OE Dahl N Rosencher, et al. 2007 Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial J Thromb Haemost. 5 11 2178 85 17764540 10.1111/j.1538-7836.2007.02748.x 1:CAS:528:DC%2BD2sXhsVSis7fM (Pubitemid 47617868)
25. S Schulman C Kearon AK Kakkar, et al. 2009 Dabigatran versus warfarin in the treatment of acute venous thromboembolism N Engl J Med. 361 24 2342 52 19966341 10.1056/NEJMoa0906598 1:CAS:528:DC%2BD1MXhsFGqsrbN
26. BN Beasley EF Unger R Temple 2011 Anticoagulant options-why the FDA approved a higher but not a lower dose of dabigatran N Engl J Med. 364 19 1788 90 21488759 10.1056/NEJMp1103050 1:CAS:528:DC%2BC3MXlvFyquro%3D
27. R Pisters DA Lane R Nieuwlaat, et al. 2010 A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey Chest 138 5 1093 100 20299623 10.1378/chest.10-0134
28. • van Ryn J, Stangier J, Haertter S, et al.: Dabigatran etexilate-a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6):1116-27. This discusses pharmacology data on coagulation assays and reversal of anticoagulant activity under dabigatran.