Recent advances in the management of atrial fibrillation
David Geffen School of Medicine at UCLA, and VA Greater Los Angeles Health Care System, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA
* Corresponding author. Tel: +1 310 268 3436; fax: +1 310 473 0724. E-mail address: bramah.singh{at}va.gov or bsingh{at}ucla.edu
Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, with over 3 million cases in the USA and 4.5 million in Europe. Its incidence is rising rapidly, and the number of individuals with AF is expected to triple or even quadruple between now and 2050. Most patients with AF are over 65 years of age and present many co-morbidities, in particular, hypertension (37%), heart failure (23%), coronary artery disease (18%), and diabetes (15%). The majority of patients with AF are elderly and 83% are aged over 65 years. This subset of patients is likely to continue to increase in number. AF is a major source of morbidity and mortality, being associated with reduced left ventricular function, exercise tolerance and quality of life, as well as a two-fold increase in cardiac mortality. In particular, the risk of stroke is increased five-fold in the presence of AF. Furthermore, patients with AF may experience symptoms adversely affecting their daily life. For all these reasons, restoration and maintenance of sinus rhythm in patients with AF is clearly an important therapeutic goal.
The articles comprising this Supplement, in which newer aspects of AF management are discussed in depth by leaders in the field, reflect the debates on these controversial topics at the second CREATE Annual Advisory Meeting held in Berlin on 5 October 2007.
Dr Stefan Hohnloser and colleagues, in their article ‘Prevention of Stroke in Patients with AF: Current Strategies and Future Directions’, address the issue of stroke triggered by the thrombo-embolic complications of AF. Owing to the greatly increased risk of stroke in patients with AF, the prevention and control of this arrhythmia is critical, as is the need for optimal and continuous anticoagulation. However, the stroke risk associated with AF is not homogeneous and varies by up to 20-fold according to the clinical features of the arrhythmia.
The efficacy, safety, and above all the shortcomings of current antithrombotic therapies for patients with AF [anticoagulants, notably the coumarin class of vitamin K antagonists (VKA), such as warfarin, and anti-platelet agents, such as aspirin] are critically reviewed. To date, VKA are the only orally active anticoagulant agents for stroke prevention in patients with AF. However, ximelagatran may now have ushered in the era of oral anticoagulants not requiring monitoring of coagulation. Ximelagatran did not survive, because of liver toxicity, but the compound nevertheless showed that oral anticoagulants may be safely and effectively administered to patients with AF without any monitoring of coagulation. A number of other oral agents are now being studied, including dabigatran, an oral thrombin inhibitor currently under investigation for stroke prevention in patients with AF, among other indications. Another drug in development is idraparinux, a long-acting indirect inhibitor of factor Xa that can be administered parenterally once a week. Other significant developments also give credence to the authors' claim that the introduction of these novel antithrombotic agents into clinical trials suggests that the goal of safer and more convenient anticoagulation therapy may now be within reach.
Drs Paul Dorian and Bramah Singh discuss the topic ‘Upstream Therapies to Prevent AF’. The concept of upstream therapies and the principal agents investigated, including renin–angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), statins, steroids, and N-3 polyunsaturated fatty acids, are reviewed. The mechanisms by which upstream therapies may prevent or reduce AF appear to be multiple, including the prevention of structural remodelling by reducing fibrosis, inflammation, and oxidative stress. These therapies may also act by improving haemodynamics, for example, by lowering blood pressure and reducing left ventricular and atrial wall stress, and by preventing coronary artery disease.
A plethora of clinical studies on a variety of agents have been published. However, most data supporting the beneficial clinical effect of upstream therapies in patients with AF are derived from observational, non-randomized, retrospective studies, or post-hoc analyses of large trials primarily designed with AF as a pre-specified endpoint. Thus, it should be emphasized that although numerous well-designed, placebo-controlled trials are ongoing, much of the existing data will not support logical analysis.
Drs Etienne Aliot and Jeremy N. Ruskin discuss ‘Controversies in Ablation of Atrial Fibrillation’. There is little doubt that the last decade or so has witnessed the development of techniques enabling cardiologists to successfully ablate AF and this approach is now increasingly employed. Techniques of catheter ablation of AF continue to evolve and will undoubtedly lead to wider use of this therapeutic strategy. All in all, the currently available data clearly suggest that ablation of AF is here to stay.
The authors address a number of controversial issues regarding AF ablation. They indicate that a wide range of patients with AF are now candidates for ablation. However, not all such patients may respond to this therapy, whereas in others, this operation may achieve complete suppression of AF and restore sustained sinus rhythm. For example, patients with symptomatic paroxysmal AF generally have a high rate of response to ablation, which restores sinus rhythm with a low rate of complications. Clearly, this may not be the case in elderly patients with long-standing persistent AF. Comparative data derived from large-scale controlled studies are lacking. However, a number of trials comparing catheter ablation in AF vs. drug therapy or a combination of the two approaches suggest that catheter ablation, alone or combined with drug therapy, achieves higher rates of AF suppression. On the other hand, no acceptable definitive trials that allow interpretation of the effects of AF ablation relative to age, disease, ejection fraction, and anti-arrhythmic drug regimens (single and multiple) have yet been published.
Drs A. John Camm and James A. Reiffel discuss the topic ‘Defining Endpoints in Clinical Trials on AF’ in considerable depth and clarity, the objective of their article being to review the main issues in the choice of endpoints for clinical trials evaluating treatments for AF. Four endpoints and the controversies concerning their use are reviewed—time to first recurrence of AF or atrial tachyarrhythmia (AT), freedom from AF or AT recurrence during 1 year, mortality and quality of life. The authors note that time to first recurrence of AF or AF/AT was the primary endpoint of the CTAF, SAFE-T, EURIDIS and ADONIS trials, and was part of the composite primary endpoint in the Prevention of Atrial Fibrillation after Cardioversion trial (PAFAC). The selection of primary and secondary endpoints for clinical trials in patients with AF will depend on the principal objective of the trial, as well as the demographic and clinical characteristics of the patients targeted. As emphasized by the authors, hard endpoints such as stroke, mortality, and hospitalization are most relevant to patients with persistent AF at high risk of these outcomes. Time to first event is now increasingly criticized as a primary endpoint, despite its practical advantages, as it does not accurately reflect clinically important parameters such as the frequency, type, and duration of AF recurrence and the overall AF burden.
The CREATE (Cardiac Rhythm/Electrophysiology And Targeted Education) Annual Advisory Meetings offer a unique opportunity for experts from different parts of the world to exchange their views and experiences with regard to such controversial topics, to reach consensus on certain issues, and to highlight the lack of consensus on others.
 |
The CREATE Scientific Committee 2007 |
|---|
 Top The CREATE Scientific Committee... |
|---|
Etienne Aliot
Centre Hospitalier Brabois
Vandoeuvre lès Nancy
France
A. John Camm
St George's Hospital Medical School
London
UK
Stefan H. Hohnloser
JW Goethe University
Frankfurt am Main
Germany
Peter R. Kowey
Main Line Health Heart Center
Lankenau Hospital
Wynnewood
PA
USA
Eric N. Prystowsky
St. Vincent Hospital and Health Center Program
Indianapolis
IN
USA
Jeremy Ruskin
Massachusetts General Hospital
Boston
MA
USA
Bramah Singh
David Geffen School of Medicine at UCLA and
VA Greater Los Angeles Healthcare System
Los Angeles
CA
USA
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||