title: Effects of Digoxin on Acute, Atrial Fibrillation–Induced Changes in Atrial Refractoriness Vernakalant Hydrochloride for the Rapid Conversion of Atrial Fibrillation After Cardiac Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial Control of rate versus rhythm in rheumatic atrial fibrillation: a randomized study. Efficacy and safety of intravenous dofetilide for rapid termination of atrial fibrillation and atrial flutter. Development and Validation of the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) Questionnaire in Patients With Atrial Fibrillation Optimal treatment strategy for patients with paroxysmal atrial fibrillation: J-RHYTHM Study. Clinical efficacy of antazoline in rapid cardioversion of paroxysmal atrial fibrillation -- a protocol of a single center, randomized, double-blind, placebo-controlled study (the AnPAF Study) Ibutilide versus amiodarone in atrial fibrillation: A double-blinded, randomized study Conversion efficacy and safety of intravenous ibutilide compared with intravenous procainamide in patients with atrial flutter or fibrillation. Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. Intravenous Dofetilide Investigators. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. Comparison of effectiveness and safety of ranolazine versus amiodarone for preventing atrial fibrillation after coronary artery bypass grafting. Efficacy and safety of dofetilide, a new class III antiarrhythmic agent, in acute termination of atrial fibrillation or flutter after coronary artery bypass surgery. Dofetilide Post-CABG Study Group. Randomized, crossover, controlled comparison of oral loading versus intravenous infusion of propafenone in recent-onset atrial fibrillation. Conversion efficacy of intravenous ibutilide compared with intravenous amiodarone in patients with recent-onset atrial fibrillation and atrial flutter. Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study. Effect of dronedarone on cardiovascular events in atrial fibrillation. 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 Clinical, haemodynamic, and antiarrhythmic effects of long term treatment with amiodarone of patients in heart failure. Increased mortality after dronedarone therapy for severe heart failure. Comparison of intravenously administered dofetilide versus amiodarone in the acute termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind, placebo-controlled study. Efficacy and safety of ibutilide fumarate for the conversion of atrial arrhythmias after cardiac surgery. Intravenous amiodarone in treatment of recent-onset atrial fibrillation: results of a randomized, controlled study. Dronedarone for prevention of atrial fibrillation: a dose-ranging study. Efficacy and safety of intravenously administered dofetilide in acute termination of atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled trial. Danish Dofetilide in Atrial Fibrillation and Flutter Study Group. Conversion of recent onset atrial fibrillation with single loading oral dose of propafenone: is in-hospital admission absolutely necessary? Efficacy of flecainide for the reversion of acute onset atrial fibrillation. Conversion of recent-onset atrial fibrillation to sinus rhythm: effects of different drug protocols. The effect of ranolazine on maintaining sinus rhythm in patients with resistant atrial fibrillation Conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm: the effect of no treatment and high-dose amiodarone. A randomized, placebo-controlled study. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. Effects of a high dose intravenous bolus amiodarone in patients with atrial fibrillation and a rapid ventricular rate. A prospective, randomized controlled trial comparing the efficacy and safety of sotalol, amiodarone, and digoxin for the reversion of new-onset atrial fibrillation. Intravenous propafenone for converting recent onset atrial fibrillation in emergency departments: a randomized placebo-controlled multicenter trial. FAPS Investigators Study Group. Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens. Intravenous propafenone in paroxysmal atrial fibrillation: A randomized, placebo‐controlled, double‐blind, multicenter clinical trial Value of single oral loading dose of propafenone in converting recent-onset atrial fibrillation. Results of a randomized, double-blind, controlled study. Propafenone for conversion of recent-onset atrial fibrillation. A controlled comparison between oral loading dose and intravenous administration. Conversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo. Randomised trial of low-dose amiodarone in severe congestive heart failure A Randomized, Placebo-Controlled Study of Vernakalant (Oral) for the Prevention of Atrial Fibrillation Recurrence After Cardioversion Rate control vs rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study. Effectiveness of amiodarone as a single oral dose for recent-onset atrial fibrillation. Oral Propafenone To Convert Recent-Onset Atrial Fibrillation in Patients with and without Underlying Heart Disease Atrial fibrillation: the rate versus rhythm management controversy. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. Comparison between propafenone and digoxin administered intravenously to patients with acute atrial fibrillation. PAFIT-3 Investigators. The Propafenone in Atrial Fibrillation Italian Trial. A randomized, controlled trial of RSD1235, a novel anti-arrhythmic agent, in the treatment of recent onset atrial fibrillation. Comparison of oral loading dose of propafenone and amiodarone for converting recent-onset atrial fibrillation. PARSIFAL Study Group. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. [Effectiveness and side effects of the treatment with propafenone and flecainide for recent-onset atrial fibrillation]. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation. The safety of amiodarone in patients with heart failure. Intravenous flecainide versus amiodarone for recent-onset atrial fibrillation. Effectiveness of intravenous propafenone for conversion of recent‐onset atrial fibrillation: A placebo‐controlled study Beneficial effects of low dose amiodarone in patients with congestive cardiac failure: a placebo-controlled trial. A Comparison of Amiodarone and Digoxin in the Treatment of Atrial Fibrillation Complicating Suspected Acute Myocardial Infarction Intravenous propafenone versus intravenous amiodarone in the management of atrial fibrillation of recent onset: a placebo-controlled study. [Dofetilide to patients with heart failure and left ventricular dysfunction]. Amiodarone use after acute myocardial infarction complicated by heart failure and/or left ventricular dysfunction may be associated with excess mortality. Dofetilide in patients with left ventricular dysfunction and either heart failure or acute myocardial infarction: Rationale, design, and patient characteristics of the DIAMOND studies Intravenous digoxin in acute atrial fibrillation. Results of a randomized, placebo-controlled multicentre trial in 239 patients. The Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group. Dofetilide in patients with congestive heart failure and left ventricular dysfunction: safety aspects and effect on atrial fibrillation. The Danish Investigators of Arrhythmia and Mortality on Dofetilide (DIAMOND) Study Group. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Rapid loading of sotalol or amiodarone for management of recent onset symptomatic atrial fibrillation: a randomized, digoxin-controlled trial.
abstract: Background Atrial fibrillation ( AF ) shortens the atrial effective refractory period ( ERP ) and predisposes to further episodes of AF . The acute changes in atrial refractoriness may be related to tachycardia-induced intracellular calcium overload . The purpose of this study was to determine whether digoxin , which increases intracellular calcium , potentiates the acute effects of AF on atrial refractoriness in humans . Methods and Results In 38 healthy adults , atrial ERP was measured at basic drive cycle lengths ( BDCLs ) of 350 and 500 ms after autonomic blockade . Nineteen patients had been treated with digoxin for 2 weeks . After a several-minute episode of AF , atrial ERP was measured serially at alternating BDCLs . Compared with pre-AF ERPs , the first post-AF ERPs were significantly shorter in both the digoxin and the control groups ( P < 0.001 ) . The post-AF ERP at a BDCL of 350 ms shortened to a greater degree in the digoxin group ( 37±16 ms ) than in the control group ( 20±13 ms , P < 0.001 ) ; similar changes occurred at a BDCL of 500 ms . During post-AF determinations of the atrial ERP , secondary AF episodes occurred significantly more often in the digoxin group ( 32 % versus 16%;P < 0.04 ) . Conclusions After a brief episode of AF , digoxin augments the shortening that occurs in atrial refractoriness and predisposes to the reinduction of AF . These effects occur in the setting of autonomic blockade and therefore are more likely to be due to the effects of digoxin on intracellular calcium than to its vagotonic effects Background —Postoperative atrial arrhythmias are common and are associated with considerable morbidity . This study was design ed to evaluate the efficacy and safety of vernakalant for the conversion of  atrial fibrillation ( AF ) or  atrial flutter ( AFL ) after cardiac surgery . Methods and Results —This was a prospect i ve , r and omized , double-blind , placebo-controlled trial of vernakalant for the conversion of AF or AFL  after coronary artery bypass graft , valvular surgery , or both . Patients were r and omly assigned 2:1 to receive a 10-minute infusion of 3 mg/kg vernakalant or placebo . If AF or AFL was present after a 15-minute observation period , then a second 10-minute infusion of 2 mg/kg vernakalant or placebo was given . The primary end point was the conversion of postcardiac surgery AF or AFL to sinus rhythm within 90 minutes of dosing . In patients with AF , 47 of 100 ( 47 % ) who received vernakalant converted to SR compared with 7 of 50 ( 14 % ) patients who received placebo ( P<0.001 ) . The median time to conversion was 12 minutes . Vernakalant was not effective in converting postoperative AFL to sinus rhythm . Two serious adverse events occurred within 24 hours of vernakalant administration ( hypotension and complete atrioventricular block ) . There were no cases of torsades de pointes , sustained ventricular tachycardia , or ventricular fibrillation . There were no deaths . Conclusions —Vernakalant was safe and effective in the rapid conversion of AF to sinus rhythm in patients who had AF after cardiac surgery . Clinical Trial Registration — clinical trials.gov . Identifier : NCT00125320 BACKGROUND Patients with rheumatic heart disease and atrial fibrillation incur significant morbidity and mortality . It is not known which approach , rate control or maintenance of sinus rhythm might be most appropriate . The present study was undertaken to compare the strategy of ventricular rate control versus maintenance of sinus rhythm in rheumatic atrial fibrillation , and to evaluate the role of amiodarone in this patient population . METHODS AND RESULTS We prospect ively studied 144 patients with chronic rheumatic atrial fibrillation in a double-blind protocol -rhythm control ( group I : 48 patients each with amiodarone -group Ia ; and  placebo -group  Ib ) and compared the effects with the ventricular rate control ( group II ) by diltiazem ( n=48 , open-label ) . Direct current cardioversion was attempted in group I. The mean age of the study population was 38.6+/-10.3 years , left atrial size was 4.7+/-0.6 cm , atrial fibrillation duration was 6.1+/-5.4 years , and 72.9 % patients had undergone valvular interventions . At 1 year , 45 patients with sinus rhythm in group I compared to 48 patients in group II demonstrated significant increase in exercise to sinus rhythm time , had improvement in functional class and quality of life score . There was no difference in hospitalization rates , systemic bleeds or incidence of thromboembolism . Five patients died in group II but none in group I ( p=0.02 ) . In group I , 73/87 ( 83.9 % ) patients converted , and 45/86 ( 52.3 % ) patients maintained sinus rhythm at 1 year . Conversion rates were 38/43 ( 88.4 % ) with amiodarone versus 34/44 ( 77.3 % ) with placebo ( p=0.49 ) : corresponding rate for maintaining sinus rhythm was 29/42 ( 69.1 % ) versus 16/44 ( 36.4 % ) , p=0.008 respectively . CONCLUSIONS Maintenance of sinus rhythm appeared to be superior to ventricular rate control in patients with rheumatic atrial fibrillation in terms of an effect on mortality and morbidity . Sinus rhythm could be restored in the majority and amiodarone was superior to placebo in this regard Dofetilide may be advantageous in terminating  atrial fibrillation/atrial flutter ( AFl )  when there are contraindications for class I drugs ( left ventricular dysfunction and /or manifest myocardial ischemia ) and beta blockers . In particular , its successful outcome in usually drug-resistant AFl is promising and underscores the importance of selective class III action for terminating AFl Background —Atrial fibrillation ( AF ) has a deleterious impact on health-related quality -of-life ( HRQoL ) , but measuring this outcome is difficult . A comprehensive , vali date d , disease-specific question naire to measure the spectrum of QoL domains affected by AF and its treatment is not available . We developed and vali date d a 20-item question naire , Atrial Fibrillation Effect on QualiTy -of-life ( AFEQT ) , in a 6-center , prospect i ve , observational study . Methods and Results —Factor analyses established 4 conceptual domains ( Symptoms , Daily Activities , Treatment Concern , and Treatment Satisfaction ) from which individual domain and global scores were calculated . Participants from 6 centers completed the AFEQT at baseline , at month 1 , and at month 3 . Psychometric analyses included internal consistency and known-group validity . Test-retest reliability was assessed by comparing 1-month changes in scores among those with no change in therapy . Effect size was used to assess responsiveness after intervention . Among 219 patients age 62±11.9 years , 94 % completed the AFEQT at baseline and 3 months ; 66 % had paroxysmal , 24 % persistent , 5 % longst and ing persistent , and 5 % permanent AF .  Internal consistency was > 0.88 for all scales . Lower AFEQT scores were observed with increased AF severity , categorized as asymptomatic , mild , moderate and severe , respectively : 71.2±20.6 , 71.3±19.2 , 57.9±19.0 , and 42.0±21.2 . Intraclass correlations for Overall , Symptoms , Daily Activities , Treatment Concern , and Satisfaction scores were 0.8 , 0.5 , 0.8 , 0.7 , and 0.7 , respectively . Changes in 3-month scores were larger after ablation than with pharmacological adjustments , and both were greater than those observed in stable patients . Conclusions —This initial validation of AFEQT supports its use as an outcome in studies and a means to clinical ly follow patients with AF Background Although previous clinical trials demonstrated the non-inferiority of a rate control to rhythm control strategy for management of atrial fibrillation ( AF ) , the optimal treatment strategy for paroxysmal AF ( PAF ) remains unclear . Methods and Results A r and omized , multicenter comparison of rate control vs rhythm control in Japanese patients with PAF ( the Japanese Rhythm Management Trial for Atrial Fibrillation ( J-RHYTHM ) study ) was conducted . The primary endpoint was a composite of total mortality , symptomatic cerebral infa rct ion , systemic embolism , major bleeding , hospitalization for heart failure , or physical/psychological disability requiring alteration of treatment strategy . In the study , 823 patients with PAF were followed for a mean period of 578 days . The primary endpoint occurred in 64 patients ( 15.3 % ) assigned to rhythm control and in 89 patients ( 22.0 % ) to rate control ( P=0.0128 ) . No significant differences between the treatment strategies were observed in the incidences of death , stroke , bleeding and heart failure . Meanwhile , significantly fewer patients requested changes of assigned treatment strategy in the rhythm control vs the rate control group , which was accompanied by improvement in AF-specific quality of life scores . Conclusion The J-RHYTHM study showed that rhythm control was associated with fewer primary endpoints than rate control . However , mortality and cardiovascular morbidity were not affected by the treatment strategy ( umin-CTR No. C000000106 ) Background Rapid conversion of  atrial fibrillation ( AF ) to sinus rhythm may be achieved by the administration of class IA , IC and III antiarrhythmic drugs or vernakalant hydrochloride . However , that treatment may be related to potential pro-arrhythmia , lack of efficacy or the exceptionally high cost of a compound used . Antazoline is a first generation antihistaminic agent with chinidin-like properties . When administered intravenously , antazoline exerts a strong antiarrhythmic effect on supraventricular arrhythmia , especially on AF , facilitating rapid conversion to sinus rhythm . Despite a relative lack of published data antazoline has been marketed in Pol and and widely used in cardiology wards and emergency rooms for many years due to its efficacy , safety and rapid onset of action within minutes of administration . Methods / design A r and omized , double blind , placebo-controlled , superiority clinical trial was design ed to assess clinical efficacy of antazoline in rapid conversion of AF to sinus rhythm .  Eligible patients will present AF lasting less than 43 hours , will be in stable cardio-pulmonary condition and will have no prior history of advanced heart failure or significant valvular disease . Long-term antiarrhythmic therapy is not considered an exclusion criterion . Subjects who fulfill selection criteria will be r and omly assigned to receive intravenously either antazoline or placebo in divided doses and observed for 1.5 hours after conversion to sinus rhythm or after the last i.v . bolus . Primary end point will be the conversion of AF to sinus rhythm confirmed in an electrocardiogram ( ECG ) during the observation period . Secondary end points will be comprised of time to conversion and return of AF during the observation period . Special consideration will be given to the observation of any adverse events . A sample size of 80 patients was calculated based on the following assumptions : two-tailed test , a type I error of 0.01 , a power of 90 % , efficacy of placebo 5 % , efficacy of antazoline 50 % and 20 % drop-out rate to fulfill the criteria of intention-to-treat analysis . Due to the presumed lack of statistical power , the secondary end points and safety endpoints will be considered exploratory . Clinical trials registry Clinical Trials.gov , Objective Ibutilide , a class III antiarrhythmic drug , has been shown to convert atrial fibrillation to sinus rhythm more rapidly than procainamide or sotalol . Our objective was to compare the efficacy and safety of ibutilide and amiodarone in patients after cardiac surgery . Design Prospect i ve , r and omized , double-blinded study . Setting Intensive care unit of a university hospital . Patients Forty adults with an onset of atrial fibrillation within 3 hrs after admission . Interventions Before the administration of antiarrhythmic drugs , a 24-hr Holter electrocardiograph was attached . Patients in the ibutilide group received ibutilide 0.008 mg/kg body weight over 10 mins ; treatment was repeated if atrial fibrillation or flutter persisted . If sinus rhythm was not achieved within 4 hrs , amiodarone 5 mg/kg was administered over 30 mins , followed by amiodarone 15 mg/kg over 24 hrs . Patients in the amiodarone group received amiodarone 5 mg/kg over 30 mins , followed by amiodarone 15 mg/kg over 24 hrs if atrial fibrillation or flutter continued . Measurements and Main Results Within the first 4 hrs , atrial fibrillation was converted in nine of 20 patients ( 45 % ) in group ibutilide and in ten of 20 patients ( 50 % ) in group amiodarone ( not significant ) . Mean time for conversion overall was 385 mins in group ibutilide and 495 mins in group amiodarone ( not significant ) . In group amiodarone , the protocol was discontinued in two patients because of severe arterial hypotension . Atrial fibrillation recurred in 11 of 20 patients ( 55 % ) in group ibutilide and in seven of 20 patients ( 35 % ) in group amiodarone ( not significant ) . Ventricular arrhythmia did not occur during the first 24 hrs of the protocol . Conclusions Ibutilide has no significant advantage over amiodarone for the conversion of atrial fibrillation to sinus rhythm in either time to conversion or conversion overall , but severe hypotension was not seen with ibutilide OBJECTIVES This multicenter study compared the efficacy and safety of ibutilide versus procainamide for conversion of recent-onset atrial flutter or fibrillation . BACKGROUND Ibutilide fumarate is an intravenous ( IV ) class III antiarrhythmic agent that has been shown to be significantly more effective than placebo in the pharmacologic conversion of atrial flutter and fibrillation to sinus rhythm . Procainamide is commonly used for conversion of recent-onset atrial fibrillation to normal sinus rhythm . METHODS One hundred twenty-seven patients ( age range 22 to 92 years ) with atrial flutter or fibrillation of 3 h to 90 days ' ( mean 21 days ) duration were r and omized to receive either two 10-min IV infusions of 1 mg of ibutilide fumarate , separated by a 10-min infusion of 5 % dextrose in sterile water , or three successive 10-min IV infusions of 400 mg of procainamide hydrochloride . RESULTS Of the 127 patients , 120 were evaluated for efficacy : 35 ( 58.3 % ) of 60 in the ibutilide group compared with 11 ( 18.3 % ) of 60 in the procainamide group had successful termination within 1.5 h of treatment ( p < 0.0001 ) . Seven patients were found to have violated the protocol and were not included in the final evaluation . In the patients with atrial flutter , ibutilide had a significantly higher success rate than procainamide ( 76 % [ 13 of 17 ] vs. 14 % [ 3 of 22 ] , p=0.001 ) . Similarly , in the atrial fibrillation group , ibutilide had a significantly higher success rate than procainamide ( 51 % [ 22 of 43 ] vs. 21 % [ 8 of 38 ] , p=0.005 ) . One patient who received ibutilide , which was found to be a protocol violation , had sustained polymorphic ventricular tachycardia requiring direct current cardioversion . Seven patients who received procainamide became hypotensive . CONCLUSIONS This study establishes the superior efficacy of ibutilide over procainamide when administered to patients to convert either atrial fibrillation or atrial flutter to sinus rhythm .  Hypotension was the major adverse effect seen with procainamide . A low incidence of serious proarrhythmia was seen with the administration of ibutilide occurring at the end of infusion OBJECTIVES This study sought to determine the safety and efficacy of a single bolus of intravenous dofetilide , a pure class III antiarrhythmic agent , for the termination of sustained atrial fibrillation or flutter . BACKGROUND Dofetilide is a highly selective blocker of the rapid component of the delayed rectifier current causing action potential prolongation . These effects , and preliminary clinical data , suggest that it may be effective in the treatment of atrial fibrillation and flutter . METHODS Ninety-one patients with sustained atrial fibrillation ( 75 patients ) or flutter ( 16 patients ) were entered into a double-blind , r and omized multicenter study of one of two doses of dofetilide ( 4 or 8 micrograms/kg body weight ) or placebo . RESULTS Dofetilide  effectively terminated the arrhythmia in 31 % of patients receiving 8 micrograms/kg , a statistically significant difference from those receiving 4 micrograms/kg ( conversion rate 12.5 % , p < 0.05 ) or placebo ( no conversion , p < 0.01 ) . Patients with atrial flutter had a greater response to dofetilide ( 54 % conversion rate ) than those with atrial fibrillation ( 14.5 % conversion rate , p < 0.001 ) . CONCLUSIONS Intravenous dofetilide can convert sustained atrial fibrillation or flutter to sinus rhythm . However , its efficacy is greater in flutter -- a response that contrasts with the poorer response seen with class I agents . This finding potentially represents an important advance in the pharmacologic termination of atrial flutter BACKGROUND Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects .  Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects . METHODS In two identical multicenter , double-blind , r and omized trials , one conducted in Europe ( Clinical Trials.gov number , NCT00259428 [ Clinical Trials.gov ] ) and one conducted in the United States , Canada , Australia , South Africa , and Argentina ( termed the non-European trial , NCT00259376 [ Clinical Trials.gov ] ) , we evaluated the efficacy of dronedarone , with 828 patients receiving 400 mg of the drug twice daily and 409 patients receiving placebo .  Rhythm was monitored transtelephonically on days 2 , 3 , and 5 ; at 3 , 5 , 7 , and 10 months ; during recurrence of arrhythmia ; and at nine scheduled visits during a 12-month period . The primary end point was the time to the first recurrence of atrial fibrillation or flutter . RESULTS In the European trial , the median times to the recurrence of arrhythmia were 41 days in the placebo group and 96 days in the dronedarone group ( P=0.01 ) . The corresponding duration s in the non-European trial were 59 and 158 days ( P=0.002 ) . At the recurrence of arrhythmia in the European trial , the mean ( + /-SD ) ventricular rate was 117.5+/-29.1 beats per minute in the placebo group and 102.3+/-24.7 beats per minute in the dronedarone group ( P<0.001 ) ; the corresponding rates in the non-European trial were 116.6+/-31.9 and 104.6+/-27.1 beats per minute ( P<0.001 ) . Rates of pulmonary toxic effects and of thyroid and liver dysfunction were not significantly increased in the dronedarone group . CONCLUSIONS Dronedarone was significantly more effective than placebo in maintaining sinus rhythm and in reducing the ventricular rate during recurrence of arrhythmia Atrial  fibrillation ( AF )  is common after coronary artery bypass grafting ( CABG ) and increases the morbidity and cost . Amiodarone reduces AF after CABG . Ranolazine , an antianginal agent , also prolongs atrial refractoriness and inhibits after depolarizations and triggered activity ; effects that could decrease AF after CABG . The present study compared amiodarone versus ranolazine for the prevention of AF after CABG . A retrospective cohort study of patients undergoing CABG at Aspirus Hospital from June 2008 to April 2010 . The patients received either amiodarone ( 400 mg preoperatively followed by 200 mg twice daily for 10 to 14 days ) or ranolazine ( 1,500 mg preoperatively followed by 1,000 mg twice daily for 10 to 14 days ) . The primary end point was any identified AF after CABG . A total of 393 consecutive patients undergoing CABG ( mean age 65 ± 10 years , 72 % men ) received either amiodarone ( n = 211 [ 53.7 % ] ) or ranolazine ( n = 182 [ 46.3 % ] ) . AF occurred in 26.5 % of the amiodarone-treated patients compared to 17.5 % of the ranolazine-treated patient ( p = 0.035 ) . The univariate predictors of AF included amiodarone use , age , chronic lung disease , and congestive heart failure . The multivariate predictors of AF included amiodarone use ( odds ratio 1.7 , 95 % confidence interval 1.01 to 2.91 , p = 0.045 vs ranolazine ) , age ( odds ratio 2.2 per 10 years , 95 % confidence interval 1.63 to 2.95 , p < 0.001 ) , and chronic lung disease ( odds ratio 1.86 , 95 % confidence interval 1.00 to 3.43 , p = 0.049 ) . No difference was found in the risk of adverse events between the 2 therapies . In conclusion , ranolazine was independently associated with a significant reduction of AF compared to amiodarone after CABG , with no difference in the incidence of adverse events . R and omized studies should be conducted to confirm these results Ninety-eight patients , who developed atrial fibrillation/flutter after coronary artery bypass grafting within 1 - 6 days after surgery , were included into a double-blind , placebo-controlled , r and omized trial to assess the efficacy and safety of dofetilide . Patients were r and omly allocated to dofetilide 4 micrograms/kg i.v . ( n = 33 ) , dofetilide 8 micrograms/kg i.v . ( n = 32 ) or placebo ( n = 33 ) given intravenously over 15 min at a constant infusion rate . Responders were defined as patients who converted to sinus rhythm at any time during the initial 3 h after the start of the infusion . The conversion rates were 24 % ( 8/33 ) on placebo , 36 % ( 12/33 ) on dofetilide 4 micrograms/kg , and 44 % ( 14/32 ) on dofetilide 8 micrograms/kg . The P-values ( two-tailed ) were 0.27 for dofetilide 4 micrograms/kg vs. placebo , 0.11 for dofetilide 8 micrograms/kg vs. placebo , and 0.10 for dose-response relationship . Short episodes of aberrant ventricular conduction and ventricular tachycardia were seen separately in three subjects after dofetilide 8 micrograms/kg . No episodes of torsades de pointes were noted . No negative inotropic effect was noted . In conclusion , dofetilide was well tolerated , but the effects on atrial fibrillation/flutter did not attain statistical significance , possibly due to the high placebo conversion rate A population of 123 patients with recent-onset ( < 72 hours ) atrial fibrillation ( AF ) without heart failure was r and omly treated with propafenone ( PFN ) intravenously ( i.v . ) ( 2 mg/kg bolus followed by 0.0078 mg/kg/min infusion ) or in a single oral dose ( o.s . ) ( 600 mg ) , or with placebo ( PLA ) ( phase 1 ) . If AF persisted 8 hours later , patients on active drugs received the alternative formulation ( crossover ) , and patients receiving PLA remained on PLA ( phase 2 ) . A 24-hour Holter monitoring was performed and conversion to sinus rhythm ( SR ) at 1 , 4 , and 8 hours of each phase was used as the criterion of efficacy . Conversion to SR occurred within 1 hour in 48 % of patients with i.v.-PFN , 15 % with o.s.-PFN , and in 17 % with PLA ( both P < 0.05 vs i.v.-PFN ) . Oral PFN was superior to PLA at 4 hours ( 71 % vs 33 % , P = 0.001 ) and 8 hours ( 78 % vs 48 % , P < 0.01 ) , and 1 at 8 hours also superior to i.v.-PFN ( 53 % , P < 0.03 ) . The mean conversion time within 4 hours was shorter with i.v.-PFN ( 25 + /- 15 ' ) than with o.s.-PFN ( 167 + /- 166 ' , P < 0.001 ) or with PLA ( 156 + /- 107 ' , P < 0.001 ) . The rates of conversion to SR with i.v.-PFN after o.s.-PFN failure were comparable to PLA at any observation time , whereas nonresponders to i.v.-PFN who received o.s.-PFN had significantly higher conversion rates than with placebo at both 4 hours ( 65 % vs 19 % ) and 8 hours ( 76 % vs 24 % ; both P < 0.045 ) . Neither serious adverse effects nor episodes of regular tachycardia with 1:1 AV conduction were noted . PFN administered intravenously or in a single oral loading dose was safe and efficacious in converting recent-onset AF to SR . The rates of conversion were different with different routes of administration : i.v.-PFN was superior to o.s.-PFN over a short observation period , while the overall efficacy of o.s.-PFN was superior at 8 hours AIM The aim of our study was to compare the efficacy and safety of ibutilide and amiodarone ( intravenously ) in converting  recent-onset atrial fibrillation ( AF ) and atrial flutter ( Af )  to sinus rhythm ( SR ) . METHODS The study was prospect i ve , r and omized and included 152 ( 103 men and 49 women ) consecutive patients with AF or Af of 3 - 48 h duration .  Ibutilide is a selective class III antiarrhythmic agent which when administered intravenously can terminate AF and Af .  Amiodarone is also a class III antiarrhythmic agent that when given intravenously or orally has proved to be more effective than other agents in terminating AF and Af [ B.N. Singh , F.V. Mody , B. Lopez , J.S. Sarma . Antiarrhythmic agents for atrial fibrillation : focus on prolonging atrial repolarization . Am J Cardiol 1999 Nov 4 ; 84 : 161R-173R . ] . Seventy-nine patients ( 56 with AF and 23 with Af ) that consisted group A were treated with ibutilide .  Seventy-three ( 52 with AF and 21 with Af ) consisted group B and were treated with intravenous infusion of amiodarone . RESULTS The conversion rate of group A ( ibutilide ) was significantly higher than the conversion rate of group B ( amiodarone ) ( 80 % vs. 57 % , p=0.0054 ) . As regards the kind of arrhythmia separately , for AF there was n't significant difference ( 77 % vs. 69 % , p = ns ) whereas for Af ibutilide was superior to amiodarone ( 87 % vs. 29 % , p=0.003 ) . The conversion rates of ibutilide did n't differ for AF and Af ( 77 % vs. 87 % , p = ns ) . CONCLUSIONS Ibutilide is more effective than amiodarone in converting recent-onset Af to SR whereas both drugs are equally effective in converting recent-onset AF to SR STUDY OBJECTIVES To investigate the efficacy and safety of amiodarone administered as the drug of first choice in the conversion of atrial fibrillation , regardless of its duration . DESIGN : Prospect i ve , r and omized , controlled clinical study . SETTING : Tertiary cardiac referral center . PATIENTS Two-hundred eight consecutive patients ( 102 men ; mean [ + /- SD ] age , 65 + /- 10 years ) with atrial fibrillation . INTERVENTIONS One-hundred eight patients received amiodarone , and 100 patients received placebo treatment . Patients r and omized to amiodarone received 300 mg IV for 1 h , and then 20 mg/kg for 24 h. They were also given 600 mg/d orally , divided into three doses , for 1 week , and thereafter 400 mg/d for 3 weeks . Patients r and omized to placebo treatment received an identical amount of saline solution IV over 24 h , and oral placebo treatment for 1 month . MEASUREMENTS AND RESULTS Baseline clinical characteristics were similar in the two groups . Conversion to sinus rhythm was achieved in 87 of 108 patients ( 80.05 % ) who received amiodarone , and in 40 of 100 patients ( 40 % ) in the placebo group ( p < 0.0001 ) . Statistical analysis showed that the duration of the arrhythmia and the size of the left atrium affected both the likelihood of conversion to sinus rhythm and the time to conversion in both groups . No side effects requiring discontinuation of treatment were observed in either group . CONCLUSIONS Amiodarone appears to be safe and effective in the termination of atrial fibrillation . However , extreme cases with a large left atrium and long-lasting arrhythmia need long-term therapy BACKGROUND Dronedarone is a new antiarrhythmic drug that is being developed for the treatment of patients with atrial fibrillation . METHODS We conducted a multicenter trial to evaluate the use of dronedarone in 4628 patients with atrial fibrillation who had additional risk factors for death . Patients were r and omly assigned to receive dronedarone , 400 mg twice a day , or placebo . The primary outcome was the first hospitalization due to cardiovascular events or death . Secondary outcomes were death from any cause , death from cardiovascular causes , and hospitalization due to cardiovascular events . RESULTS The mean follow-up period was 21+/-5 months , with the study drug discontinued prematurely in 696 of the 2301 patients ( 30.2 % ) receiving dronedarone and in 716 of the 2327 patients ( 30.8 % ) receiving placebo , mostly because of adverse events . The primary outcome occurred in 734 patients ( 31.9 % ) in the dronedarone group and in 917 patients ( 39.4 % ) in the placebo group , with a hazard ratio for dronedarone of 0.76 ( 95 % confidence interval [ CI ] , 0.69 to 0.84 ; P<0.001 ) . There were 116 deaths ( 5.0 % ) in the dronedarone group and 139 ( 6.0 % ) in the placebo group ( hazard ratio , 0.84 ; 95 % CI , 0.66 to 1.08 ; P=0.18 ) . There were 63 deaths from cardiovascular causes ( 2.7 % ) in the dronedarone group and 90 ( 3.9 % ) in the placebo group ( hazard ratio , 0.71 ; 95 % CI , 0.51 to 0.98 ; P=0.03 ) , largely due to a reduction in the rate of death from arrhythmia with dronedarone . The dronedarone group had higher rates of bradycardia , QT-interval prolongation , nausea , diarrhea , rash , and an increased serum creatinine level than the placebo group . Rates of thyroid- and pulmonary-related adverse events were not significantly different between the two groups . CONCLUSIONS Dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation . ( Clinical Trials.gov number , NCT00174785 . 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 Twenty two patients with heart failure were studied in a double blind crossover trial to compare amiodarone ( 200 mg/day ) with placebo . Each agent was given for three months . Extrasystoles and complex ventricular arrhythmias were common during ambulatory electrocardiographic monitoring and during exercise testing at entry to the study . Breathlessness and tiredness as assessed by visual analogue scores and duration of treadmill exercise did not become worse during amiodarone treatment . During the placebo and amiodarone phases of the study left ventricular ejection fraction and cardiac index determined by first pass radionuclide ventriculography were similar , both at rest and during upright bicycle exercise . Exercise induced ventricular tachycardia was abolished and simple and complex ventricular arrhythmias observed on 24 hour ambulatory monitoring were greatly diminished during amiodarone treatment . Three patients died , all suddenly , during the placebo phase . In two patients amiodarone was withdrawn after a further myocardial infa rct ion in one and a worsening of symptoms of ventricular arrhythmia in the other . In contrast with other antiarrhythmic agents amiodarone is effective in suppressing ventricular arrhythmias in heart failure without causing adverse haemodynamic effects . Because frequent ventricular arrhythmias are known to be associated with a poor prognosis in heart failure , these data suggest that amiodarone may improve the poor prognosis in patients with heart failure BACKGROUND Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone , but it does not contain iodine and thus does not cause iodine-related adverse reactions . Therefore , it may be of value in the treatment of patients with heart failure . METHODS In a multicenter study with a double-blind design , we planned to r and omly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of  dronedarone twice a day or placebo . The primary end point was the composite of death from any cause or hospitalization for heart failure . RESULTS After inclusion of 627 patients ( 310 in the dronedarone group and 317 in the placebo group ) , the trial was prematurely terminated for safety reasons , at the recommendation of the data and safety monitoring board , in accordance with the board 's predefined rules for termination of the study . During a median follow-up of 2 months , 25 patients in the dronedarone group ( 8.1 % ) and 12 patients in the placebo group ( 3.8 % ) died ( hazard ratio in the dronedarone group , 2.13 ; 95 % confidence interval [ CI ] , 1.07 to 4.25 ; P=0.03 ) . The excess mortality was predominantly related to worsening of heart failure--10 deaths in the dronedarone group and 2 in the placebo group . The primary end point did not differ significantly between the two groups ; there were 53 events in the dronedarone group ( 17.1 % ) and 40 events in the placebo group ( 12.6 % ) ( hazard ratio , 1.38 ; 95 % CI , 0.92 to 2.09 ; P=0.12 ) . More increases in the creatinine concentration were reported as serious adverse events in the dronedarone group than in the placebo group . CONCLUSIONS In patients with severe heart failure and left ventricular systolic dysfunction , treatment with dronedarone was associated with increased early mortality related to the worsening of heart failure . ( Clinical Trials.gov number , NCT00543699 . AIMS This study compared the efficacy and safety of intravenous dofetilide with amiodarone and placebo in converting atrial fibrillation or flutter to sinus rhythm . METHODS AND RESULTS One hundred and fifty patients with atrial fibrillation or flutter ( duration range 2 h-6 months ) were given 15-min intravenous infusions of 8 microg . kg(-1)of dofetilide ( n=48 ) , 5 mg . kg(-1)of amiodarone ( n=50 ) , or placebo ( n=52 ) and monitored continuously for 3 h. Sinus rhythm was restored in 35 % , 4 % , and 4 % of patients , respectively ( P<0.001 , dofetilide vs placebo;P = ns , amiodarone versus placebo ) . Dofetilide was more effective in atrial flutter than in atrial fibrillation ( cardioversion rates 75 % and 22 % , respectively;P=0.004 ) . The mean time to conversion with dofetilide was 55+/-15 min . Dofetilide prolonged the QTc interval ( + 16 % at 20 min ) . Amiodarone substantially decreased the ventricular rate in non-converters ( -18 beats . min(-1)at 30 min ) . Two patients given dofetilide ( 4 % ) had non-sustained ventricular tachycardias , and four ( 8 % ) had torsade de pointes , in one case requiring electrical cardioversion . CONCLUSION Intravenous dofetilide is significantly more effective than amiodarone or placebo in restoring sinus rhythm in patients with atrial fibrillation or flutter . However , when infused intravenously at this dose and rate , dofetilide causes a significant incidence of torsade de pointes BACKGROUND Atrial arrhythmias occur commonly after cardiac surgery and are a cause of significant morbidity and increased hospital costs , yet there is no well-studied treatment strategy to deal with them expeditiously . The purpose of this study was to determine the efficacy and safety of ibutilide fumarate , an approved drug for the rapid conversion of atrial fibrillation and flutter , in patients after cardiac surgery . METHODS AND RESULTS Patients with atrial fibrillation or flutter occurring 1 to 7 days after surgery and lasting 1 hour to 3 days were r and omized to receive two 10-minute blinded infusions of placebo or 0.25 , 0.5 , or 1.0 mg of ibutilide fumarate . Treatment was considered successful if sinus rhythm was restored for any period of time by hour 1.5 . A total of 302 patients were r and omized , 201 with fibrillation and 101 with flutter . Treatment with ibutilide result ed in significantly higher conversion rates than placebo , and efficacy was dose related ( placebo 15 % ; ibutilide 0.25 mg 40 % , 0.5 mg 47 % , and 1.0 mg 57 % ) . Conversion rates at all doses were higher for atrial flutter than for atrial fibrillation . Mean time to conversion decreased as the dose was increased . Polymorphic ventricular tachycardia was the most serious adverse effect and occurred in 1.8 % of the ibutilide-treated patients compared with 1.2 % of patients who received placebo . CONCLUSIONS Ibutilide is a useful and safe treatment alternative for the atrial arrhythmias that occur after cardiac surgery OBJECTIVES This study was design ed to determine the efficacy of intravenous amiodarone in the management of  recent-onset atrial fibrillation .  BACKGROUND The optimal approach for acute atrial fibrillation has not been established . Amiodarone is a unique antiarrhythmic agent with activity in both supraventricular and ventricular tachyarrhythmias , but its value for the restoration of sinus rhythm in patients with recent-onset atrial fibrillation has not been demonstrated . METHODS Sample size was calculated to detect a 25 % increase in reversion rate with amiodarone with a statistical power of 80 % . One hundred consecutive patients with recent-onset ( < 1 week ) atrial fibrillation and not taking antiarrhythmic agents were r and omized to receive either intravenous amiodarone , 5 mg/kg body weight in 30 min followed by 1,200 mg over 24 h , or an identical amount of saline . Both groups received intravenous digoxin , 0.5 mg initially , followed by 0.25 mg at 2 h and 0.25 mg every 6 h thereafter , to complete 24 h while the ventricular rate was > 100 beats/min . Amiodarone and digoxin  blood levels were determined . Both groups were homogeneous regarding underlying heart disease , time from onset to treatment , initial ventricular rate and left atrial size . RESULTS By the end of the 24-h treatment period , 34 patients ( 68 % , 95 % confidence interval [ CI ] 53 % to 80 % ) in the amiodarone group and 30 ( 60 % , 95 % CI 45 % to 74 % ) in the control group had returned to sinus rhythm ( p = 0.532 ) . Mean times ( + /-SD ) of conversion were 328 + /- 335 and 332 + /- 359 min , respectively ( p = 0.957 ) . Among patients who did not convert to sinus rhythm , treatment with amiodarone was associated with a slower ventricular rate ( 82 + /- 15 beats/min in the amiodarone group vs. 91 + /- 23 beats/min in the control group , p = 0.022 ) . After restoration of sinus rhythm , atrial fibrillation recurred during a 15-day follow-up period in 4 ( 12 % ) of 34 patients ( 95 % CI 3 % to 27 % ) in the amiodarone group and in 3 ( 10 % ) of 30 ( 95 % CI 2 % to 26 % ) in the control group ( p = 0.861 ) . CONCLUSIONS Intravenous amiodarone , at the doses used in this study , produces a modest but not significant benefit in converting acute atrial fibrillation to sinus rhythm 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 BACKGROUND This study was design ed to assess the efficacy and safety of intravenous dofetilide in acute termination of atrial fibrillation ( AF ) and flutter ( AFL ) .  Dofetilide , an investigational class III antiarrhythmic agent , selectively inhibits the rapid component of the delayed rectifier potassium current , thus prolonging the effective refractory period and duration of the action potential . Dofetilide can be administered intravenously and has a rapid onset of electrophysiologic action . METHODS AND RESULTS Ninety-six patients with AF ( n = 79 ) or AFL ( n = 17 ) with a median arrhythmia duration of 62 days ( range 1 to 180 ) were r and omized to placebo ( n = 30 ) or 8 micrograms/kg IV dofetilide ( n = 66 ) over 30 minutes . Conversion was defined as termination of the atrial arrhythmia within 3 hours from the start of infusion . The conversion rate was 30.3 % after dofetilide and 3.3 % after placebo ( P < .006 ) . Conversion rate was higher in AFL than in AF : 64 % versus 24 % ( P = . 012 ) . In nonconverters , there was no statistically significant difference between the change in heart rate among the dofetilide-treated compared with the placebo-treated patients ( P = . 42 ) . Torsade de pointes ventricular tachycardia developed in 2 patients ( 3 % ) . In both patients , drug infusion was discontinued before the event because of prolongation of the QT interval . CONCLUSIONS Intravenous dofetilide is effective in acute termination of AF and AFL of medium duration , with a particularly high efficacy rate in AFL . A small but serious risk of proarrhythmia must be anticipated A population of 283 patients with recent onset ( < 72 hours ) AF , without heart failure , who received a single 450- or 600-mg oral dose of propafenone , or digoxin 1 mg , or placebo for conversion to sinus rhythm ( SR ) , was studied to determine whether a routine admission to the hospital for drug administration is justified . Previous bradyarrhythmias or sick sinus syndrome ( SSS ) , and concomitant use of antiarrhythmic drugs were exclusion criteria . None of the 283 patients studied experienced VT or VF and none of them needed implantation of a temporary pacemaker . Periods of atrial tachyarrhythmias with regularization of atrial waves and 1:1 AV conduction were observed in only two cases , both receiving placebo . No predictor of proarrhythmia was found among the clinical variables considered ( age , etiology , arrhythmia duration , atrial dimension , and blood potassium ) . No serious hemodynamic adverse effects were noted in either group . The rates of conversion to SR after 4 hours were : 80 ( 57 % ) of 141 patients who received propafenone and 35 ( 25 % ) of 142 patients who received digoxin or placebo ( P < 0.001 ) . Acute oral treatment with propafenone is simple and effective for the conversion of recent onset AF to SR in patients without clinical signs of heart failure . The routine admission of these patients to the hospital is not necessary . Home-based administration of oral propafenone to a selected group of patients could significantly increase the cost effectiveness of this treatment The efficacy and safety of intravenous flecainide to convert recent-onset atrial fibrillation ( AF ) ( present for greater than or equal to 30 minutes and less than or equal to 72 hours and a ventricular response greater than or equal to 120 beats/min ) was investigated . A total of 102 patients without severe heart or circulatory failure were r and omized to receive either intravenous flecainide ( 2 mg/kg , maximum dose 150 mg ; 51 patients ) or placebo ( 51 patients ) in a double-blind trial . Digoxin ( 500 micrograms intravenously ) was administered to all patients who had not previously been receiving digoxin .  The  electrocardiogram  was monitored continuously during the study . In 29 ( 57 % ) patients stable sinus rhythm was restored within 1 hour after flecainide and in only 7 ( 14 % ) given placebo ( chi square 18.9 ; p = 0.000013 ; odds ratio 8.3 ; 95 % confidence interval 2.9 - 24.8 ) . Reversion to sinus rhythm within 1 hour after starting the trial medication was considered a pretrial end point and likely to be due to a drug effect . At the end of the 6-hour monitoring period , 34 patients ( 67 % ) in the flecainide group were in sinus rhythm whereas only 18 ( 35 % ) in the placebo group had reverted ( chi square 8.83 , p = 0.003 ; odds ratio 3.67 ; 95 % confidence interval 1.5 - 9.1 ) . Significant hypotension , although short lived , was more common in the flecainide group . One patient given flecainide developed torsades de pointes and was successfully electrically cardioverted . Flecainide is useful for the management of recent-onset AF both for control of the ventricular response and conversion to sinus rhythm . ( ABSTRACT TRUNCATED AT 250 WORDS UNLABELLED In a population of 417 hospitalized patients , the efficacy and safety of different drug regimens administered to convert atrial fibrillation ( AF ) of recent onset ( < or = 7 days duration ) to sinus rhythm were evaluated . All patients were in NYHA Class < or = 2 , and free of heart failure . They were r and omly allocated to treatment with placebo in 121 patients ; i.v . amiodarone , 5 mg/kg bolus , followed by 1.8 g/24 hours in 51 patients ; i.v . propafenone , 2 mg/kg bolus , followed by 0.0078 mg/kg/min in 57 patients ; p.o . propafenone , 600 mg p.o . in a single dose in 119 patients ; and p.o . flecainide , 300 mg p.o . in a single dose in 69 patients . All patients were continuously monitored by  Holter ECG  , and the number of conversions to sinus rhythm was measured at 1 , 3 , and 8 hours . RESULTS ( 1 ) I.v . propafenone result ed in a higher conversion rate within 1 hour compared with the oral loading regimens of propafenone or flecainide , but the conversion rates at 3 and 8 hours were comparable , approximately 75 % at 8 hours ; 2 ) i.v . amiodarone was not different from placebo until 8 hours when it was associated with 57 % of conversions ; ( 3 ) conversion to sinus rhythm at 8 hours was observed in 37 % of the placebo treated patients . Serious adverse effects occurred in few patients : two patients treated with flecainide and one treated with i.v . propafenone experienced left ventricular decompensation ; one patient treated with placebo and two treated with flecainide had atrial flutter with rapid ventricular response . In conclusion , single-dose , oral loading with propafenone or flecainide are acceptable alternatives to conventional drug regimens in selected hospitalized patients . In addition , the measure of a placebo effect is m and atory in studies of recent-onset AF Background Atrial fibrillation ( AF ) may arise out of anomalous impulse activity at atrial venous junctions . Triggered activity may be a source of abnormal impulse activity . Ranolazine is an anti-anginal agent , which inhibits normal and abnormal late Na+ channel current in the ventricle and peak Na+ channel current in the atrium . This produces an energy sparing effect and stabilizes cardiac membranes . Ranolazine is a potent inhibitor of triggered activity . The purpose of this report is to describe our initial experience with ranolazine used in patients with resistant AF . Methods Seven patients ( 4 males , 3 females , 67 ± 9 years ) who developed recurrent AF within hours to a few days of restoring sinus rhythm despite AF ablation and /or failing one or more anti-arrhythmic agents  were started on ranolazine ( 500 - 1000 mg/twice/day ) after stopping all other anti-arrhythmic therapy .  All but one patient had some form of associated structural heart disease . Results Two patients received no apparent benefit from ranolazine  developing recurrent AF within 2 days . All other patients derived significant benefit . Four patients have experienced no recurrent AF . The other patient relapsed at 3 months and again at 6 months . The mean time in sinus rhythm to date , or to the first relapse , for the five responders was 27 ± 11 weeks . No clinical ly evident pro-arrhythmic episodes occurred . Conclusion Ranolazine was helpful in maintaining sinus rhythm in the majority of patients in which more established measures had failed . A controlled prospect i ve trial is warranted to further investigate the efficacy of ranolazine in AF BACKGROUND Spontaneous conversion of recent onset paroxysmal atrial fibrillation  to  normal sinus rhythm  occurs commonly and is not affected by low-dose amiodarone treatment . METHODS In a r and omized , placebo-controlled trial of 100 patients with paroxysmal atrial fibrillation of recent onset ( < 48 h ) we compared the effects of treatment with continuous intravenous amiodarone 125 mg per hour ( total 3 g ) and intravenous placebo .  Patients in the placebo group who did not convert to normal sinus rhythm within 24 h were started on amiodarone therapy . RESULTS Conversion to normal sinus rhythm occurred within 24 h in 32 of 50 patients ( 64 % ) in the placebo group , most of whom converted within 8 h. Lower conversion rates were observed in patients with hypertension , ischaemic heart disease or congestive heart failure and in patients with echocardiographic findings of left atrial diameter above 45 mm , ejection fraction below 45 % or significant mitral regurgitation . However , in most patients these clinical or echocardiographic risk factors of decreases in conversion rate were not present . In such patients the spontaneous conversion rate was approximately 90 % . The conversion rate during 24 h of treatment in the amiodarone group was 92 % ( P=0.0017 , compared to the placebo group ) . In this group , the conversion rate was largely unaffected by baseline characteristics . Of the 18 patients who did not convert with placebo , 15 ( 85 % ) converted after being crossed over to amiodarone . All patients not responding to high-dose amiodarone were in chronic atrial fibrillation within 1 month . In patients still in atrial fibrillation after 8 h of treatment , the pulse rate decreased significantly more in the amiodarone as compared to the placebo group ( 83+/-15 vs 114+/-20 beats . min(-1 ) , P=0.0014 ) . CONCLUSION The spontaneous conversion of recent onset paroxysmal atrial fibrillation is high and approaches 90 % in specific clinical and echocardiographically defined subgroups . Intravenous high-dose amiodarone safely facilitates conversion of paroxysmal atrial fibrillation . However , such treatment should be reserved for patients with unfavourable risk factor profiles , not converting during 8 h of observation or requiring rate control CONTEXT Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes ( ACS ) . OBJECTIVE To determine the efficacy and safety of ranolazine during long-term treatment of patients with non-ST-elevation ACS . DESIGN , SETTING , AND PATIENTS A r and omized , double-blind , placebo-controlled , multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine ( initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily , n = 3279 ) or matching placebo ( n = 3281 ) , and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial between October 8 , 2004 , and February 14 , 2007 . MAIN OUTCOME MEASURES The primary efficacy end point was a composite of cardiovascular death , myocardial infa rct ion ( MI ) , or recurrent ischemia through the end of study . The major safety end points were death from any cause and symptomatic documented arrhythmia . RESULTS The primary end point occurred in 696 patients ( 21.8 % ) in the ranolazine group and 753 patients ( 23.5 % ) in the placebo group ( hazard ratio [ HR ] , 0.92 ; 95 % confidence interval [ CI ] , 0.83 - 1.02 ; P = .11 ) . The major secondary end point ( cardiovascular death , MI , or severe recurrent ischemia ) occurred in 602 patients ( 18.7 % ) in the ranolazine group and 625 ( 19.2 % ) in the placebo group ( HR , 0.96 ; 95 % CI , 0.86 - 1.08 ; P = .50 ) . Cardiovascular death or MI occurred in 338 patients ( 10.4 % ) allocated to ranolazine and 343 patients ( 10.5 % ) allocated to placebo ( HR , 0.99 ; 95 % CI , 0.85 - 1.15 ; P = .87 ) . Recurrent ischemia was reduced in the ranolazine group ( 430 [ 13.9 % ] ) compared with the placebo group ( 494 [ 16.1 % ] ; HR , 0.87 ; 95 % CI , 0.76 - 0.99 ; P = .03 ) . QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients ( 0.9 % ) receiving ranolazine compared with 10 patients ( 0.3 % ) receiving placebo .  Symptomatic documented arrhythmias did not differ between the ranolazine ( 99 [ 3.0 % ] ) and placebo ( 102 [ 3.1 % ] ) groups ( P = .84 ) . No difference in total mortality was observed with ranolazine compared with placebo ( 172 vs 175 ; HR , 0.99 ; 95 % CI , 0.80 - 1.22 ; P = .91 ) . CONCLUSIONS The addition of ranolazine to st and ard treatment for ACS was not effective in reducing major cardiovascular events .  Ranolazine did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia . Our findings provide support for the safety and efficacy of ranolazine as antianginal therapy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00099788 BACKGROUND Amiodarone , given as intravenous bolus has not yet been studied in patients with atrial fibrillation and a high ventricular rate . METHODS One hundred consecutive patients with atrial fibrillation and a ventricular rate above 135 bpm were r and omized to receive either 450 mg amiodarone or 0.6 mg digoxin given as a single bolus through a peripheral venous access . If the ventricular rate exceeded 100 bpm after 30 min , another 300 mg amiodarone or 0.4 mg digoxin were added . Primary endpoints of the study were the ventricular rate and the occurrence of sinus rhythm after 30 and 60 min . Secondary endpoints were blood pressure during the first hour after drug administration , and safety regarding drug induced hypotension , and phlebitis at the infusion site . RESULTS Baseline heart rate was 144+/-19 in the amiodarone group and 145+/-15 in the digoxin group ( p=0.72 ) . Following amiodarone , heart rate was 104+/-25 after 30 min compared to 116+/-23 in the digoxin group ( p=0.02 ) and 94+/-22 versus 105+/-22 after 60 min ( p=0.03 ) . After 30 min , sinus rhythm was documented in 14 ( 28 % ) patients following amiodarone compared to 3 ( 6 % ) patients in the digoxin group ( p=0.003 ) , and after 60 min in 21 ( 42 % ) versus 9 ( 18 % ) patients ( p=0.012 ) . Asymptomatic hypotension was observed in 4 amiodarone treated patients , and superficial phlebitis in 1 patient . CONCLUSIONS Amiodarone , given as an intravenous bolus is relatively safe and more effective than digoxin for heart rate control and conversion to sinus rhythm in patients with atrial fibrillation and a rapid ventricular rate STUDY OBJECTIVE A prospect i ve , r and omized controlled trial of new-onset atrial fibrillation was conducted to compare the efficacy and safety of sotalol and amiodarone ( active treatment ) with rate control by digoxin alone for successful reversion to sinus rhythm at 48 hours . METHODS We prospect ively r and omly assigned 120 patients with atrial fibrillation of less than 24 hours ' duration to treatment with sotalol , amiodarone , or digoxin using a single intravenous dose followed by 48 hours of oral treatment . Patients had ECG monitoring for 48 hours , and time of reversion , adequacy of rate control , and numbers of adverse events were compared . After 48 hours , those still in atrial fibrillation underwent cardioversion according to a st and ardized protocol . After 48 hours of therapy and attempted cardioversion , the number of patients whose rhythms had successfully reverted were compared . RESULTS There was a significant reduction in the time to reversion with both sotalol ( 13 . 0+/-2.5 hours , P < .01 ) and amiodarone ( 18.1+/-2.9 hours , P < .05 ) treatment compared with digoxin only ( 26.9+/-3.4 hours ) . By 48 hours , the active treatment group was significantly more likely to have reverted to sinus rhythm than the rate control group ( 95 % versus 78 % , P < .05 ; risk ratio 5.4 , 95 % confidence interval [ CI ] 1.5 to 19.2 ) . In those patients whose rhythms did not revert to sinus rhythm , there was superior ventricular rate control in the sotalol group at both 24 and 48 hours compared with those who received either amiodarone or digoxin . There were also fewer adverse events in the active treatment group compared with the rate control group . CONCLUSION Immediate pharmacologic therapy for new-onset atrial fibrillation with class III antiarrhythmic drugs ( sotalol or amiodarone ) improves complication-free 48-hour reversion rates compared with rate control with digoxin Atrial fibrillation ( AF ) is one of the most frequent dysrhythmias in patients coming to emergency departments ( EDs ) , and pharmacological treatment is frequently performed . The aim of this r and omized placebo-controlled multicenter trial was to compare propafenone ( a class 1C antidysrhythmic agent ) , administered i.v . in the ED , with placebo in the treatment of recent-onset AF ( < 72 h ) . We r and omly allocated 156 patients ( 88 males ; 68 females ) from 18 to 80 years old , with recent-onset AF , to receive i.v . propafenone ( 2 mg/kg for 10 min ) or the matching placebo . The patients were followed for 2 h. Exclusion criteria were the presence of one of the following : lack of informed consent , clinical evidence of heart failure , clinical hyperthyroidism , recent acute myocardial infa rct ion , atrioventricular block , cardiac valve dysfunction , a history of bronchial asthma , and current treatment with antidysrhythmic agents including digitalis . The two groups did not differ significantly in terms of sex , age , body weight , or estimated time elapsed since the beginning of atrial fibrillation . Conversion to sinus rhythm occurred in 13 of the 75 patients who received the placebo ( 17.3 % ) and in 57 of the 81 patients who were given propafenone ( 70.3 % ) . In conclusion , intravenous propafenone administration in the ED can be considered a safe and effective approach for converting AF to sinus rhythm OBJECTIVES We compared the effects of five pharmacologic regimens on the circadian rhythm and exercise-induced changes of ventricular rate ( VR ) in patients with chronic atrial fibrillation ( CAF ) . BACKGROUND Systematic comparison of st and ardized drug regimens on 24 h VR control in CAF have not been reported . METHODS In 12 patients ( 11 male , 69+/-6 yr ) with CAF , the effects on VR by 5 st and ardized daily regimens : 1 ) 0.25 mg digoxin , 2 ) 240 mg diltiazem-CD , 3 ) 50 mg atenolol , 4 ) 0.25 mg digoxin + 240 mg diltiazem-CD , and 5 ) 0.25 mg digoxin + 50 mg atenolol ; were studied after 2 week treatment assigned in r and om order . The VR data were analyzed by ANOVA with repeated measures . The circadian phase differences were evaluated by cosinor analysis . RESULTS The 24-h mean ( + /-SD ) values of VR ( bpm ) were - digoxin : 78.9 + /- 16.3 , diltiazem : 80.0+/-15.5 , atenolol : 75.9+/-11.7 , digoxin + diltiazem : 67.3+/-14.1 and digoxin + atenolol : 65.0+/-9.4 . Circadian patterns were significant in each treatment group ( p < 0.001 ) . The VR on  digoxin + atenolol  was significantly lower than that on digoxin ( p < 0.0001 ) , diltiazem ( p < 0.0002 ) and atenolol ( p < 0.001 ) . The time of peak VR on Holter was significantly delayed with regimens 3 and 5 which included atenolol ( p < 0.03 ) . During exercise , digoxin and digoxin + atenolol treatments result ed in the highest and lowest mean VR respectively . The exercise Time-VR plots of all groups were nearly parallel ( p = ns ) . The exercise duration was similar in all treatment groups ( p = ns ) . CONCLUSIONS This study indicates that digoxin and diltiazem , as single agents at the doses tested , are least effective for controlling ventricular rate in atrial fibrillation during daily activity . Digoxin + atenolol produced the most effective rate control reflecting a synergistic effect on the AV node . The data provides a basis for testing the effects of  chronic suppression of diurnal fluctuations of VR  on left atrial and ventricular function in CAF Background : Pharmacological conversion of paroxysmal atrial fibrillation is frequently necessary . The aim of this study was to compare intravenous propafenone , a class Ic antiar‐rhythmic agent , with placebo in paroxysmal atrial fibrillation ( AF ) of recent onset ( < 72 h ) AIMS To evaluate the efficacy and safety of a single loading oral dose of propafenone in the interruption of recent-onset atrial fibrillation . METHODS After a complete medical history , physical examination , 12-lead ECG , chest X-ray , and routine biochemical laboratory testing , 55 consecutive patients with recent-onset atrial fibrillation were r and omized double-blind in the emergency department for the administration of either a single oral dose ( 450 to 750 mg ) of propafenone ( 29 cases ) or a placebo ( 26 cases ) . After the 24-h observation period , comprehensive echocardiographic examination was performed . RESULTS The groups were homogeneous as regards biological , clinical and echocardiographic characteristics . Two hours after treatment , 12 patients ( 41 % ) on propafenone but only two ( 8 % ) on placebo had converted to sinus rhythm ( P = 0.005 ) . This striking difference was maintained 6 h after treatment ( 65 vs 31 % ; P = 0.015 ) but lessened at 12 h ( 69 % vs 42 % ; P = 0.060 ) and was insignificant at the end of the 24-h treatment period ( 79 % , vs 73 % ; P = 0.752 ) . Apart from hypotension , transient in three cases and sustained in one whose later echocardiographic examination demonstrated left systolic ventricular dysfunction , propafenone was well tolerated . CONCLUSION Although there is no significant difference in the rates of conversion 24 h after treatment , propafenone works faster than placebo in achieving sinus rhythm . This rapid action of oral propafenone can be useful to solve quickly the clinical problems of a high proportion of patients arriving at the emergency department with acute atrial fibrillation STUDY OBJECTIVE To compare placebo vs two different regimens of propafenone administration -- intravenous administration or short-term oral loading -- in converting recent-onset atrial fibrillation to sinus rhythm . DESIGN Single-blind placebo-controlled study . PATIENTS Eighty-seven patients with atrial fibrillation of recent onset ( < or = 7 days ' duration ) admitted to the hospital without signs of organic heart disease ( n = 42 ) or with systemic hypertension without signs or symptoms of heart failure ( n = 45 ) . The patients were assigned r and omly to treatment with intravenous propafenone ( 29 patients ) , oral propafenone ( 29 patients ) , or placebo ( 29 patients ) . INTERVENTIONS Administration of propafenone intravenously ( 2-mg/kg bolus followed by 0.0078 mg/kg/min ) or as short-term oral loading ( 600 mg orally single dose ) . Patients were su bmi tted to Holter monitoring and conversion to sinus rhythm was evaluated at 1 , 3 , and 8 h. RESULTS Conversion to sinus rhythm was obtained within 1 h in 28 % with intravenous propafenone , in 3 % with oral propafenone , and in 3 % with placebo . At 3 h , the efficacy of intravenous propafenone ( 41 % ) and of oral propafenone ( 55 % ) were statistically superior to placebo ( 10 % of conversions ) and at 8 h either intravenous or oral propafenone were effective in almost two thirds of the patients with a statistical difference vs placebo , whose efficacy was 24 % . No major side effects were observed . CONCLUSIONS Propafenone as an oral loading dose is an efficacious and fast way of treating atrial fibrillation of recent onset and due to its simplicity of administration and safety can be preferred to the intravenous route AIMS A r and omized , double-blind study with a high dose of digoxin administered intravenously for conversion of atrial fibrillation ( not due to haemodynamic alternations ) to sinus rhythm , and for rate control in converters and non-converters was set up . Outcome measures were conversion within 12 h ; time to conversion ; early rate control ; and stable slowing within 12 h. METHODS We studied 40 patients with recent onset ( < 1 week ) atrial fibrillation ; controls received saline intravenously , the other patients digoxin 1.25 mg .  RESULTS One patient converted before digoxin administration . Conversion occurred in 9/19 patients on digoxin and in 8/20 on placebo ( ns ) . The mean time to conversion tended to be shorter only for digoxin . Two late conversions on placebo were observed within 24 h. Heart rate during atrial fibrillation decreased after 30 min for converters and non-converters ( P < 0.05 ) . For all patients on digoxin , heart rate after 30 min was lower compared to baseline ( P < 0.002 ) and to placebo ( P < 0.02 ) . Persistent , stable slowing occurred only in 3/10 non-converters on digoxin ( P < 0.05 ) , and two patients developed bradyarrhythmias . QTc was shortened immediately after conversion in all patients . Converters had baseline characteristics similar to those of non-converters . CONCLUSIONS Intravenous digoxin offers no substantial advantages over placebo in recent onset atrial fibrillation with respect to conversion , and provides weak rate control In severe heart failure many deaths are sudden and are presumed to be due to ventricular arrhythmias . The GESICA trial evaluated the effect of low-dose amiodarone on two-year mortality in patients with severe heart failure . Our prospect i ve multicentre trial included 516 patients on optimal st and ard treatment for heart failure . Patients were r and omised to 300 mg/day amiodarone ( 260 ) or to st and ard treatment ( 256 ) . Intention-to-treat analysis showed 87 deaths in the amiodarone group ( 33.5 % ) compared with 106 in the control group ( 41.4 % ) ( risk reduction 28 % ; 95 % CI 4%-45 % ; log rank test p = 0.024 ) . There were reductions in both sudden death ( risk reduction 27 % ; p = 0.16 ) and death due to progressive heart failure ( risk reduction 23 % ; p = 0.16 ) . Fewer patients in the amiodarone group died or were admitted to hospital due to worsening heart failure ( 119 versus 149 in the control group ; risk reduction 31 % ; 95 % CI 13 - 46 % ; p = 0.0024 ) . The decrease in mortality and hospital admission was present in all subgroups examined and independent of the presence of non-sustained ventricular tachycardia . Side-effects were reported in 17 patients ( 6.1 % ) ; amiodarone was withdrawn in 12 . Low-dose amiodarone proved to be an effective and reliable treatment , reducing mortality and hospital admission in patients with severe heart failure independently of the presence of complex ventricular arrhythmias Background — Vernakalant , a relatively atrial-selective antiarrhythmic drug , has previously demonstrated efficacy for the acute conversion of atrial fibrillation ( AF ) to sinus rhythm . This study was design ed to determine the most appropriate oral dose of vernakalant for the prevention of AF recurrence postcardioversion . Methods and Results — Patients with nonpermanent AF were r and omized to 150 , 300 , or 500 mg vernakalant or placebo twice daily for up to 90 days . The efficacy analysis was conducted on 605 of 735 patients who entered the maintenance phase on day 3 after cardioversion . The time to the first recurrence of symptomatic sustained AF was significantly longer in the 500 mg vernakalant group , with a median of > 90 days versus 29 days in the placebo group ( hazard ratio , 0.735 ; P=0.0275 ) . No significant effect was seen at the lower doses . The percent of patients in sinus rhythm at day 90 was 41 % , 39 % , and 49 % in the 150-mg ( n=147 ) , 300-mg ( n=148 ) , and 500-mg ( n=150 ) vernakalant groups , respectively , compared with 36 % in the placebo group ( n=160 ) . There were no vernakalant-related proarrhythmic events . Related serious adverse events occurred in 2 patients in the 150-mg vernakalant group and in 1 patient in each of the other groups . Conclusions — Vernakalant , 500 mg twice daily , appears to be effective and safe for the prevention of AF recurrence after cardioversion . The absence of proarrhythmia and favorable safety profile is an important finding for the drug . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00526136 STUDY OBJECTIVES The relative risks and benefits of strategies of rate control vs rhythm control in patients with atrial fibrillation ( AF ) remain to be fully explored . DESIGN The How to Treat Chronic Atrial Fibrillation ( HOT CAFE ) Polish trial was design ed to evaluate in a r and omized , multicenter , and prospect i ve manner the feasibility and long-term outcomes of rate control vs rhythm control strategies in patients with persistent AF . PATIENTS Our study population comprised 205 patients ( 134 men and 71 women ; mean [ + /- SD ] age , 60.8 + /- 11.2 years ) with a mean AF duration of 273.7 + /- 112.4 days . The mean observation period was 1.7 + /- 0.4 years . One hundred one patients were r and omly assigned to the rate control group and received rate-slowing therapy guided by repeated 24-h Holter monitoring . Direct current cardioversion and atrioventricular junctional ablation with pacemaker placement were alternative nonpharmacologic strategies for patients with tachycardia that was resistant to medical therapy . One hundred four patients were r and omized to sinus rhythm restoration and maintenance using serial cardioversion supported by a predefined stepwise antiarrhythmic drug regimen ( ie , disopyramide , propafenone , sotalol , and amiodarone ) . In both groups , thromboembolic prophylaxis followed current guidelines . MEASUREMENTS AND RESULTS At the end of follow-up , 63.5 % of patients in the rhythm control arm remained in sinus rhythm . No significant differences in the composite end point ( ie , all-cause mortality , number of thromboembolic events , or major bleeding ) were found between the rate control group and the rhythm control group ( odds ratio , 1.98 ; 95 % confidence interval , 0.28 to 22.3 ; p > 0.71 ) . The incidence of hospital admissions was much lower in the rate control arm ( 12 % vs 74 % , respectively ; p < 0.001 ) . New York Heart Association functional class improved in both study groups , while mean exercise tolerance , as measured by the maximal treadmill workload , improved only in the rhythm control group ( 5.2 + /- 5.1 vs 7.6 + /- 3.3 metabolic equivalents , respectively ; p < 0.001 ) . The rhythm control strategy led to an increased mean left ventricular fractional shortening ( 29 + /- 7 % vs 31 + /- 7 % , respectively ; p < 0.01 ) . One episode of pulmonary embolism occurred in the rate control group despite oral anticoagulation therapy , while three patients in the rhythm control arm of the study experienced ischemic strokes ( not significant ) . CONCLUSIONS The Polish HOT CAFE study revealed no significant differences in major end points between the rate control group and the rhythm control group The efficacy of amiodarone has been proved in long-term maintenance of sinus rhythm ( SR ) in patients with paroxysmal atrial fibrillation ( AF ) . The present study evaluates the efficacy and safety of a single oral dose of amiodarone in patients with recent-onset AF ( < 48 hours ) . Seventy-two patients were r and omized to receive 30 mg/kg of either amiodarone or placebo .  Conversion to SR was verified by 24-hour Holter monitoring . Ten patients were excluded because of SR in the beginning of monitoring or technical failure during Holter monitoring . The remaining study groups were comparable ( n = 31 for each ) , except that in the placebo group beta blockers were more common . The patients receiving amiodarone  converted to SR more effectively than those receiving placebo ( p<0.0001 ) . At 8 hours , approximately 50 % of patients in the amiodarone group and 20 % in the placebo group ( Holter successful ) had converted to SR , whereas after 24 hours the corresponding figures were 87 % and 35 % , respectively . The median time for conversion ( 8.7 hours for amiodarone and 7.9 hours for placebo ) did not differ in the groups . Amiodarone was hemodynamically well tolerated , and the number of adverse events in the study groups was similar . Amiodarone as a single oral dose of 30 mg/kg appears to be effective and safe in patients with recent-onset AF The optimal way to convert recent-onset atrial fibrillation to sinus rhythm is a subject of much debate . The effectiveness of intravenous propafenone  has been shown [ 1 - 3 ] , but the full antiarrhythmic effect of this regimen depends not only on the parent compound but on its 5-hydroxylated metabolite [ 4 , 5 ] . This dependence provides a strong rationale for the use of oral loading regimens [ 3 ] . Results of previous controlled studies have shown that oral loading of propafenone is highly effective in converting recent-onset atrial fibrillation to sinus rhythm [ 6 , 7 ] . Safety is a major concern with antiarrhythmic therapy . One of the primary proarrhythmic risks of propafenone and flecainide is the transformation of atrial fibrillation to flutter with 1:1 atrioventricular conduction and hemodynamic impairment [ 8 - 10 ] . We sought to determine whether the effectiveness and safety of propafenone differ in patients who have structural heart disease and patients who do not . Methods From June 1990 to June 1994 , consecutive patients with recent-onset atrial fibrillation ( 7 days ) who presented to one of three centers were considered for enrollment .  Onset of arrhythmia was documented by electrocardiography or by an abrupt onset of palpitations with subsequent evidence of atrial fibrillation on electrocardiography . Patients were excluded for any of the following reasons : age greater than 80 years , heart failure greater than NYHA ( New York Heart Association ) class II , mean ventricular rate during atrial fibrillation less than 70 beats/min , recent myocardial infa rct ion ( within < 6 months ) , unstable angina pectoris , previous or current electrocardiographic evidence ventricular preexcitation or complete bundle-branch block , previous electrocardiographic evidence of second- or third-degree atrioventricular block or bifascicular block , the sick sinus syndrome , hypokalemia ( potassium level < 3.5 mEq/L ) , renal or hepatic failure with severe hypoxia ( Pao 2 < 55 mm Hg ) , severe metabolic disturbances , or known thyroid dysfunction . Patients who were receiving long-term digoxin therapy or antiarrhythmic drugs or had received such treatments within 8 hours before study entry were also excluded . Patients who had atrial fibrillation that lasted 72 hours or longer were enrolled only if they were receiving long-term  warfarin therapy for anticoagulation . Patients provided informed consent . Eligible patients had a 24-hour Holter monitor applied ; after 1 to 2 hours of observation to assess the stability of atrial fibrillation , they were r and omly assigned by center in a single-blind manner to receive propafenone ( 300 mg in two tablets as a single oral dose ) or placebo . All patients received intravenous saline throughout the study period . The electrocardiogram was monitored by telemetry , blood pressure was measured every 2 hours , and 12-lead electrocardiography was done every hour for the first 4 hours and then every 2 hours for the next 4 hours . When patients converted to sinus rhythm , 12-lead electrocardiography was done immediately . Conversion was defined as a stable sinus rhythm that lasted for at least 1 hour . Eight hours after the study drug was administered , physicians could continue treatment with the study drug or switch to a different therapeutic option . Holter monitor tapes were analyzed by two blinded observers using computer scanning systems ( Marquette 8000 , Milwaukee , Wisconsin , and Del Mar Avionics , Irvine , California ) to determine the time of conversion to sinus rhythm and whether an abnormal rhythm was present . Within 24 hours after enrollment , echocardiography was done for each patient and left atrial diameter was measured in the left parasternal long-axis view . On the basis of clinical history and the results of physical examination , echocardiography , and chest radiography , patients were classified as having structural heart disease ( defined as the presence of cardiac abnormalities other than atrial fibrillation ) , hypertension without structural heart disease ( defined as previously recognized systemic hypertension according to the criteria of the World Health Organization ) , or neither . Continuous outcomes and baseline characteristics of the patients were compared by using the chi-square statistic and t-test as appropriate . The rates of conversion to sinus rhythm were assessed at 3 and 8 hours . Odds ratios and corresponding CIs were calculated according to the methods of Gardner and Altman [ 11 ] . We did logistic regression analysis to describe how the interaction of treatment with the presence or absence of heart disease and hypertension affected the probability of conversion to sinus rhythm . Analyses were done using SPS software , version 6.1.3 ( SPS , Inc. , Chicago , Illinois ) . Results Patients During the study period , 407 patients presented to the three centers and were screened for eligibility . Two hundred forty-three patients were eligible , and 240 gave consent . A total of 164 patients were excluded for one or more of the following reasons : age greater than 80 years ( n = 10 ) , heart failure greater than NYHA class II ( n = 33 ) , recent myocardial infa rct ion ( n = 20 ) , bundle-branch block ( n = 24 ) , the sick sinus syndrome ( n = 6 ) , severe hypoxia ( n = 13 ) , thyroid dysfunction ( n = 12 ) , and previous antiarrhythmic treatment ( n = 63 ) . Two hundred forty patients were r and omly assigned to receive propafenone ( n = 119 ) or placebo ( n = 121 ) . The two groups were similar with regard to age , sex , cause of atrial fibrillation , NYHA class , left atrial dimension ( measured by echocardiography ) , structural heart disease , and hypertension ( Table 1 ) . The duration of atrial fibrillation before r and omization ranged from 2.5 to 120 hours and did not differ significantly between the treatment groups . Table 1 . Patient Characteristics Conversion to Sinus Rhythm and Presence of Heart Disease The probability of conversion to sinus rhythm was greater after propafenone than after placebo at 3 and 8 hours ( P < 0.001 ) ( Figure 1 ) . Corresponding odds ratios were 3.8 ( 95 % CI , 2.1 to 6.8 ) at 3 hours and 5.4 ( CI , 3.0 to 9.4 ) at 8 hours . Figure 1 . Conversion to sinus rhythm within 8 hours in patients receiving propafenone or placebo . At 8 hours , the probability of conversion to sinus rhythm was significantly higher in the propafenone group than in the placebo group for patients who had heart disease ( odds ratio , 21.7 [ CI , 5.9 to 80.1 ] ; P < 0.001 ) , patients who had hypertension ( odds ratio , 6.4 [ CI , 2.3 to 17.6 ] ; P < 0.001 ) , and patients who did not have structural heart disease ( odds ratio , 2.8 [ CI , 1.2 to 6.7 ] ; P = 0.02 ) . Conversion rates at 8 hours for patients receiving propafenone were similar among the three heart disease subgroups , but conversion rates for patients receiving placebo differed significantly ( 56 % for patients without structural heart disease , 27 % for patients with hypertension , and 17 % patients with structural heart disease [ P = 0.009 by logistic regression model ] ) . At 3 hours , the probability of conversion to sinus rhythm was higher in the propafenone group than in the placebo group for patients who did not have heart disease ( 48 % for propafenone compared with 26 % for placebo ; odds ratio , 2.6 [ CI , 1.2 to 6.0 ] ; P = 0.02 ) , patients who had hypertension ( 41 % for propafenone compared with 16 % for placebo ; odds ratio , 3.5 [ CI , 1.2 to 10.5 ] ; P = 0.02 ) , and patients who had structural heart disease ( 47 % for propafenone compared with 7 % for placebo ; odds ratio , 12.3 [ CI , 2.5 to 60.5 ] ; P < 0.001 ) . By logistic regression analysis , no significant correlation between heart disease and treatment was seen at 3 hours ( P = 0.2 ) . Mean time SD for conversion to sinus rhythm within 8 hours was 181 118 minutes for propafenone and 181 112 minutes for placebo ( P > 0.2 ) . Adverse Effects Sustained atrial flutter or tachycardia ( lasting 1 min ) occurred in eight patients ( 7 % ) receiving propafenone and seven patients ( 6 % ) receiving placebo ( P > 0.2 ) , regardless of heart disease status . Among these patients , atrioventricular conduction was 2:1 in two patients receiving propafenone ( heart rate , 115 to 140 beats/min ) and three patients receiving placebo ( heart rate , 120 to 150 beats/min ) , 3:1 in six patients receiving propafenone ( heart rate , 60 to 95 beats/min ) and three patients receiving placebo ( heart rate , 60 to 100 beats/min ) , and 1:1 in one patient receiving placebo ( heart rate , 240 beats/min ) . This patient developed atrial flutter and collapsed . Pauses in ventricular rate lasting longer than 2 seconds were seen in one patient ( 1 % ) receiving propafenone and three patients ( 2 % ) receiving placebo ( P > 0.2 ) . Among patients receiving propafenone , nine ( 8 % ) had the following adverse effects : QRS complexes of the electrocardiogram greater than 120 ms ( n = 3 ) , hypotension ( n = 2 ) , slight hypotension and bradycardia at conversion ( n = 3 ) , and phases of junctional rhythm after conversion ( n = 1 ) . No ventricular proarrhythmic effects occurred . Discussion Oral loading of propafenone was effective for conversion to sinus rhythm in our study , as it has been in smaller studies [ 3 , 6 , 7 , 12 , 13 ] . The recent findings of Wijffels and colleagues [ 14 ] in a model of chronic atrial fibrillation in animals indicate that electrophysiologic remodeling occurs within a few hours of persistent atrial fibrillation and results primarily from changes in atrial refractoriness that enhance the persistence of atrial fibrillation . This observation provides a strong rationale for prompt conversion to sinus rhythm . Therefore , oral loading of propafenone ( which has an effectiveness similar to that of intravenous propafenone [ 3 ] ) offers many advantages over such regimens as oral quinidine and intravenous amiodarone , which require titration of dose or a longer period of time to achieve an effect [ 6 , 13 , 15 ] . In controlled trials , propafenone was shown to be more effective and to take effect more quickly than amiodarone [ 13 ] or digoxin plus quinidine [ 6 ] . Intravenous amiodarone  was no more effective than placebo The fundamental management strategy for atrial fibrillation ( AF ) is still debated . There is no doubt that those patients at risk of thromboembolic events should be offered anticoagulant therapy . However , it is uncertain whether rhythm control ( restoration and maintenance of sinus rhythm ) or rate control ( adjustment to a physiological ventricular rate while allowing AF to continue ) is the preferred primary treatment option for the reduction of symptoms and major cardiovascular ( CV ) outcomes associated with AF . Several well conducted trials comparing the two strategies led to the conclusion that there was little to choose between them . However , guidelines leaned towards recommending rate control as the initial strategy , and reserved rhythm control for those who remained symptomatic . Recently this status quo is being increasingly challenged by the clear demonstration that left atrial catheter ablation is effective at suppressing AF resistant to traditional antiarrhythmic drugs , such as those that failed to demonstrate any superiority when compared with rate control . Also , recently introduced antiarrhythmic therapy may have superior efficacy with regard to reducing unexpected CV hospitalization , CV mortality and stroke . In addition , there is a growing perception that atrial remodelling should be best prevented by early rhythm control rather than delaying until rate control has proven unsatisfactory . For these reasons the results of large r and omised clinical trials , which recruit patients soon after the presentation of AF and compare ' aggressive ' modern rhythm control against the guideline approach of primary rate control , are eagerly awaited . In the meantime the pendulum of clinical opinion has begun to swing towards a rhythm control strategy OBJECTIVES This study was design ed to compare two treatment strategies in patients with atrial fibrillation(AF ) :  rhythm-control ( restoration and maintenance of sinus rhythm ) and rate-control ( pharmacologic or invasive rate-control and anticoagulation ) . BACKGROUND Atrial fibrillation is the most common arrhythmia . It is unclear whether a strategy of rhythm- or rate-control is better in terms of mortality , morbidity , and quality of life . METHODS The Strategies of Treatment of Atrial Fibrillation ( STAF ) multicenter pilot trial r and omized 200 patients ( 100 per group ) with persistent AF to rhythm- or rate-control .  The combined primary end point was a combination of death , cardiopulmonary resuscitation , cerebrovascular event , and systemic embolism . RESULTS After 19.6 + /- 8.9 months ( range 0 to 36 months ) there was no difference in the primary end point between rhythm-control ( 9/100 ; 5.54%/year ) and rate-control ( 10/100 ; 6.09%/year ; p = 0.99 ) . The percentage of patients in sinus rhythm in the rhythm-control group after up to four cardioversions during the follow-up period ( rate-control group ) was 23 % ( 0 % ) at 36 months . Eighteen primary end points occurred in atrial fibrillation ; only one occurred in sinus rhythm ( p = 0.049 ) . CONCLUSIONS The STAF pilot study showed no differences between the two treatment strategies in all end points except hospitalizations . These data suggest that there was no benefit in attempting rhythm-control in these patients with a high risk of arrhythmia recurrence . It remains unclear whether the results in the rhythm-control group would have been better if sinus rhythm had been maintained in a higher proportion of patients , as all but one end point occurred during AF In recent-onset atrial fibrillation , intravenous propafenone has been shown to effectively restore sinus rhythm , whereas the efficacy of intravenous digoxin has been question ed . We directly compared these 2 drugs and placebo in acute atrial fibrillation . One hundred twenty-three patients with atrial fibrillation lasting < 72 hours were r and omized to a 10-minute intravenous infusion of either propafenone ( 2 mg/kg , 41 patients ) or digoxin ( 0.007 mg/kg , 40 patients ) or placebo ( 42 patients ) . After 1 hour , nonconverted propafenone or digoxin patients were switched to the alternative drug , while nonconverted placebo patients were r and omized to either propafenone or digoxin . The observation time ended 1 hour later . By 1 hour , conversion rates were 49 % in the propafenone group , 32 % in the digoxin group ( p = 0.12 ) , and 14 % in placebo group ( p < 0.001 vs propafenone , p = 0.08 vs digoxin ) . After crossover , digoxin converted 5 % of propafenone patients , while propafenone converted 48 % of digoxin patients ( p < 0.05 ) . In the 36 nonconverted  placebo patients , sinus rhythm was obtained in 53 % of cases with propafenone , and in 5 % with digoxin ( p < 0.05 ) . Globally , among the 116 patients who received a drug as first treatment , 30 of 60 patients ( 50 % ) were converted by propafenone versus 14 of 56 ( 25 % ) by digoxin ( p < 0.01 ) ( odds ratio 2.0 , 95 % confidence interval 1.19 to 3.36 ) . In nonconverters , the ventricular rate reduction was faster ( 15 vs 45 minutes ) and more prominent ( -24 % vs -14 % ) with propafenone than with digoxin . In conclusion , intravenous propafenone  terminates atrial fibrillation more effectively than either placebo or intravenous digoxin . In addition , in nonconverted patients , it obtains a more rapid and marked control of the ventricular rate OBJECTIVES The purpose of this study was to determine the efficacy and safety of intravenous RSD1235 in terminating  recent onset atrial fibrillation ( AF ) .  BACKGROUND Anti-arrhythmic drugs currently available to terminate AF have limited efficacy and safety . RSD1235 is a novel atrial selective anti-arrhythmic drug . METHODS This was a phase II , multi-centered , r and omized , double-blinded , step-dose , placebo-controlled , parallel group study . Fifty-six patients from 15 U.S. and Canadian sites with AF of 3 to 72 h duration were r and omized to one of two  RSD1235  dose groups or to placebo . The two RSD1235 groups were RSD-1 ( 0.5 mg/kg followed by 1 mg/kg ) or RSD-2 ( 2 mg/kg followed by 3 mg/kg ) , by intravenous infusion over 10 min ; a second dose was given only if AF was present . The primary end point was termination of AF during infusion or within 30-min after the last infusion . Secondary end points included the number of patients in sinus rhythm at 0.5 , 1 , and 24 h post-last infusion and time to conversion to sinus rhythm . RESULTS The RSD-2 dose showed significant differences over placebo in : 1 ) termination of AF ( 61 % vs. 5 % , p < 0.0005 ) ; 2 ) patients in sinus rhythm at 30 min ( 56 % vs. 5 % , p < 0.001 ) ; 3 ) sinus rhythm at 1 h ( 53 % vs. 5 % , p = 0.0014 ) ; and 4 ) median time to conversion to SR ( 14 vs. 162 min , p = 0.016 ) . There were no serious adverse events related to RSD1235 . CONCLUSIONS RSD1235 , a new atrial-selective anti-arrhythmic agent , appears to be efficacious and safe for converting recent onset AF to sinus rhythm In patients with recent-onset atrial fibrillation ( AF ) , restoration of sinus rhythm is considered to be the first-line therapeutic option . Although this conversion might be obtained by direct-current shock or intravenous antiarrhythmic drugs , administration of an oral loading dose of class I or III antiarrhythmic drugs is more simple and convenient . This prospect i ve , r and omized , multicenter study compares the time to conversion to sinus rhythm obtained with an oral loading dose of propafenone or amiodarone .  Patients with recent-onset AF ( < 2 weeks ) , without contraindications for the 2 drugs , were r and omly assigned to be treated with propafenone ( 600 mg for the first 24 hours and if necessary a repeated dose of 300 mg for 24 hours ) or amiodarone ( 30 mg/kg for the first 24 hours and if necessary a repeated dose of 15 mg/kg for 24 hours ) . Exact conversion time during the first 24 hours was determined by Holter monitoring . In each treatment group 43 patients with the same baseline characteristics were included . The median time for restoration of sinus rhythm was shorter ( p = 0.05 ) in the propafenone ( 2.4 hours ) than in the amiodarone ( 6.9 hours ) group . After 24 hours ( 56 % in the propofenone and 47 % in the amiodarone group ) and 48 hours , the same proportion of patients in the 2 groups recovered sinus rhythm ( no serious adverse events were noticed ) . Thus , oral loading dose of propafenone or amiodarone was safe with a similar conversion rate of recent-onset AF .  Propafenone had a faster action BACKGROUND Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation . However , recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits of sinus rhythm . We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation . METHODS We r and omly assigned 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aim ed at rate control or rhythm control . Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication . Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs . The end point was a composite of death from cardiovascular causes , heart failure , thromboembolic complications , bleeding , implantation of a pacemaker , and severe adverse effects of drugs . RESULTS After a mean ( + /-SD ) of 2.3+/-0.6 years , 39 percent of the 266 patients in the rhythm-control group had sinus rhythm , as compared with 10 percent of the 256 patients in the rate-control group . The primary end point occurred in 44 patients ( 17.2 percent ) in the rate-control group and in 60 ( 22.6 percent ) in the rhythm-control group . The 90 percent ( two-sided ) upper boundary of the absolute difference in the primary end point was 0.4 percent ( the prespecified criterion for noninferiority was 10 percent or less ) . The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups . CONCLUSIONS Rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion BACKGROUND The authors report their experience in recent-onset atrial fibrillation treated with intravenous flecainide and propafenone , in comparison with the placebo group . METHODS We r and omized 352 ( 138 in the flecainide group , 164 in the propafenone group and 50 in the control group ) consecutive patients ( 167 males , 185 females , mean age 59 + /- 12 years ) with recent-onset atrial fibrillation . The  electrocardiogram  of all patients was monitored for at least 24 hours . RESULTS The restoration of sinus rhythm occurred in 72.5 , 80.4 , 86.2 and 89.8 % of patients in the flecainide group ; in 54.3 , 68.3 , 75 and 92.1 % in the propafenone group ; in 22.2 , 27.8 , 35.2 and 46.3 % in the control group , at 1 , 3 , 6 and 24 hours respectively . The occurrence of side effects was the same in all treatment groups , and occurred in about 10 % of patients in the flecainide and propafenone groups , and in 4 % in the control group . In our study population the treatment of recent-onset atrial fibrillation with flecainide was faster in converting the arrhythmia to sinus rhythm ( p < 0.005 at 1 hour , p < 0.05 at 3 hours , p = 0.05 at 6 hours ) . However within 24 hours the efficacy of either flecainide or propafenone was the same ( p = NS at 24 hours ) . CONCLUSIONS Side effects were similar in both treatment groups . In particular malignant arrhythmias did not occur in the treatment groups and in the control group OBJECTIVES This r and omized double-blind study compared the efficacy and safety of intravenous vernakalant and amiodarone for the acute conversion of  recent-onset atrial fibrillation ( AF ) .  BACKGROUND Intravenous vernakalant has effectively converted recent-onset AF and was well tolerated in placebo-controlled studies . METHODS A total of 254 adult patients with AF ( 3 to 48 h duration ) eligible for cardioversion were enrolled in the study . Patients received either a 10-min infusion of vernakalant ( 3 mg/kg ) followed by a 15-min observation period and a second 10-min infusion ( 2 mg/kg ) if still in AF , plus a sham amiodarone infusion , or a 60-min infusion of amiodarone ( 5 mg/kg ) followed by a maintenance infusion ( 50 mg ) over an additional 60 min , plus a sham vernakalant infusion . RESULTS Conversion from AF to sinus rhythm within the first 90 min ( primary end point ) was achieved in 60 of 116 ( 51.7 % ) vernakalant patients compared with 6 of 116 ( 5.2 % ) amiodarone patients ( p < 0.0001 ) . Vernakalant result ed in rapid conversion ( median time of 11 min in responders ) and was associated with a higher rate of symptom relief compared with amiodarone ( 53.4 % of vernakalant patients reported no AF symptoms at 90 min compared with 32.8 % of amiodarone patients ; p = 0.0012 ) . Serious adverse events or events leading to discontinuation of study drug were uncommon . There were no cases of torsades de pointes , ventricular fibrillation , or polymorphic or sustained ventricular tachycardia . CONCLUSIONS Vernakalant demonstrated efficacy superior to amiodarone for acute conversion of recent-onset AF . Both vernakalant and amiodarone were safe and well tolerated in this study . ( A Phase III Superiority Study of Vernakalant vs Amiodarone in Subjects With Recent Onset Atrial Fibrillation [ AVRO ] ; NCT00668759 ) BACKGROUND Uncertainty persists about the safety and efficacy of amiodarone for the management of heart failure . METHODS AND RESULTS We r and omized 3029 patients with chronic heart failure to receive carvedilol or metoprolol  and followed patients for a median of 58 months . One hundred fifty-five of 1466 patients in New York Heart Association ( NYHA ) Class II and 209 of 1563 in Class III or IV received amiodarone at baseline . Persistence with amiodarone treatment was high and 66 % received amiodarone after 4 years . During follow-up , 38.7 % and 58.9 % of patients receiving amiodarone in NYHA Classes II and III + IV died versus 26.2 % and 43.3 % not receiving amiodarone ( P < .001 ) . This difference was maintained in multivariable analysis ( hazard ratio [ HR ] 1.5 , 95 % confidence interval [ CI ] 1.2 - 1.7 , P < .001 ) . The difference was explained by an increased risk of death due to circulatory failure ( HR 2.4 , CI 1.9 - 3.1 , P < .001 ) in patients receiving amiodarone .  Sudden death was not different ( HR 1.07 , CI 0.8 - 1.4 , P = .7 ) . The increased risk was similar across NYHA classes with HR of 1.60 ( CI 1.2 - 2.1 , P < .001 ) in NYHA Class II versus 1.58 ( CI 1.3 - 1.9 , P < .001 ) in Classes III + IV . CONCLUSIONS Treatment with amiodarone was associated with an increased risk of death from circulatory failure independent of functional class In a r and omized , double-blind , controlled study of 98 patients with atrial fibrillation ( AF ) ( present for > or = 30 minutes , < or = 72 hours , and a ventricular response of > or = 100 beats/min ) , intravenous flecainide ( 2 mg/kg , maximum 150 mg ) was compared with intravenous amiodarone ( 7 mg/kg ) and placebo .  Exclusion criteria included significant left ventricular dysfunction , inotrope dependence , recent antiarrhythmic therapy , hypokalemia , and pacemaker dependence . Reversion to stable sinus rhythm within 2 hours of starting medication was considered likely to be due to drug effect . Twenty of 34 patients ( 59 % ) given flecainide , 11 of 32 ( 34 % ) given amiodarone , and 7 of 32 ( 22 % ) given placebo reverted to stable sinus rhythm in < or = 2 hours after starting medication ( chi-square 9.87 , p = 0.007 ) . More patients reverted to stable rhythm with flecainide than with placebo ( p = 0.005 ; odds ratio 5.1 , 95 % confidence interval 1.54 to 17.5 ) . There was no significant difference between amiodarone and placebo or between flecainide and amiodarone . However , after 8 hours there were no significant differences in reversion between the treatment groups : flecainide ( n = 23 , 68 % ) , amiodarone ( n = 19 , 59 % ) , and placebo ( n = 18 , 56 % ) . Amiodarone promptly reduced the ventricular rate , and this effect was maintained for 8 hours in those whose reversion to stable sinus rhythm was unsuccessful : flecainide was no more effective than placebo in controlling ventricular rate . Adverse effects were not significantly different in the 3 groups . Thus , intravenous flecainide results in earlier reversion of AF than does intravenous amiodarone or placebo . Amiodarone , although less effective in reverting AF , slows the rapid ventricular response . ( ABSTRACT TRUNCATED AT 250 WORDS To evaluate the efficacy of propafenone in converting recent‐onset atrial fibrillation ( AF ) lasting < 7 days , 182 patients were treated intravenously with propafenone ( Group 1 , n = 98 ) and with placebo 0.9 % saline solution ( Group 2 , n = 84 ) in a double blind study . The treatment was continued until sinus rhythm ( SR ) was restored , but for no more than 24 h. Eighty‐nine patients treated with propafenone ( 90.8 % ) and 27 patients treated with placebo ( 32.1 % ) responded to the treatment and SR was restored ( p < 0.0005 ) . The mean time for SR restoration was 2.51± 2.77 h in Group 1 , and 17.15± 7.8 h in Group 2 ( p < 0.0005 ) . In both groups the patients in whom SR was not restored ( nonresponders ) had larger left atrial size and longer duration of AF than responders at the onset of the arrhythmia . Nonresponders in Group 1 showed a decrease in mean ventricular rate ( MVR ) from 143± 16 to 101± 18 ( p < 0.0005 ) , while in the nonresponders in Group 2 no reduction of MVR was observed . Two patients whose SR was restored with propafenone had sinus st and still lasting 3.4 and 3.8 s , respectively . Propafenone used intravenously is an effective , quick , and safe drug for treating AF . Moreover , it significantly reduces MVR in nonresponders The effects of amiodarone in a low dosage ( 200 mg every 8 h for 2 weeks , then 200 mg/day ) was assessed in a double-blind placebo-controlled trial in 34 patients with a history of severe congestive heart failure but no sustained ventricular arrhythmia .  Left ventricular ejection fraction , treadmill exercise tolerance and 48 h electrocardiographic monitoring were assessed before and repeatedly after beginning amiodarone or placebo therapy over 6 months , and side effects were monitored . In patients receiving amiodarone , the ejection fraction increased significantly from 19 + /- 7 to 29 + /- 15 % at 6 months ( p less than 0.01 from baseline ) , but not significantly in 14 placebo-treated patients ( 18 + /- 5 to 22 + /- 9 % ) . Exercise tolerance increased significantly in amiodarone-treated patients ( median 433 s to 907 s , p less than 0.05 ) , but not significantly in placebo-treated patients ( 757 to 918 s ) . Nonsustained ventricular tachycardia was present in 88 % of amiodarone-treated patients before , but in only 21 % of patients after 6 months of treatment ( p = 0.06 ) ; it was seen in 43 % of placebo-treated patients at baseline and in 50 % after 6 months . Fifty percent of amiodarone-treated patients had side effects ( principally nausea ) and the drug was withdrawn in 28 % of cases ; no life-threatening effects were seen . Low dose amiodarone appears to have a multifaceted potential to produce benefits in arrhythmia control , exercise tolerance and ventricular function in patients with a history of severe congestive heart failure , but better control of side effects ( principally nausea ) appears essential . Effects on mortality could not be determined from this study ; such assessment requires a larger cohort of patients Summary : Thirty-four patients with atrial fibrillation complicating suspected acute myocardial infa rct ion were r and omised to treatment with intravenous amiodarone ( n = 18 ) or intravenous digoxin ( n = 16 ) . After 24 h , similar proportions of patients in each group had reverted to sinus rhythm . However , there was a tendency towards earlier reversion with amiodarone . At 4 h , 72 % of the amiodarone group had reverted to sinus rhythm , compared with 31 % of the digoxin group ( p < 0.1 ) . This tendency was more marked in patients with definite infa rct ion ( at 4 h , amiodarone 75 % reversion , digoxin 10 % reversion ) . Neither drug had a significant effect on blood pressure . Atrial fibrillation may cause serious haemodynamic deterioration in acute myocardial infa rct ion . In comparison with digoxin , amiodarone offers more rapid control of the ventricular response rate and may , in addition , restore sinus rhythm more rapidly UNLABELLED The efficacy and safety of intravenous propafenone , amiodarone , or placebo were compared in the treatment of atrial fibrillation ( AF ) of recent onset ( duration < or = 48 hours ) . METHODS 143 patients ( 77 men , mean age 63 + /- 12 years ) were studied , of whom 46 received propafenone ( 2 mg/kg over 15 minutes followed by 10 mg/kg over the next 24 hours ) , 48 received amiodarone ( 300 mg intravenously over 1 hour , followed by 20 mg/kg over the next 24 hours , plus 1,800 mg/day orally , in 3 divided doses ) , and 49 received placebo ( the equivalent amount of saline i.v . over 24 hours ) . Digoxin was administered to all patients who had not previously received it . RESULTS Conversion to normal sinus rhythm occurred in 36 of 46 patients ( 78.2 % ) receiving propafenone , in 40 of 48 patients ( 83.3 % ) receiving amiodarone , and in 27 of the 49 ( 55.10 % ) controls ( P < 0.02 , drug vs placebo , between drugs NS ) . The mean time to conversion was 2 + /- 3 hours for propafenone , 7 + /- 5 hours for amiodarone , and 13 + /- 9 for placebo ( P < 0.05 ) . Patients who converted had smaller atria than those who did not ( diameter : 42.7 + /- 5 vs 47.2 + /- 7 mm , P < 0.001 for all ) . Treatment was discontinued in one patient in the amiodarone group because of an allergic reaction and in two patients in the propafenone group because of excessive QRS widening . No side effects were observed in the placebo group . CONCLUSIONS Both drugs tested intravenously were equally effective and safe for the rapid conversion of recent-onset atrial fibrillation to sinus rhythm . However , propafenone offered the advantage of more rapid conversion than amiodarone INTRODUCTION Dofetilide , a new class III antiarrhythmic drug , was tested for its ability to reduce mortality and morbidity in patients with congestive heart failure and left ventricular dysfunction . METHODS In 34 Danish centers , 1518 patients with NYHA class III or IV heart failure and wall motion index of the left ventricle < or = 1.2 ( ejection fraction < or = 35 % ) were r and omized to receive dofetilide or placebo in a double blind study . The dose of dofetilide was adjusted to renal function and the QT interval . Patients were monitored continuously with ekg during the first three days in the study . Minimum follow up was one year . RESULTS Dofetilide did not affect mortality . Hospitalizations for worsening of heart failure were reduced significantly , hazard ratio 0.75 ( 0.63 - 0.89 ) Dofetilide effectively converted atrial fibrillation to sinus rhythm . After one year , 61 % of patients with atrial fibrillation had converted on dofetilide and 33 % on placebo ( p < 0.001 ) . DISCUSSION Dofetilide can be used to convert atrial fibrillation to sinus rhythm and to maintain sinus rhythm in patients with congestive heart failure and left ventricular dysfunction .  Dofetilide does not affect mortality BACKGROUND We sought to assess the association of amiodarone use with mortality during consecutive periods in patients with post-acute myocardial infa rct ion with left ventricular systolic dysfunction and /or HF treated with a contemporary medical regimen . METHODS This study used data from VALIANT , a r and omized comparison of valsartan , captopril  , or both in patients with acute myocardial infa rct ion with HF and /or left ventricular systolic dysfunction . We compared baseline characteristics of 825 patients treated with amiodarone at r and omization with 13,875 patients not treated with amiodarone .  Using Cox models , we examined the association of amiodarone use with subsequent mortality during consecutive periods after r and omization ( days 1 - 16 , 17 - 45 , 46 - 198 , and 199 - 1096 ) . RESULTS Patients treated with amiodarone were older , had higher Killip class , and were more likely to have a history of diabetes mellitus and hypertension . Adjusting for baseline predictors of mortality , we found that amiodarone use was associated with a significant increase in mortality during 3 of the 4 periods : hazard ratio 1.5 , 95 % CI ( 1.1 - 2.0 ) , P = .02 , for days 1 to 16 ; 2.1 ( 1.5 - 2.9 ) , P < .001 , for days 17 to 45 ; 1.1 ( 0.83 - 1.46 ) , P = .51 , for days 46 to 198 ; and 1.4 ( 1.2 - 1.6 ) , P < .001 , for days 199 to 1096 . CONCLUSION In this study , amiodarone use was associated with excess early and late all-cause and cardiovascular mortality . These observational findings are in contrast to earlier r and omized trials of amiodarone and need to be vali date d prospect ively Background : Attempts to prolong life with antiarrhythmic drugs in patients at increased risk of sudden cardiac death have so far been disappointing or inconclusive AIMS The DAAF Trial was design ed to investigate whether digoxin , within 16 h of its use , increases the rate of conversion to sinus rhythm in patients with acute atrial fibrillation . METHODS AND RESULTS In a r and omized , double-blind multicentre trial the effects of intravenous digoxin and placebo , ( mean dose 0.88 + /- 0.35 mg and 0.96 + /- 0.37 mg ) were compared in 239 patients with a mean age of 66.2 + /- 13.0 years and atrial fibrillation of , at most , 7 days ' duration . The mean arrhythmia duration was 21.7 + /- 30.4 h and baseline heart rate 122.0 + /- 23.0 beats.min-1 . At 16 h , 46 % of the placebo group and 51 % of the digoxin group had converted to sinus rhythm , ( ns ) . Time to sinus rhythm was shorter in the digoxin group , but the difference was not significant . Digoxin had a pronounced and rapid effect on heart rate , which was already significant at 2 h ; 104.6 + /- 20.9 beats.min-1 vs 116.8 + /- 22.5 beats.min-1 ( P = 0.0001 ) . CONCLUSION Acute intravenous treatment with digoxin does not increase the rate of conversion to sinus rhythm , but has a fast acting and clinical ly significant effect on heart rate and should remain an alternative in haemodynamically stable patients INTRODUCTION . Atrial fibrillation is a frequent cause of worsening of symptoms in patients with congestive heart failure . The drugs currently available for maintenance of sinus rhythm all have major side effects . METHODS . In 34 Danish coronary care units , 1518 patients with congestive heart failure and reduced left ventricular systolic function were r and omized to receive either placebo or a new class III antiarrhythmic drug , dofetilide . The dose of dofetilide was adjusted according to the presence of atrial fibrillation , the length of the QT interval , and renal function . Patients were continuously monitored electrocardiographically for the first 3 days of the study . The primary end point was all-cause mortality and follow-up was for at least 1 year . RESULTS . In the dofetilide/placebo groups , 311/317 patients  died ( 41%/42 % ) . The hazard ratio for dofetilide treatment was 0.95 ( 95 % confidence interval , 0.81 - 1.11 ) . Treatment with dofetilide reduced worsening of heart failure significantly ( hazard ratio , 0.75 ; 0.63 - 0.89 ) . After 1 year , 61 % of patients with atrial fibrillation at the start of the study had converted to sinus rhythm on dofetilide , vs. 33 % in the placebo group . After conversion to sinus rhythm , 78%/43 % of patients in the dofetilide/placebo groups remained in sinus rhythm for at least 1 year . There were 25 instances ( 3 % ) of torsade de pointes ventricular tachycardia in the dofetilide group and none in the placebo group . CONCLUSION . In patients with congestive heart failure , dofetilide can effectively convert atrial fibrillation to sinus rhythm and maintain sinus rhythm after conversion . Hospitalization for congestive heart failure is reduced . Dofetilide does not affect mortality . (c)2001 by CHF , BACKGROUND Currently available antiarrhythmic drugs have limited efficacy for acute termination of atrial fibrillation and flutter , especially if the arrhythmia is not of recent onset . The purpose of this multicenter study was to determine the efficacy and safety of repeated doses of intravenous ibutilide , a class III antiarrhythmic drug , in terminating atrial fibrillation or flutter . METHODS AND RESULTS Two hundred sixty-six patients with sustained atrial fibrillation ( n = 133 ) or flutter ( n = 133 ) , with an arrhythmia duration of 3 hours to 45 days , were r and omized to receive up to two 10-minute infusions , separated by 10 minutes , of ibutilide ( 1.0 and 0.5 mg or 1.0 and 1.0 mg ) or placebo . The conversion rate was 47 % after ibutilide and 2 % after placebo ( P < .0001 ) . The two ibutilide dosing regimens did not differ in conversion efficacy ( 44 % versus 49 % ) . Efficacy was higher in atrial flutter than fibrillation ( 63 % versus 31 % , P < .0001 ) . In atrial fibrillation but not flutter , conversion rates were higher in patients with a shorter arrhythmia duration or a normal left atrial size . Arrhythmia termination occurred a mean of 27 minutes after start of the infusion . Of 180 ibutilide-treated patients , 15 ( 8.3 % ) developed polymorphic ventricular tachycardia during or soon after the infusion . The arrhythmia required cardioversion in 3 patients ( 1.7 % ) and was nonsustained in 12 patients ( 6.7 % ) . CONCLUSIONS Intravenous ibutilide given in repeated doses is effective in rapidly terminating atrial fibrillation and flutter and under monitored conditions is an alternative to current cardioversion options BACKGROUND Amiodarone and sotalol are commonly used for the maintenance of sinus rhythm , but the efficacy of these agents administered as high-dose infusions for rapid conversion of atrial fibrillation is unknown . Use in this context would facilitate drug initiation in patients in whom ongoing prophylactic therapy is indicated . METHODS We assessed the efficacy and safety of rapid high-dose intravenous infusions of amiodarone and sotalol for heart rate control and rapid reversion to sinus rhythm in patients who came to the emergency department with recent-onset symptomatic atrial fibrillation . Patients ( n = 140 ) were r and omized to receive 1.5mg/kg of sotalol infused in 10 minutes , 10mg/kg of amiodarone in 30 minutes , or 500 microg of digoxin in 20 minutes . Electrical cardioversion was attempted for patients not converting to sinus rhythm within 12 hours . RESULTS The rapid infusion of sotalol or amiodarone result ed in more rapid rate control than digoxin . Each of the 3 trial strategies result ed in similar rates of pharmacological conversion to sinus rhythm  ( amiodarone , 51 % ; sotalol , 44 % ; digoxin , 50 % ; P = not significant ) . The overall rates of cardioversion after trial drug infusion and defibrillation were high for all groups ( amiodarone , 94 % ; sotalol , 95 % , ; digoxin , 98 % ; P = not significant ) , but there was a trend toward a higher incidence of serious adverse reactions in the amiodarone group . CONCLUSION The rapid infusion of sotalol or amiodarone in patients with symptomatic recent-onset atrial fibrillation results in rapid control of ventricular rate . Even with high-dose rapid infusions , all 3 agents are associated with a poor overall reversion rate within 12 hours . Almost all patients were returned to sinus rhythm with a combination of pharmacological therapy and electrical cardioversion
target: Moreover all the anti-arrhythmic agents that are used in treatment of AF were potentially pro-arrhythmic especially in patients with coronary artery disease and structurally abnormal heart .
background: Although atrial fibrillation ( AF ) is the most common sustained arrhythmia seen during daily cardiovascular physician practice , its management remained a challenge for cardiology physician as there was no single anti-arrhythmic agents proved to be effective in converting atrial fibrillation and kept its effectiveness in maintaining sinus rhythm over long term .
  Some of these drugs also have serious non cardiac side effects that limit its long term use in the management of atrial fibrillation .
  Several new and investigational anti-arrhythmic agents are emerging but data supporting their effectiveness and safety are still limited .