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DOI: 10.1160/TH10-10-0642
Treatments for stroke prevention in atrial fibrillation: A network meta-analysis and indirect comparisons versus dabigatran etexilate
Financial support:This project was funded by Boehringer Ingelheim International GmbH (BI). BI is developing dabigatran etexilate (Pradaxa→) for stroke prevention in patients with atrial fibrillation. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors, and are fully responsible for all content and editorial decisions, and were involved at all stages of manuscript development.Publikationsverlauf
Received:
11. Oktober 2010
Accepted:
20. Oktober 2010
Publikationsdatum:
24. November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201006/lookinside/thumbnails/10-1160-th10-10-0642-1.jpg)
Summary
Patients with atrial fibrillation at moderate to high risk of stroke are not always anticoagulated despite a lack of contraindications to vitamin K antagonists (VKAs) like warfarin. These patients are treated with aspirin, aspirin-clopidogrel combination therapy or even receive no thromboprophylaxis. The oral direct thrombin inhibitor, dabigatran etexilate 150 mg BID and 110 mg BID, might represent an alternative for these patients; however, no head-to-head clinical trial data exist versus these alternative treatments. A network meta-analysis (NMA) was performed to indirectly compare dabigatran etexilate with antiplatelets and placebo. Compared with placebo, dabigatran etexilate 150 mg BID was estimated to significantly reduce the risk of any stroke (ischaemic and haemorrhagic) by 75% (relative risk [RR] 0.25; 95% confidence interval [CI] 0.12–0.51), ischaemic stroke by 77% (RR 0.23; 95% CI 0.14–0.38), systemic embolism by 83% (RR 0.17; 95% CI 0.05–0.50) and mortality by 36% (RR 0.64; 95% CI 0.45–0.91). Dabigatran etexilate 150 mg BID was estimated to significantly reduce the risk of any stroke compared with aspirin monotherapy by 63% (RR 0.37; 95% CI 0.20–0.69) and aspirin plus clopidogrel by 61% (RR 0.39; 95% CI 0.21–0.72). Trends toward reduced risk with both dabigatran etexilate regimens were found for most clinical outcomes. Relative risk estimates of dabigatran etexilate versus adjusted-dose VKAs within the NMA were consistent with results from the head-to-head randomised trial of these two strategies. Indirect evidence suggests treatment with dabigatran etexilate offers benefit for the prevention of stroke, systemic embolism and mortality over antiplatelets and placebo. There was no indication of increased intracranial or extracranial haemorrhage with dabigatran etexilate compared to antiplatelet agents.
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References
- 1 Wolf PA. et al. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.. Stroke 1991; 22: 983-988.
- 2 Slot KB. et al., for the Oxfordshire Community Stroke Project, the International Stroke Trial (UK); Lothian Stroke Register. Impact of functional status at six months on long term survival in patients with ischemic stroke: prospective cohort studies.. Br Med J 2008; 7640: 376-379.
- 3 Dulli DA. et al. Atrial fibrillation is associated with severe acute ischemic stroke.. Neuroepidemiology 2003; 22: 118-123.
- 4 Luengo-Fernandez R. et al. Population-Based Study of Determinants of Initial Secondary Care Costs of Acute Stroke in the United Kingdom.. Stroke 2006; 37: 2579-2587.
- 5 Fuster V. et al. American College of Cardiology/American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm Association; Heart Rhythm Society.. 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).. Circulation 2006; 114: e257-e354.
- 6 Samsa GP. et al. Quality of anticoagulation management among patients with atrial fibrillation: results of a review of medical records from 2 communities.. Arch Intern Med. 2000; 160: 967-973.
- 7 Boulanger L. et al. Patterns of use of antithrombotic therapy and quality of anticoagulation among patients with nonvalvular atrial fibrillation in clinical practice.. Int J Clin Pract 2006; 60: 258-264.
- 8 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.
- 9 Connolly SJ. et al. RE-LY Steering Committee and Investigators.. Dabigatran versus warfarin in patients with atrial fibrillation.. N Engl J Med 2009; 361: 1139-1151.
- 10 Connolly SJ. et al. Correction: Newly identified events in the RE-LY trial.. New Engl J Med 2010; 363: 1875-1876.
- 11 Lip GY, Edwards SJ. Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis.. Thromb Res 2006; 118: 321-333.
- 12 Hart RG. et al. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.. Ann Intern Med 2007; 146: 857-867.
- 13 Cooper NJ. et al. Mixed comparison of stroke prevention treatments in individuals with nonrheumatic atrial fibrillation.. Arch Intern Med 2006; 166: 1269-1275.
- 14 National Institute for Health and Clinical Excellence.. Proposed Health Technology Appraisal. Dabigatran etexilate for the prevention of stroke in atrial fibrillation: draft scope (pre-referral).. Apr 2009. Available at: http://www.nice.org.uk/media/A90/A9/AtrialFibrillationDabigatranPRDraftScope.pdf. Accessed Jun 23, 2010.
- 15 Moher D. et al. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement.. Lancet 1999; 354: 1896-1900.
- 16 Jadad AR. et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials 1996; 17: 1-12.
- 17 Thorlund K. et al. Frequentist and Bayesian multiple-treatments meta-analyses of rare events: risk of malignancies following anti-TNF therapy in rheumatoid arthritis patients.. 17th Cochrane Colloquium, Singapore, 11–14 Ocober 2009: Abstract P10-3.
- 18 Altman DG. Confidence intervals for the number needed to treat.. Br Med J 1998; 317: 1309-1312.
- 19 The ACTIVE Investigators. et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation.. N Engl J Med 2009; 360: 2066-2078.
- 20 Gulløv AL. et al. Fixed minidose warfarin and aspirin alone and in combination vs. adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study.. Arch Intern Med 1998; 158: 1513-1521.
- 21 Gulløv AL. et al. Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation: the AFASAK 2 study. Atrial Fibrillation Aspirin and Anticoagulation.. Arch Intern Med 1999; 159: 1322-1328.
- 22 The SPAF II Investigators.. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study.. Lancet 1994; 343: 687-691.
- 23 The SPAF II Investigators.. Bleeding during antithrombotic therapy in patients with atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators.. Arch Intern Med 1996; 156: 409-416.
- 24 Hu DY. et al. The randomized study of efficiency and safety of antithrombotic therapy in nonvalvular atrial fibrillation: warfarin compared with aspirin.. Zhonghua Xin Xue Guan Bing Za Zhi 2006; 34: 295-298.
- 25 Lu Y, Zhang J. Anticoagulant treatment on chronic non-valvular atrial fibrillation in the elderly patients.. Chin J Emergency Med 2006; 15: 54-56.
- 26 Posada IS, Barriales V. Alternate-day dosing of aspirin in atrial fibrillation. LASAF Pilot Study Group.. Am Heart J 1999; 138: 137-143.
- 27 Connolly SJ. et al. Canadian Atrial Fibrillation Anticoagulation (CAFA) study.. J Am Coll Cardiol 1991; 18: 349-355.
- 28 Ezekowitz MD. et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators.. N Engl J Med 1992; 327: 1406-1412.
- 29 Hellemons BS. et al. Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin.. Br Med J 1999; 319: 958-964.
- 30 Mant J. et al. BAFTA investigators; Midland Research Practices Network (MidReC).. 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.
- 31 Morocutti C. et al. Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation. SIFA (Studio Italiano Fibrillazione Atriale) Investigators.. Stroke 1997; 28: 1015-1021.
- 32 Pengo V. et al. Effectiveness of fixed minidose warfarin in the prevention of thromboembolism and vascular death in nonrheumatic atrial fibrillation.. Am J Cardiol 1998; 82: 433-437.
- 33 Pérez-Gómez F. et al. NASPEAF Investigators.. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study.. J Am Coll Cardiol 2004; 44: 1557-1566.
- 34 Petersen P. et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK Study.. Lancet 1989; 1: 175-179.
- 35 Rash A. et al. A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO).. Age Ageing 2007; 36: 151-156.
- 36 The ACTIVE Writing Group of the ACTIVE Investigators. et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE W): a randomised controlled trial.. Lancet 2006; 367: 1903-1912.
- 37 The Amadeus Investigators. et al. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial.. Lancet 2008; 371: 315-321.
- 38 The BAATAF Investigators.. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators.. N Engl J Med 1990; 323: 1505-1511.
- 39 The EAFT Study Group.. Secondary prevention in non-rheumatic atrial fibrillation after transient ischemic attack or minor stroke. EAFT (European Atrial Fibrillation Trial) Study Group.. Lancet 1993; 342: 1255-1262.
- 40 The Stroke Prevention in Atrial Fibrillation Investigators.. Stroke Prevention in Atrial Fibrillation Study. Final Results.. Circulation 1991; 84: 527-539.
- 41 The SPAF III Investigators.. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial.. Lancet 1996; 348: 633-638.
- 42 Olsson SB. Executive Steering Committee of the SPORTIF III Investigators.. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORT-IF III): randomised controlled trial.. Lancet 2003; 362: 1691-1698.
- 43 Albers GW. et al. for the SPORTIF Executive Steering Committee for the SPORT-IF V Investigators.. Ximelagatran vs. warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial.. J Am Med Assoc 2005; 293: 690-698.
- 44 Connolly S. et al. AVERROES: Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Strokes.. Proceedings of the European Society of Cardiology Congress; 2010 Aug 28-Sep 1; Stockholm, Sweden.
- 45 Cooper NJ. et al. Addressing between-study heterogeneity and inconsistency in mixed treatment comparisons: Application to stroke prevention treatments in individuals with non-rheumatic atrial fibrillation.. Stat Med 2009; 28: 1861-1881.
- 46 Connolly SJ. et al. Challenges of establishing new antithrombotic therapies in atrial fibrillation.. Circulation 2007; 116: 449-455.