Antithrombotic Management of Atrial Fibrillation

Atrial fibrillation is the most frequently occurring heart arrhythmia and highly prevalent in the elderly population. The most important clinical consequences of atrial fibrillation are congestive heart failure due to a too low or too high ventricular heart rate and thromboembolic complications due to embolization of clots that have formed due to stasis in the nonfunctional atria. To prevent the latter complication, all patients with atrial fibrillation need to be treated with anticoagulants, most often vitamin K antagonists (VKAs). In fact, millions of people worldwide use VKAs for the prevention of thromboembolic complications of atrial fibrillation, and atrial fibrillation is by far the most common indication for the use of VKAs.[1] In recent years a steady increase in the knowledge about the efficacy and safety of antithrombotic agents, in particular VKAs, has been accumulated in various patient categories.[2] This issue of Seminars in Thrombosis and Hemostasis aims to present the current state of the art in this field.

In a consensus document presented by a multidisciplinary group of experts, the efficacy and safety of anticoagulants in patients with atrial fibrillation is outlined.[3] In addition, this article explains that although current guidelines clearly define the indications for treatment, there are barriers among physicians and patients on the implementation of oral anticoagulation, and it discusses the factors that may determine this resistance.

In subsequent articles, these topics are explored more thoroughly. Fitzmaurice et al describe in greater detail the exact indication and efficacy of antiplatelet agents and VKAs in patients with atrial fibrillation.[4] Risk stratification strategies to identify patients with absolute and relative indications for VKAs are outlined in this article as well.

Elderly patients may represent a group of patients in which the appropriate antithrombotic management is most difficult. These patients may expect a relatively high efficacy of treatment with VKAs but simultaneously have a much higher risk of bleeding complications. Based on a thorough review of the data and recent research findings, Hylek et al conclude there is sufficient evidence that these patients may benefit from treatment with VKAs as well.[5] However, they rightfully argue that a better understanding of the pathological changes that predispose to hemorrhage, hazards of polypharmacy, and factors that contribute to variability in dose response will facilitate a more informed use of these medications in clinical care.

One of the major problems with the use of anticoagulant treatment for patients with atrial fibrillation is the implementation of the various guidelines on this subject. Despite the overwhelming evidence that prevention of thromboembolic complications by the use of antithrombotic agents is beneficial in virtually all patient categories, a large proportion of the patients with atrial fibrillation do not receive the proper treatment. Pisters et al present the available data on this topic and the potential consequences of insufficient treatment.[6] It is on one hand reassuring to see that the number of patients with atrial fibrillation who use VKAs is increasing worldwide, but on the other hand, further improvement is warranted. It should be stressed, however, that there will always be room for individual choices in a given patient because patients may present with specific characteristics (such as comorbidity or other medications) or circumstances on which the trial evidence is less clear,[7] and in these cases individual clinical judgment is required.

Levi et al discuss the various factors that determine whether a patient who is treated with VKAs remains in the therapeutic target range.[8] Apart from patient factors, the management strategy to control the anticoagulant treatment is an important determinant. Management strategies that improve the time in the therapeutic target range are computer-assisted dosing algorithms and centralized care in anticoagulation clinics. In addition, self-testing of the international normalized ratio and self-dosing of VKAs has been introduced over the past 20 years and been shown to be an effective and safe treatment modality.[9] An analysis compared >30,000 Italian patients who were persistently using VKA treatment management via an anticoagulation clinic, the general practitioner, or a combined modality.[10] These data may be very useful to improve the efficacy and safety of anticoagulant management in real-life practice.

Lastly, Harenberg et al describe the new anticoagulant agents that are currently being developed.[11] Indeed, in recent years a large number of new antithrombotic agents have been developed and tested in clinical trials, and many of these new agents will become available for clinical practice in the very near future.[12] The need for new anticoagulant agents is quite obvious. First, the current agents are insufficiently effective and relatively unsafe. Furthermore, current anticoagulant agents are often cumbersome with regard to their clinical use, requiring repeated laboratory control and frequent dose adjustments. Increasing knowledge on the function of the hemostatic system in vivo has resulted in a new generation of anticoagulant agents. Harenberg et al review the current classes of new anticoagulants and the efficacy and safety of these agents in clinical trials so far. Atrial fibrillation may be one of the most important indications for the new anticoagulants, and many large clinical trials evaluating the efficacy and safety of the new agents for this condition are currently ongoing.

Taken together, the articles in the current issue of Seminars in Thrombosis and Hemostasis represent a wide array of useful information on the state of the art of antithrombotic management in patients with atrial fibrillation, and we hope that practicing physicians and scientists in this area will find it useful.

REFERENCE

• 1 Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;  126(3, Suppl) 204S-233S
• 2 Hirsh J, Guyatt G, Albers G W, Schunemann H J. Proceedings of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: evidence-based guidelines.  Chest. 2004;  126(3, Suppl) 172S-696S
• 3 Levi M, Hobbs R, Jacobson A K et al.. Improving oral anticoagulation management in patients with atrial fibrillation: current status and perspectives.  Semin Thromb Hemost. 2009;  35(6) 527-542
• 4 Fitzmaurice D A, Hobbs F D. Anticoagulant management in patients with atrial fibrillation.  Semin Thromb Hemost. 2009;  35(6) 543-547
• 5 Hylek E M. Antithrombotic prophylaxis in elderly patients with atrial fibrillation.  Semin Thromb Hemost. 2009;  35(6) 548-553
• 6 Pisters R, de Vos C B, Nieuwlaat R, Crijns H JGM. Use and underuse of oral anticoagulation for stroke prevention in atrial fibrillation: old and new paradigms.  Semin Thromb Hemost. 2009;  35(6) 554-559
• 7 Levi M, Hovingh G K, Cannegieter S C, Vermeulen M, Büller H R, Rosendaal F R. Bleeding in patients receiving vitamin K antagonists who would have been excluded from trials on which the indication for anticoagulation was based.  Blood. 2008;  111(9) 4471-4476
• 8 Levi M, de Peuter O, Kamphuisen P W. Management strategies for optimal control of anticoagulation in patients with atrial fibrillation.  Semin Thromb Hemost. 2009;  35(6) 560-567
• 9 Levi M. Self-management of anticoagulation.  Expert Rev Cardiovasc Ther. 2008;  6(7) 979-985
• 10 Prisco D, Antonucci E, Grifoni E et al.. Different models for oral anticoagulation management may be applied provided that minimal assistance criteria are fulfilled—an Italian experience.  Semin Thromb Hemost. 2009;  35(6) 568-573
• 11 Harenberg J. New anticoagulants for the antithrombotic management of atrial fibrillation.  Semin Thromb Hemost. 2009;  35(6) 574-586
• 12 Levi M. New antithrombotics in the treatment of thromboembolic disease.  Eur J Intern Med. 2005;  16(4) 230-237