title: Comparison of rate and rhythm control in hypertension patients with atrial fibrillation. What Should be the Primary Treatment in Atrial Fibrillation: Ventricular Rate Control or Sinus Rhythm Control with Long-term Anticoagulation? Effect of quinidine on maintaining sinus rhythm after conversion of atrial fibrillation or flutter. A multicentre study from Stockholm. Dose-response relations of azimilide in the management of symptomatic, recurrent, atrial fibrillation. Antiarrhythmic efficacy of azimilide in patients with atrial fibrillation. Maintenance of sinus rhythm after conversion to sinus rhythm. Effect of dronedarone on cardiovascular events in atrial fibrillation. Analysis of Cause-Specific Mortality in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study 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 Increased mortality after dronedarone therapy for severe heart failure. An evaluation of the strategy of maintenance of sinus rhythm by antiarrhythmic drug therapy after ablation and pacing therapy in patients with paroxysmal atrial fibrillation. Comparison of rate and rhythm control in patients with atrial fibrillation and nonischemic heart failure. Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial A randomized trial of circumferential pulmonary vein ablation versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation: the APAF Study. The Drug And Pace Health cliNical Evaluation (DAPHNE) study: a randomized trial comparing sotalol versus beta-blockers to treat symptomatic atrial fibrillation in patients with brady-tachycardia syndrome implanted with an antitachycardia pacemaker. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. Continuous vs episodic prophylactic treatment with amiodarone for the prevention of atrial fibrillation: a randomized trial. Rate control versus rhythm control for patients with persistent atrial fibrillation with mild to moderate heart failure: results from the RAte Control versus Electrical cardioversion (RACE) study. 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. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. Mending the rhythm does not improve prognosis in patients with persistent atrial fibrillation: a subanalysis of the RACE study. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. Maintenance of sinus rhythm and survival in patients with heart failure and atrial fibrillation. Digoxin in atrial fibrillation: report from the Stockholm Cohort study of Atrial Fibrillation (SCAF) Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. Propafenone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. 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. Effect of n-3 polyunsaturated fatty acids and rosuvastatin in patients with heart failure: results of the GISSI-HF trial
abstract: BACKGROUND Atrial fibrillation ( AF ) is a very common cardiac arrhythmia , and is associated with an increased mortality in patients with hypertension . Whether the best therapeutic approach for these patients is to restore sinus rhythm ( SR ) or to adequately control the ventricular rate is still controversial . The aim of this study is to compare both strategies in patients with hypertension . METHODS AND RESULTS Two hundred and twenty-one patients with hypertension and AF of duration > 48 h were r and omly assigned to either the rhythm ( n=155 ) or rate ( n=66 ) control group . Exercise capacity was improved in the rhythm control group in the 1st year of the study ( p<0.0001 ) . There were no statistically significant differences in the embolic event rate and the total mortality between the 2 groups at the end of the study ( p = NS ) . CONCLUSIONS Although restoring and maintaining SR had a beneficial effect on exercise capacity in patients with hypertension and AF , no significant difference was found in terms of the total mortality and the embolic event rates . Thus , rate control is an acceptable primary strategy in patients with AF and hypertension Recent trials have favoured ventricular rate control in atrial fibrillation ( AF ) management , however the present study investigated whether the restoration and maintenance of sinus rhythm with long-term anticoagulation therapy was superior in terms of embolic events and death in 534 patients with an AF duration > 48 h. Patients were r and omized and received sinus rhythm control with either aspirin ( group 1 ) or warfarin ( group 2 ) , or they were given ventricular rate control ( group 3 ) . Cardioversion to sinus rhythm was attempted in 425 patients and was successful in 387 ( 91.1 % ) of them . After 3 years ' follow-up there were 12 , two and 15 embolic events in groups 1 , 2 and 3 respectively ( significant difference between groups 1 and 2 , and 2 and 3 ) and overall mortalities were four , two and 12 , respectively ( significant difference between groups 2 and 3 ) . It is concluded that patients with an AF duration > 48 h might benefit considerably from sinus rhythm restoration and long-term warfarin therapy in terms of embolic events and mortality In a controlled study comprising 176 patients ,  quinidine in the form of Kinidin Durules was found to reduced significantly the recurrence of the atrial fibrillation  during a 1-year follow-up period after successful electric shock conversion . After one year , 51 per cent ( 52/101 ) of the patients in the quinidine group , and 28 per cent ( 21/75 ) in the control group remained in sinus rhythm ( P smaller than 0.001 ) . No less than 43 per cent of the patients converted to sinus rhythm during treatment with maintenance doses of quinidine sulphate before intended DC conversion . Gastrointestinal side-effects were not uncommon , and caused interruption of quinidine treatment in some cases We evaluated the efficacy and safety of azimilide , a new class III antiarrhythmic agent that blocks both the slow and fast components of the cardiac-delayed rectifier potassium currents in 4 r and omized , double-blind , placebo-controlled trials with similar protocol s. The purpose of this study was to assess the relation between dose and effect . A total of 1,380 patients with a documented history of symptomatic atrial fibrillation ( AF ) , atrial flutter , or both , were enrolled . After a 3-day loading period during which the assigned dose was given twice a day , subjects received placebo or azimilide ( 35 , 50 , 75 , 100 , or 125 mg once a day ) for the duration of the study period . The primary end point of the studies was the time to symptomatic arrhythmia recurrence with a transtelephonic electrocardiogram typical of AF , atrial flutter , or paroxysmal supraventricular tachycardia . For each study , Kaplan-Meier estimates of the median time to recurrence were computed for placebo and for each azimilide dose . Cox proportional-hazards modeling was used to estimate hazard ratios for each active dose . Each of the 2 highest azimilide doses ( 100 and 125 mg/day ) significantly prolonged the time to recurrence of arrhythmia . For the 100 mg/day dose , the hazard ratio was 1.34 , 95 % confidence interval 1.05 to 1.72 ; p = 0.02 . For the 125 mg/day dose , the hazard ratio was 1.32 , 95 % confidence interval 1.07 to 1.62 ; p = 0.01 . Patients with a history of either ischemic heart disease or congestive heart failure had a significantly greater treatment effect from azimilide than those without it . Torsades de Pointes occurred in 0.9 % of patients receiving either of the 2 effective doses . Thus , doses of azimilide < 100 mg/day are not effective for control of AF , whereas doses of 100 and 125 mg/day are effective with an acceptable risk of serious toxicity 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 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 —Expectations that reestablishing and maintaining sinus rhythm in patients with atrial fibrillation might improve survival were disproved in the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study . This report describes the cause-specific modes of death in the AFFIRM treatment groups . Methods and Results —All deaths in patients enrolled in AFFIRM underwent blinded review by the AFFIRM Events Committee , and a mode of death was assigned . In AFFIRM , 2033 patients were r and omized to a rhythm-control strategy and 2027 patients to a rate-control strategy .  During a mean follow-up of 3.5 years , there were 356 deaths in the rhythm-control patients and 310 deaths in the rate-control patients ( P = 0.07 ) . In the rhythm-control group , 129 patients ( 9 % ) died of a cardiac cause , and in the rate-control group , 130 patients ( 10 % ) died ( P = 0.95 ) . Both groups had similar rates of arrhythmic and nonarrhythmic cardiac deaths . The numbers of vascular deaths were similar in the 2 groups : 35 ( 3 % ) in the rhythm-control group and 37 ( 3 % ) in the rate-control group ( P = 0.82 ) . There were no differences in the rates of ischemic stroke and central nervous system hemorrhage . In the rhythm-control group , there were 169 noncardiovascular deaths ( 47.5 % of the total number of deaths ) , whereas in the rate-control arm , there were 113 noncardiovascular deaths ( 36.5 % of the total number of deaths ) ( P = 0.0008 ) . Differences in noncardiovascular death rates were due to pulmonary and cancer-related deaths . Conclusions —Management of atrial fibrillation with a rhythm-control strategy conferred no advantage over a rate-control strategy in cardiac or vascular mortality and may be associated with an increased noncardiovascular death rate Background —In patients with left ventricular dysfunction , atrial fibrillation and flutter ( AF and AFl , respectively ) are common arrhythmias associated with increased morbidity and mortality . The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm , which might reduce mortality and hospitalizations . Methods and Results —In the Danish Investigations of Arrhythmia and Mortality ON  Dofetilide  ( DIAMOND ) studies , 506 patients were in AF-AFl at baseline . Over the course of study , cardioversion occurred in 148 ( 59 % ) dofetilide- and 86 ( 34 % ) placebo-treated patients . In these patients , the probability of maintaining sinus rhythm for 1 year was 79 % with dofetilide versus 42 % with placebo ( P < 0.001 ) . Dofetilide had no effect on all-cause mortality , but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality ( risk ratio [ RR ] , 0.44 ; 95 % CI , 0.30 to 0.64;P < 0.0001 ) . In addition , dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause ( RR , 0.70 ; 95 % CI , 0.56 to 0.89;P ≤0.005 ) or congestive heart failure ( RR , 0.69 ; 95 % CI , 0.51 to 0.93;P ≤0.02 ) rehospitalization . Conclusions —Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease . The present study suggests that restoration of sinus rhythm is associated with improved survival BACKGROUND 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 Permanent atrial fibrillation develops in many patients after ablation and pacing therapy .  We compared a strategy that initially allowed patients to remain in atrial fibrillation with a strategy that initially attempted to restore and maintain sinus rhythm . METHODS AND RESULTS In this multicentre r and omized controlled trial , 68 patients affected by severely symptomatic paroxysmal atrial fibrillation were assigned , after successful atrioventricular junction ablation and pacing treatment  , to antiarrhythmic drug therapy with amiodarone , propafenone , flecainide or sotalol and were compared with 69 patients assigned , after successful AV junction ablation and pacing treatment , to no antiarrhythmic drug therapy . The patients were followed-up for 12 to 24 months ( mean 16+/-4 ) . The drug arm patients had a 57 % reduction in the risk of developing permanent atrial fibrillation ( 21 % vs 37 % , P=0.02 ) . Evaluation after 12 months revealed similar quality of life scores and echocardiographic parameters in the two groups , but the drug arm patients had more episodes of heart failure and hospitalizations ( P=0.05 ) . The outcome was similar between the 40 patients who developed permanent atrial fibrillation and the 97 who did not . CONCLUSION Conventional antiarrhythmic therapy reduces the risk of development of permanent atrial fibrillation after ablation and pacing therapy . The present data do not support the concept that the development of permanent atrial fibrillation is related to an adverse outcome when a perfect control of heart rate is obtained by ablation and pacing Atrial fibrillation ( AF ) is a very common cardiac arrhythmia with an increased mortality in patients with heart failure . Whether the best therapeutic approach to these patients is to restore sinus rhythm or to adequately control the ventricular rate is still controversial . The aim of this study was to compare both strategies in patients with AF and nonischemic heart failure . One hundred and fifty-four patients with AF duration greater than 48 hours and nonischemic left ventricular dysfunction were r and omized either to a rhythm ( n = 84 ) or rate ( n = 74 ) control group . The composite end points of the study were embolism , death , and exercise capacity .  The average age of the patients was 61 + /- 10 years in the rhythm control group and 58 + /- 12 years in the rate control group ( P = NS ) . The average follow-up period was 35 + /- 21 months in the rhythm control group and 37 + /- 19 months in the rate control group ( P = NS ) . In the first year of the study , exercise capacity and left ventricular ejection fraction ( LVEF ) were improved in the rhythm control group compared to the exercise capacity and LVEF of the rate control group ( P < 0.0001 and P = 0.0005 , respectively ) . There were no statistically significant differences in the embolic event rate between the two groups ( P = NS ) . The mortality rate , especially for death due to pump failure , was significantly higher in the rate control group at the end of the study ( P < 0.0001 ) . Restoring and maintaining sinus rhythm had a beneficial effect on mortality and exercise capacity in patients with nonischemic heart failure and AF BACKGROUND Arrhythmias cause much morbidity and mortality after myocardial infa rct ion , but in previous trials , antiarrhythmic drug therapy has not been convincingly effective . Dofetilide , a new class III agent , was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infa rct ion . METHODS In 37 Danish coronary-care units , 1510 patients with severe left-ventricular dysfunction ( wall motion index < or = 1.2 , corresponding to ejection fraction < or = 0.35 ) were enrolled in a r and omised , double-blind study comparing dofetilide ( n=749 ) with placebo ( n=761 ) . The primary endpoint was all-cause mortality . Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths . Analyses were by intention to treat . FINDINGS No significant differences were found between the dofetilide and placebo groups in all-cause mortality ( 230 [ 31 % ] vs 243 [ 32 % ] ) , cardiac mortality ( 191 [ 26 % ] vs 212 [ 28 % ] ) , or total arrhythmic deaths ( 129 [ 17 % ] vs 140 [ 18 % ] ) . Atrial fibrillation or flutter was present in 8 % of the patients at study entry . In these patients , dofetilide was significantly better than placebo at restoring sinus rhythm ( 25 of 59 vs seven of 56 ; p=0.002 ) . There were seven cases of torsade de pointes ventricular tachycardia , all in the dofetilide group . INTERPRETATION In patients with severe left-ventricular dysfunction and recent myocardial infa rct ion , treatment with dofetilide did not affect all-cause mortality , cardiac mortality , or total arrhythmic deaths . Dofetilide was effective in treating atrial fibrillation or flutter in this population OBJECTIVES We compared ablation strategy with antiarrhythmic drug therapy ( ADT ) in patients with paroxysmal atrial fibrillation ( PAF ) . BACKGROUND Atrial fibrillation ( AF ) ablation strategy is superior to ADT in patients with an initial history of PAF , but its role in patients with a long history of AF as compared with ADT remains a challenge . METHODS One hundred ninety-eight patients ( age , 56 + /- 10 years ) with PAF of 6 + /- 5 years ' duration ( mean AF episodes 3.4/month ) who had failed ADT were r and omized to AF ablation by circumferential pulmonary vein ablation ( CPVA ) or to the maximum tolerable doses of another ADT , which included flecainide , sotalol , and amiodarone . Crossover to CPVA was allowed after 3 months of ADT . RESULTS By Kaplan-Meier analysis , 86 % of patients in the CPVA group and 22 % of those in the ADT group who did not require a second ADT were free from recurrent atrial tachyarrhythmias ( AT ) ( p < 0.001 ) ; a repeat ablation was performed in 9 % of patients in the CPVA group for recurrent AF ( 6 % ) or atrial tachycardia ( 3 % ) . At 1 year , 93 % and 35 % of the CPVA and ADT groups , respectively , were AT-free . Ejection fraction , hypertension , and age independently predicted AF recurrences in the ADT group . Circumferential pulmonary vein ablation was associated with fewer cardiovascular hospitalizations ( p < 0.01 ) . One transient ischemic attack and 1 pericardial effusion occurred in the CPVA group ; side effects of ADT were observed in 23 patients . CONCLUSIONS Circumferential pulmonary vein ablation is more successful than ADT for prevention of PAF with few complications . Atrial fibrillation ablation warrants consideration in selected patients in whom ADT had already failed and maintenance of sinus rhythm is desired . ( A Controlled R and omized Trial of CPVA Versus Antiarrhythmic Drug Therapy in for Paroxysmal AF : APAF/01 ; http:// clinical trials.gov/ct/show ; NCT00340314 ) BACKGROUND Atrial tachyarrhythmias ( ATAs ) are mainly treated by pharmacologic therapy for rate control or rhythm control . The aim of our study was to compare sotalol ( S ) versus beta-blocking agents ( BB ) in terms of prevention of ATA , cardioversions ( CVs ) , and cardiovascular hospitalizations ( H ) in patients paced for bradycardia-tachycardia form of sinus node disease ( BT-SND ) . METHODS One hundred thirty-five patients ( 67 males , aged 73 + /- 7 years ) were enrolled in a prospect i ve , parallel , r and omized , single-blind , multicenter study . All patients received a dual chamber rate adaptive pacemaker ; after 1 month , 66 patients were r and omly assigned to BB ( 62 + /- 26 and 104 + /- 47 mg/d for atenolol and metoprolol , respectively ) and 69 patients to S ( 167 + /- 66 mg/d ) . RESULTS After an observation period of 12 months , the percentage of patients free from ATA recurrences was 29 % in both BB and S group . Cardioversion and H were significantly ( P < .01 ) fewer in the 12 months after implantation than in the 12 months before both in patients treated with S ( CV 69.4 % vs 22.2 % , H 91.7 % vs 33.3 % ) and in patients treated with BB ( CV 58.5 % vs 17.1 % , H 82.9 % vs 26.8 % ) . Kaplan-Meier survival analysis showed a nonsignificant trend toward a lower incidence of the composite end point ( CV + H ) among BB patients . CONCLUSIONS In the complex context of " hybrid therapy " in patients with BT-SND implanted with a modern dual chamber rate adaptive pacemaker device delivering atrial antitachycardia pacing , no differences were found between the use of beta-blocker and the use of S , at the relatively low dose achieved after clinical titration , in terms of prevention of cardiovascular H or need for atrial CV BACKGROUND The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation , because the prevention of recurrences can improve cardiac function and relieve symptoms . Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence , but this agent has not been tested in a large , r and omized trial . METHODS We undertook a prospect i ve , multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone . We r and omly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone , given in an open-label fashion . The patients in the group assigned to sotalol or propafenone underwent a second r and omization to determine whether they would receive sotalol or propafenone first ; if the first drug was unsuccessful the second agent was prescribed . Loading doses of the drugs were administered and electrical cardioversion was performed ( if necessary ) within 21 days after r and omization for all patients in both groups . The follow-up period began 21 days after r and omization . The primary end point was the length of time to a first recurrence of atrial fibrillation . RESULTS Of the 403 patients in the study , 201 were assigned to  amiodarone  and 202 to either sotalol ( 101 patients ) or propafenone ( 101 patients ) . After a mean of 16 months of follow-up , 71 of the patients who were assigned to amiodarone ( 35 percent ) and 127 of those who were assigned to sotalol or propafenone ( 63 percent ) had a recurrence of atrial fibrillation ( P<0.001 ) . Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone , as compared with 11 percent of those treated with sotalol or propafenone ( P=0.06 ) . CONCLUSIONS Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation CONTEXT Amiodarone effectively suppresses atrial fibrillation but causes many adverse events . OBJECTIVE To compare major events in patients r and omized to receive episodic amiodarone treatment with those who received continuous amiodarone treatment  while still aim ing to prevent atrial fibrillation . DESIGN , SETTING , AND PARTICIPANTS A r and omized trial of 209 ambulatory patients with recurrent symptomatic persistent atrial fibrillation , conducted from December 2002 through March 2007 at 7 Dutch medical centers . INTERVENTION Patients were r and omly assigned to receive either episodic or continuous amiodarone treatment after electrical cardioversion following amiodarone loading . Episodic amiodarone treatment was discontinued after a month of sinus rhythm and reinitiated if atrial fibrillation relapsed ( 1 month peri-electrical cardioversion ) . In the continuous treatment group amiodarone was maintained throughout . MAIN OUTCOME MEASURES The primary end point was a composite of amiodarone and underlying heart disease-related major events . The secondary end points were all-cause mortality and cardiovascular hospitalizations . RESULTS After a median follow-up of 2.1 years ( range , 0.4 - 2.5 years ) , 51 ( 48 % ) of those receiving episodic treatment vs 64 ( 62 % ) receiving continuous treatment had sinus rhythm ( P = .05 ) . There were 85 atrial fibrillation recurrences ( 80 % ) among the episodic treatment group vs 56 ( 54 % ) in the continuous treatment group ( P < .001 ) . No significant difference existed in the incidence of the primary composite end point between each group ( 37 [ 35 % ] episodic vs 34 [ 33 % ] continuous ; incidence rate difference , 0.2 ; 95 % confidence interval [ CI ] , -10.2 to 10.6 ) . However , there were nonstatistically significant differences in the incidence of amiodarone-related major events ( 20 [ 19 % ] episodic vs 25 [ 24 % ] continuous ; incidence rate difference , -2.0 ; 95 % CI , -8.7 to 4.6 ) and underlying heart disease-related major events ( 17 [ 16 % ] episodic vs 9 [ 9 % ] continuous ; incidence rate difference , 3.6 ; 95 % CI , -1.6 to 8.7 ) . All-cause mortality and cardiovascular hospitalizations were higher among those receiving episodic treatment ( 56 [ 53 % ] vs 35 [ 34 % ] , P = .02 ) . CONCLUSIONS In this study population , there was no difference in the composite of amiodarone and cardiac major adverse events between groups . However , patients receiving episodic treatment had a significantly increased rate of atrial fibrillation recurrence and a significantly higher rate of all-cause mortality and cardiovascular hospitalizations . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00392431 BACKGROUND This study was conducted to compare rate- and rhythm-control therapy in patients with persistent atrial fibrillation ( AF ) and mild to moderate chronic heart failure ( CHF ) .  Rate control is not inferior to rhythm control in preventing mortality and morbidity in patients with AF . In CHF , this issue is still unsettled . METHODS In this predefined analysis of the RACE study , a total of 261 patients were in New York Heart Association ( NYHA ) classes II and III at baseline . These patients were analyzed . The primary end point was a composite of cardiovascular mortality , hospitalization for CHF , thromboembolic complications , bleeding , pacemaker implantation , and life-threatening drug side effects . Furthermore , quality of life was compared . RESULTS After 2.3 + /- 0.6 years , the primary end point occurred in 29 ( 22.3 % ) of the 130 rate-control patients and in 32 ( 24.4 % ) of the 131 rhythm-control patients . More cardiovascular deaths , hospitalization for CHF , and bleeding occurred under rate control . Thromboembolic complications , drug side effects , and pacemaker implantation were more frequent under rhythm control . Quality of life did not differ between strategies . In patients successfully treated with rhythm control , the prevalence of end points was not different from those who were in AF at study end . However , the type of end point was different : mortality , bleeding , hospitalization for heart failure , and pacemaker implantation occurred less frequently . CONCLUSIONS In patients with mild to moderate CHF , rate control is not inferior to rhythm control . However , if sinus rhythm can be maintained , outcome may be improved . A prospect i ve r and omized trial is necessary to confirm these results 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 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 AIMS To compare outcome of AF patients with effective rhythm control with patients treated with rate control .  METHODS AND RESULTS Out of the 266 AF patients r and omized to rhythm control in the RACE study , 49 patients turned to long-term sinus rhythm and were continuously treated with oral anticoagulation . The incidence of the primary endpoint in these patients was compared to that in 178 patients out of the initial 256 rate-control patients of RACE who were in AF and using oral anticoagulation continuously . Baseline characteristics of both groups were not different . After a mean follow-up of 2.3+/-0.6 years , the primary endpoint ( a composite of cardiovascular mortality , heart failure , thrombo-embolic complications ( TECs ) , bleeding , serious adverse effects of antiarrhythmic drugs and pacemaker implants ) was 22.4 % in the rhythm-control group vs. 15.2 % in the rate-control group . Multivariable regression analysis indicated coronary artery disease , heart failure , and digitalis as independent risk indicators of cardiovascular morbidity and mortality . Chronic sinus rhythm did not matter . CONCLUSION Among patients who remained on warfarin  , those who mostly were maintained in sinus rhythm under a rhythm-control strategy did not have a superior prognosis compared to those who remained in AF under a rate-control strategy 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 OBJECTIVES The goal of this study was to evaluate the relationship between the presence of sinus rhythm and outcomes in patients with a history of congestive heart failure ( CHF ) and atrial fibrillation ( AF ) . BACKGROUND The value of sinus rhythm maintenance in patients with AF and heart failure ( HF ) is uncertain . METHODS A total of 1,376 patients with AF , ejection fraction < or = 35 % , and heart failure symptoms were r and omized to a rhythm- or rate-control strategy .  Detailed efficacy analyses were used to evaluate the independent effects of treatment strategy and the presence of sinus rhythm on cardiovascular outcomes . RESULTS Overall , 445 ( 32 % ) patients died and 402 ( 29 % ) experienced worsening HF . The rhythm-control strategy was not predictive of cardiovascular mortality ( hazard ratio [ HR ] : 0.90 , 95 % confidence interval [ CI ] : 0.70 to 1.16 ; p = 0.41 ) , all-cause death ( HR : 0.86 , 95 % CI : 0.69 to 1.08 ; p = 0.19 ) , or worsening HF ( HR : 0.86 , 95 % CI : 0.68 to 1.10 ; p = 0.23 ) . In analyses devised to isolate the effect of underlying rhythm , sinus rhythm was not associated with cardiovascular mortality [ HR : 1.22 , 95 % CI : 0.80 to 1.87 ; p = 0.35 ) , total mortality [ HR : 1.11 , 95 % CI : 0.78 to 1.58 ; p = 0.57 ) , or worsening HF [ HR : 0.62 , 95 % CI : 0.37 to 1.02 ; p = 0.059 ) . CONCLUSIONS A rhythm-control strategy or the presence of sinus rhythm are not associated with better outcomes in patients with AF and CHF Background Recent studies of patients with heart failure and of patients receiving intensive care indicate that digoxin may increase mortality if the patient has atrial fibrillation ( AF ) . Objective To study which patients receive  digoxin treatment for AF and what the prognosis is for patients given this treatment . Method 2824 patients with AF were studied prospect ively for a mean of 4.6 years . Information about medication was obtained from the local hospital registry . Information about diagnoses , hospitalisations and deaths was obtained from national registries . Propensity score matching and Cox regression was used to account for confounding . Results Factors associated with digoxin use were permanent AF ( hazard ratio ( HR ) = 3.2 , confidence interval ( CI ) 2.7 to 3.9 ) , absence of pacemaker ( HR = 2.3 , CI 1.6 to 3.2 ) , history of heart failure ( HR = 2.0 , CI 1.7 to 2.5 ) , treatment in an internal medicine ward rather than a cardiology ward ( HR = 1.6 , CI 1.3 to 2.0 ) , female sex ( HR = 1.6 , CI 1.3 to 1.9 ) and age ≥80 years ( HR = 1.4 , CI 1.1 to 1.7 ) . More patients with than without digoxin died ( 51 % vs 31 % , p<0.001 ) . After adjustment for covariates , however , no disadvantages related to digoxin use could be found for all-cause mortality , myocardial infa rct ion , ischaemic stroke , time to readmission to hospital or days at hospital/year at risk . The only end point significantly associated with digoxin use was pacemaker implantations , which were more common in digoxin-treated patients ( HR = 2.0 , CI 1.2 to 3.4 ) . Conclusion Digoxin is mainly given to an elderly and frailer subset of patients with AF and is thus associated with an increased mortality . When differences in patient characteristics are accounted for digoxin use seems to have a neutral effect on mortality and major cardiovascular events in patients with AF 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 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 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 , Epidemiological , experimental studies and post hoc analyses of r and omized trials suggested that n-3 polyunsaturated fatty acids ( PUFA ) and statins could be beneficial in chronic heart failure . Two double-blind , placebo-controlled , r and omized clinical trials investigated the efficacy and safety of n-3 PUFA 1 g daily ( R1 ) and rosuvastatin 10 mg daily ( R2 ) in patients with heart failure . In total , 6975 and 4574 patients were r and omized in R1 and R2 , respectively ; the main reason for excluding patients from R2 being the open-label administration of statin treatment . Primary end points were death , and death or admission to hospital for cardiovascular reasons .  n-3 PUFA , but not rosuvastatin , significantly decreased the two co primary end points : 56 and 44 patients needed to be treated with n-3 PUFA for a median duration of 3.9 years to avoid one death or one cumulative event . Both drugs were safe and were tolerated . A simple and safe treatment with n-3 PUFA provides a beneficial advantage in patients with heart failure in a context of usual care
target: Assessment of the comparative effectiveness of individual AADs on CV hospitalization and mortality end points is not possible with the current evidence
background: AIM To assess , through a systematic review , evidence for the effects of antiarrhythmic drugs ( AADs ) on  cardiovascular ( CV ) hospitalization and mortality .