Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study

Abstract

Objective-To assess and compare the safety and eYcacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation. Design-Prospective, randomised, single blind, placebo controlled study. Setting-Tertiary cardiac referral centre. Patients-186 consecutive patients (97 men, 89 women; mean (SD) age, 63 (10) years) with recurrent, symptomatic atrial fibrillation. Interventions-65 patients were randomised to amiodarone, 61 to sotalol, and 60 to placebo. Patients receiving amiodarone were maintained at a dose of 200 mg/day after a 30 day loading phase. The sotalol dose was 160-480 mg daily, as tolerated. Main outcome measures-Recurrence of atrial fibrillation or side eVects. Results-In the amiodarone group, 31 of the 65 patients developed atrial fibrillation after an average of six months, while 15 (11 in sinus rhythm and four in atrial fibrillation) experienced significant side eVects after an average of 16 months. In the sotalol group, relapse to atrial fibrillation occurred in 47 of the 61 patients after an average of eight months; three experienced side eVects during the titration phase. In the placebo group, 53 of the 60 patients developed atrial fibrillation after an average of four months (p < 0.001 for amiodarone and sotalol v placebo; p < 0.001 for amiodarone v sotalol). Conclusions-Both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation. Amiodarone is more eVective but causes more side eVects. (Heart 2000;84:251-257) Keywords: amiodarone; sotalol; atrial fibrillation Various antiarrhythmic drugs, especially those belonging to class I (quinidine, procainamide, flecainide, propafenone), have been used to prevent recurrence of atrial fibrillation in patients with paroxysmal atrial fibrillation or with chronic atrial fibrillation after successful cardioversion. However, their use is fraught with problems, including incomplete eYcacy, proarrhythmic properties, and possibly increased mortality. [1][2][3][4][5][6][7][8][9][10] Recently, the development of new antiarrhythmic agents has focused on the class III mode of action-that is, the prolongation of myocardial repolarisation and refractoriness.2-5 11-13 Only two antiarrhythmic agents that are available on the market and are suitable for long term administration possess this property-sotalol and amiodarone. [14][15][16][17][18] Previous studies suggest that both these drugs are eVective in the management of refractory atrial fibrillation. However, the data must be interpreted with caution because of small sample sizes, short follow up, and the fact that most of the studies were not controlled or randomised.This prospective, randomised, single blind trial was designed: first, to determine whether amiodarone and sotalol are superior to placebo for the long term maintenance of sinus rhythm in patients with recurrent, symptomatic atrial fibrillation; second, to examine the safety of the drugs when used in this setting; and third, to compare ...

ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation

“…570 In patients with paroxysmal AF, amiodarone was more effective than propafenone 575 and sotalol, 562 but this advantage was offset by a higher incidence of side effects. 562 In patients who develop recurrent AF during long-term therapy with oral amiodarone, intravenous amiodarone exerted an additional therapeutic effect to terminate recurrences. 576 Amiodarone increases the success rate of electric cardioversion and prevents relapses by suppressing atrial ectopy in patients with persistent AF.…”

Effects of Antiarrhythmic Drugs on Fibrillation in the Remodeled Atrium

“…4 -6 A key component of AFrelated remodeling is downregulation of L-type Ca 2ϩ -channel protein, which reduces atrial effective refractory period (ERP) and decreases physiological ERP rate adaptation. 7,8 Two recent controlled studies indicate that amiodarone is uniquely effective in treating AF 9,10 ; however, the underlying mechanistic basis is unknown. Mibefradil, a T-type Ca 2ϩ -current blocker, prevents atrial electrical remodeling 11,12 but was never studied in clinical AF and is no longer clinically available because of adverse drug interactions related to CYP 3A4 inhibition.…”

Atorvastatin Given prior to Electrical Cardioversion Does Not Affect the Recurrence of Atrial Fibrillation in Patients with Persistent Atrial Fibrillation Who Are on Antiarrhythmic Therapy

“…Of the antiarrhythmic drugs presently available, oral amiodarone is more efficacious than other drugs for the maintenance of sinus rhythm after EC [26,27] . The AF recurrence rate is approximately 30-40% with amiodarone.…”