A group of Japanese researchers report the results of a study carried out to determine the effectiveness of amiodarone (Cordarone) in the treatment of paroxysmal AF patients who had received no benefit from treatment with other antiarrhythmic drugs. It is estimated that 3% of Japanese people over the age of 70 years suffer from atrial fibrillation (AF) and this percentage is expected to increase to 4.5% over the next 20 years. In comparison, the number of people in the USA with AF was estimated at 5 million in 2000 and is expected to increase 2- to 3-fold over the next 50 years. Currently recommended first-line treatment for paroxysmal (intermittent) AF involves the use of antiarrhythmic drugs such as flecainide, propafenone, disopyramide, sotalol and amiodarone. Class I drugs (flecainide and propafenone) are contraindicated in patients with heart disease and low left ventricular ejection fraction. The Japanese study included 49 men and 22 women (average age of 68 years) with paroxysmal AF (52% had underlying heart disease) who had proven refractory to therapy with at least two antiarrhythmic drugs other than amiodarone. The study participants were hospitalized for 2 weeks during which time they were given a loading dose of 400 mg/day of amiodarone. The dose was subsequently reduced to 200 mg/day (maintenance dose) and further adjusted downwards (minimum dose was 50 mg/day) if no recurrence was observed for 6 or 12 months.
After an average follow-up of 4 years, 54% of patients had experienced AF recurrence. Patients who experienced recurrence were significantly more likely to have
asymptomatic AF (24% vs 3%), less likely to be on RAAS inhibitors (ACE inhibitors, angiotensin II receptor blockers or aldosterone antagonists) (29% vs 64%),
and more likely to have normal/high left ventricular ejection fraction (LVEF). It was also clear that amiodarone therapy was significantly less effective in
patients with mixed (neither purely vagal nor purely adrenergic) AF. Multivariate analysis confirmed that amiodarone was more effective in patients with symptomatic AF,
lower LVEF, and either vagal or adrenergic AF.
The researchers speculate that mixed AF is less related to a dysfunction of the autonomic nervous system, but more related to the influence of degeneration or
fibrosis of atrial tissue. The progression to permanent AF over the follow-up period was 31%. Patients with diabetes, asymptomatic AF, and normal/high LVEF
and those not on RAAS inhibitors were more likely to progress to permanent AF; however, multivariate analysis showed that only asymptomatic AF was a statistically
significant predictor of progression to permanent AF. The incidence of pulmonary toxicity among the study participants was 1.4%/year.
The researchers conclude that amiodarone is most effective in maintaining sinus rhythm in patients with impaired LVEF and least effective in those with
asymptomatic or mixed AF. They surmise that amiodarone is less effective in the case of asymptomatic AD because this type of AF is likely to have been
present for much longer prior to “official” diagnosis and thus have allowed time for extensive remodeling.