Abstract
Atrial fibrillation (AF) is the most frequently encountered sustained arrhythmia with a prevalence of 0.5–10%, depending predominantly on age. The arrhythmia is associated with significant morbidity and mortality, mainly due to thromboembolic events including stroke and systemic embolisms. These complications can be effectively prevented with anticoagulation therapy either with vitamin K antagonists (VKA) or with non-vitamin K antagonists (NOAC). VKA therapy is effective in preventing strokes but these medications are difficult to use, are associated with significant bleeding risk, and have pharmacokinetic/dynamic properties that make their use cumbersome. NOACs—either factor II or factor Xa inhibitors—have been developed over the past two decades and have been tested against VKA in large randomized controlled trials. This trial evidence was complemented more recently by increasing real-world data comprising several 100,000 patients. Finally, NOACs have been examined for their use in specific clinical situations, for example, in patients undergoing cardioversion, catheter ablation, or coronary interventions. In all of these clinical scenarios, NOACs have been similarly effective or—in many instances—even superior to treatment with VKA. Recent guidelines, therefore, recommend NOAC therapy for stroke prevention in AF as first-line therapy.
Zusammenfassung
Vorhofflimmern ist die häufigste anhaltende Arrhythmie mit einer Prävalenz von 0,5–10 %, abhängig vom Alter. Diese Herzrhythmusstörung ist mit einer deutlich erhöhten Morbidität und Mortalität assoziiert, hauptsächlich aufgrund thromboembolischer Ereignisse einschließlich Schlaganfällen und systemischer Embolien. Diese Komplikationen können effektiv durch eine Antikoagulationstherapie verhindert werden, entweder mit Vitamin-K-Antagonisten (VKA) oder Non-Vitamin-K-Antagonisten/neuen oralen Antikoagulanzien (NOAC). Die VKA-Therapie bietet einen effektiven Schutz vor Schlaganfällen, ist aber aufgrund signifikant erhöhter Blutungsrisiken und schwieriger pharmakokinetischer und -dynamischer Eigenschaften mühsam im Alltag einzusetzen. NOAC hemmen selektiv entweder den Faktor II oder Faktor Xa, sind eine Entwicklung der letzten 20 Jahre und wurden in großen randomisierten Studien (RCT) mit VKA verglichen. Diese Daten wurden durch „Real-World-Daten“, die einige Hunderttausend Patienten umfassen, ergänzt. Schließlich wurden NOAC in speziellen klinischen Situationen getestet, z. B. bei Patienten, bei denen eine Kardioversion, eine Katheterablation oder eine Koronarintervention durchgeführt wurde. In diesen klinischen Szenarien zeigten sich NOAC der VKA-Therapie überlegen oder waren zumindest von gleicher Effektivität. Daher empfehlen die aktuellen Behandlungsleitlinien die NOAC-Therapie als Behandlung der Wahl zur Schlaganfallprophylaxe bei Patienten mit Vorhofflimmern.
Similar content being viewed by others
References
Bennell MC, Qiu F, Micieli A et al (2015) Identifying predictors of cumulative healthcare costs in incident atrial fibrillation: a population-based study. J Am Heart Assoc 4:e1684
Chugh SS, Havmoeller R, Narayanan K et al (2014) Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation 129:837–847
Kannel WB, Wolf PA, Benjamin EJ, Levy D (1998) Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 82:2N–9N
Wolf PA, Mitchell JB, Baker CS et al (1998) Impact of atrial fibrillation on mortality, stroke, and medical costs. Arch Intern Med 158:229–234
Henninger N, Goddeau RP Jr, Karmarkar A et al (2016) Atrial fibrillation is associated with a worse 90-day outcome than other cardioembolic stroke subtypes. Stroke 47:1486–1492
van Gage BF, Walraven C, Pearce L et al (2004) Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation 110:2287–2292
Hart RG (2007) Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 146:857
Connolly SJ, Eikelboom J, Joyner CD et al (2011) Apixaban in patients with atrial fibrillation. N Engl J Med 364:806–817
Kirchhof P, Benussi S, Kotecha D et al (2016) 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC endorsed by the European Stroke Organisation (ESO). Eur Heart J 37:2893–2962
Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139–1151
ROCKET AF Investigators, Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891
Granger CB, Alexander JH, McMurray JJ et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992
Giugliano RP, Ruff CT, Braunwald E et al (2013) Once-daily edoxaban versus warfarin in patients with atrial fi brillation. N Engl J Med 369:2093–2104
Ruff CT, Giugliano RP, Braunwald E et al (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383:955–962
Macle L, Cairns J, Leblanc K et al (2016) 2016 focused update of the Canadian cardiovascular society guidelines for the management of atrial fibrillation. Can J Cardiol 32:1170–1185
Gorst-Rasmussen A, Skjøth F, Larsen TB et al (2015) Dabigatran adherence in atrial fibrillation patients during the first year diagnosis: a nationwide cohort study. J Thromb Haemost 13:495–504
Steinberg BA, Holmes DN, Piccini JP et al (2013) Early adoption of dabigatran and its dosing in US patients with atrial fibrillation: results from outcomes registry for better informed treatment of atrial fibrillation. J Am Heart Assoc 2:e535. https://doi.org/10.1161/JAHA.113.000535
Yao X, Abraham NS, Sangaralingham LR et al (2016) Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. J Am Heart Assoc. https://doi.org/10.1161/JAHA.116.003725
Lip GY, Keshishian A, Kamble S et al (2016) Real-world comparison of major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban, or warfarin. A propensity-score matched analysis. Thromb Haemost 116:975–986
Deitelzweig S, Farmer C, Luo X et al (2017) Risk of major bleeding in patients with non-valvular atrial fibrillation treated with oral anticoagulants: a systematic review of real-world observational studies. Curr Med Res Opin 33:1583–1594
Hohnloser SH, Basic E, Näbauer M (2017) Comparative risk of major bleeding with new oral anticoagulants (NOACs) and phenprocoumon in patients with atrial fibrillation: a post-marketing surveillance study. Clin Res Cardiol 106:618–662
Grönberg T, Hartikainen JE, Nuotio I et al (2016) Anticoagulation, CHA2DS2VASc Score, and thromboembolic risk of cardioversion of acute atrial fibrillation (from the FinCV Study). Am J Cardiol 117:1294–1298
Nagarakanti R, Ezekowitz MD, Oldgren J et al (2011) Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation 123:131–136
Piccini JP, Stevens SR, Lokhnygina Y et al (2013) Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial. J Am Coll Cardiol 61:1998–2006
Flaker G, Lopes RD, Al-Khatib SM et al (2014) Efficacy and safety of apixaban in patients after cardioversion for atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). J Am Coll Cardiol 63:1082–1087
Plitt A, Ezekowitz MD, De Caterina R et al (2016) Cardioversion of atrial fibrillation in ENGAGE AF-TIMI 48. Clin Cardiol 39:345–346
Cappato R, Ezekowitz MD, Klein AL et al (2014) Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 35:3346–3355
Goette A, Merino JL, Ezekowitz MD et al (2016) Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial. Lancet 388:1995–2003
Ezekowitz MD, Pollack CV, Sanders P et al (2016) Apixaban compared with parenteral heparin and/or vitamin K antagonist in patients with nonvalvular atrial fibrillation undergoing cardioversion: rationale and design of the EMANATE trial. Am Heart J 179:59–68
Calkins H, Kuck KH, Cappato R et al (2012) 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace 14:528–606
Di Biase L, Burkhardt JD, Santangeli P et al (2014) Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial fibrillation with different anticoagulation management: results from the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) randomized trial. Circulation 129:2638–2644
Hohnloser SH (2016) Treatment safety of non-vitamin K oral anticoagulants in patients with atrial fibrillation. Herz 41:37–47
Cappato R, Marchlinski FE, Hohnloser SH et al (2015) Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J 36:1805–1811
Calkins H, Willems S, Gerstenfeld EP et al (2017) Uninterrupted dabigatran versus warfarin for ablation in atrial fibrillation. N Engl J Med 376:1627–1636
Cardoso R, Knijnik L, Bhonsale A et al (2017) An updated meta-analysis of novel oral anticoagulants versus vitamin K antagonists for uninterrupted Anticoagulation in atrial fibrillation catheter ablation. Heart Rhythm. https://doi.org/10.1016/j.hrthm.2017.09.011
Lip GY, Windecker S, Huber K et al (2014) Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Eur Heart J 35:3155–3179
Dewilde WJM, Oirbans T, Verheugt FWA et al (2013) Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 381:1107–1115
Jackson LR II, Ju C, Zettler M et al (2015) Outcomes of patients with acute myocardial infarction undergoing percutaneous coronary intervention receiving an oral anticoagulant and dual antiplatelet therapy: a comparison of clopidogrel versus prasugrel from the TRANSLATE-ACS study. JACC Cardiovasc Interv 8:1880–1889
Gibson CM, Mehran R, Bode C et al (2016) Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med 375:2423–2434
Cannon CP, Bhatt DL, Oldgren J et al (2017) Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. https://doi.org/10.1056/NEJMoa1708454
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
J. W. Erath reports receiving travel support and lecture fees from ZOLL Medical and Servier and is a fellow of the Boston Scientific heart rhythm fellowship program, outside the submitted work. S. H. Hohnloser reports receiving consulting fees from Bayer Healthcare, Boehringer Ingelheim, Gilead, J&J, Medtronic, Pfizer, St. Jude Medical, Sanofi-Aventis, and Zoll Medical, as well as lecture fees from Boehringer Ingelheim, Bayer Healthcare, Bristol-Myers Squibb, Pfizer, St. Jude Medical, Sanofi-Aventis, and Cardiome, outside the submitted work.
This article does not contain any studies with human participants or animals performed by any of the authors.
Rights and permissions
About this article
Cite this article
Erath, J.W., Hohnloser, S.H. Anticoagulation in atrial fibrillation. Herz 43, 2–10 (2018). https://doi.org/10.1007/s00059-017-4648-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00059-017-4648-0