title: Warfarin Versus Aspirin for Prevention of Cognitive Decline in Atrial Fibrillation: Randomized Controlled Trial (Birmingham Atrial Fibrillation Treatment of the Aged Study) Occurrence of death and stroke in patients in 47 countries 1 year after presenting with atrial fibrillation: a cohort study Rhythm Control Versus Rate Control and Clinical Outcomes in Patients With Atrial Fibrillation: Results From the ORBIT-AF Registry. A randomised, controlled study of rate versus rhythm control in patients with chronic atrial fibrillation and heart failure: (CAFÉ-II Study) Atrial fibrillation: an observational study with outpatients. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. Rhythm control versus rate control for atrial fibrillation and heart failure. Quality of life in atrial fibrillation: the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. A comparison of rate control and rhythm control in patients with atrial fibrillation. Real-life observations of clinical outcomes with rhythm- and rate-control therapies for atrial fibrillation RECORDAF (Registry on Cardiac Rhythm Disorders Assessing the Control of Atrial Fibrillation).
abstract: Background and Purpose — Atrial fibrillation is associated with decline of cognitive function . Observational evidence suggests that anticoagulation might protect against this decline . We report the first r and omized controlled trial evidence on the effect of anticoagulation on cognitive function in elderly patients with atrial fibrillation . Methods — A total of 973 patients aged ≥75 years with atrial fibrillation were recruited from primary care and r and omly assigned to warfarin ( n=488 ; target international normalized ratio , 2–3 ) or aspirin ( n=485 ; 75 mg/d ) . Neither participants nor investigators were masked to group assignment . Follow-up was for a mean of 2.7 years ( SD , 1.2 ) . Cognitive outcome was assessed using the Mini-Mental State Examination at 9- , 21- , and 33-month follow-up . Participants who had a stroke were censored from the analysis , which was by intention to treat with imputation for missing data . Results — There was no difference between mean Mini-Mental State Examination scores in people assigned to warfarin or aspirin at 9 or 21 months . At 33-month follow-up , there was a nonsignificant difference of 0.56 in favor of warfarin that decreased to 0.49 ( 95 % confidence interval , –0.01 to 0.98 ) after imputation . Conclusions — We found no evidence that anticoagulation confers clinical ly important protection over aspirin against cognitive decline as measured by the Mini-Mental State Examination in atrial fibrillation in the first 33 months of treatment other than that provided by preventing clinical stroke . Clinical Trial Registration — URL : http://www.controlled-trials.com . Unique identifier : IS RCT N89345269 BACKGROUND Atrial fibrillation is an important cause of morbidity and mortality worldwide , but scant data are available for long-term outcomes in individuals outside North America or Europe , especially in primary care setting s. METHODS We did a cohort study using a prospect i ve registry of patients in 47 countries who presented to a hospital emergency department with atrial fibrillation or atrial flutter as a primary or secondary diagnosis . 15 400 individuals were enrolled to determine the occurrence of death and strokes ( the primary outcomes ) in this cohort over eight geographical regions ( North America , western Europe , and Australia ; South America ; eastern Europe ; the Middle East and Mediterranean crescent ; sub-Saharan Africa ; India ; China ; and southeast Asia ) 1 year after attending the emergency department . Patients from North America , western Europe , and Australia were used as the reference population , and compared with patients from the other seven regions FINDINGS Between Dec 24 , 2007 , and Oct 21 , 2011 , we enrolled 15 400 individuals to the registry . Follow-up was complete for 15 361 ( 99·7 % ) , of whom 1758 ( 11 % ) died within 1 year . Fewer deaths occurred among patients presenting to the emergency department with a primary diagnosis of atrial fibrillation compared with patients who had atrial fibrillation as a secondary diagnosis ( 377 [ 6 % ] of 6825 patients vs 1381 [ 16 % ] of 8536 , p<0·0001 ) . Twice as many patients had died by 1 year in South America ( 192 [ 17 % ] of 1132 ) and Africa ( 225 [ 20 % ] of 1137 ) compared with North America , western Europe , and Australia ( 366 [ 10 % ] of 3800 , p<0·0001 ) . Heart failure was the most common cause of death ( 519 [ 30 % ] of 1758 ) ; stroke caused 148 ( 8 % ) deaths . 604 ( 4 % ) of 15361 patients had had a stroke by 1 year ; 170 ( 3 % ) of 6825 for whom atrial fibrillation was a primary diagnosis and 434 ( 5 % ) of 8536 for whom it was a secondary diagnosis ( p<0·0001 ) . The highest number of strokes occurred in patients in Africa ( 89 [ 8 % ] of 1137 ) , China ( 143 [ 7 % ] of 2023 ) , and southeast Asia ( 88 [ 7 % ] of 1331 ) and the lowest occurred in India ( 20 [ < 1 % ] of 2536 ) . 94 ( 3 % ) of 3800 patients in North America , western Europe , and Australia had a stroke . INTERPRETATION Marked unexplained inter-regional variations in the occurrence of stroke and mortality suggest that factors other than clinical variables might be important . Prevention of death from heart failure should be a major priority in the treatment of atrial fibrillation . FUNDING Boehringer Ingelheim OBJECTIVES The study sought to evaluate clinical outcomes in clinical practice with rhythm control versus rate control strategy for management of atrial fibrillation ( AF ) . BACKGROUND R and omized trials have not demonstrated significant differences in stroke , heart failure , or mortality between rhythm and rate control strategies . The comparative outcomes in contemporary clinical practice are not well described . METHODS Patients managed with a rhythm control strategy targeting maintenance of sinus rhythm were retrospectively  compared with a strategy of rate control alone in a AF registry across various U.S. practice setting s. Unadjusted and adjusted ( inverse-propensity weighted ) outcomes were estimated . RESULTS The overall study population ( N = 6,988 ) had a median of 74 ( 65 to 81 ) years of age , 56 % were males , 77 % had first detected or paroxysmal AF , and 68 % had CHADS2 score ≥2 . In unadjusted analyses , rhythm control was associated with lower all-cause death , cardiovascular death , first stroke/non- central nervous system systemic embolization/transient ischemic attack , or first major bleeding event ( all p < 0.05 ) ; no difference in new onset heart failure ( p = 0.28 ) ; and more frequent cardiovascular hospitalizations ( p = 0.0006 ) . There was no difference in the incidence of pacemaker , defibrillator , or cardiac resynchronization device implantations ( p = 0.99 ) . In adjusted analyses , there were no statistical differences in clinical outcomes between rhythm control and rate control treated patients ( all p > 0.05 ) ; however , rhythm control was associated with more cardiovascular hospitalizations ( hazard ratio : 1.24 ; 95 % confidence interval : 1.10 to 1.39 ; p = 0.0003 ) . CONCLUSIONS Among patients with AF , rhythm control was not superior to rate control strategy for outcomes of stroke , heart failure , or mortality , but was associated with more cardiovascular hospitalizations Background : Atrial fibrillation ( AF ) and heart failure ( HF ) often coexist . The aim was to investigate whether restoring sinus rhythm ( SR ) could improve cardiac function , symptoms , exercise capacity and quality of life ( QoL ) in patients with chronic heart failure . Methods : Patients with HF and persistent AF receiving guideline -recommended treatments , including anticoagulants , were eligible for the study . Patients were r and omised to either rhythm ( treated with amiodarone for at least 3 months prior to attempting biphasic external cardioversion and continued amiodarone long-term if SR was restored ) or rate control . Anticoagulants were continued throughout the study regardless of rhythm , unless contraindications developed . Both groups were treated with beta blockers and /or digoxin to reduce the heart rate to < 80 bpm at rest and < 110 bpm after walking . Symptoms , walk distance ( 6-minute corridor walk test , 6MWT ) , QoL and cardiac function were assessed at baseline and 1 year . Results : 61 patients with HF and persistent AF ( median duration 14 months ( IQR 5 to 32 ) ) were r and omly assigned to a rate or rhythm control strategy . Of patients assigned to rhythm control ( n = 30 ) , 66 % were in SR at 1 year , and 90 % of those assigned to rate control ( n = 31 ) achieved the heart rate target . At 1 year , NYHA class ( p = 0.424 ) and 6MWT distance ( p = 0.342 ) were similar between groups but patients assigned to rhythm control had improved LV function ( p = 0.014 ) , NT-proBNP concentration ( p = 0.046 ) and QoL ( p = 0.019 ) compared with those assigned to rate control . Greatest improvement was seen in patients in whom SR was maintained . Conclusion : Restoring SR in patients with AF and heart failure may improve QoL and LV function when compared with a strategy of rate control BACKGROUND Atrial fibrillation ( AF ) is the most common sustained arrhythmia with serious clinical consequences in the absence of treatment . However , there are limited data on the treatment of these patients in Argentina . The objective was to describe the therapeutic management of patients with nonacute AF by Argentinean cardiologists and to determine the incidence of clinical events after 12 months follow-up . METHODS The Atrial Fibrillation study in Argentina ( FARAON ) was an observational , descriptive , prospect i ve , national , and multicentric study that included out patients with AF , followed for 12 months . The study included 38 sites in Argentina . Each research er included the first 10 patients who met the inclusion criteria of being over 21 and also being an AF carrier documented by electrocardiogram or Holter within 12 months prior to or at the time of enrollment . RESULTS A total of 373 patients were included , mean age 70 ± 11.5 years , 40 % women ; 65 % had AF rhythm at the time of inclusion , 57 % had permanent AF , and 56 % were asymptomatic . At the time of enrollment , 40 % of physicians opted for rhythm control strategy . β-blockers and amiodarone were the most used drugs . Patients with rhythm control drugs had higher success rate than those with frequency control drug therapy ( 80 % vs 57 % ) . CONCLUSION Cardiologists in Argentina receive patients with AF that are mostly permanent AF . More than half of the patients are asymptomatic . They opt primarily by controlling the pace . When choosing antiarrhythmic drugs , nearly half of them indicated amiodarone 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 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 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 It is common practice to restore and maintain sinus rhythm in patients with atrial fibrillation and heart failure . This approach is based in part on data indicating that atrial fibrillation is a predictor of death in patients with heart failure and suggesting that the suppression of atrial fibrillation may favorably affect the outcome . However , the benefits and risks of this approach have not been adequately studied . METHODS We conducted a multicenter , r and omized trial comparing the maintenance of sinus rhythm ( rhythm control ) with control of the ventricular rate ( rate control ) in patients with a left ventricular ejection fraction of 35 % or less , symptoms of congestive heart failure , and a history of atrial fibrillation . The primary outcome was the time to death from cardiovascular causes . RESULTS A total of 1376 patients were enrolled ( 682 in the rhythm-control group and 694 in the rate-control group ) and were followed for a mean of 37 months . Of these patients , 182 ( 27 % ) in the rhythm-control group died from cardiovascular causes , as compared with 175 ( 25 % ) in the rate-control group ( hazard ratio in the rhythm-control group , 1.06 ; 95 % confidence interval , 0.86 to 1.30 ; P=0.59 by the log-rank test ) . Secondary outcomes were similar in the two groups , including death from any cause ( 32 % in the rhythm-control group and 33 % in the rate-control group ) , stroke ( 3 % and 4 % , respectively ) , worsening heart failure ( 28 % and 31 % ) , and the composite of death from cardiovascular causes , stroke , or worsening heart failure ( 43 % and 46 % ) . There were also no significant differences favoring either strategy in any predefined subgroup . CONCLUSIONS In patients with atrial fibrillation and congestive heart failure , a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes , as compared with a rate-control strategy . ( Clinical Trials.gov number , NCT00597077 . OBJECTIVE The objective of this prespecified sub study of the AFFIRM study , in which no differences in survival or event rates were found in patients with atrial fibrillation ( AF ) r and omized to either rate control or rhythm control , was to test the null hypothesis that quality of life ( QoL ) is equal with rate- versus rhythm-control treatment strategies in AF . METHODS Fifty-six ( 25 % ) of AFFIRM sites were r and omly selected to recruit AFFIRM patients for the QoL sub study . Instruments used in the QoL assessment were ( 1 ) Perceived Health ;  ( 2 ) the  Cantril Ladder of Life ;  ( 3 ) the  Short Form 36 survey ;  ( 4 ) the  QoL Index ;  and ( 5 ) the  Symptom Checklist : Frequency and Severity .  Data were collected at baseline , 2 months , 12 months , and annually ; data are reported through 4 years of follow-up . RESULTS Baseline characteristics of the AFFIRM QoL patients ( n = 716 ) were generally similar to those of the rest of AFFIRM patients .  Quality -of-life scores were similar in rate- and rhythm-control assignment groups at all time points . Quality -of-life scores were similar whether the actual rhythm was sinus or AF . Scores increased from baseline to subsequent time points similarly for both groups ; these improvements were not additive over time . CONCLUSIONS Quality of life was comparable between rate- and rhythm-control treatment strategies . In addition , QoL was similar with sinus rhythm versus AF . Attempts to improve QoL by restoring sinus rhythm will usually be unsuccessful BACKGROUND There are two approaches to the treatment of atrial fibrillation : one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm , and the other is the use of rate-controlling drugs , allowing atrial fibrillation to persist . In both approaches , the use of anticoagulant drugs is recommended . METHODS We conducted a r and omized , multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death . The primary end point was overall mortality . RESULTS A total of 4060 patients ( mean [ + /-SD ] age , 69.7+/-9.0 years ) were enrolled in the study ; 70.8 percent had a history of hypertension , and 38.2 percent had coronary artery disease . Of the 3311 patients with echocardiograms , the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent . There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy ( mortality at five years , 23.8 percent and 21.3 percent , respectively ; hazard ratio , 1.15 [ 95 percent confidence interval , 0.99 to 1.34 ] ; P=0.08 ) . More patients in the rhythm-control group than in the rate-control group were hospitalized , and there were more adverse drug effects in the rhythm-control group as well . In both groups , the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic . CONCLUSIONS Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy , and there are potential advantages , such as a lower risk of adverse drug effects , with the rate-control strategy . Anticoagulation should be continued in this group of high-risk patients OBJECTIVES RECORDAF is the first worldwide , prospect i ve , observational survey of management of atrial fibrillation ( AF ) in unselected , community-based patients . BACKGROUND Primary outcomes were therapeutic success and clinical outcomes associated with rhythm-control and rate-control strategies . METHODS Patients with recent-onset AF were included ( n = 5,604 ) . Treatment strategy ( rhythm control or rate control ) was noted at baseline . Follow-up was 12 months . Therapeutic success required that strategy was unchanged without clinical events . Further maintenance of sinus rhythm was required in the rhythm-control group , and heart rate ≤80 beats/min in the rate-control group . RESULTS Data from 5,171 patients were assessable . Therapeutic success was 54 % overall ( rhythm control 60 % vs. rate control 47 % ) , a result driven by control of AF : rhythm control , 81 % vs. rate control , 74 % . After adjustment for propensity score quintiles , the rhythm-control strategy was significantly related to superior therapeutic success ( odds ratio : 1.34 , 95 % confidence interval : 1.15 to 1.55 ; p = 0.0002 ) . Clinical events occurred in 18 % of patients . The arrhythmia management strategy was not predictive of clinical events . The type ( persistent ) , presence at baseline visit , and duration ( > 3 months ) of AF , together with age older than 75 years and the presence of heart failure , predicted progression to permanent AF . The choice of rhythm control reduced the likelihood of AF progression ( odds ratio : 0.20 , 95 % confidence interval : 0.17 to 0.25 ; p < 0.0001 ) . CONCLUSIONS Clinical outcomes in AF patients were driven mainly by hospitalizations for arrhythmia/proarrhythmia and other cardiovascular causes , but not by the choice of rate or rhythm strategy . Rhythm-control patients progressed less rapidly to permanent AF
target: As such , evidence was insufficient to recommend rhythm or rate control as the first-line therapy for AF in older adults .
background: Atrial fibrillation ( AF ) is highly prevalent in older adults and has been associated with increased morbidity and mortality .
  To reduce this AF-related morbidity in older adults , antiarrhythmic drugs ( AADs ) are regularly used for rhythm control , assuming that increasing time in sinus rhythm reduces AF-related morbidity .
  However , whether AADs can improve clinical outcomes in older adults remains unclear because of the increased risk for adverse drug events compared with rate control .
  The aim of this study was to determine the impact of rhythm control versus rate control on clinical outcomes in older adults with AF .