title: 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 Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. Prospective comparison of flecainide versus quinidine for the treatment of paroxysmal atrial fibrillation/flutter. The Flecainide Multicenter Atrial Fibrillation Study Group. Long-term maintenance of normal sinus rhythm in patients with current symptomatic atrial fibrillation: amiodarone vs propafenone, both in low doses. Outpatient treatment of recent-onset atrial fibrillation with the "pill-in-the-pocket" approach. Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study. Sotalol versus propafenone for long-term maintenance of normal sinus rhythm in patients with recurrent symptomatic atrial fibrillation. Efficacy and safety of sustained-release propafenone (propafenone SR) for patients with atrial fibrillation. Effect of quinidine on maintaining sinus rhythm after conversion of atrial fibrillation or flutter. A multicentre study from Stockholm. [Sotalol and quinidine/verapamil (Cordichin) in chronic atrial fibrillation--conversion and 12-month follow-up--a randomized comparison]. Maintenance of sinus rhythm after electrical cardioversion of persistent atrial fibrillation; sotalol vs bisoprolol. Prevention of atrial fibrillation after cardioversion: results of the PAFAC trial. Quinidine in maintenance of sinus rhythm after electroconversion of chronic atrial fibrillation. A controlled clinical study. 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 Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. Dronedarone for prevention of atrial fibrillation: a dose-ranging study. Double-blind placebo-controlled trial of aprindine and digoxin for the prevention of symptomatic atrial fibrillation. Asymptomatic or "silent" atrial fibrillation: frequency in untreated patients and patients receiving azimilide. [A comparison between amiodarone and disopyramide in a delayed-release formulation in the prevention of recurrences of symptomatic atrial fibrillation]. A randomized placebo-controlled trial of pre-treatment and short- or long-term maintenance therapy with amiodarone supporting DC cardioversion for persistent atrial fibrillation. 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. [Propafenone versus hydroquinidine in long-term pharmacological prophylaxis of atrial fibrillation]. Pilsicainide for conversion and maintenance of sinus rhythm in chronic atrial fibrillation: a placebo-controlled, multicenter study. Efficacy of propafenone for maintaining sinus rhythm in patients with recent onset or persistent atrial fibrillation after conversion: a randomized, placebo-controlled study Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: a randomized, double-blind, placebo-controlled study. [Therapy of paroxysmal atrial fibrillation. Cardiac glycosides alone or combined with anti-arrhythmia agents?]. Propafenone versus disopyramide for maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation: A randomized, double-blind study [A comparison between flecainide and sotalol in the prevention of recurrences of paroxysmal atrial fibrillation]. Treatment of atrial fibrillation and paroxysmal supraventricular tachycardia with bidisomide. The Atrial Fibrillation Investigation with Bidisomide (AFIB) Investigators. Suppression of paroxysmal atrial tachyarrhythmias--results of the SOPAT trial. 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. Disopyramide in the maintenance of sinus rhythm after electroconversion of atrial fibrillation. A placebo-controlled one-year follow-up study. 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. Efficacy and safety of flecainide acetate in the maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation or atrial flutter. Efficacy and proarrhythmic hazards of pharmacologic cardioversion of atrial fibrillation: prospective comparison of sotalol versus quinidine. Propafenone for conversion and prophylaxis of atrial fibrillation. Propafenone Atrial Fibrillation Trial Investigators. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. Propafenone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation. 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.
abstract: Background 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 . Methods and Results Patients with AF or AFl ( n=325 ) were r and omized to 125 , 250 , or 500 & mgr;g dofetilide or placebo twice daily . Dosages were adjusted for QTc response and , after 105 patients were enrolled , for calculated creatinine clearance ( ClCr ) . Pharmacological cardioversion rates for 125 , 250 , and 500 & mgr;g dofetilide were 6.1 % , 9.8 % , and 29.9 % , respectively , versus 1.2 % for placebo ( 250 and 500 & mgr;g 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 & mgr;g dofetilide , respectively , and 0.25 for placebo ( 500 & mgr;g 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 ) . Conclusions 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 ClCr are necessary to minimize a small but nonnegligible proarrhythmic risk CONTEXT Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation ( AF ) .  Pulmonary vein isolation ( PVI ) with radiofrequency ablation may cure AF , obviating the need for antiarrhythmic drugs and anticoagulation . OBJECTIVE To determine whether PVI is feasible as first-line therapy for treating patients with symptomatic AF . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve r and omized study conducted from December 31 , 2001 , to July 1 , 2002 , of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs . INTERVENTION Patients were r and omized to receive either PVI using radiofrequency ablation ( n=33 ) or antiarrhythmic drug treatment ( n=37 ) , with a 1-year follow-up . MAIN OUTCOME MEASURES Recurrence of AF , hospitalization , and quality of life assessment . RESULTS Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up . At the end of 1-year follow-up , 22 ( 63 % ) of 35 patients who received antiarrhythmic drugs had at least 1 recurrence of symptomatic AF compared with 4 ( 13 % ) of 32 patients who received PVI ( P<.001 ) . Hospitalization during 1-year follow-up occurred in 19 ( 54 % ) of 35 patients in the antiarrhythmic drug group compared with 3 ( 9 % ) of 32 in the PVI group ( P<.001 ) . In the antiarrhythmic drug group , the mean ( SD ) number of AF episodes decreased from 12 ( 7 ) to 6 ( 4 ) , after initiating therapy ( P = .01 ) . At 6-month follow-up , the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey . There were no thromboembolic events in either group . Asymptomatic mild or moderate pulmonary vein stenosis was documented in 2 ( 6 % ) of 32 patients in the PVI group . CONCLUSION Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF . Larger studies are needed to confirm its safety and efficacy In order to compare the efficacy and long-term tolerability of flecainide acetate versus quinidine , 239 patients with paroxysmal atrial fibrillation were prospect ively treated with flecainide ( n = 122 ) or quinidine ( n = 117 ) in an open-label , r and omized 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 prospect i ve 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 STUDY OBJECTIVES 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 . DESIGN Prospect i ve , r and omized , single-blind trial . SETTING Tertiary cardiac referral center . PATIENTS One hundred forty-six consecutive patients ( 72 men ; mean age , 63 + /- 10 years [ + /- SD ] ) with recurrent symptomatic AF . INTERVENTIONS We studied 146 patients after restoration of sinus rhythm ; patients were r and omized 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 clinical ly 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 . CONCLUSIONS 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 BACKGROUND In-hospital administration of flecainide and propafenone in a single oral loading dose has been shown to be effective and superior to placebo in terminating atrial fibrillation . We evaluated the feasibility and the safety of self-administered oral loading of flecainide and propafenone in terminating atrial fibrillation of recent onset outside the hospital . METHODS We administered either flecainide or propafenone orally to restore sinus rhythm in 268 patients with mild heart disease or none who came to the emergency room with atrial fibrillation of recent onset that was hemodynamically well tolerated . Of these patients , 58 ( 22 percent ) were excluded from the study because of treatment failure or side effects . Out-of-hospital self-administration of flecainide or propafenone -- the " pill-in-the-pocket " approach -- after the onset of heart palpitations was evaluated in the remaining 210 patients ( mean age [ + /-SD ] , 59+/-11 years ) . RESULTS During a mean follow-up of 15+/-5 months , 165 patients ( 79 percent ) had a total of 618 episodes of arrhythmia ; of those episodes , 569 ( 92 percent ) were treated 36+/-93 minutes after the onset of symptoms . Treatment was successful in 534 episodes ( 94 percent ) ; the time to resolution of symptoms was 113+/-84 minutes . Among the 165 patients with recurrences , the drug was effective during all the arrhythmic episodes in 139 patients ( 84 percent ) . Adverse effects were reported during one or more arrhythmic episodes by 12 patients ( 7 percent ) , including atrial flutter at a rapid ventricular rate in 1 patient and noncardiac side effects in 11 patients . The numbers of monthly visits to the emergency room and hospitalizations were significantly lower during follow-up than during the year before the target episode ( P<0.001 for both comparisons ) . CONCLUSIONS In a selected , risk-stratified population of patients with recurrent atrial fibrillation , pill-in-the-pocket treatment is feasible and safe , with a high rate of compliance by patients , a low rate of adverse events , and a marked reduction in emergency room visits and hospital admissions OBJECTIVE To assess and compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation . DESIGN Prospect i ve , r and omised , single blind , placebo controlled study . SETTING Tertiary cardiac referral centre . PATIENTS 186 consecutive patients ( 97 men , 89 women ; mean ( SD ) age , 63 ( 10 ) years ) with recurrent , symptomatic atrial fibrillation . INTERVENTIONS 65 patients were r and omised to amiodarone , 61 to sotalol , and 60 to placebo . Patients receiving amiodarone were maintained at a dose of 200 mg/day after a 30 day loading phase . The sotalol dose was 160 - 480 mg daily , as tolerated . MAIN OUTCOME MEASURES Recurrence of atrial fibrillation or side effects . RESULTS In the amiodarone group , 31 of the 65 patients developed atrial fibrillation after an average of six months , while 15 ( 11 in sinus rhythm and four in atrial fibrillation ) experienced significant side 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 ) . CONCLUSIONS 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 This prospect i ve , r and omized , 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 The objective of this r and omized , 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 r and omly 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 review ed 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 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 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 r and omly 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 AIMS 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 . METHODS Patients ( n=128 ) were r and omized 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 . RESULTS 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 . CONCLUSION 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 AIMS 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 prospect ively assessed in a multi-centre double-blind , placebo-controlled , r and omised trial using daily trans-telephonic monitoring . METHODS AND RESULTS 1182 patients with persistent AF were prospect ively enrolled , 848 patients were successfully cardioverted and then r and omised 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 . CONCLUSION 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 One hundred patients were subjected to a controlled study of the effectiveness of quinidine treatment upon the maintenance of sinus rhythm after electroconversion .  The quinidine series was treated with a long-acting preparation of quinidine sulphate , which was given in a dosage to achieve serum levels between 4 and 6 mg/l . The control series received no quinidine . The maintenance rate did not differ significantly in the two series during the first three months , but for the remaining observation time until I2 months a sigmficant difference in favour of quinidine was present . Identical results were found in a cross-over experiment , in which 24 patients served as their own controls . Further analysis broughtforward that quinidine was effective only if the atrial fibrillation had lasted for less than one year before electroconversion . Complications due to 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 r and om 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 Background —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 . Methods and Results —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 . Conclusions —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 BACKGROUND AND METHODS In the Cardiac Arrhythmia Suppression Trial , design ed to test the hypothesis that suppression of ventricular ectopy after a myocardial infa rct ion reduces the incidence of sudden death , patients in whom ventricular ectopy could be suppressed with encainide , flecainide , or moricizine  were r and omly assigned to receive either active drug or placebo . The use of encainide and flecainide was discontinued because of excess mortality . We examined the mortality and morbidity after r and omization to encainide or flecainide or their respective placebo . RESULTS Of 1498 patients , 857 were assigned to receive encainide or its placebo ( 432 to active drug and 425 to placebo ) and 641 were assigned to receive flecainide or its placebo ( 323 to active drug and 318 to placebo ) . After a mean follow-up of 10 months , 89 patients had died : 59 of arrhythmia ( 43 receiving drug vs. 16 receiving placebo ; P = 0.0004 ) , 22 of nonarrhythmic cardiac causes ( 17 receiving drug vs. 5 receiving placebo ; P = 0.01 ) , and 8 of noncardiac causes ( 3 receiving drug vs. 5 receiving placebo ) . Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infa rct ion with shock ( 11 patients receiving drug and 3 receiving placebo ) or to chronic congestive heart failure ( 4 receiving drug and 2 receiving placebo ) . There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia , proarrhythmia , syncope , need for a permanent pacemaker , congestive heart failure , recurrent myocardial infa rct ion , angina , or need for coronary-artery bypass grafting or angioplasty . CONCLUSIONS There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infa rct ion in patients treated with encainide or flecainide .  Nonlethal events , however , were equally distributed between the active-drug and placebo groups . The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown AIMS Dronedarone , a benzofurane derivative without iodine substituents , shares the electrophysiologic properties of amiodarone . This study was design ed to determine the most appropriate dose of dronedarone for prevention of  atrial fibrillation ( AF )  after cardioversion . METHODS AND RESULTS Patients with persistent AF were r and omly 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 . CONCLUSION 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 A multicenter , placebo-controlled , r and omized , 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 r and omly 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 BACKGROUND 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 . METHODS AND RESULTS 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 . CONCLUSIONS 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 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 r and om 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 , st and ard 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 AIMS 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 . METHODS AND RESULTS In this double-blind study , 161 subjects with persistent AF were r and omized to one of three groups-placebo ( n=38 ) ; amiodarone 400 mg BD for 2 weeks prior to DCCV and 200 mg daily for 8 weeks followed by placebo for 44 weeks ( n=62 , short-term amiodarone ) ; amiodarone 400 mg BD for 2 weeks then 200 mg 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 . CONCLUSIONS 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 To compare the efficacy and safety of sotalol and quinidine  after conversion of atrial fibrillation ( AF ) of < 6 months , a prospect i ve multicenter trial enrolled 121 patients who were r and omized 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 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 r and omized prospect i ve 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 ( st and ard electrocardiogram or dynamic registration ) documentation . According to a r and omized 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 BACKGROUND 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 . METHODS We r and omly 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 . RESULTS 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 infa rct ion , most likely not related to pilsicainide administration . CONCLUSIONS 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 Objective — 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 . Methods — This study consisted of 110 consecutive patients with recent onset and persistent AF . After restoration of sinus rhythm , patients were r and omized 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 . Results — 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 ) . Conclusion — 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 . ( Acta Cardiol 2004 ; 59(3 ) : 255 - 261 OBJECTIVES 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 . BACKGROUND 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 . METHODS After successful conversion to sinus rhythm , 394 patients with a history of persistent atrial fibrillation were r and omly 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 . RESULTS 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 . CONCLUSIONS 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 a prospect i ve study 45 patients with paroxysmal atrial fibrillation were r and omly 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 Summary Safety and efficacy of propafenone and disopyramide for long-term maintenance of sinus rhythm after electrical cardioversion was studied in 56 patients with chronic altrial fibrillation ( median arrhythmia duration , 5 months ) . After cardioversion , patients were r and omly 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 r and omized 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 OBJECTIVES 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 ) . METHODS Sixty-six patients with PAF ( > or = 3 episodes of atrial fibrillation in the last year ) in sinus rhythm , were r and omized 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 . RESULTS 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 clinical ly significant . CONCLUSION 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 clinical ly significant adverse events were uncommon . A higher value of basal cardiac rate was predictive of atrial fibrillation recurrences in the patients during treatment BACKGROUND 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 r and omized , placebo-controlled clinical trial design ed 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 . METHODS AND RESULTS In this clinical trial , 1227 patients with atrial fibrillation and 187 with paroxysmal supraventricular tachycardia were r and omly 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 ) . CONCLUSIONS Bidisomide in the doses tested did not have a clinical ly important antiarrhythmic effect . The AFIB study provided a novel clinical trial design to test antiarrhythmic drugs for both safety and efficacy AIM The indication to treat paroxysmal atrial fibrillation ( PAF ) is controversial . The Suppression of Paroxysmal Atrial Tachyarrhythmias ( SOPAT ) trial was design ed 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 ? METHODS AND RESULTS Within 60 months 172 centres in Germany , Pol and , and The Slovak Republic prospect ively enrolled 1033 patients ( mean age 60 years , 62 % male ) with documented frequent episodes of symptomatic PAF . Patients were r and omised 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 . CONCLUSION 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 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 r and omized , 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 In this multicentre study , 90 patients who left hospital in sinus rhythm after electroconversion of atrial fibrillation were r and omized 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 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 r and omized 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 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 r and omized 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 OBJECTIVES This study compared the efficacy and safety of sotalol and quinidine for conversion and prevention of recurrent  atrial fibrillation .  BACKGROUND 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 purpose s , but its safety has recently been question ed . 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 . METHODS Fifty consecutive patients with persistent atrial fibrillation were r and omized to receive quinidine or sotalol for up to 7 days to restore sinus rhythm . Patients were followed up for 6 months . RESULTS 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 ) . CONCLUSIONS 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 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 r and omized 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 BACKGROUND AND OBJECTIVES The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined . This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study , a r and omized clinical trial comparing warfarin , aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation . METHODS Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents . The relative risk of cardiac mortality , including arrhythmic death , in patients receiving antiarrhythmic drug therapy  was determined and adjusted for other cardiac risk factors . RESULTS In patients receiving antiarrhythmic drug therapy , cardiac mortality was increased 2.5-fold ( p = 0.006 , 95 % confidence interval [ CI ] 1.3 to 4.9 ) and arrhythmic death was increased 2.6-fold ( p = 0.02 , 95 % CI 1.2 to 5.6 ) . Among patients with a history of congestive heart failure , those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 ( p less than 0.001 , 95 % CI 1.9 to 11.6 ) compared with that of patients not so treated ; the relative risk of arrhythmic death in the treated group was 3.7 ( p = 0.01 , 95 % CI 1.3 to 10.4 ) . Patients without a history of congestive heart failure had no increased risk of cardiac mortality ( relative risk 0.70 , 95 % CI 0.2 to 3.1 ) during antiarrhythmic drug therapy . After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death , patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death . However , in patients with a history of heart failure who received antiarrhythmic drug therapy , the relative risk of cardiac death was 3.3 ( p = 0.05 , 95 % CI 0.99 to 11.1 ) and that of arrhythmic death was 5.8 ( p = 0.009 , 95 % CI 1.5 to 21.7 ) compared with the risk in patients not taking antiarrhythmic medications . CONCLUSIONS Although antiarrhythmic drug therapy was not r and omly determined in this trial , the data suggest that in patients with atrial fibrillation and a history of congestive heart failure , the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm 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 r and omized 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 r and omized 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 This study was performed to evaluate , using a r and omized 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 r and omized 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 To compare the relative safety of flecainide acetate to propafenone HCl during long-term treatment ( 12 months ) , we conducted a r and omized , 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 design ated 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 clinical ly 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
target: No other antiarrhythmic showed a significant effect on mortality compared with controls .
  Class IA , IC , and III drugs are effective in maintaining sinus rhythm but increase adverse effects , and class IA drugs may increase mortality
background: BACKGROUND A variety of antiarrhythmic drugs have been used to prevent recurrence of atrial fibrillation after conversion to sinus rhythm .
  We performed a systematic review to determine the effect of long-term treatment with those drugs on death , embolisms , adverse effects , and atrial fibrillation recurrence .