Medical treatment of atrial fibrillation has been carried out most frequently with digoxin, quinidine, propafenone or flecainide. In spite of unequivocal efficacy, the use of class I antiarrhythmic agents is the subject of considerable controversy. In addition to increased mortality in patients with ventricular arrhythmias after myocardial infarction, proarrhythmic effects with flecainide have also been described in patients with supraventricular arrhythmias. A meta-analysis of long-term treatment of atrial fibrillation with quinidine disclosed that the mortality in those treated with quinidine at 2.9% was significantly higher than those receiving placebo at 0.8%. In consideration of the prevailing uncertainty with the use of class I antiarrhythmic agents, class III antiarrhythmic drugs such as sotalol and amiodarone have been administered for supraventricular arrhythmias with increasing frequency. Treatment of atrial fibrillation with sotalol Sotalol is a noncardioselective beta-adrenergic receptor blocker with antiarrhythmic properties of class III. This drug prolongs the duration of the action potential and the refractory periods in atrial and ventricular myocardium and slows the AV-conduction as well as the sinus node rate. On oral administration, there is good resorption and a half-time of seven to 18 hours. The effective oral dose varies between 80 and 320 mg/12 hours. For conversion of acute supraventricular arrhythmias, an i.v. bolus of 0.5 to 1.5 mg/kg has been used. The results of clinical studies with sotalol in the treatment of atrial fibrillation are shown in Table 1. In a study by Campbell, in acute atrial fibrillation, incurred postoperatively after cardiovascular surgery, in 17 of 20 patients (85%) sinus rhythm was re-established with an i.v. bolus of 1 mg/kg sotalol followed by an infusion of 0.2 mg/kg/h. Other studies in acute atrial fibrillation have shown successful conversion rates of 23 to 30% in which one investigation demonstrated dose dependency. On oral administration of sotalol for paroxysmal or chronic atrial fibrillation, Antman and Singh reported achieving sinus rhythm in 8 to 27%; after electrical cardioversion, however. sinus rhythm resulted in 45 to 55%. Juul-Moller showed that six months after cardioversion sinus rhythm was maintained in 52% of patients treated with sotalol and 48% of those given quinidine. In a randomized study of prophylactic treatment after aortocoronary bypass surgery, atrial fibrillation was observed postoperatively in 2.4% receiving sotalol, 15.3% of those given metoprolol and 28% without prophylactic treatment. In one study, atrial fibrillation was observed in 24 of 150 patients (16%) receiving sotalol as compared with 49 of 150 (33%) with placebo. For prophylactic prevention of recurrent atrial fibrillation. sotalol appears comparable to class I antiarrhythmic drugs. Potential advantages include fewer side-effects and a lower incidence of proarrhythmic complications. Sotalol can be regarded as a drug of first choice for patients with atrial fibrillation and no signs of manifest heart failure. Treatment of atrial fibrillation with amiodarone Amiodarone prolongs the action potential and the effective refractory periods in the atria and ventricles. Because of its complex pharmacokinetics with very slow elimination (T1/2: four to eight weeks) and toxicside-effects, the use of amiodarone for supraventricular arrhythmias is problematic. Since the maintenance dose for supraventricular arrhythmias is rarely more than 200 mg/d, the risk of severe adverse reactions, however, is lower than that described in many studies using higher doses for treatment of ventricular arrhythmias. The results of the most relevant studies are summarized in Table 2. Using i.v. amiodarone for treatment of acute atrial fibrillation, sinus rhythm was achieved by Faniel in 81% of the patients within 24 hours and by Strasberg in 73%.McAlister treated patients with acute atrial fibrillation after cardiovascular surgery with either amiodarone or quinidine. After oral saturation with quinidine 25 of 39 patients (64%) converted to sinus rhythm; with the currently unusually low loading dose of i.v. amiodarone (5 mg/kg), sinus rhythm was achieved in only 17 of 41 patients (41%). For newly-incurred atrial fibrillation after myocardial infarction, Cowan compared the oral administration of amiodarone and digoxin. The rate of conversion in both groups was almost identical (83% vs 75%). On oral treatment with 200 to 600 mg amiodarone daily, in another study, atrial fibrillation was suppressed in 97%. Additionally, in a study of 95 patients, after an average of three unsuccessful attempts of treatment with other antiarrhythmic agents, a loading dose of 600 to 1200 mg amiodarone daily for five days followed by a maintenance dose of 200 mg daily resulted in sinus rhythm in 78% of the patients. In a prospective study in chronic atrial fibrillation, Zehender compared amiodarone with quinidine and the combination of quinidine with verapamil. Sinus rhythm was achieved in 25% with quinidine alone and the rate of success was increased to 55% with the addition of verapamil while amiodarone resulted in conversion to sinus rhythm in 60%. A further advantage of amiodarone is good control of the ventricular rate, even in patients who do not convert to sinus rhythm. In patients with left ventricular heart failure who are not adequately controlled with digoxin alone, amiodarone in an antiarrhythmic drug of first choice. In general, amiodarone is an important agent in reserve for various supraventricular arrhythmias which do not respond to sotalol or other class I antiarrhythmic drugs.
