Antiarrhythmic efficacy of azimilide in patients with atrial fibrillation. Maintenance of sinus rhythm after conversion to sinus rhythm. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. Circumferential pulmonary-vein ablation for chronic atrial fibrillation. Comparative effects of carvedilol and amiodarone on conversion and recurrence rates of persistent atrial fibrillation. Efficacy and proarrhythmic hazards of pharmacologic cardioversion of atrial fibrillation: prospective comparison of sotalol versus quinidine. Effects of oral propafenone administration before electrical cardioversion of chronic atrial fibrillation: a placebo-controlled study. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Long-term risk of recurrent atrial fibrillation as documented by an implantable monitoring device: implications for optimal patient care. A Randomized, Placebo-Controlled Study of Vernakalant (Oral) for the Prevention of Atrial Fibrillation Recurrence After Cardioversion Intravenous amiodarone versus verapamil for acute conversion of paroxysmal atrial fibrillation to sinus rhythm. Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. Amiodarone versus sotalol for atrial fibrillation. The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. A randomized assessment of the incremental role of ablation of complex fractionated atrial electrograms after antral pulmonary vein isolation for long-lasting persistent atrial fibrillation. Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. Propafenone for conversion and prophylaxis of atrial fibrillation. Propafenone Atrial Fibrillation Trial Investigators. Success of serial external electrical cardioversion of persistent atrial fibrillation in maintaining sinus rhythm; a randomized study. Natural History and Long-Term Outcomes of Ablated Atrial Fibrillation Vernakalant is superior to ibutilide for achieving sinus rhythm in patients with recent-onset atrial fibrillation: a randomized controlled trial at the emergency department Amiodarone, sotalol, or propafenone in atrial fibrillation: which is preferred to maintain normal sinus rhythm? Propafenone versus sotalol for suppression of recurrent symptomatic atrial fibrillation.
BACKGROUND Azimilide dihydrochloride ( azimilide ) is an investigational antiarrhythmic drug that has been tested in patients with a variety of arrhythmias . In patients with atrial fibrillation , it has shown excellent efficacy in some previous trials and minimal efficacy in others . METHODS Patients who had symptomatic atrial fibrillation for > 48 hours but < 6 months were eligible for this multicenter , r and omized , placebo-controlled clinical trial . Patients were admitted to a hospital and r and omly assigned to receive either azimilide 125 mg or a matched placebo twice daily for 3 days and then once daily . Patients who were in sinus rhythm spontaneously or had sinus rhythm restored by electric cardioversion on day 4 were discharged from the hospital .  Recurrence of atrial fibrillation was documented by electrocardiogram . In the primary efficacy analysis , time to recurrence in the 2 treatment groups was compared with the log-rank test in the subgroup of patients with structural heart disease . Safety was assessed as deaths , adverse events , and serious adverse events . RESULTS A total of 446 patients were r and omized in the study ; 314 were in the subgroup with structural heart disease . The median time to arrhythmia recurrence in both treatment groups with structural heart disease was 13 days , and the difference between treatments was not significant ( P = .4596 , n = 314 ) . The relative risk for recurrence ( placebo : azimilide ) was 1.104 ( 95 % CI 0.849 - 1.436 ) . There was 1 death in the placebo group and 3 in the azimilide group . CONCLUSIONS Azimilide did not demonstrate clinical ly important or statistically significant efficacy in reducing the risk for arrhythmia recurrence in patients with structural heart disease who were in atrial fibrillation and converted to sinus rhythm 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 We conducted a r and omized , controlled trial of circumferential pulmonary-vein ablation for the treatment of chronic atrial fibrillation . METHODS A total of 146 patients with a mean ( + /-SD ) age of 57+/-9 years who had chronic atrial fibrillation were r and omly assigned to receive amiodarone and undergo two cardioversions during the first three months alone ( the control group ) or in combination with circumferential pulmonary-vein ablation . Cardiac rhythm was assessed with daily telephonic transmissions for one year . The left atrial diameter and the severity of symptoms were assessed at 12 months . RESULTS Among the 77 patients assigned to undergo circumferential pulmonary-vein ablation , ablation was repeated because of recurrent atrial fibrillation in 26 percent of patients and atypical atrial flutter in 6 percent . An intention-to-treat analysis showed that 74 percent of patients in the ablation group and 58 percent of those in the control group were free of recurrent atrial fibrillation or flutter without antiarrhythmic-drug therapy at one year ( P=0.05 ) . Among the 69 patients in the control group , 53 ( 77 percent ) crossed over to undergo circumferential pulmonary-vein ablation for recurrent atrial fibrillation by one year and only 3 ( 4 percent ) were in sinus rhythm without antiarrhythmic-drug therapy or ablation . There were significant decreases in the left atrial diameter ( 12+/-11 percent , P<0.001 ) and the symptom severity score ( 59+/-21 percent , P<0.001 ) among patients who remained in sinus rhythm after circumferential pulmonary-vein ablation . Except for atypical atrial flutter , there were no complications attributable to circumferential pulmonary-vein ablation . CONCLUSIONS Sinus rhythm can be maintained long term in the majority of patients with chronic atrial fibrillation by means of circumferential pulmonary-vein ablation independently of the effects of antiarrhythmic-drug therapy , cardioversion , or both . The maintenance of sinus rhythm is associated with a significant decrease in both the severity of symptoms and the left atrial diameter Pretreatment with antiarrhythmic agents could improve cardioversion and recurrence rates in patients with persistent atrial fibrillation . In a prospect i ve controlled trial , 145 patients were r and omly assigned to treatment with carvedilol , amiodarone , or placebo for 4 weeks before electrical cardioversion . Although the 2 drugs had similar effects on cardioversion rates , amiodarone was superior in terms of sinus rhythm maintenance after conversion OBJECTIVES This study compared the efficacy and safety of sotalol and quinidine for conversion and prevention of recurrent  atrial fibrillation .  BACKGROUND Atrial fibrillation is the most common arrhythmia . Pharmacologic therapy has been advocated for both immediate restoration of sinus rhythm and prevention of recurrent atrial fibrillation .  Quinidine is the therapeutic mainstay for both purpose s , but its safety has recently been question ed . Although sotalol has been used successfully to maintain sinus rhythm after direct current cardioversion , its efficacy in pharmacologically reverting atrial fibrillation has not been examined . METHODS Fifty consecutive patients with persistent atrial fibrillation were r and omized to receive quinidine or sotalol for up to 7 days to restore sinus rhythm . Patients were followed up for 6 months . RESULTS Quinidine was more effective than sotalol in terminating atrial fibrillation ( 60 % vs. 20 % , p = 0.009 ) . When nonresponders to drug therapy underwent subsequent direct current cardioversion , total conversion rates in the quinidine and sotalol groups were comparable ( 88 % vs. 68 % , p = 0.17 ) , as was the efficacy of the two drugs in preventing recurrent atrial fibrillation . Side effects necessitating drug discontinuation were more often observed with quinidine . No patient receiving sotalol but four patients receiving quinidine had drug-associated arrhythmia ( torsade de pointes in three patients , sustained ventricular tachycardia in one patient ) . Precordial QT dispersion determined on the surface electrocardiogram ( ECG ) increased with quinidine ( mean + /- SD 34 + /- 9 vs. 44 + /- 16 ms , p = 0.02 ) , indicating enhanced inhomogeneity in ventricular repolarization . There was no change in QT dispersion in patients receiving sotalol ( 36 + /- 18 vs. 40 + /- 17 ms , p = 0.44 ) . CONCLUSIONS Quinidine is more effective than sotalol in terminating atrial fibrillation but is associated with more side effects . The proarrhythmic risk may be related to quinidine 's propensity to increase disparity in ventricular repolarization . This risk warrants careful ECG monitoring during the 1st 4 to 7 days of therapy . Because most proarrhythmic effects occurred shortly after restoration of sinus rhythm , observation should continue > or = 2 to 3 days after sinus rhythm is reestablished OBJECTIVES Our aim was to evaluate the benefits and risks of administering propafenone before electrical defibrillation for chronic atrial fibrillation . BACKGROUND In this context , an antiarrhythmic drug-although potentially useful in preventing early recurrence of arrhythmia-could adversely affect the defibrillation threshold and reduce the cardioversion success rate . METHODS We r and omly assigned 100 patients with chronic atrial fibrillation to oral treatment with either placebo ( 51 patients ) or 750 mg/day of propafenone ( 49 patients ) for 48 h before administration of direct current shock . After successful cardioversion , all patients received propafenone therapy and were followed up for 48 h. RESULTS Before defibrillation , three patients in the propafenone group ( 6.1 % ) had reversion to sinus rhythm and one had sustained ventricular tachycardia . Shock efficacy ( 82.4 % vs. 84.4 % ) and the cumulative effective energy ( 395 + /- 258 vs. 421 + /- 236 J ) were not different between the placebo and propafenone groups . In the propafenone group , 11 patients had their arrhythmia transformed into atrial flutter and required a lower energy level for arrhythmia conversion than did the other patients with continued atrial fibrillation ( 245 + /- 197 vs. 493 + /- 215 J , p < 0.01 ) ; the latter patients showed a trend ( p < 0.10 ) toward higher energy requirements than that of patients who received placebo . The incidence of asymptomatic bradyarrhythmias was higher in the propafenone group ( 28.9 % vs. 7.1 % , p < 0.02 ) , but more patients who received placebo had early recurrence of atrial fibrillation ( 16.7 % vs. 0 % , p < 0.02 ) . Two days after cardioversion , more patients given propafenone ( 73.5 % vs. 52.9 % , p < 0.05 ) were discharged from the hospital with sinus rhythm . During the in-hospital stay , propafenone was withdrawn from six patients ( 6.6 % ) because of side effects . CONCLUSIONS Propafenone , given before electrical cardioversion for chronic atrial fibrillation does not affect the mean defibrillation threshold or the rate of successful arrhythmia conversion . It decreases the recurrence of atrial fibrillation early after shock , thus allowing more patients to be discharged from the hospital with sinus rhythm ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American – Australian – African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association AND ROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific Heart Rhythm Society aPTT : activated partial thromboplastin time ARB : angiotensin-receptor blocker ARISTOTLE : Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation ATHENA : A placebo-controlled , double-blind , parallel arm Trial to assess the efficacy of dronedarone 400 mg b.i.d . for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ATRIA : AnTicoagulation and Risk factors In Atrial fibrillation AVERROES : Apixaban VErsus acetylsalicylic acid ( ASA ) to Reduce the Rate Of Embolic Stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment AVRO : A prospect i ve , r and omized , double-blind , Active-controlled , superiority study of Vernakalant vs. amiodarone in Recent Onset atrial fibrillation b.i.d : bis in die ( twice daily ) b.p.m . : beats per minute CABANA : Catheter ABlation vs . ANtiarrhythmic drug therapy for Atrial fibrillation CABG : coronary artery bypass graft CAP : Continued Access to Protect AF CHA2DS2-VASc : Congestive heart failure or left ventricular dysfunction Hypertension , Age ≥75 ( doubled ) , Diabetes , Stroke (doubled)-Vascular disease , Age 65–74 , Sex category ( female ) CHADS2 : Congestive heart failure , Hypertension , Age ≥75 , Diabetes , Stroke ( doubled ) CI : confidence interval CRAFT : Controlled R and omized Atrial Fibrillation Trial CrCl : creatinine clearance DAFNE : Dronedarone Atrial FibrillatioN study after Electrical cardioversion DIONYSOS : R and omized Double blind trIal to evaluate efficacy and safety of drOnedarone ( 400 mg b.i.d . ) vs . amiodaroNe ( 600 mg q.d . for 28 daYS , then 200 mg qd thereafter ) for at least 6 mOnths for the maintenance of Sinus rhythm in patients with atrial fibrillation EAST : Early treatment of Atrial fibrillation for Stroke prevention Trial EHRA : European Heart Rhythm Association ECG : electrocardiogram EMA : European Medicines Agency ERATO : Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation EURIDIS : EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm FAST : atrial Fibrillation catheter Ablation vs . Surgical ablation Treatment FDA : Food and Drug Administration Flec-SL : Flecainide Short-Long trial HAS-BLED : Hypertension , Abnormal renal/liver function , Stroke , Bleeding history or predisposition , Labile INR , Elderly , Drugs/alcohol concomitantly HF-PEF : heart failure with preserved ejection fraction HF-REF : heart failure with reduced ejection fraction HR : hazard ratio HRS : Heart Rhythm Society ICH : intracranial haemorrhage INR : international normalized ratio i.v . : intravenous J-RHYTHM : Japanese RHYTHM management trial for atrial fibrillation LAA : left atrial appendage LoE : level of evidence LVEF : left ventricular ejection fraction MANTRA-PAF : Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation NICE : National Institute for Health and Clinical Excellence NOAC : novel oral anticoagulant NSAID : non-steroidal anti-inflammatory drug NYHA : New York Heart Association OAC : oral anticoagulant or oral anticoagulation o.d . : omni die ( every day ) PALLAS : Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of st and ard therapy PCI : percutaneous coronary intervention PREVAIL : Prospect i ve R and omized EVAluation of the LAA closure device In patients with atrial fibrillation v s. Long-term warfarin therapy PROTECT AF : WATCHMAN LAA system for embolic PROTECTion in patients with Atrial Fibrillation PT : prothrombin time RAAFT : Radio frequency Ablation Atrial Fibrillation Trial RE-LY : R and omized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate ROCKET-AF : Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in atrial fibrillation RRR : relative risk reduction TE : thromboembolism TIA : transient ischaemic attack t.i.d . : ter in die ( three times daily ) TOE : transoesophageal echocardiogram TTR : time in therapeutic range VKA : vitamin K antagonist Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition , taking into account the impact on OBJECTIVES The present study determined the incidence and time course of atrial fibrillation ( AF ) recurrences  in patients with a history of AF and fitted with an implantable monitoring device .  BACKGROUND The long-term risk of undetected recurrence of AF in patients receiving stable antiarrhythmic therapy remains uncertain . METHODS In 110 patients with a class I indication for physiologic pacing and a history of AF , a pacemaker with dedicated functions for AF detection and electrogram storage was implanted , and antiarrhythmic drug treatment was optimized . Patients were regularly followed up with evaluation of AF-related symptoms , a  resting electrocardiogram ( ECG ) , and  interrogation of device memory .  The incidence of AF recurrences lasting > 48 h in asymptomatic patients presenting in sinus rhythm ( SR ) at the respective follow-up visit constituted the primary end point of this prospect i ve study . RESULTS During 19 + /- 11 months , 678 follow-up visits were performed . Atrial fibrillation was documented in 51 patients ( 46 % ) by ECG recording and in 97 patients ( 88 % ) by a review of stored electrograms ( p < 0.0001 ) . Device interrogation revealed AF recurrences lasting > 48 h in 50 patients , 19 of whom ( 38 % ) were completely asymptomatic and in SR at subsequent follow-up . In 11 ( 16 % ) of 67 patients with device-confirmed freedom from AF for > or =3 months , AF lasting > 48 h recurred subsequently . CONCLUSIONS This prospect i ve study demonstrates a high incidence of recurrent AF despite optimized antiarrhythmic therapy . Of particular note , AF relapses > 48 h remained totally asymptomatic in a significant proportion of patients . Freedom from AF for > or =3 months did not preclude subsequent long-lasting AF recurrence 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 Abstract Amiodarone and verapamil are well-known antiarrhythmic drugs used for treatment of ventricular and supraventricular arrhythmias . Although verapamil is the drug of choice for control of the atrioventricular node , it has also been reported to terminate atrial fibrillation . 1–3 Amiodarone has been used extensively for drug-refractory ventricular tachycardia but seldom for termination of paroxysmal atrial fibrillation . 4–6 To our knowledge , no comparative study with amiodarone and verapamil has been reported . Because of this , we compared the efficacy of intravenous amiodarone versus verapamil for conversion of paroxysmal atrial fibrillation to sinus rhythm in a single-blind r and omized study This study was performed to evaluate , using a r and omized double-blind , placebo-controlled protocol , the long-term efficacy and safety of propafenone and sotalol in maintaining sinus rhythm after conversion of recurrent symptomatic atrial fibrillation ( AF  )  . The maintenance of sinus rhythm in patients with recurrent AF has several potential benefits , the most important being a reduced risk of thromboembolic events .  Three hundred patients with recurrent AF ( > or = 4 episodes in the last year ) and AF at enrollment lasting < 48 hours were r and omized to receive either propafenone ( mean daily dose 13 + /- 1.5 mg/kg ; 102 patients ) , sotalol ( mean daily dose 3 + /- 0.4 mg/kg ; 106 patients ) , or placebo ( 92 patients ) . After 1-year follow-up , Kaplan-Meier estimates of the proportion of patients remaining in sinus rhythm were comparable between propafenone ( 63 % ) and sotalol ( 73 % ) and superior to placebo ( 35 % ; p = 0.001 vs both drugs ) . Symptomatic recurrences occurred later with propafenone and sotalol than with placebo . Nine patients ( 9 % ) in the propafenone group , 11 ( 10 % ) in the sotalol group , and 3 ( 3 % ) in the placebo group discontinued therapy due to adverse effects . Malignant nonfatal arrhythmias due to proarrhythmic effects were documented with sotalol only , and occurred < 72 hours from the beginning of therapy in 4 patients ( 4 % ) . During recurrences , the ventricular rate was significantly reduced in patients taking propafenone and sotalol ( p = 0.001 for both drugs vs placebo ) . The likelihood of remaining in sinus rhythm during follow-up was higher in younger patients with smaller left atrial size and without concomitant heart disease . In patients with recurrent symptomatic AF , propafenone and sotalol are not significantly different from each other and are superior to placebo in maintaining sinus rhythm at 1 year . Recurrences occur later and tend to be less symptomatic with propafenone and sotalol compared with placebo BACKGROUND Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization . Sinus rhythm may be maintained with antiarrhythmic drugs , but some of these drugs increase the risk of death . METHODS We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals . We r and omly assigned 762 patients to receive dofetilide , a novel class III antiarrhythmic agent , and 756 to receive placebo in a double-blind study . Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment . The primary end point was death from any cause . RESULTS During a median follow-up of 18 months , 311 patients in the dofetilide group ( 41 percent ) and 317 patients in the placebo group ( 42 percent ) died ( hazard ratio , 0.95 ; 95 percent confidence interval , 0.81 to 1.11 ) . Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure ( risk ratio , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ) . Dofetilide was effective in converting atrial fibrillation to sinus rhythm . After one month , 22 of 190 patients with atrial fibrillation at base line ( 12 percent ) had sinus rhythm restored with dofetilide , as compared with only 3 of 201 patients ( 1 percent ) given placebo . Once sinus rhythm was restored , dofetilide was significantly more effective than placebo in maintaining sinus rhythm ( hazard ratio for the recurrence of atrial fibrillation , 0.35 ; 95 percent confidence interval , 0.22 to 0.57 ; P<0.001 ) . There were 25 cases of torsade de pointes in the dofetilide group ( 3.3 percent ) as compared with none in the placebo group . CONCLUSIONS In patients with congestive heart failure and reduced left ventricular function , dofetilide was effective in converting atrial fibrillation , preventing its recurrence , and reducing the risk of hospitalization for worsening heart failure .  Dofetilide had no effect on mortality BACKGROUND AND OBJECTIVES The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined . This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study , a r and omized clinical trial comparing warfarin , aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation . METHODS Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents . The relative risk of cardiac mortality , including arrhythmic death , in patients receiving antiarrhythmic drug therapy  was determined and adjusted for other cardiac risk factors . RESULTS In patients receiving antiarrhythmic drug therapy , cardiac mortality was increased 2.5-fold ( p = 0.006 , 95 % confidence interval [ CI ] 1.3 to 4.9 ) and arrhythmic death was increased 2.6-fold ( p = 0.02 , 95 % CI 1.2 to 5.6 ) . Among patients with a history of congestive heart failure , those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 ( p less than 0.001 , 95 % CI 1.9 to 11.6 ) compared with that of patients not so treated ; the relative risk of arrhythmic death in the treated group was 3.7 ( p = 0.01 , 95 % CI 1.3 to 10.4 ) . Patients without a history of congestive heart failure had no increased risk of cardiac mortality ( relative risk 0.70 , 95 % CI 0.2 to 3.1 ) during antiarrhythmic drug therapy . After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death , patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death . However , in patients with a history of heart failure who received antiarrhythmic drug therapy , the relative risk of cardiac death was 3.3 ( p = 0.05 , 95 % CI 0.99 to 11.1 ) and that of arrhythmic death was 5.8 ( p = 0.009 , 95 % CI 1.5 to 21.7 ) compared with the risk in patients not taking antiarrhythmic medications . CONCLUSIONS Although antiarrhythmic drug therapy was not r and omly determined in this trial , the data suggest that in patients with atrial fibrillation and a history of congestive heart failure , the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm BACKGROUND The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial . METHODS In this double-blind , placebo-controlled trial , we r and omly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone ( 267 patients ) , sotalol ( 261 patients ) , or placebo ( 137 patients ) and monitored them for 1 to 4.5 years . The primary end point was the time to recurrence of atrial fibrillation beginning on day 28 , determined by means of weekly transtelephonic monitoring . RESULTS Spontaneous conversion occurred in 27.1 percent of the amiodarone group , 24.2 percent of the sotalol group , and 0.8 percent of the placebo group , and direct-current cardioversion failed in 27.7 percent , 26.5 percent , and 32.1 percent , respectively . The median times to a recurrence of atrial fibrillation were 487 days in the amiodarone group , 74 days in the sotalol group , and 6 days in the placebo group according to intention to treat and 809 , 209 , and 13 days , respectively , according to treatment received . Amiodarone was superior to sotalol ( P<0.001 ) and to placebo ( P<0.001 ) , and sotalol was superior to placebo ( P<0.001 ) . In patients with ischemic heart disease , the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy ( P=0.53 ) . Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity . There were no significant differences in major adverse events among the three groups . CONCLUSIONS Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm .  Amiodarone is superior for maintaining sinus rhythm , but both drugs have similar efficacy in patients with ischemic heart disease . Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance In a single-blind r and omized study , the efficacy and safety of intravenous propafenone ( 2 mg/kg body weight per 10 min ) versus flecainide ( 2 mg/kg per 10 min ) were assessed in 50 patients with atrial fibrillation or flutter . Treatment was considered successful if sinus rhythm occurred within 1 h. Conversion to sinus was achieved in 11 ( 55 % ) of 20 patients with atrial fibrillation treated with propafenone and in 18 ( 90 % ) of 20 with atrial fibrillation treated with flecainide ( p less than 0.02 ) . If atrial fibrillation was present less than or equal to 24 h , conversion to sinus rhythm was achieved in 8 ( 57 % ) of 14 patients in the propafenone group and 13 ( 93 % ) of 14 in the flecainide group ( p less than 0.05 ) . Atrial flutter was converted in two ( 40 % ) of five patients treated with propafenone and in one ( 20 % ) of five with flecainide ( p = NS ) . Mean time to conversion was 16 + /- 10 min in the propafenone group versus 18 + /- 13 min in the flecainide group ( p = NS ) . QRS lengthening ( 83 + /- 15 to 99 + /- 20 ms ) was observed only in the patients treated with flecainide ( p less than 0.001 ) . Patients successfully treated with propafenone showed significantly higher plasma levels than those whose arrhythmia did not convert to sinus rhythm . Transient adverse effects were more frequent in the flecainide group ( 40 % ) than in the propafenone group ( 8 % ) ( p less than 0.01 ) . In conclusion , at a dose of 2 mg/kg in 10 min , flecainide is more effective than propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm . However , considering the propafenone plasma levels and very few adverse effects , the dose or infusion rate , or both , used in the propafenone group may not have been sufficient to achieve an optimal effect . Neither drug seems very effective in patients with atrial flutter OBJECTIVES This study sought to determine whether ablation of complex fractionated atrial electrograms ( CFAEs ) after antral pulmonary vein isolation ( APVI ) further improves the clinical outcome of APVI in patients with long-lasting persistent atrial fibrillation ( AF ) . BACKGROUND Ablation of CFAEs has been reported to eliminate persistent AF . However , residual pulmonary vein arrhythmogenicity is a common mechanism of recurrence . METHODS In this r and omized study , 119 consecutive patients ( mean age 60 + /- 9 years ) with long-lasting persistent AF underwent APVI with an irrigated-tip radiofrequency ablation catheter . Antral pulmonary vein isolation result ed in termination of AF in 19 of 119 patients ( Group A , 16 % ) . The remaining 100 patients who still were in AF were r and omized to no further ablation and underwent cardioversion ( Group B , n = 50 ) or to ablation of CFAEs in the left atrium or coronary sinus for up to 2 additional hours of procedure duration ( Group C , n = 50 ) . RESULTS Atrial fibrillation terminated during ablation of CFAEs in 9 of 50 patients ( 18 % ) in Group C. At 10 + /- 3 months after a single ablation procedure , 18 of 50 ( 36 % ) in Group B and 17 of 50 ( 34 % ) in Group C were in sinus rhythm without antiarrhythmic drugs ( p = 0.84 ) . In Group A , 15 of 19 patients ( 79 % ) were in sinus rhythm . A repeat ablation procedure was performed in 34 of 100 r and omized patients ( for AF in 30 and atrial flutter in 4 ) . At 9 + /- 4 months after the final procedure , 34 of 50 ( 68 % ) in Group B and 30 of 50 ( 60 % ) in Group C were in sinus rhythm without antiarrhythmic drugs ( p = 0.40 ) . CONCLUSIONS Up to 2 h of additional ablation of CFAEs after APVI does not appear to improve clinical outcomes in patients with long-lasting persistent AF OBJECTIVES This study evaluated the efficacy of antiarrhythmic drugs for the treatment of  atrial fibrillation ( AF ) .  BACKGROUND The most effective and safest antiarrhythmic drug for the treatment of AF is unknown . METHODS The Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study compared two treatment strategies -- rate control and rhythm control -- in patients with AF and risk factors for stroke or death . This sub study , performed in patients r and omized to rhythm control , compared different antiarrhythmic drugs by r and omly assigning the first drug treatment to : 1 ) amiodarone , 2 ) sotalol , or 3 ) a class I drug . The primary end point was the proportion of patients alive , in sinus rhythm , with no additional cardioversions and still taking the assigned drug at one year . Comparisons were made between patients eligible for each of three drug pairs . RESULTS At one year , in 222 patients r and omized between amiodarone and class I agents , 62 % were successfully treated with amiodarone , compared with 23 % taking class I agents ( p < 0.001 ) . In 256 patients r and omized between amiodarone and sotalol , 60 % versus 38 % were successfully treated , respectively ( p = 0.002 ) . In 183 patients r and omized between sotalol and class I agents , 34 % versus 23 % were successfully treated , respectively ( p = 0.488 ) , although this portion of the sub study was stopped early when amiodarone was shown to be better than class I agents . Sinus rhythm was achieved in nearly 80 % of patients at one-year follow-up with serial therapy . Adverse effects were common . CONCLUSIONS Amiodarone was more effective at one year than either sotalol or class I agents for the strategy of maintenance of sinus rhythm without cardioversion Pharmacologic therapy is widely used for restoration of sinus rhythm and prevention of recurrences of atrial fibrillation .  Because concerns have been raised about their potential proarrhythmic effects , therapeutic regimens should be evaluated by placebo-controlled studies to determine their efficacy and safety . One hundred thirty-six patients with persistent atrial fibrillation were r and omized to receive propafenone 2 mg/kg over 30 minutes , followed by oral propafenone 150 mg 3 times daily or matching placebo . Nonresponders to intravenous therapy underwent direct-current cardioversion . Both responders to intravenous therapy and converters to sinus rhythm after direct-current cardioversion were followed for 6 months in a double-blind oral treatment period of propafenone 150 mg 3 times daily or matching placebo .  Pharmacologic conversion to sinus rhythm was achieved in 29 % of the patients taking propafenone and in 17 % of patients taking placebo ( p > or = 0.10 ) . Subsequent direct-current cardioversion in nonresponders was equally successful ( 70 % ) in both groups ( p > or = 0.10 ) . The proportion of patients free from recurrent symptomatic arrhythmia at 6 months was 67 % for the propafenone and 35 % for the placebo group ( p < 0.01 ) . Time to atrial fibrillation relapse was more favorable with propafenone than with placebo ( p < 0.001 ) . The incidence of drug-related side effects was 10 % in the propafenone group and 14 % in the placebo group . Thus , " slow " infusion of propafenone seems to be of limited value for terminating atrial fibrillation . Oral propafenone at a low dosage 150 mg 3 times daily is well tolerated and effective in maintaining sinus rhythm for 6 months after pharmacologic or electrical restoration of sinus rhythm AIMS The aim of this prospect i ve , r and omized study was to determine the efficacy of a serial external electrical cardioversion strategy in maintaining sinus rhythm after 12 months in patients with recurrent persistent atrial fibrillation . METHODS AND RESULTS Ninety patients with persistent atrial fibrillation lasting more than 72 h but less than 1 year were r and omized in a one to one fashion to repetition of up to two electrical cardioversions in the event of relapse of atrial fibrillation detected within 1 month of the previous electrical cardioversion ( Group AGG ) , or to non-treatment of atrial fibrillation relapse ( Group CTL ) .  ECGs  were scheduled at 6 h , 7 days , and 1 month .  Clinical examination and ECGs  were repeated during the 6-month and 12-month follow-up examinations .  Echocardiography  was repeated during the 6-month follow-up examination . Clinical and echocardiographic characteristics were similar in the two groups . All patients were treated with antiarrhythmic drugs before electrical cardioversion and throughout follow-up . After 12 months , sinus rhythm was maintained in 53 % of Group AGG patients and in 29 % of Group CTL patients ( P<0.03 ) . After 6 months , left ventricular ejection fraction had recovered significantly only in Group AGG ( 56.8 + /- 9.0 % at enrollment vs 60.4 + /- 9.4 % at 6 months , P < 0.001 ) . CONCLUSION These results demonstrate that an aggressive policy towards persistent atrial fibrillation by means of repetition of electrical cardioversion after early atrial fibrillation recurrence is useful in maintaining sinus rhythm after 12 months Background —Atrial  fibrillation ( AF ) ablation  is increasingly used in clinical practice . We aim ed to study the natural history and long-term outcomes of ablated AF . Methods and Results —We followed 831 patients after pulmonary vein isolation ( PVI ) performed in 2005 . We documented clinical outcomes using our prospect i ve AF registry with most recent up date on this group of patients in October 2009 . In the first year after ablation , 23.8 % had early recurrence . Over long-term follow-up ( 55 months ) , only 8.9 % had late arrhythmia recurrence defined as occurring beyond the first year after ablation . Repeat ablations in patients with late recurrence revealed conduction recovery in at least 1 of the previously isolated PVs in all of them and right-sided triggers with isoproterenol testing in 55.6 % . At last follow-up , clinical improvement was 89.9 % ( 79.4 % arrhythmia-free off antiarrhythmic drugs and 10.5 % with AF controlled with antiarrhythmic drugs ) . Only 4.6 % continued to have drug-resistant AF . It was possible to safely discontinue anticoagulation in a substantial proportion of patients with no recurrence in the year after ablation ( CHADS score ⩽2 , stroke incidence of 0.06 % per year ) . The procedure-related complication rate was very low . Conclusions —Pulmonary vein isolation is safe and efficacious for long-term maintenance of sinus rhythm and control of symptoms in patients with drug-resistant AF . It obviates the need for antiarrhythmic drugs , negative dromotropic agents , and anticoagulants in a substantial proportion of patients Aims Ibutilide is a rapid‐acting antiarrhythmic drug with worldwide use for conversion of recent‐onset atrial fibrillation . Vernakalant , approved in the EU in 2010 , is likewise used intravenously , with proven efficacy and safety compared with placebo and amiodarone in r and omized clinical trials . The aim of our study was to compare the time to conversion and the conversion rate within 90 min in patients with recent‐onset atrial fibrillation treated with vernakalant or ibutilide .  Methods and results A r and omized controlled trial registered at clinical trials.gov ( NCT01447862 ) was performed in 100 patients with recent‐onset atrial fibrillation treated at the emergency department of a tertiary care hospital . Patients received up to two short infusions of vernakalant ( n = 49 ; 3 mg/kg followed by 2 mg/kg if necessary ) or ibutilide ( n = 51 ; 1 mg followed by another 1 mg if necessary ) according to the manufacturer 's instructions . Clinical and laboratory variables , adverse events , conversion rates , and time to conversion were recorded . Time to conversion of AF to sinus rhythm was significantly shorter in the vernakalant group compared with the ibutilide group ( median time : 10 vs. 26 min , P = 0.01 ) , and likewise the conversion success within 90 min was significantly higher in the vernakalant group ( 69 vs. 43 % , log‐rank P = 0.002 ) . No serious adverse events occurred . Conclusion Vernakalant was superior to ibutilide in converting recent‐onset atrial fibrillation to sinus rhythm in the emergency department setting UNLABELLED This r and omized study compared the efficacy and safety of amiodarone , propafenone and sotalol in the prevention of atrial fibrillation . METHODS The population consisted of 214 consecutive patients ( mean age 64 + /- 8 years , 106 men ) with recurrent symptomatic atrial fibrillation . After restoration of sinus rhythm , patients were r and omized to amiodarone ( 200 mg/day ) , propafenone ( 450 mg/day ) or sotalol ( 320 + /- 20 mg/day ) . Follow-up evaluations were conducted at 1 , 2 , 4 and 6 months , and at 3-month intervals thereafter . The proportion of patients developing recurrent atrial fibrillation and /or experiencing unacceptable adverse effects was measured in the three groups by the Kaplan-Meier method . RESULTS Recurrent atrial fibrillation occurred in 25 of the 75 patients treated with amiodarone compared to 51 of the 75 patients treated with sotalol and 24 of the 64 patients treated with propafenone . Fourteen patients treated with amiodarone , five with sotalol , and one with propafenone experienced adverse effects while in sinus rhythm , necessitating discontinuation of treatment ( P < 0.001 for amiodarone and propafenone vs sotalol ) . The difference between amiodarone and propafenone was statistically nonsignificant when all events were included in the analysis . However , if the analysis was limited to recurrent atrial fibrillation events , amiodarone was more effective than propafenone ( P < 0.05 ) . CONCLUSIONS Amiodarone and propafenone were superior to sotalol in maintaining long-term normal sinus rhythm in patients with atrial fibrillation .  Amiodarone tended to be superior to propafenone , though its long-term efficacy was limited by adverse side effects Because conventional antiarrhythmic therapy is often ineffective in maintaining sinus rhythm or is associated with adverse side effects in patients with atrial fibrillation ( AF ) , there is a clinical need to test newer agents . One hundred patients with AF who had unsuccessful therapy with 1.9 + /- 1.0 type IA antiarrhythmic agents were r and omized to receive either propafenone ( n = 50 ) or sotalol ( n = 50 ) . Patients were stratified into 4 groups based on AF pattern ( chronic vs paroxysmal ) and left atrial size ( large [ > or = 4.5 cm ] vs small [ < 4.5 ] ) . The proportion of patients remaining in sinus rhythm on each agent was calculated for each group by the Kaplan-Meier method . For patients r and omized to propafenone , 46 + /- 8 % , 41 + /- 8 % and 30 + /- 8 % remained in sinus rhythm at 3 , 6 and 12 months , respectively , after cardioversion . A similar proportion of patients treated with sotalol remained in sinus rhythm at follow-up ( 49 + /- 7 % , 46 + /- 8 % and 37 + /- 8 % at 3 , 6 and 12 months , respectively ; p = NS ) . The proportion of patients remaining in sinus rhythm on propafenone and sotalol was not dependent on arrhythmia pattern or left atrial dimension . Except for constipation that occurred more frequently in patients treated with propafenone , adverse side effects were equally distributed between the 2 therapies . Two patients receiving sotalol died during follow-up . Propafenone and sotalol , 2 new antiarrhythmic agents , were found to be equally effective in maintaining sinus rhythm in 100 patients with recurrent AF . Response rates were not affected by arrhythmia pattern , left atrial size or unsuccessful prior drug therapy . ( ABSTRACT TRUNCATED AT 250 WORDS
No other antiarrhythmic showed a significant effect on mortality compared with controls .
Class IA , IC , and III drugs are effective in maintaining sinus rhythm but increase adverse effects , and class IA drugs may increase mortality
BACKGROUND A variety of antiarrhythmic drugs have been used to prevent recurrence of atrial fibrillation after conversion to sinus rhythm .
We performed a systematic review to determine the effect of long-term treatment with those drugs on death , embolisms , adverse effects , and atrial fibrillation recurrence .