Continuous vs episodic prophylactic treatment with amiodarone for the prevention of atrial fibrillation: a randomized trial.

CONTEXT

Amiodarone effectively suppresses atrial fibrillation but causes many adverse events.

OBJECTIVE

To compare major events in patients randomized to receive episodic amiodarone treatment with those who received continuous amiodarone treatment while still aiming to prevent atrial fibrillation.

DESIGN, SETTING, AND PARTICIPANTS: A randomized trial of 209 ambulatory patients with recurrent symptomatic persistent atrial fibrillation, conducted from December 2002 through March 2007 at 7 Dutch medical centers.

INTERVENTION

Patients were randomly assigned to receive either episodic or continuous amiodarone treatment after electrical cardioversion following amiodarone loading. Episodic amiodarone treatment was discontinued after a month of sinus rhythm and reinitiated if atrial fibrillation relapsed (1 month peri-electrical cardioversion). In the continuous treatment group amiodarone was maintained throughout.

MAIN OUTCOME MEASURES

The primary end point was a composite of amiodarone and underlying heart disease-related major events. The secondary end points were all-cause mortality and cardiovascular hospitalizations.

RESULTS

After a median follow-up of 2.1 years (range, 0.4-2.5 years), 51 (48%) of those receiving episodic treatment vs 64 (62%) receiving continuous treatment had sinus rhythm (P = .05). There were 85 atrial fibrillation recurrences (80%) among the episodic treatment group vs 56 (54%) in the continuous treatment group (P < .001). No significant difference existed in the incidence of the primary composite end point between each group (37 [35%] episodic vs 34 [33%] continuous; incidence rate difference, 0.2; 95% confidence interval [CI], -10.2 to 10.6). However, there were nonstatistically significant differences in the incidence of amiodarone-related major events (20 [19%] episodic vs 25 [24%] continuous; incidence rate difference, -2.0; 95% CI, -8.7 to 4.6) and underlying heart disease-related major events (17 [16%] episodic vs 9 [9%] continuous; incidence rate difference, 3.6; 95% CI, -1.6 to 8.7). All-cause mortality and cardiovascular hospitalizations were higher among those receiving episodic treatment (56 [53%] vs 35 [34%], P = .02).

CONCLUSIONS

In this study population, there was no difference in the composite of amiodarone and cardiac major adverse events between groups. However, patients receiving episodic treatment had a significantly increased rate of atrial fibrillation recurrence and a significantly higher rate of all-cause mortality and cardiovascular hospitalizations.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00392431.