Our hypothesis is that episodic amiodarone treatment (i.e. amiodarone treatment 1 month prior until 1 month after cardioversion) is associated with a lower morbidity and a higher quality of life compared to continuous prophylactic amiodarone treatment while atrial fibrillation is still effectively suppressed. The latter means that at the end of the study permanent atrial fibrillation is prevented in comparable percentage of patients (70%) in both treatment strategies. However, this will be accomplished at the cost of a higher number of electrical cardioversions (2-3) in the episodic treatment group compared to the continuous treatment group.

Primary objective

To determine differences in adverse event rates between patients with persistent atrial fibrillation who are randomized to episodic amiodarone treatment (EAT) strategy and patients who are randomized to continuous amiodarone treatment (CAT) strategy, while atrial fibrillation is still effectively suppressed.

Adverse events can be related to:

1. amiodarone use
2. atrial fibrillation itself or underlying heart disease.

Secondary objective

To determine differences in quality of life between patients with persistent atrial fibrillation who are randomized to the EAT strategy and patients who are randomized to the CAT strategy.

Inclusion criteria:

1. Symptomatic persistent atrial fibrillation for at least 48 hours- 1 year (present episode).
2. Older than 18 years of age.
3. Ventricular rate during AF > 75 beats per minute, documented on rest-ECG without rate control.
4. At least two weeks of oral anticoagulation therapy before screening.
5. Written informed consent.

Exclusion criteria:

1. Contra indications for amiodarone (severe chronic obstructive pulmonary disease or QTc > 440ms).
2. History of relapse of AF during adequate amiodarone treatment (i.e. adequate amiodarone and desethylamiodarone plasma levels).
3. Concomitant treatment with class I or III antiarrhythmic drugs. Amiodarone should not have been used during the last 3 months.
4. Other (non) cardiac QT prolonging drugs (if not possible to discontinue).
5. First episode of persistent atrial fibrillation.
6. More than three relapses of persistent atrial fibrillation necessitating electrical cardioversion during the last three years.
7. Known sick sinus syndrome.
8. History of second or third degree AV conduction disturbances.
9. Intraventricular conduction disturbances (QRS> 140ms).
10. Pacemaker treatment.
11. Hemodynamically significant valvular disease.
12. Patients with heart failure with symptoms according to NYHA class III or IV.
13. Unstable angina pectoris.
14. Recent myocardial infarction (< 3 months).
15. PTCA, CABG, other cardiac surgery or major non-cardiac surgery within the last three months.
16. History of hyperthyroidism or hypothyroidism.
17. Serious pulmonary, hepatic, haematological, metabolic, renal, gastrointestinal, CNS or psychiatric disease.
18. Pregnant and non-pregnant women who are pre-menopausal and are not practising an acceptable method of contraception.
19. Treatment with any other investigational agent.
20. Presence of any disease that is likely to shorten life expectancy to < 1 year.
21. Any condition that in the opinion of the investigator would jeopardise the evaluation of efficacy or safety or be associated with poor adherence to the protocol.