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Dr. Jean-Yves Le Heuzey,
Therapy for AF is often directed toward the maintenance of sinus rhythm obtained after a cardioversion or by antiarrhythmic agents. The objectives of this rhythm control strategy include relief of symptoms, better exercise tolerance, prevention of embolism and avoidance of cardiomyopathy which together lead to a better quality of life and better survival.
An accepted strategy is to control the ventricular response rate of AF with the depression of conduction across the AV node by pharmacological agents or ablation of the atrioventricular junction and pacemaker implantation. The rationale for using a rate-control strategy is that most symptoms in AF may be caused by an irregular ventricular rate which may be treated by rate-control drugs. Additionally, effective rate-control drugs may prevent tachycardia-induced cardiomyopathy and the adverse effects of drugs.
Three recent randomized trials compared rhythm and rate control in atrial fibrillation (Table).
In the PIAF trial (1), the two strategies yielded similar clinical results regarding symptoms but exercise tolerance was better in the rhythm-control group.
In the AFFIRM trial (2), 4060 patients with recurrent AF were randomized to one of the two strategies. In this study, there was no survival benefits with the rhythm-control strategy (mortality at 5 years, 23.8% versus 21.3% in the rhythm and rate control group, respectively, p=0.08). The number of hospitalizations [1374 (80.1%) versus 1220 (73.0%), p <0.001] and the proportion of adverse drug effects were greater in the rhythm-control group, especially prolongation of the QT interval, torsade de pointes and bradycardia.
The third randomized trial, Rate control vs electrical cardioversion for persistent atrial fibrillation, RACE (3), compared the two strategies in 522 patients with recurrent persistent AF. The primary end-point was a composite of death from cardiovascular causes, heart failure, bleeding, thrombo-embolic complications, implantation of a pacemaker, and severe adverse effects of drugs.
The primary end-point occurred in 17.2% of the patients in the rate-control group and in 22.6% of the patients in the rhythm-control group which represents a trend in favour of rate control.
These studies show that rate-control is not inferior to rhythm-control strategy and may be an appropriate first choice therapy in patients with recurrent AF. It must be emphasized that most of these studies included patients with structural heart diseases and risk factors of recurrence and thrombo-embolism. Their results cannot be extrapolated to other patients, especially the young patients without underlying cardiopathy.
Patients without symptoms who have experienced at least one cardioversion to restore sinus rhythm can remain in AF with rate-control therapy and prevention of thrombo-embolism.
For patients with disabling symptoms during AF, a drug limiting cardiac rate during the episode can be used. An anti-arrhythmic drug therapy is generally used to maintain the sinus rhythm after the termination of AF.
For patients without heart disease, the first-line therapy includes one of the following drugs : flecainide, propafanone, or sotalol. Second-line therapy includes amiodarone or dofetilide. Third-line therapy includes disopyramide, procainamide, quinidine and non-pharmacological options. For adrenergic AF, beta-blockers and sotalol are the initial drugs of choice.
For patients experiencing heart failure, solely amiodarone can be used.
For patients with coronary artery disease, sotalol represents the initial drug. In case of recurrence, amiodarone can be used.
In case of hypertension, the choice of antiarrhythmic drugs depends on the importance of left ventricular hypertrophy (LVH). If LVH is < 14 mm, flecainide and propafenone can be used as first-line therapy. Second line therapy includes amiodarone or sotalol. Third-line therapy includes disopyramide or quinidine. If LVH is ≥ 14 mm, amiodarone is the only drug that can be used.
It has been demonstrated for many years that anticoagulants might be used in permanent atrial fibrillation (AFASAK, BAATAF, SPAF, CAFA, SPINAF…). The AFFIRM trial has clearly demonstrated that this anticoagulation might be pursued in patients for whom the rhythm control strategy is chosen. Even if the sinus rhythm is restored, patients with high risk of thrombo-embolic events must be continuously treated by anticoagulants (age > 65 years, history of stroke or TIA, diabetes, left atrial enlargement, congestive heart failure…).
Atrial fibrillation is characterized by frequent recurrences. Different strategies could be used to maintain sinus rhythm. Rate control is not inferior to rhythm control for the prevention of morbidity and mortality and may be an appropriate strategy in patients with numerous risk factors of recurrence and/or asymptomatic AF episodes. In other patients, especially young patients without structural heart disease and with symptomatic episodes of AF, rhythm control remains the first strategy.
Table : Main characteristics of PIAF, RACE and AFFIRM studies
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
1. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation -Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomized trial. Lancet 2000; 356:1789-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11117910&dopt=Abstract
2. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12466506&dopt=Abstract
3. Van Gelder IC, Hagens VE, Bosker HA, Kingma J.H., Kamp O., Kingma T., et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002;347:1834-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12466507&dopt=Abstract
Prof. J.Y. Le Heuzey Paris, France Nucleus member of the Working Group on Arrythmias
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