Atrial fibrillation (AF) is the commonest cardiac arrhythmia, with a prevalence of 1% in the general population.1
This equates to 2.3 million US adults currently affected, with the number expected to increase to 7.5 million by 2050, due in part to an ageing population.2
AF is associated with substantial morbidity and mortality from stroke, thromboembolism, and heart failure, and is an independent predictor of increased mortality.3
The economic burden is enormous, with an estimated annual cost of US$ 26 billion for treating AF and its complications in the US alone.5
The association between AF and stroke is well recognized, and hence the priority in treating AF is to identify those at high risk of stroke and anticoagulate accordingly. There remains controversy regarding rate control versus rhythm control, but it is now accepted that rhythm control should be adopted for those who are symptomatic despite adequate rate control. However, determining which patients are symptomatic can be difficult because symptoms are often insidious and vague (palpitations, lethargy, shortness of breath, decreased exercise tolerance) and often attributed to ageing. Many patients tolerate and adapt lifestyles to their symptoms, not realizing the full impact of AF until sinus rhythm is restored. In this group, a therapeutic trial of cardioversion may be undertaken to see if symptoms are improved by maintaining sinus rhythm.
Randomized controlled trial data from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) study suggested no morbidity or mortality benefit of rhythm control over rate control with a strategy involving antiarrhythmic drugs and/or direct current cardioversion.6
However, subsequent reanalysis did show a significant survival advantage in those maintaining sinus rhythm, but it is unclear whether this relationship is causal or whether sinus rhythm is a marker for some other factors.8
Catheter ablation is significantly more effective in maintaining sinus rhythm than antiarrhythmic drugs.9
There is also emerging data suggesting that there may be some mortality benefit of curative catheter ablation, though this requires further prospective evaluation.15
Recent multicenter registry data also suggests that risk of stroke may be reduced after successful catheter ablation of AF, although the risk-benefit ratio of oral anticoagulation in this setting is still being prospectively evaluated through randomized trials.16
At present, catheter ablation is reserved for patients who have symptoms refractory to at least one antiarrhythmic drug. The evolution of percutaneous ablation techniques is causing a shift in management trends, with early ablation strategies aiming to halt progression to long-standing persistent or permanent AF.17
The current medical benchmark of success is arbitrarily set high (recurrence of AF or atrial tachycardia for ≥30 seconds ± symptoms).21
Although benchmarks are necessary to compare treatments, they do not necessarily correlate with measures of success from the patient’s perspective. For example, those with recurrent arrhythmia after catheter ablation meeting this criterion often have good improvement in their symptoms.22
For patients, the most important outcomes are symptom improvement, avoiding medication, reduction of stroke risk and death.
At present, antiarrhythmic drugs remain first-line agents in managing AF. Of the agents used, amiodarone is the most closely studied and is also the most effective in maintaining sinus rhythm.23
Its use is usually restricted to the short-term due to the high incidence of major side effects, and hence there has been a tremendous drive to find a pharmacological alternative. Dronedarone is a novel structural analog of amiodarone which is recommended for rhythm control in AF in both European and US guidelines.20
In this review, we discuss the evidence for dronedarone and its potential role in treating AF.