Asymptomatic or "silent" atrial fibrillation: frequency in untreated patients and patients receiving azimilide. Propafenone versus disopyramide for maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation: a randomized, double-blind study. PRODIS Study Group. Comparison of the safety and efficacy of flecainide versus propafenone in hospital out-patients with symptomatic paroxysmal atrial fibrillation/flutter. The Flecainide AF French Study Group. A randomized placebo-controlled trial of pre-treatment and short- or long-term maintenance therapy with amiodarone supporting DC cardioversion for persistent atrial fibrillation. Propafenone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Maintenance of sinus rhythm after electrical cardioversion of persistent atrial fibrillation; sotalol vs bisoprolol. [A comparison between flecainide and sotalol in the prevention of recurrences of paroxysmal atrial fibrillation]. Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study. [Sotalol and quinidine/verapamil (Cordichin) in chronic atrial fibrillation--conversion and 12-month follow-up--a randomized comparison]. Azimilide for the treatment of atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia: results of a randomized trial and insights on the concordance of symptoms and recurrent arrhythmias. Long-term maintenance of normal sinus rhythm in patients with current symptomatic atrial fibrillation: amiodarone vs propafenone, both in low doses. Sotalol versus quinidine for the maintenance of sinus rhythm after direct current conversion of atrial fibrillation. Efficacy of propafenone for maintaining sinus rhythm in patients with recent onset or persistent atrial fibrillation after conversion: a randomized, placebo-controlled study. Antiarrhythmic efficacy of azimilide in patients with atrial fibrillation. Maintenance of sinus rhythm after conversion to sinus rhythm. The efficacy of quinidine and disopyramide in the maintenance of sinus rhythm after electroconversion from atrial fibrillation. A double-blind study comparing quinidine, disopyramide and placebo. Suppression of paroxysmal atrial tachyarrhythmias--results of the SOPAT trial. Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. Maintenance of sinus rhythm with oral d,l-sotalol therapy in patients with symptomatic atrial fibrillation and/or atrial flutter. d,l-Sotalol Atrial Fibrillation/Flutter Study Group. Azimilide vs. placebo and sotalol for persistent atrial fibrillation: the A-COMET-II (Azimilide-CardiOversion MaintEnance Trial-II) trial. Sotalol versus propafenone for long-term maintenance of normal sinus rhythm in patients with recurrent symptomatic atrial fibrillation. Treatment of atrial fibrillation and paroxysmal supraventricular tachycardia with bidisomide. The Atrial Fibrillation Investigation with Bidisomide (AFIB) Investigators. Dronedarone for prevention of atrial fibrillation: a dose-ranging study. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study. [Therapy of paroxysmal atrial fibrillation. Cardiac glycosides alone or combined with anti-arrhythmia agents?]. [Effects of amiodarone versus sotalol in treatment of atrial fibrillation: a random controlled clinical study]. Efficacy and proarrhythmic hazards of pharmacologic cardioversion of atrial fibrillation: prospective comparison of sotalol versus quinidine. A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study. Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: a randomized, double-blind, placebo-controlled study. Prospective comparison of flecainide versus quinidine for the treatment of paroxysmal atrial fibrillation/flutter. The Flecainide Multicenter Atrial Fibrillation Study Group. Amiodarone versus quinidine in the prophylaxis of atrial fibrillation. Disopyramide in the maintenance of sinus rhythm after electroconversion of atrial fibrillation. A placebo-controlled one-year follow-up study. Prevention of atrial fibrillation after cardioversion: results of the PAFAC trial. Effect of quinidine on maintaining sinus rhythm after conversion of atrial fibrillation or flutter. A multicentre study from Stockholm. Pilsicainide for conversion and maintenance of sinus rhythm in chronic atrial fibrillation: a placebo-controlled, multicenter study. [Propafenone versus hydroquinidine in long-term pharmacological prophylaxis of atrial fibrillation]. Propafenone for conversion and prophylaxis of atrial fibrillation. Propafenone Atrial Fibrillation Trial Investigators. Efficacy and safety of sotalol versus quinidine for the maintenance of sinus rhythm after conversion of atrial fibrillation. SOCESP Investigators. The Cardiology Society of São Paulo. Amiodarone versus sotalol for atrial fibrillation. Efficacy and safety of flecainide acetate in the maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation or atrial flutter. Safety of long-term flecainide and propafenone in the management of patients with symptomatic paroxysmal atrial fibrillation: report from the Flecainide and Propafenone Italian Study Investigators. Quinidine in maintenance of sinus rhythm after electroconversion of chronic atrial fibrillation. A controlled clinical study. Efficacy and safety of sustained-release propafenone (propafenone SR) for patients with atrial fibrillation. Efficacy of azimilide for the maintenance of sinus rhythm in patients with paroxysmal atrial fibrillation in the presence and absence of structural heart disease. Maintenance of sinus rhythm with metoprolol CR initiated before cardioversion and repeated cardioversion of atrial fibrillation: a randomized double-blind placebo-controlled study. [A comparison between amiodarone and disopyramide in a delayed-release formulation in the prevention of recurrences of symptomatic atrial fibrillation]. Efficacy and safety of sotalol in digitalized patients with chronic atrial fibrillation. The Sotalol Study Group. Double-blind placebo-controlled trial of aprindine and digoxin for the prevention of symptomatic atrial fibrillation. Maintenance of sinus rhythm after DC reversion of atrial fibrilllation. A double-blind controlled trial of long-acting quinidine bisulphate. Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in patients with reduced left ventricular function: a Danish investigations of arrhythmia and mortality on dofetilide (diamond) substudy. Efficacy of amiodarone for the termination of chronic atrial fibrillation and maintenance of normal sinus rhythm: a prospective, multicenter, randomized, controlled, double blind trial. Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation.
Asymptomatic, or "silent" atrial fibrillation could increase the risk of stroke. Little is known about the frequency of asymptomatic atrial fibrillation in patients who also have symptomatic atrial fibrillation; similarly, little is known about the effect of antiarrhythmic drug therapy on asymptomatic atrial fibrillation.
                Patients in sinus rhythm with a history of symptomatic atrial fibrillation or atrial flutter received placebo or azimilide (35 to 125 mg) once daily for 6 or 9 months in 4 similar double-blind trials. The end point was the first recurrence of a symptomatic ECG-documented supraventricular arrhythmia. Routine transtelephonic electrocardiograms, in the absence of symptoms, were recorded for 30 seconds every 2 weeks until patients completed follow-up or documented a symptomatic supraventricular arrhythmia. Of the 1380 patients, 489 received placebo. Among these patients receiving placebo, 303 transmitted at least one routine ECG while asymptomatic. Asymptomatic atrial fibrillation was recorded in 50 (17%) within 6 months and before recurrence of symptomatic supraventricular arrhythmia. In the 3 trials evaluating azimilide in therapeutic doses (100 and 125 mg), asymptomatic atrial fibrillation occurred in 49 of 382 (13%) receiving azimilide and 43 of 233 (18%) receiving placebo. Although drug effect on time to first asymptomatic event was not statistically significant (hazard ratio, 0.70; P=0.09), there was a 40% reduction in asymptomatic atrial fibrillation on azimilide compared with placebo (P=0.03) when repeated observations were considered.
                Asymptomatic atrial fibrillation is common in untreated patients with a history of symptomatic atrial fibrillation (and is likely underestimated by this analysis). Azimilide may reduce the occurrence of this silent arrhythmia. Safety and efficacy of propafenone and disopyramide for long-term maintenance of sinus rhythm after electrical cardioversion was studied in 56 patients with chronic atrial fibrillation (median arrhythmia duration, 5 months). After cardioversion, patients were randomly assigned to receive double-blind propafenone 300 mg tid (25 patients) or disopyramide 250 mg tid (31 patients). Downward dose adjustment was allowed in case of intolerable side effects. The endpoints were arrhythmia recurrence; and side effects not amenable to dose reduction. For patients randomized to propafenone (mean dose, 878 +/- 65 mg/day), 66% [95% confidence interval [(CI) 46-85%] and 55% (95% CI, 34-76%) remained in sinus rhythm at 3 and 6 months, respectively (Kaplan-Meier method). Similar figures were found with disopyramide (mean dose, 704 +/- 81 mg/day): 71% (95% CI, 54-87%) and 67% (95% CI, 50-84%) at 3 and 6 months, respectively (p = NS). In the patients with a relapse of atrial fibrillation, the ventricular rate while still using the prophylactic agents did not increase significantly compared with precardioversion. However, one patient on disopyramide had an excessively high relapse heart rate (170 vs. 100 beats/min). Side effects were more frequent on disopyramide. Side effects necessitating drug discontinuation occurred in 12 patients: 4 patients (16%) on propafenone and 8 (26%) on disopyramide. Severe adverse effects occurred in two patients, who developed heart failure while on disopyramide. There were no proarrhythmic events or deaths. Thus, propafenone and disopyramide are equally effective for maintaining sinus rhythm after cardioversion of atrial fibrillation. Propafenone is, however, better tolerated than disopyramide, which may cause heart failure. To assess the cardiac and extracardiac safety and efficacy of flecainide versus propafenone in patients suffering from episodes of paroxysmal atrial fibrillation (AF) or atrial flutter, 97 patients were enrolled in a randomized, open-label, long-term, parallel, comparative multicenter study. The diagnosis of paroxysmal AF or atrial flutter had to be fully documented prior to inclusion in the study. Of the 97 patients enrolled in the study, 48 patients (25 men, 23 women, mean age 62.4 +/- 12.3 years) received flecainide; 49 patients (26 men, 23 women, mean age 63.6 +/- 12.2 years) received propafenone. The initial dose of flecainide was 50 mg twice daily, and this could be increased in steps of 50 mg twice daily every 4 days to a maximum of 300 mg/day. The initial dose of propafenone was 300 mg twice daily and this could be increased in steps of 300 mg every 4 days to a maximum of 1200 mg/day. At each visit, medical events, vital sign measurements (blood pressure, pulse rate), concomitant medications, adverse experiences, and study drug dosage changes were evaluated. Routine clinical laboratory tests were evaluated at the month 6 visit, and a 24-hr Holter recording was obtained at the month 1 visit. Almost half (45) of the patients were discontinued from the study before completing 1 year of therapy. The probability of successful treatment versus time--i.e., the proportion of patients who remained on therapy over the course of 1 year therapy--was 0.619 for the flecainide group and 0.469 for the propafenone group (p = 0.079; difference not significant). The difference is largely attributed to the higher proportion of patients in the propafenone group (9) than in the flecainide group (2) who experienced side effects important enough to stop the treatment. (The incidence of side effects was not statistically different between treatment groups, although it was higher in the propafenone group.) The proportion of patients who discontinued treatment due to inadequate response was similar in the 2 groups: 11 patients (22.9%) in the flecainide group and 12 patients (24.4%) in the propafenone group withdrew from the study, primarily because of an inadequate response, i.e., they experienced an increase in duration, frequency, and severity of attacks of AF or atrial flutter. Neurologic signs, central and peripheral, were mostly encountered in the flecainide group (8.5%), and, gastrointestinal effects were more often reported in the propafenone group (16.7%). In paroxysmal AF and paroxysmal atrial flutter, flecainide and propafenone are equally effective. However, in this study the probability of a patient's staying on flecainide after 1 year had a tendency to be higher than the probability of staying on propafenone, due to a greater proportion of secondary effects with propafenone. The efficacy of cardioversion (DCCV) for restoration of sinus rhythm (SR) in persistent atrial fibrillation (AF) is limited by a high relapse rate. Relapse may be reduced by amiodarone but no placebo-controlled trials of efficacy have been performed and the appropriate duration of therapy is unknown.
                In this double-blind study, 161 subjects with persistent AF were randomized to one of three groups-placebo (n=38); amiodarone 400mg BD for 2 weeks prior to DCCV and 200mg daily for 8 weeks followed by placebo for 44 weeks (n=62, short-term amiodarone); amiodarone 400mg BD for 2 weeks then 200mg daily for 52 weeks (n=61, long-term amiodarone). Spontaneous reversion to SR occurred before DCCV in 21% (26/123) patients on amiodarone and none of the 38 patients on placebo (absolute difference 21%, 95% confidence interval (CI): 10 to 29%, P=0.002). At 8 weeks following DCCV, 51% (63/123) patients on amiodarone remained in SR compared to 16% (6/38) taking placebo (difference-35% 95% CI: -48 to -18%, P<0.001). At 1 year, 49% (30/61) patients on long-term amiodarone were in SR compared to 33% (21/62) taking short-term amiodarone (difference-15%, 95% CI: -31 to 2%, P=0.085). There was no difference in adverse event rate or quality of life scores between groups.
                Amiodarone pre-treatment before electrical DCCV for persistent AF allows chemical conversion in one-fifth of patients without altering the efficacy of subsequent DC conversion. Amiodarone is more effective than placebo in the maintenance of SR when continued for 8 weeks following successful DCCV. More patients taking long-term amiodarone remained in SR at 52 weeks, but more had serious adverse effects requiring discontinuation of therapy. Eight weeks of adjuvant therapy with amiodarone following successful DCCV may be the preferred option. Because conventional antiarrhythmic therapy is often ineffective in maintaining sinus rhythm or is associated with adverse side effects in patients with atrial fibrillation (AF), there is a clinical need to test newer agents. One hundred patients with AF who had unsuccessful therapy with 1.9 +/- 1.0 type IA antiarrhythmic agents were randomized to receive either propafenone (n = 50) or sotalol (n = 50). Patients were stratified into 4 groups based on AF pattern (chronic vs paroxysmal) and left atrial size (large [> or = 4.5 cm] vs small [< 4.5]). The proportion of patients remaining in sinus rhythm on each agent was calculated for each group by the Kaplan-Meier method. For patients randomized to propafenone, 46 +/- 8%, 41 +/- 8% and 30 +/- 8% remained in sinus rhythm at 3, 6 and 12 months, respectively, after cardioversion. A similar proportion of patients treated with sotalol remained in sinus rhythm at follow-up (49 +/- 7%, 46 +/- 8% and 37 +/- 8% at 3, 6 and 12 months, respectively; p = NS). The proportion of patients remaining in sinus rhythm on propafenone and sotalol was not dependent on arrhythmia pattern or left atrial dimension. Except for constipation that occurred more frequently in patients treated with propafenone, adverse side effects were equally distributed between the 2 therapies. Two patients receiving sotalol died during follow-up. Propafenone and sotalol, 2 new antiarrhythmic agents, were found to be equally effective in maintaining sinus rhythm in 100 patients with recurrent AF. Response rates were not affected by arrhythmia pattern, left atrial size or unsuccessful prior drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS) The purpose of the study was to compare the efficacy and safety of sotalol and bisoprolol in the maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation.
                Patients (n=128) were randomized to sotalol (80 mg b.i.d.) or bisoprolol (5 mg x day(-1)). Patients with contraindications to beta-blockers, class III antiarrhythmic drugs or prior treatment with use of study medication for prevention of atrial fibrillation were excluded. Follow-up clinical evaluation was performed 1 day and 1 month after cardioversion and thereafter at 3-month intervals.
                There were no group differences in baseline clinical characteristics. After a follow-up of 12 months, 59% of all patients were still in sinus rhythm. The fraction remaining in sinus rhythm was calculated for the two groups by Kaplan--Meier analysis. During follow-up, 41% of patients on sotalol and 42% on bisoprolol developed atrial fibrillation (ns). In two patients (3.1%) on sotalol, life-threatening proarrhythmias (torsade de pointes tachycardias) occurred, whereas none were found in the bisoprolol group. Symptomatic bradycardias occurred in two patients on sotalol and three on bisoprolol.
                This study demonstrates that sotalol (160 mg x day(-1)) and bisoprolol (5 mg x day(-1)) are equally effective in maintaining sinus rhythm. Because of the side effects of sotalol, bisoprolol seems to be advantageous for maintenance of sinus rhythm after cardioversion of atrial fibrillation.
                Copyright 2001 The European Society of Cardiology. Aim of the present study was to assess the efficacy and safety of flecainide (F) and sotalol (S) for the prevention of recurrences of paroxysmal atrial fibrillation (PAF).
                Sixty-six patients with PAF (> or = 3 episodes of atrial fibrillation in the last year) in sinus rhythm, were randomized to pharmacological oral treatment with F (20 patients-Group A), with S (20 patients-Group B) and placebo (P) (26 patients-Group C). During the follow-up (one year duration) were evaluated on I, III, VI and XII months the number and tolerance of the atrial fibrillation recurrences, cardiac and/or noncardiac side effects. The patients with more than two recurrences in the same follow-up interval withdrew from the study. In each patient 14 clinical and laboratory variables were evaluated.
                After 12 months were arrhythmia-free respectively 70% of Group A patients, 60% of Group B patients, 27% of Group C patients. Univariate analysis showed that treatment with F was related to decrease of atrial fibrillation recurrences (one recurrence 67%, two recurrences 81%, three recurrences 81%), treatment with S was related to decrease of recurrences (two recurrences 59%); the variable most significantly related to the risk of arrhythmia recurrence is the higher value of basal cardiac rate (one recurrence t = 2.15, two t = 2.22, three t = 2.96, four t = 2.06). There was not statistically significant difference in maintenance of sinus rhythm at the end of the follow-up between the groups of patients on F and S (p = 0.163); treatment efficacy was significantly higher than P (p = 0.002). Multivariate analysis showed that treatment with F and S decreases the risk of arrhythmia recurrence respectively of 85% and 76% versus placebo at the end of the follow-up. The incidence of cardiac and/or noncardiac side effects was not clinically significant.
                F and S are both effective and safe for prevention of PAF, with 70% and 60% respectively of patients arrhythmia-free after 12 months of treatment. Side effects were common, but clinically significant adverse events were uncommon. A higher value of basal cardiac rate was predictive of atrial fibrillation recurrences in the patients during treatment. To assess and compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation.
                Prospective, randomised, single blind, placebo controlled study.
                Tertiary cardiac referral centre.
                186 consecutive patients (97 men, 89 women; mean (SD) age, 63 (10) years) with recurrent, symptomatic atrial fibrillation.
                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.
                Recurrence of atrial fibrillation or side effects.
                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 effects 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 effects 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).
                Both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation. Amiodarone is more effective but causes more side effects. Atrial fibrillation is one of the most common arrhythmias, leading at least in a subset of patients to severe symptoms (palpitations, weakness, syncope), and to hemodynamic impairment especially in the clinical setting of left ventricular dysfunction. Thus, in many cases restauration of sinus rhythm is indicated because of the negative effects of reduced cardiac output. Quinidine has been the first line drug for many years and has been proven to be highly effective especially when combined with Verapamil. But there is growing concern about using quinidine and other class I-anti-arrhythmic agents because of some hints in clinical trials for increased longterm mortality on these drugs. This study was undertaken to test the efficacy of Sotalol, a beta-blocker with additional strong class-III antiarrhythmic action, compared to a fixed combination of Quinidine and Verapamil for conversion of chronic atrial fibrillation and maintenance of sinus rhythm after medical or electrical cardioversion. To avoid early proarrhythmic effects, potassium values in the range of "high"-normal values (> 4.3 mval/L) were tried to be obtained. 82 patients were randomly assigned to receive either Sotalol or Quinidine/Verapamil. There was no difference between the groups as far as the underlying heart disease, duration of atrial fibrillation (mean 219 days) and other clinical features including echocardiographic parameters were concerned. The dose of the drug was weight-related individually adjusted, and the drug was continued thereafter. If sinus rhythm could not be established at that time, electric cardioversion was performed and the drug was continued in lower dosage thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) Azimilide hydrochloride is an investigational antiarrhythmic medication that had shown evidence of efficacy in prolonging the time to recurrence of atrial fibrillation (AF) or atrial flutter (AFL) and paroxysmal supraventricular tachycardia (PSVT). This study was designed to confirm efficacy of 125 mg daily azimilide.
                The primary endpoint was ECG-documented recurrence of AF, AFL, or PSVT, followed for a maximum of 180 days. Four hundred eighty-two patients were enrolled in the United States and Canada (422 with AF or AFL and 60 with PSVT). The primary efficacy analysis included 402 patients with AF-AFL and 56 patients with PSVT. There was no significant difference in the time to first recurrence of symptomatic supraventricular arrhythmia in the AF-AFL stratum (median of 38 days for azimilide versus 27 days for placebo; hazard ratio [HR] of 1.14, P = 0.29). Similarly, there was no difference in time to recurrence in the PSVT stratum (>180 days for azimilide versus 135 days for placebo; HR = 1.28, P = 0.55). There were three deaths in the azimilide group and one in the placebo group. Four patients had nonsustained ventricular tachycardia (one torsades de pointes), all in the azimilide group. Asymptomatic recurrence was frequent in the AF-AFL group (8% with azimilide and 11% with placebo), but was absent in the PSVT group. False recurrence was common in both groups.
                Azimilide 125 mg daily was not associated with significant prolongation of the time to recurrent symptomatic supraventricular arrhythmias. There was substantial discordance between symptoms and recurrence. To compare the efficacy and safety of amiodarone and propafenone when used for the prevention of atrial fibrillation (AF) and maintenance of normal sinus rhythm in patients with refractory AF.
                Prospective, randomized, single-blind trial.
                Tertiary cardiac referral center.
                One hundred forty-six consecutive patients (72 men; mean age, 63 +/- 10 years [+/- SD]) with recurrent symptomatic AF.
                We studied 146 patients after restoration of sinus rhythm; patients were randomized to amiodarone, 200 mg/d, or propafenone, 450 mg/d. Follow-up clinical evaluations were conducted at the first, second, fourth, and sixth months, and at 3-month intervals thereafter. The proportion of patients relapsing to AF and/or experiencing side effects was calculated for each group using the Kaplan-Meier method. End point of the study was recurrence of AF or occurrence of side effects necessitating discontinuation of medication. Measurements and results: Of 146 patients, 72 received amiodarone and 74 received propafenone. The two groups were clinically similar. Of the 72 patients receiving amiodarone, AF developed in 25 patients, after an average of 9.8 months, compared to 33 of the 74 patients receiving propafenone after an average of 3.8 months. Twelve patients receiving amiodarone and 2 patients receiving propafenone had side effects necessitating withdrawal of medication while still in sinus rhythm.
                Amiodarone tends to be more effective than propafenone in maintaining sinus rhythm in patients with AF, but this advantage is offset by a higher incidence of side effects. This open, parallel-group study compares quinidine and sotalol treatment for maintenance of sinus rhythm after direct current conversion of patients with chronic atrial fibrillation. The patients from 15 centers in Sweden were randomized to sotalol (98 patients) or quinidine (85 patients) after 2 hours of sinus rhythm after direct current conversion. According to primary efficacy assessment, 52% of the patients in the sotalol group and 48% of the patients in the quinidine group remained in sinus rhythm during the following 6-month treatment period (NS). Furthermore, 34% of the patients treated with sotalol and 22% of the patients treated with quinidine relapsed into atrial fibrillation (NS). Heart rate after relapsing into atrial fibrillation was higher in the patients treated with quinidine (109 beats/min) than in the patients treated with sotalol (78 beats/min, p less than 0.001). Patients treated with sotalol were found to be less symptomatic at the time of relapse compared with relapsing patients in the quinidine group. In terms of safety, more patients were withdrawn from quinidine than from sotalol treatment (26% vs. 11%, p less than 0.05), and sotalol was generally better tolerated than quinidine. Twenty-eight percent of the patients treated with sotalol and 50% of the patients treated with quinidine reported side effects (p less than 0.01). The difference was primarily a result of early (within the first month of treatment) gastrointestinal and skin side effects in the group of patients treated with quinidine.(ABSTRACT TRUNCATED AT 250 WORDS) The aim of this study was to investigate the efficacy and safety of propafenone in the prevention of atrial fibrillation (AF) relapse after restoration of sinus rhythm.
                This study consisted of 110 consecutive patients with recent onset and persistent AF. After restoration of sinus rhythm, patients were randomized to propafenone (n: 58, age: 60 +/- 12 years) or placebo (n: 52, age: 62 +/- 10 years).There were 11 withdrawals (7 in the propafenone and 4 in the placebo group) during follow-up. Follow-up evalutations were conducted at the first, 3rd and then at an interval of three months during 15 months. The clinical characteristics in both groups were comparable. The AF relapse was analysed by the Kaplan-Meier method.
                At 15-month follow-up, AF relapsed in 20 (39%) and 31 (65%) patients in the propafenone and placebo groups, respectively (p = 0.015). In subgroup analysis, AF recurrence was significantly lower in the propafenone group than in the placebo group only in the recent onset AF patients with spontaneous conversion (21% vs. 61%, p = 0.01). However, the AF relapse rates were similar in patients with persistent AF and with recent AF who converted to sinus rhythm pharmacologically or electrically in the propafenone and placebo groups. Four patients on propafenone and one on placebo had adverse effects necessitating discontinuation of the drug (p = 0.36).
                At 15 months, propafenone seems to be superior to placebo for maintaining sinus rhythm in patients with recent onset or peristent AF. This superiority originates mainly from patients with recent onset AF in whom sinus rhythm occurred spontaneously. Its adverse effects are similar to placebo. Azimilide dihydrochloride (azimilide) is an investigational antiarrhythmic drug that has been tested in patients with a variety of arrhythmias. In patients with atrial fibrillation, it has shown excellent efficacy in some previous trials and minimal efficacy in others.
                Patients who had symptomatic atrial fibrillation for > 48 hours but < 6 months were eligible for this multicenter, randomized, placebo-controlled clinical trial. Patients were admitted to a hospital and randomly assigned to receive either azimilide 125 mg or a matched placebo twice daily for 3 days and then once daily. Patients who were in sinus rhythm spontaneously or had sinus rhythm restored by electric cardioversion on day 4 were discharged from the hospital. Recurrence of atrial fibrillation was documented by electrocardiogram. In the primary efficacy analysis, time to recurrence in the 2 treatment groups was compared with the log-rank test in the subgroup of patients with structural heart disease. Safety was assessed as deaths, adverse events, and serious adverse events.
                A total of 446 patients were randomized in the study; 314 were in the subgroup with structural heart disease. The median time to arrhythmia recurrence in both treatment groups with structural heart disease was 13 days, and the difference between treatments was not significant (P = .4596, n = 314). The relative risk for recurrence (placebo:azimilide) was 1.104 (95% CI 0.849-1.436). There was 1 death in the placebo group and 3 in the azimilide group.
                Azimilide did not demonstrate clinically important or statistically significant efficacy in reducing the risk for arrhythmia recurrence in patients with structural heart disease who were in atrial fibrillation and converted to sinus rhythm. In order to compare the relative efficacy of quinidine, disopyramide and a placebo in the maintenance of sinus rhythm after cardioversion from atrial fibrillation and in order to examine the incidence of side-effects, 82 patients with continuous atrial fibrillation (duration more than 1 month but less than 3 years) were randomized in a double-blind fashion to receive quinidine, disopyramide or placebo. Six months after cardioversion there was no significant difference between any of the three groups as regards the number of patients remaining in sinus rhythm. The greater distortion of the atrial architecture which occurs in patients with rheumatic mitral valve disease may explain the failure of these anti-arrhythmic agents to prolong the duration of sinus rhythm in this study, in which patients with valvular heart disease comprised 76% of the total group. The indication to treat paroxysmal atrial fibrillation (PAF) is controversial. The Suppression of Paroxysmal Atrial Tachyarrhythmias (SOPAT) trial was designed to answer the following questions: (1) What is the average rate of spontaneous events of symptomatic PAF with and without anti-arrhythmic medication? (2) what is the prevalence of severe side-effects? and (3) is the fixed combination of Quinidine + Verapamil inferior to the efficacy of sotalol or not?
                Within 60 months 172 centres in Germany, Poland, and The Slovak Republic prospectively enrolled 1033 patients (mean age 60 years, 62% male) with documented frequent episodes of symptomatic PAF. Patients were randomised to either Quinidine + Verapamil 480/240 mg/d (high dose; 263 patients), Quinidine + Verapamil 320/160 mg/d (low dose; 255 patients), Sotalol 320 mg/d (264 patients) or placebo (251 patients), of which 1012 patients entered the intention-to-treat analysis. The primary endpoint was the time to first recurrence of symptomatic PAF or premature discontinuation. Secondary outcome parameters were the total number of symptomatic episodes and tolerability of the tested drugs. Patients were followed for a period of up to 12 months by daily and symptom-triggered trans-telephonic ECG-monitoring (Tele-ECG). The mean time under treatment was 233 +/- 152 days. Regarding the primary endpoint, all active treatments were superior to placebo and not different from each other. A total of 756 patients reached the primary endpoint within 105.7 +/- 8.7 d (mean +/- SEM) in the placebo group, vs. Quinidine + Verapamil (high dose) (150.4 +/- 10 d, p = 0.0061), vs. Quinidine + Verapamil (low dose) (148.9 +/- 10.6 d, p = 0.0006), vs. Sotalol (145.6 +/- 93 d, p = 0.0007). All three treatments were also effective in the reduction of AF burden (days with symptomatic AF [%] mean +/- SD, p vs. placebo): Quinidine + Verapamil (high dose) (3.4 +/- 12, p = 0.0001), Quinidine + Verapamil (low dose) (4.5 +/- 12.3, p = 0.008) and Sotalol (2.9 +/- 6.5, p = 0.026) compared to placebo (6.1 +/- 13.5). A total of four deaths, 13 syncopes, and one ventricular tachycardia (VT) occurred during the active study period, of which one death and one VT were related to Quinidine/Verapamil.
                Taken together, anti-arrhythmic therapy with the fixed combination of Quinidine + Verapamil is as effective as Sotalol in the reduction of the recurrence rate of symptomatic PAF with a low but definite risk of severe side-effects. This study evaluated the efficacy of antiarrhythmic drugs for the treatment of atrial fibrillation (AF).
                The most effective and safest antiarrhythmic drug for the treatment of AF is unknown.
                The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study compared two treatment strategies--rate control and rhythm control--in patients with AF and risk factors for stroke or death. This substudy, performed in patients randomized to rhythm control, compared different antiarrhythmic drugs by randomly assigning the first drug treatment to: 1) amiodarone, 2) sotalol, or 3) a class I drug. The primary end point was the proportion of patients alive, in sinus rhythm, with no additional cardioversions and still taking the assigned drug at one year. Comparisons were made between patients eligible for each of three drug pairs.
                At one year, in 222 patients randomized between amiodarone and class I agents, 62% were successfully treated with amiodarone, compared with 23% taking class I agents (p < 0.001). In 256 patients randomized between amiodarone and sotalol, 60% versus 38% were successfully treated, respectively (p = 0.002). In 183 patients randomized between sotalol and class I agents, 34% versus 23% were successfully treated, respectively (p = 0.488), although this portion of the substudy was stopped early when amiodarone was shown to be better than class I agents. Sinus rhythm was achieved in nearly 80% of patients at one-year follow-up with serial therapy. Adverse effects were common.
                Amiodarone was more effective at one year than either sotalol or class I agents for the strategy of maintenance of sinus rhythm without cardioversion. Currently d,l-sotalol is widely used to prevent recurrence of atrial fibrillation and/or atrial flutter, although a randomized dose-response study has not previously been conducted to guide therapy for this indication. This study summarizes findings of a double-blind, placebo-controlled, multicenter, randomized trial evaluating the efficacy, safety, and dose-response relation of 3 fixed doses of d,l-sotalol (80, 120, and 160 mg twice daily) for the maintenance of sinus rhythm in 253 patients with atrial fibrillation and/or atrial flutter. All patients were in sinus rhythm at randomization. Treatment (69 patients on placebo, 59 on 80 mg, 63 on 120 mg, and 62 on 160 mg given twice daily) was continued for 12 months or until documented recurrence of symptomatic atrial fibrillation and/or flutter. Transtelephonic electrocardiographic monitoring was used to detect symptomatic recurrences. Demographic characteristics were not different in the 4 groups. Structural heart disease was present in 57% of patients. Patients with a history of heart failure were excluded. The time from randomization to symptomatic arrhythmia recurrence was significantly longer in the 2 higher d,l-sotalol dose groups than in the placebo group. The median times to recurrence were 27, 106, 229, and 175 days for the placebo, 80, 120, and 160 mg groups, respectively. There were no deaths or cases of torsade de pointes, sustained ventricular tachycardia, or ventricular fibrillation reported. Thus, d,l-sotalol appeared to be both safe and effective in maintaining sinus rhythm in patients with symptomatic atrial fibrillation and/or flutter. Further, the 120-mg twice daily dose appeared to provide the most favorable benefit and/or risk. Treatment of atrial fibrillation remains a major clinical challenge owing to the limited efficacy and safety of anti-arrhythmic drugs, particularly in patients with structural heart disease.
                To evaluate the efficacy of azimilide, a new class III anti-arrhythmic drug, we studied 658 patients with symptomatic persistent atrial fibrillation, adequate anticoagulant therapy, and planned electrical cardioversion. Patients were randomized to placebo, azimilide (125 mg o.d.), or sotalol (160 mg b.i.d.). Primary efficacy analysis was based on event recurrence, which was defined as atrial fibrillation lasting>24 h, or requiring DC cardioversion. Median time to recurrence was 14 days for azimilide, 12 days for placebo, and 28 days for sotalol (P=0.0320 when comparing azimilide with placebo; P=0.0002 when comparing azimilide with sotalol). The placebo-to-azimilide hazard ratio was 1.291 (95% CI: 1.022-1.629) and the sotalol-to-azimilide hazard ratio was 0.652 (95% CI: 0.523-0.814). Adverse events causing patient withdrawal were more frequent (P<0.01) in patients on azimilide (12.3%) and on sotalol (13.9%) than on placebo (5.4%). Eight patients in the sotalol (3.5%) and 16 in the azimilide (7.6%) group interrupted the study because of QTc prolongation. Torsade de pointes was reported in five patients of the azimilide group. The percentage of patients who completed the 26 week study period without events were 19% for azimilide, 15% for placebo, and 33% for sotalol (P<0.01). Unsuccessful day 4 cardioversion, arrhythmia recurrence, and adverse events were the main causes of withdrawal from the study.
                This study demonstrates that the anti-arrhythmic efficacy of azimilide is slightly superior to placebo but significantly inferior to sotalol in patients with persistent AF. The modest anti-arrhythmic efficacy and high rate of torsade de pointes and marked QTc prolongation limit azimilide utilization for the treatment of AF. This prospective, randomized, single-blinded, placebo-controlled study compared the efficacy and safety of sotalol and propafenone when used for long-term prevention of atrial fibrillation. For the long-term maintenance of normal sinus rhythm, propafenone seems to be more effective than sotalol. Atrial fibrillation and paroxysmal supraventricular tachycardia are common disorders of the heart rhythm for which antiarrhythmic drug therapy is commonly prescribed. The Atrial Fibrillation Investigation with Bidisomide (AFIB) study was a randomized, placebo-controlled clinical trial designed to accomplish three goals in a single protocol: (1) to determine the efficacy of the antiarrhythmic drug bidisomide in the treatment of these two arrhythmias; (2) to establish the appropriate dose range for bidisomide; and (3) to detect an adverse mortality effect of bidisomide if one were present in patients with atrial fibrillation.
                In this clinical trial, 1227 patients with atrial fibrillation and 187 with paroxysmal supraventricular tachycardia were randomly assigned to bidisomide (200, 400, or 600 mg BID) or placebo; patient groups with each arrhythmia were analyzed separately. Symptomatic recurrences of atrial fibrillation and paroxysmal supraventricular tachycardia were documented with the use of transtelephonic ECG monitoring. The time to the first symptomatic arrhythmia recurrence was measured in each patient and compared among treatment groups. Among the atrial fibrillation patients, there was no significant difference in the time to first symptomatic recurrence between the placebo group and any of the three bidisomide treatment groups; the hazard ratios (placebo:treatment) were 1.19, 1.03, and 1.14 for bidisomide 200, 400, and 600 mg BID, respectively. Among paroxysmal supraventricular tachycardia patients, there was a similar lack of a significant treatment effect; the hazard ratios were 1.30, 1.93, and 1.59 for bidisomide 200, 400, and 600 mg BID, respectively. In the primary safety analysis of mortality, 3 of 493 patients taking placebo died, compared with 9 of 488 patients taking one of the two higher doses of bidisomide (P>.10).
                Bidisomide in the doses tested did not have a clinically important antiarrhythmic effect. The AFIB study provided a novel clinical trial design to test antiarrhythmic drugs for both safety and efficacy. Dronedarone, a benzofurane derivative without iodine substituents, shares the electrophysiologic properties of amiodarone. This study was designed to determine the most appropriate dose of dronedarone for prevention of atrial fibrillation (AF) after cardioversion.
                Patients with persistent AF were randomly allocated to 800, 1200, 1600 mg daily doses of dronedarone or placebo. The main analysis was conducted on 199/270 patients, who entered the maintenance phase following pharmacological cardioversion or, if unsuccessful, DC cardioversion. Within 6-month follow-up, the time to AF relapse increased on dronedarone 800 mg, with a median of 60 days vs 5.3 days in the placebo group (relative risk reduction 55% [95% CI, 28 to 72%] P=0.001). No significant effect was seen at higher doses. Spontaneous conversion to sinus rhythm on dronedarone occurred in 5.8 to 14.8% of patients (P=0.026). There were no proarrhythmic reactions. Drug-induced QT prolongation was only noticed in the 1600 mg group. Premature drug discontinuations affected 22.6% of subjects given 1600 mg dronedarone versus 3.9% on 800 mg and were mainly due to gastrointestinal side effects. No evidence of thyroid, ocular or pulmonary toxicity was found.
                Dronedarone, at a 800 mg daily dose, appears to be effective and safe for the prevention of AF relapses after cardioversion. The absence of thyroid side effects and of proarrhythmia are important features of the drug. Further studies are needed to better delineate the antiarrhythmic profile of the drug. This double-blind, multicenter, placebo-controlled study determined the efficacy and safety of dofetilide in converting atrial fibrillation (AF) or atrial flutter (AFl) to sinus rhythm (SR) and maintaining SR for 1 year.
                Patients with AF or AFl (n=325) were randomized to 125, 250, or 500 microgram dofetilide or placebo twice daily. Dosages were adjusted for QTc response and, after 105 patients were enrolled, for calculated creatinine clearance (Cl(Cr)). Pharmacological cardioversion rates for 125, 250, and 500 microgram dofetilide were 6.1%, 9.8%, and 29.9%, respectively, versus 1.2% for placebo (250 and 500 microgram versus placebo; P=0.015 and P<0.001, respectively). Seventy percent of pharmacological cardioversions with dofetilide were achieved in 24 hours and 91% in 36 hours. For the 250 patients who successfully cardioverted pharmacologically or electrically, the probability of remaining in SR at 1 year was 0.40, 0.37, 0.58 for 125, 250, and 500 microgram dofetilide, respectively, and 0.25 for placebo (500 microgram versus placebo, P=0.001). Two cases of torsade de pointes occurred, 1 on day 2 and the other on day 3 (0.8% of all patients given active drug); 1 sudden cardiac death, classified as proarrhythmic, occurred on day 8 (0.4% of all patients given active drug).
                Dofetilide, a new class III antiarrhythmic agent, is moderately effective in cardioverting AF or AFl to SR and significantly effective in maintaining SR for 1 year. In-hospital initiation and dosage adjustment based on QTc and Cl(Cr) are necessary to minimize a small but nonnegligible proarrhythmic risk. In a prospective study 45 patients with paroxysmal atrial fibrillation were randomly assigned to one of three groups (of 15 patients each): group I received oral digoxin, three times 0.125 mg up to twice 0.25 mg daily; group II oral digoxin twice 0.125 mg and quinidine hydrogen sulphate 750-1000 mg daily; group III oral digoxin three times 0.125 mg and flecainide 200-300 mg daily. During a mean observation period of 11 months digoxin alone was significantly less effective (P less than 0.05) in reducing or suppressing paroxysms of atrial fibrillation than digoxin plus quinidine or flecainide. Flecainide with digoxin was more effective than the drug regimen in groups I and II (P less than 0.05). Two patients each in groups I and III had side effects, eight in group II. The results suggest that, at the chosen dosage, flecainide produces fewer side effects than quinidine. To evaluate the effects and adverse reactions of amiodarone and sotalol in treatment of atrial fibrillation.
                One hundred and two patients with atrial fibrillation, 56 males and 46 females, aged 56 +/- 11, were randomized into 2 equal groups: amiodarone group, taking amiodarone 600 mg/d for 7 days, 400 mg/d for 7 days, 200 mg/d for 7 days, and then 200 mg/d as maintenance dosage if conversion to sinus rhythm occurred; and sotalol group, taking sotalol 40-80 mg/d for one week, 160 mg/d for 2 weeks and then 40-80 mg/d as maintenance dosage if conversion to sinus rhythm occurred. If the cardiac rhythm failed to be converted to sinus rhythm after three week the medication was stopped. All the patients were followed up for 12-24 months and therapeutic effects were evaluated by echocardiography, electrocardiogram and Holter monitor.
                (1) Conversion to sinus rhythm occurred in 40 patients in the amiodarone group with an effective rate of 78.4%, and in 36 patients in the sotalol group with an effective rate of 70.6%. (2) Conversion to sinus rhythm occurred in the first week in 34 patients of the amiodarone group and in 10 patients of the sotalol group. (3) 67.5% of the patients with conversion to sinus rhythm in the amiodarone group and 41.7% of the patients with conversion to sinus rhythm in the sotalol group maintained sinus rhythm in the following 12 months; and 44.4% patients with conversion to sinus rhythm in the amiodarone group and 26.7% of the patients with conversion to sinus rhythm in the following 24 months. (4) 10 patients in the sotalol group taking a maintenance dosage of 80 mg/d showed atrial ventricular block and severe bradycardia during the follow-up of 6-2 months, then the medication was stopped, but there was no severe arrhythmia in amiodarone group. (5) It was difficult to maintain sinus rhythm when atrial fibrillation lasting longer than 12 months was a predictive factor of failure to maintain sinus rhythm.
                There is no significant difference between amiodarone and sotalol in converting atrial fibrillation to sinus rhythm. However, amiodarone is more effective in maintenance of sinus rhythm than sotalol. The adverse reaction of amiodarone on heart is less severe than that of sotalol. This study compared the efficacy and safety of sotalol and quinidine for conversion and prevention of recurrent atrial fibrillation.
                Atrial fibrillation is the most common arrhythmia. Pharmacologic therapy has been advocated for both immediate restoration of sinus rhythm and prevention of recurrent atrial fibrillation. Quinidine is the therapeutic mainstay for both purposes, but its safety has recently been questioned. Although sotalol has been used successfully to maintain sinus rhythm after direct current cardioversion, its efficacy in pharmacologically reverting atrial fibrillation has not been examined.
                Fifty consecutive patients with persistent atrial fibrillation were randomized to receive quinidine or sotalol for up to 7 days to restore sinus rhythm. Patients were followed up for 6 months.
                Quinidine was more effective than sotalol in terminating atrial fibrillation (60% vs. 20%, p = 0.009). When nonresponders to drug therapy underwent subsequent direct current cardioversion, total conversion rates in the quinidine and sotalol groups were comparable (88% vs. 68%, p = 0.17), as was the efficacy of the two drugs in preventing recurrent atrial fibrillation. Side effects necessitating drug discontinuation were more often observed with quinidine. No patient receiving sotalol but four patients receiving quinidine had drug-associated arrhythmia (torsade de pointes in three patients, sustained ventricular tachycardia in one patient). Precordial QT dispersion determined on the surface electrocardiogram (ECG) increased with quinidine (mean +/- SD 34 +/- 9 vs. 44 +/- 16 ms, p = 0.02), indicating enhanced inhomogeneity in ventricular repolarization. There was no change in QT dispersion in patients receiving sotalol (36 +/- 18 vs. 40 +/- 17 ms, p = 0.44).
                Quinidine is more effective than sotalol in terminating atrial fibrillation but is associated with more side effects. The proarrhythmic risk may be related to quinidine's propensity to increase disparity in ventricular repolarization. This risk warrants careful ECG monitoring during the 1st 4 to 7 days of therapy. Because most proarrhythmic effects occurred shortly after restoration of sinus rhythm, observation should continue > or = 2 to 3 days after sinus rhythm is reestablished. We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF).
                Five hundred and four amiodarone-naïve patients were randomized to receive dronedarone 400 mg bid (n = 249) or amiodarone 600 mg qd for 28 days then 200 mg qd (n = 255) for at least 6 months. Primary composite endpoint was recurrence of AF (including unsuccessful electrical cardioversion, no spontaneous conversion and no electrical cardioversion) or premature study discontinuation. Main safety endpoint (MSE) was occurrence of thyroid-, hepatic-, pulmonary-, neurologic-, skin-, eye-, or gastrointestinal-specific events, or premature study drug discontinuation following an adverse event.
                Median treatment duration was 7 months. The primary composite endpoint was 75.1 and 58.8% with dronedarone and amiodarone, respectively, at 12 months (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.28-1.98; P < 0.0001), mainly driven by AF recurrence with dronedarone compared with amiodarone (63.5 vs 42.0%). AF recurrence after successful cardioversion was 36.5 and 24.3% with dronedarone and amiodarone, respectively. Premature drug discontinuation tended to be less frequent with dronedarone (10.4 vs 13.3%). MSE was 39.3 and 44.5% with dronedarone and amiodarone, respectively, at 12 months (HR = 0.80; 95% CI 0.60-1.07; P = 0.129), and mainly driven by fewer thyroid, neurologic, skin, and ocular events in the dronedarone group.
                In this short-term study, dronedarone was less effective than amiodarone in decreasing AF recurrence, but had a better safety profile, specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants. The primary objective of the present study was to assess the efficacy of metoprolol CR/XL to reduce the risk of relapse after cardioversion of persistent atrial fibrillation to sinus rhythm.
                Indirect data from studies with d,l sotalol provide evidence that the beta-blocking effects of the compound are important in maintaining sinus rhythm after cardioversion of atrial fibrillation.
                After successful conversion to sinus rhythm, 394 patients with a history of persistent atrial fibrillation were randomly assigned to treatment with metoprolol CR/XL or placebo. The two treatment groups were similar with respect to all pretreatment characteristics. Patients were seen on an outpatient basis for recording of resting electrocardiogram (ECG) after one week, one, three and six months of follow-up or whenever they felt that they had a relapse into atrial fibrillation or experienced an adverse event.
                In the metoprolol CR/XL group, 96 patients (48.7%) had a relapse into atrial fibrillation compared with 118 patients (59.9%) in the placebo group (p = 0.005). Heart rate in patients after a relapse into atrial fibrillation was significantly lower in the metoprolol group (98 +/- 23 beats/min) than in the placebo group (107 +/- 27 beats/min). The rate of adverse events reported was similar in both groups when the difference in follow-up time was taken into account.
                The results of this double-blind, placebo-controlled study in patients after cardioversion of persistent atrial fibrillation showed that metoprolol CR/XL was effective in preventing relapse into atrial fibrillation or flutter. In order to compare the efficacy and long-term tolerability of flecainide acetate versus quinidine, 239 patients with paroxysmal atrial fibrillation were prospectively treated with flecainide (n = 122) or quinidine (n = 117) in an open-label, randomized trial. All patients were followed for 1 year after initiation of therapy unless their antiarrhythmic drug was discontinued due to an inadequate therapeutic response or intolerable side effects. Although both drugs were equally effective in adequately controlling recurrences of atrial fibrillation (difference, p = 0.282; not significant), fewer flecainide patients had to have their therapy discontinued due to adverse experiences (p = 0.012). Based on both endpoints (efficacy and tolerability), an estimated 70.5% of flecainide versus 55.4% of quinidine patients would remain effectively treated at the end of 1 year on therapy (p < or = 0.007). The findings of this prospective study suggest that in the treatment of paroxysmal atrial fibrillation (1) flecainide and quinidine are equally effective in the acceptable suppression of symptomatic paroxysmal atrial fibrillation; (2) flecainide is better tolerated than quinidine and is less likely to be discontinued due to adverse effects; and (3) given the overall endpoint of efficacy and tolerability, more patients are likely to continue long-term therapy with flecainide than with quinidine. nan In this multicentre study, 90 patients who left hospital in sinus rhythm after electroconversion of atrial fibrillation were randomized to double-blind treatment with either disopyramide (n = 44) or placebo (n = 46). The groups were comparable regarding age and sex distribution, duration of atrial fibrillation, heart volume and NYHA-classification. Life-table analysis was used to estimate the percentage of patients still in sinus rhythm and tolerating treatment at control visits after 1, 3, 6, 9 and 12 months. After 1 month there was already a significant difference (P less than 0.01) between the two groups (disopyramide 70%, placebo 39%), a difference that was still remaining after 12 months (disopyramide 54%, placebo 30%). Twenty-four patients, all relapsing to atrial fibrillation before six months on placebo, were converted to sinus rhythm once again. They were then treated with disopyramide in an open manner and after 12 months 37% were still in sinus rhythm. From the results of this study, disopyramide seems to be a useful drug in maintaining sinus rhythm after electroconversion of atrial fibrillation. In patients with persistent atrial fibrillation (AF), the efficacy and safety of two anti-arrhythmic drugs in preventing the recurrence of AF after successful direct current (DC) cardioversion was prospectively assessed in a multi-centre double-blind, placebo-controlled, randomised trial using daily trans-telephonic monitoring.
                1182 patients with persistent AF were prospectively enrolled, 848 patients were successfully cardioverted and then randomised to either sotalol (383 patients), quinidine plus verapamil (377 patients) or placebo (88 patients). The primary outcome parameter was AF recurrence or death. All patients received an event recorder (Tele-ECG) and had to record and transmit via telephone at least one ECG per day during follow-up. The mean follow-up period was 266 days. A total of 191,103 Tele-ECGs were recorded and transmitted. The primary outcome parameter (AF recurrence of any kind or death) was observed in 572 patients (67%) in whom at least one episode of AF recurrence was documented during follow-up, in 348 patients (41%) AF recurrence was persistent. The recurrence rates after one year for any AF were 83% for placebo, 67% for sotalol and 65% for quinidine plus verapamil, the latter being statistically superior to placebo but not different from sotalol. The recurrence rates for the secondary outcome parameter persistent AF were 77%, 49% and 38%, respectively. Quinidine plus verapamil was significantly superior to placebo and to sotalol. About 95% of all AF recurrences were initially detected in the daily Tele-ECG, about 70% of all AF recurrences occurred completely asymptomatic. Adverse events on sotalol and quinidine plus verapamil were comparable with the exception that all torsade de pointes tachycardias occurred on sotalol.
                Anti-arrhythmic treatment after DC cardioversion of persistent AF significantly decreases the recurrence rates of persistent AF compared to placebo with superiority of quinidine plus verapamil compared to sotalol. Symptoms were not reliable as clinical surrogates to detect episodes of AF. In a controlled study comprising 176 patients, quinidine in the form of Kinidin Durules was found to reduced significantly the recurrence of the atrial fibrillation during a 1-year follow-up period after successful electric shock conversion. After one year, 51 per cent (52/101) of the patients in the quinidine group, and 28 per cent (21/75) in the control group remained in sinus rhythm (P smaller than 0.001). No less than 43 per cent of the patients converted to sinus rhythm during treatment with maintenance doses of quinidine sulphate before intended DC conversion. Gastrointestinal side-effects were not uncommon, and caused interruption of quinidine treatment in some cases. Pilsicainide is a newly synthesized antiarrhythmic agent with class Ic properties. Various antiarrhythmic agents have been used to convert atrial fibrillation (AF) to sinus rhythm or decrease the rate of relapse of AF.
                We randomly assigned 62 patients with chronic AF to oral treatment of either a placebo (10 patients) or 150 mg/day of pilsicainide (52 patients) for 4 weeks before electrical cardioversion. Before oral administration of pilsicainide, 41 patients underwent transesophageal echocardiography to investigate whether there was thrombus formation in the heart chambers. Patients without pharmacologic defibrillation underwent direct current cardioversion to restore sinus rhythm. After successful cardioversion, all patients continued to receive pilsicainide and were monitored for up to 2 years.
                Before cardioversion, 11 patients in the pilsicainide group (21%) reverted to sinus rhythm. No patients in the placebo group reverted to sinus rhythm. Direct current cardioversion was performed in 51 patients; however, 8 patients were not converted to sinus rhythm (5 patients receiving pilsicainide, 3 patients receiving placebo), and 3 patients needed intracardiac cardioversion to convert to sinus rhythm. Asymptomatic bradyarrhythmias were observed in 5 patients in the pilsicainide group. During the follow-up period, 33 patients (71%) in the pilsicainide group remained in sinus rhythm at 1 month; this number decreased to 23 patients (49%) at 3 months, 20 (43%) at 6 months, 16 (34%) at 12 months, 16 (34%) at 18 months, and 16 (34%) at 24 months. All patients receiving placebo continued to receive placebo after the cardioversion, and AF recurred a few days after cardioversion in all cases. No independent discriminant variables were identified in the groups between maintenance and nonmaintenance of sinus rhythm. Although no serious side effects regarding pilsicainide have been documented, one patient died of acute myocardial infarction, most likely not related to pilsicainide administration.
                Pilsicainide is effective in restoring or maintaining sinus rhythm in patients with chronic AF lasting longer than an average duration of 22 months. No major adverse effects were observed. New antiarrhythmic class 1C agents have been proposed in the last few years in an attempt to suppress paroxysmal atrial fibrillation at long-term, as the most commonly used class 1A agents such as quinidine gave highly variable results as regards both side-effects and efficacy. The aim of this randomized prospective study is to evaluate the efficacy and safety of oral propafenone at long term in preventing paroxysmal atrial fibrillation and to compare the results with those obtained using agents such as quinidine. Two hundred patients with recurrent episodes of symptomatic atrial fibrillation were enrolled for this study with entry criteria based upon a history of more than 3 crises in the previous 6 months, with electrocardiographic (standard electrocardiogram or dynamic registration) documentation. According to a randomized selection either propafenone at 300 mg twice daily or hydroquinidine retard 250 mg twice daily were administered to the patients; clinical check-up was carried out every 3 months or if clinical course worsened. The dosages were increased if proved to be inadequate at check-up (i.e. recurrence of atrial fibrillation) up to 300 mg 3 times daily for propafenone and 500 mg twice daily for hydroquinidine. The efficacy at the 3rd month was 71% for propafenone and 60% for hydroquinidine, at the 6th month 60% for propafenone and 56% for hydroquinidine; this trend lowered progressively as the follow-up continued, to 48% for propafenone and 42% for hydroquinidine (NS). More than 70% of the responder patients assumed 600 mg twice for propafenone or 250 twice for hydroquinidine. Propafenone had a percentage of 10% side-effects and hydroquinidine 24% (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) Pharmacologic therapy is widely used for restoration of sinus rhythm and prevention of recurrences of atrial fibrillation. Because concerns have been raised about their potential proarrhythmic effects, therapeutic regimens should be evaluated by placebo-controlled studies to determine their efficacy and safety. One hundred thirty-six patients with persistent atrial fibrillation were randomized to receive propafenone 2 mg/kg over 30 minutes, followed by oral propafenone 150 mg 3 times daily or matching placebo. Nonresponders to intravenous therapy underwent direct-current cardioversion. Both responders to intravenous therapy and converters to sinus rhythm after direct-current cardioversion were followed for 6 months in a double-blind oral treatment period of propafenone 150 mg 3 times daily or matching placebo. Pharmacologic conversion to sinus rhythm was achieved in 29% of the patients taking propafenone and in 17% of patients taking placebo (p > or = 0.10). Subsequent direct-current cardioversion in nonresponders was equally successful (70%) in both groups (p > or = 0.10). The proportion of patients free from recurrent symptomatic arrhythmia at 6 months was 67% for the propafenone and 35% for the placebo group (p < 0.01). Time to atrial fibrillation relapse was more favorable with propafenone than with placebo (p < 0.001). The incidence of drug-related side effects was 10% in the propafenone group and 14% in the placebo group. Thus, "slow" infusion of propafenone seems to be of limited value for terminating atrial fibrillation. Oral propafenone at a low dosage 150 mg 3 times daily is well tolerated and effective in maintaining sinus rhythm for 6 months after pharmacologic or electrical restoration of sinus rhythm. To compare the efficacy and safety of sotalol and quinidine after conversion of atrial fibrillation (AF) of <6 months, a prospective multicenter trial enrolled 121 patients who were randomized to receive dl-sotalol (160 to 320 mg/day, 58 patients) or quinidine sulfate (600 to 800 mg/day, 63 patients). Patients with left ventricular ejection fraction of <0.40 or left atrial diameter >5.2 cm were excluded. After 6 months of follow-up, using the Kaplan-Meier method, the probabilities of success were comparable between sotalol (74%) and quinidine (68%), but recurrences occurred later with sotalol than with quinidine (69 vs 10 days, p <0.05). Four patients developed proarrhythmic events, 3 (5%) with sotalol and 1 (2%) with quinidine, which were all associated with diuretic therapy. In patients converted from recent-onset AF (< or = 72 hours), sotalol was more effective than quinidine (93% vs 64%, p = 0.01), whereas in chronic AF (> 72 hours), quinidine was more effective than sotalol (68% vs 33%, p <0.05). During recurrences, the ventricular rate was significantly reduced in patients taking sotalol (98 to 82 beats/min, p <0.05). Independent predictors of therapeutic success were recent-onset AF in the sotalol group (p <0.001) and absence of hypertension in the quinidine group (p <0.05). In conclusion, sotalol and quinidine have comparable efficacy and safety for the maintenance of sinus rhythm in the overall group. In recent-onset AF, sotalol was more effective, whereas in chronic AF, quinidine had a better result. Recurrences occurred later with sotalol when compared with quinidine. Because of proarrhythmia, these drugs should be used judiciously in patients on diuretic therapy. The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial.
                In this double-blind, placebo-controlled trial, we randomly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and monitored them for 1 to 4.5 years. The primary end point was the time to recurrence of atrial fibrillation beginning on day 28, determined by means of weekly transtelephonic monitoring.
                Spontaneous conversion occurred in 27.1 percent of the amiodarone group, 24.2 percent of the sotalol group, and 0.8 percent of the placebo group, and direct-current cardioversion failed in 27.7 percent, 26.5 percent, and 32.1 percent, respectively. The median times to a recurrence of atrial fibrillation were 487 days in the amiodarone group, 74 days in the sotalol group, and 6 days in the placebo group according to intention to treat and 809, 209, and 13 days, respectively, according to treatment received. Amiodarone was superior to sotalol (P<0.001) and to placebo (P<0.001), and sotalol was superior to placebo (P<0.001). In patients with ischemic heart disease, the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy (P=0.53). Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity. There were no significant differences in major adverse events among the three groups.
                Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is superior for maintaining sinus rhythm, but both drugs have similar efficacy in patients with ischemic heart disease. Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance.
                Copyright 2005 Massachusetts Medical Society. The efficacy and safety of flecainide were studied in the maintenance of sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter. Eighty-one patients were randomized to flecainide treatment or no treatment. Baseline characteristics of both groups were comparable. Compared to previous studies, patients could be classified as difficult-to-treat patients. Multiple regression analysis showed New York Heart Association class I for exercise tolerance (p = 0.0004) and flecainide treatment (p = 0.01) to be the main factors increasing the arrhythmia-free episode. However, Mantel-Cox lifetable analysis did not reveal significant differences between arrhythmia-free survival curves of both treatment groups. In the flecainide-treated group, 9% of patients experienced side effects, mostly related to negative dromotropic effects. The incidence of ventricular proarrhythmia in this group of patients was low. Thus, flecainide may be effective in postponing arrhythmia recurrence, even in difficult-to-treat patients. Caution should be excercised in treating patients with underlying conduction disturbances, sick sinus syndrome or characteristics favoring development of ventricular proarrhythmia. To compare the relative safety of flecainide acetate to propafenone HCl during long-term treatment (12 months), we conducted a randomized, open-label, comparative, parallel, multicenter trial in 200 patients with paroxysmal atrial fibrillation (AF) and no history of heart disease. Initial daily doses were flecainide 200 mg (n = 97) or propafenone 450 mg (n = 103). Dose escalations up to a maximum of flecainide 300 mg/day or propafenone 900 mg/day were permitted after > or = 2 attacks of paroxysmal AF. Patients were assessed for safety and drug tolerance at designated intervals over the 12-month study unless discontinued for adverse experience or inadequate response. Ten patients on flecainide reported 14 cardiac adverse experiences; 4 discontinued the drug. Seven propafenone patients reported 8 cardiac adverse experiences; 5 discontinued the drug. Three proarrhythmic events occurred: 1 propafenone patient developed ventricular tachycardia and 2 flecainide patients experienced AF with a rapid ventricular response. An intention-to-treat analysis showed that the probability of safe and effective treatment after 12 months was 77% for flecainide-treated patients and 75% for the propafenone-treated patients. There was an acceptable risk-benefit profile in patients with paroxysmal AF and no evidence of clinically significant heart disease who were treated with flecainide or propafenone for 12 months. Further, there was no statistically significant difference in safety or efficacy between flecainide and propafenone in this study. nan The objective of this randomized, double-blind, placebo-controlled clinical trial was to test the efficacy and safety of a new sustained-release preparation of the antiarrhythmic drug propafenone (propafenone SR) in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation (AF). Patients with a history of symptomatic AF who were in sinus rhythm were randomly assigned to receive placebo or propafenone SR 425, 325, or 225 mg, all twice daily. Recurrent symptomatic arrhythmias were documented using transtelephone electrocardiographic monitoring. Electrocardiograms were reviewed by an event committee that was blinded to treatment assignment. In the primary efficacy analysis, propafenone SR significantly lengthened the time to first symptomatic atrial arrhythmia recurrence at all 3 doses compared with placebo as assessed by log-rank test: propafenone SR 425 mg twice daily versus placebo twice daily, p <0.001; 325 mg twice daily versus placebo twice daily, p <0.001; and 225 mg twice daily versus placebo twice daily, p = 0.014. The median time to recurrence was 41 days in the placebo twice daily group, >300 days in the propafenone SR 425-mg group, 291 days in the 325-mg group, and 112 days in the 225-mg group. Adverse effects leading to withdrawal were higher in the propafenone SR 425-mg twice daily group than in any other group. Thus, propafenone SR has important and statistically significant antiarrhythmic effects in patients with AF. Azimilide hydrochloride (azimilide), an investigational antiarrhythmic drug, has shown variable efficacy in preventing atrial fibrillation (AF). This study was designed to assess its efficacy in maintaining sinus rhythm in patients with paroxysmal AF and heart disease. Patients with symptomatic paroxysmal AF were screened for 1 month by transtelephonic monitoring. After recording 1 episode of AF in the screening period, they were randomized to receive azimilide 125 mg or placebo once daily. Patients were stratified by the presence or absence of congestive heart failure or coronary heart disease (CHF/CHD). A maximum of 220 patients without CHF/CHD were randomized, with the remainder having CHF/CHD. Patients with CHF/CHD were monitored for 3 days during loading. The primary efficacy analysis was the time to the first symptomatic recurrence of AF in the CHF/CHD group. Secondary analyses were the time to the first recurrence in the entire population and the time to the first recurrence in those with significant structural heart disease. The median time to recurrence of AF in the CHF/CHD group was 10 days in the 2 treatment arms. Nonsignificant trends were seen toward efficacy of azimilide in the CHF/CHD group (hazard ratio 1.28, 95% confidence interval 0.97 to 1.70, p=0.087), structural heart disease group (hazard ratio 1.22, 95% confidence interval 0.96 to 1.56, p=0.11), and overall group (hazard ratio 1.22, 95% confidence interval 1.00 to 1.49, p=0.053). No patient died. In conclusion, azimilide showed a nonsignificant trend toward efficacy in maintaining sinus rhythm in patients with AF. To assess the effect of metoprolol in combination with repeated cardioversion on maintenance of sinus rhythm (SR).
                Consecutive outpatients with persistent atrial fibrillation (AF) were randomized to treatment with metoprolol CR or placebo in a double-blind fashion. Study treatment was started at least one week before direct current (DC) cardioversion. Patients were followed once a week during the first 6 weeks after cardioversion. In case of relapse during this period, a second cardioversion was performed. Total treatment time was 6 months. A total of 168 patients were randomized to metoprolol (n = 83) or placebo (n = 85). The dose of study treatment at cardioversion was 169 +/- 47 mg in the metoprolol group and 180 +/- 40 mg in the placebo group (P = 0.12). In an intention-to-treat analysis, 46 patients (55%) in the metoprolol group and 34 patients (40%) in the placebo group (P = 0.04) had SR 1 week after cardioversion, and 38 patients (46%) in the metoprolol group compared with 22 patients (26%) in the placebo group had SR after 6 months (P < 0.01).
                A treatment strategy of metoprolol CR started before cardioversion in combination with prompt second cardioversion in case of early relapse (1-6 weeks) significantly increases the proportion of patients in SR during six months of follow-up. In order to compare the efficacy in preventing recurrencies of symptomatic atrial fibrillation of amiodarone (A.) and slow release disopyramide (D.RET.), 76 consecutive patients with recent onset atrial fibrillation (1 to 24 hrs.) were enrolled. In 20 (26%) conversion to sinus rhythm was obtained by electrical cardioversion, and in 56 (74%) by oral quinidine loading. Forty-one patients (group A) were assigned at random to treatment with D.RET. (250 mg twice daily) and 35 patients (group B) to amiodarone treatment (1200 mg daily for 10 days, and subsequently 200 mg daily). The two groups were similar as to age, sex and cardiac pathology. Patients were followed as to clinical condition, standard and dynamic ECG after one and three months and every three months subsequently for an average of 13.2 months (group A) and 14.1 months (group B). Six group A patients (14%) were excluded from follow-up on account of side effects which arose during the first week of treatment. Crises of symptomatic atrial fibrillation occurred in 20 patients of group A (57%) and in 11 (32%) group patients; this difference is statistically significant (p less than 0.05). Four (10%) group A patients stopped taking the drug due to side effects of an anticholinergic type, and three (8.5%) patients developed hyperthyroidism during follow-up. The authors therefore come to the conclusion that amiodarone is more effective than slow-release disopyramide in preventing recurrencies of atrial fibrillation; besides untoward side effects are less frequent with amiodarone. nan A multicenter, placebo-controlled, randomized, double-blind trial compared the preventive effect of aprindine and digoxin on the recurrence of atrial fibrillation (AF) with placebo, and also compare the effectiveness of these 2 drugs in the prevention of AF. Patients with symptomatic paroxysmal or persistent AF who had converted to sinus rhythm (SR) were randomly assigned aprindine (40 mg/day), digoxin (0.25 mg/day) or placebo and followed up on an outpatient basis every 2 weeks for 6 months. Of the 141 patients from 36 participating centers, 47 were given aprindine, 47 digoxin, and 47 were on placebo. After the 6-month follow-up, the Kaplan-Meier estimates of the percentage of patients remaining free of recurrent symptomatic AF on aprindine, digoxin and placebo were 33.3%, 29.2% and 21.5%, respectively. In patients remaining in SR for 15 days after from the start of follow-up, freedom from recurrence was significantly more prevalent in the aprindine group than in the placebo group (p=0.0414), but there was no significant difference between the digoxin and placebo groups. The rate of adverse events was similar in the 3 groups. In conclusion, neither aprindine nor digoxin had a significant effect on preventing relapse of symptomatic AF; however, recurrence of AF occurred later with aprindine than with placebo or digoxin. Ninety-two patients were entered in a double-blind controlled trial of long-acting quinidine bisulphate for the maintenance of sinus rhythm following DC reversion of atrial fibrillation. By random selection two statistically comparable groups of patients were obtained, a control group being given a placebo and a treated group quinidine bisulphate 1.5 g. per day in two 12-hourly doses. Thirty-seven patients were followed up in the control group and twenty-eight patients in the treated group. The maintenance of sinus rhythm in the treated group was significantly longer than in the control group, especially during the first three months. The mean serum quinidine level in the treated group was 2.2+/-0.3 (SEM) mg. per litre. There was one death among the patients treated with quinidine, which may have been due to quinidine toxicity caused by a high serum quinidine level. In patients with left ventricular dysfunction, atrial fibrillation and flutter (AF and AFl, respectively) are common arrhythmias associated with increased morbidity and mortality. The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm, which might reduce mortality and hospitalizations.
                In the Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies, 506 patients were in AF-AFl at baseline. Over the course of study, cardioversion occurred in 148 (59%) dofetilide- and 86 (34%) placebo-treated patients. In these patients, the probability of maintaining sinus rhythm for 1 year was 79% with dofetilide versus 42% with placebo (P<0.001). Dofetilide had no effect on all-cause mortality, but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality (risk ratio [RR], 0.44; 95% CI, 0.30 to 0.64; P<0.0001). In addition, dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause (RR, 0.70; 95% CI, 0.56 to 0.89; P</=0.005) or congestive heart failure (RR, 0.69; 95% CI, 0.51 to 0.93; P</=0.02) rehospitalization.
                Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease. The present study suggests that restoration of sinus rhythm is associated with improved survival. We sought to assess the efficacy and safety of amiodarone for restoration and maintenance of sinus rhythm in patients with chronic atrial fibrillation in a prospective, randomized, double blind trial.
                Restoration and preservation of sinus rhythm is difficult in patients with chronic atrial fibrillation. The efficacy of oral amiodarone has not been conclusively established.
                Ninety-five patients with chronic atrial fibrillation, lasting an average of 35.6 months, were randomized to either amiodarone (600 mg/d) (47 patients) or placebo (48 patients) during four weeks. Nonresponders underwent electric cardioversion, and those who reverted continued with amiodarone (200 mg/d) or placebo. End-points were successful cardioversion and sinus rhythm maintenance.
                Sixteen patients (34.04%) in the amiodarone group reverted within 27.28 +/- 8.85 days in comparison with 0% in the placebo group (P < 0.000009). The conversion rate rose to 51.72% in patients with chronic atrial fibrillation lasting less than 12 months. Twenty-eight patients in the amiodarone group and 39 in the placebo group underwent electric cardioversion, which was successful in 19 patients (67.8%) of the amiodarone group and in 15 (38.46%) of the placebo group (P = 0.017). Altogether, conversion was obtained in 79.54% of the amiodarone group patients and in 38.46% of the placebo group patients (P < 0.0001). During follow-up, atrial fibrillation relapsed in 13 (37.14%) of 35 patients of the amiodarone group within 8.84 +/- 8.57 months and in 12 (80%; P = 0.009) of 15 patients of the placebo group within 2.74 +/- 3.41 months.
                Oral amiodarone restored sinus rhythm in one third of patients with chronic atrial fibrillation, increased the success rate of electric cardioversion, decreased the number of relapses and delayed their occurrence. This study was performed to evaluate, using a randomized double-blind, placebo-controlled protocol, the long-term efficacy and safety of propafenone and sotalol in maintaining sinus rhythm after conversion of recurrent symptomatic atrial fibrillation (AF). The maintenance of sinus rhythm in patients with recurrent AF has several potential benefits, the most important being a reduced risk of thromboembolic events. Three hundred patients with recurrent AF (> or = 4 episodes in the last year) and AF at enrollment lasting < 48 hours were randomized to receive either propafenone (mean daily dose 13 +/- 1.5 mg/kg; 102 patients), sotalol (mean daily dose 3 +/- 0.4 mg/kg; 106 patients), or placebo (92 patients). After 1-year follow-up, Kaplan-Meier estimates of the proportion of patients remaining in sinus rhythm were comparable between propafenone (63%) and sotalol (73%) and superior to placebo (35%; p = 0.001 vs both drugs). Symptomatic recurrences occurred later with propafenone and sotalol than with placebo. Nine patients (9%) in the propafenone group, 11 (10%) in the sotalol group, and 3 (3%) in the placebo group discontinued therapy due to adverse effects. Malignant nonfatal arrhythmias due to proarrhythmic effects were documented with sotalol only, and occurred < 72 hours from the beginning of therapy in 4 patients (4%). During recurrences, the ventricular rate was significantly reduced in patients taking propafenone and sotalol (p = 0.001 for both drugs vs placebo). The likelihood of remaining in sinus rhythm during follow-up was higher in younger patients with smaller left atrial size and without concomitant heart disease. In patients with recurrent symptomatic AF, propafenone and sotalol are not significantly different from each other and are superior to placebo in maintaining sinus rhythm at 1 year. Recurrences occur later and tend to be less symptomatic with propafenone and sotalol compared with placebo.
Several class IA, IC and III drugs, as well as class II (beta-blockers), are moderately effective in maintaining sinus rhythm after conversion of atrial fibrillation. However, they increase adverse events, including pro-arrhythmia, and some of them (disopyramide, quinidine and sotalol) may increase mortality. Possible benefits on clinically relevant outcomes (stroke, embolisms, heart failure) remain to be established.