title: Rate-Control Treatment and Mortality in Atrial Fibrillation Screening versus routine practice in detection of atrial fibrillation in patients aged 65 or over: cluster randomised controlled trial Digoxin in patients with permanent atrial fibrillation: data from the RACE II study. Atrial flutter: Clinical risk factors and adverse outcomes in the Framingham Heart Study. Occurrence of death and stroke in patients in 47 countries 1 year after presenting with atrial fibrillation: a cohort study Optimization of initial energy for cardioversion of atrial tachyarrhythmias with biphasic shocks. Evidence at a glance: error matrix approach for overviewing available evidence Amiodarone versus sotalol for atrial fibrillation. Surgical ablation of atrial fibrillation during mitral-valve surgery. Lack of evidence of increased mortality among patients with atrial fibrillation taking digoxin: findings from post hoc propensity-matched analysis of the AFFIRM trial. Transthoracic cardioversion of atrial fibrillation: comparison of rectilinear biphasic versus damped sine wave monophasic shocks. Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized, double-blind multicenter trial. Methods for combining randomized clinical trials: strengths and limitations. Prediction of uneventful cardioversion and maintenance of sinus rhythm from direct-current electrical cardioversion of chronic atrial fibrillation and flutter. Digoxin use and risk of mortality in hypertensive patients with atrial fibrillation Relation of digoxin use in atrial fibrillation and the risk of all-cause mortality in patients ≥65 years of age with versus without heart failure. Apixaban in patients with atrial fibrillation. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation.
abstract: Background — Current American and European guidelines emphasize the importance of rate-control treatments in treating atrial fibrillation with a Class I recommendation , although data on the survival benefits of rate control are lacking . The goal of the present study was to investigate whether patients receiving rate-control drugs  had a better prognosis compared with those without rate-control treatment . Methods and Results — This study used the National Health Insurance Research Data base in Taiwan . There were 43 879 , 18 466 , and 38 898 patients with atrial fibrillation enrolled in the groups receiving & bgr;-blockers , calcium channel blockers , and digoxin  , respectively . The reference group consisted of 168 678 subjects who did not receive any rate-control drug .  The clinical end point was all-cause mortality . During a follow-up of 4.9±3.7 years , mortality occurred in 88 263 patients ( 32.7 % ) . After adjustment for baseline differences , the risk of mortality was lower in patients receiving & bgr;-blockers ( adjusted hazard ratio=0.76 ; 95 % confidence interval=0.74–0.78 ) and calcium channel blockers ( adjusted hazard ratio=0.93 ; 95 % confidence interval=0.90–0.96 ) compared with those who did not receive rate-control medications . On the contrary , the digoxin group had a higher risk of mortality with an adjusted hazard ratio of 1.12 ( 95 % confidence interval=1.10–1.14 ) . The results were observed consistently in subgroup analyses and among the cohorts after propensity matching . Conclusions — In this nationwide atrial fibrillation cohort  , the risk of mortality was lower for patients  receiving rate-control treatment with & bgr;-blockers or calcium channel blockers , and the use of & bgr;-blockers was associated with the largest risk reduction . Digoxin use was associated with greater mortality . Prospect i ve , r and omized trials are necessary to confirm these findings Objectives To assess whether screening improves the detection of atrial fibrillation  ( cluster r and omisation ) and to compare systematic and opportunistic screening . Design Multicentred cluster r and omised controlled trial , with subsidiary trial embedded within the intervention arm . Setting 50 primary care centres in Engl and , with further individual r and omisation of patients in the intervention practice s. Participants 14 802 patients aged 65 or over in 25 intervention and 25 control practice s. Interventions Patients in intervention practice s were r and omly allocated to systematic screening ( invitation for electrocardiography ) or opportunistic screening ( pulse taking and invitation for electrocardiography if the pulse was irregular ) . Screening took place over 12 months in each practice from October 2001 to February 2003 . No active screening took place in control practice s. Main outcome measure Newly identified atrial fibrillation . Results The detection rate of new cases of atrial fibrillation was 1.63 % a year in the intervention practice s and 1.04 % in control practice s ( difference 0.59 % , 95 % confidence interval 0.20 % to 0.98 % ) . Systematic and opportunistic screening detected similar numbers of new cases ( 1.62 % v 1.64 % , difference 0.02 % , −0.5 % to 0.5 % ) . Conclusion Active screening for atrial fibrillation detects additional cases over current practice . The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography . Trial registration Current Controlled Trials IS RCT N19633732 BACKGROUND The Atrial Fibrillation Follow-up Investigation of Rhythm Management trial showed that digoxin was associated with increased mortality in patients with atrial fibrillation . OBJECTIVES To assess the association of digoxin with cardiovascular ( CV ) morbidity and mortality in patients with permanent atrial fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF : A Comparison Between Lenient Versus Strict Rate Control II trial as well as to assess the role of digoxin to achieve heart rate targets . METHODS The primary outcome was a composite of CV morbidity and mortality . Secondary outcomes included CV hospitalization and all-cause mortality or heart failure ( HF ) hospitalization . Of the 614 patients , 608 ( 99 % ) completed the dose-adjustment phase . Outcome events were analyzed from the end of the dose-adjustment phase until the end of follow-up . The median follow-up period was 2.9 years ( interquartile range 2.7 - 3.0 years ) . RESULTS In total , 284 patients ( 46.7 % ) used digoxin after the dose-adjustment phase ( median dosage 0.250 mg ; interquartile range 0.0625 - 0.750 mg ) . These patients were more often women , previously admitted for HF , had an increased left ventricular end-systolic diameter , and more often r and omized to strict rate control . By using Cox proportional hazards regression analysis , the use of digoxin was not associated with an increased risk for the primary and secondary outcomes . For the primary outcome , the 3-year estimated cumulative incidence was 12.9 % vs 13.4 % in the digoxin group vs the no-digoxin group ( unadjusted hazard ratio [ HR ] 0.97 ; 95 % confidence interval [ CI ] 0.62 - 1.52 ) . Incidence was 19.4 % vs. 19.5 % for CV hospitalization ( unadjusted HR 1.00 ; 95 % CI 0.69 - 1.45 ) and 6.6 % vs. 9.9 % for all-cause mortality or HF hospitalization ( unadjusted HR 0.62 ; 95 % CI 0.34 - 1.13 ) in the digoxin group vs the no-digoxin group . CONCLUSION The use of digoxin was not associated with increased morbidity and mortality BACKGROUND Few epidemiologic cohort studies have evaluated atrial flutter ( flutter ) as an arrhythmia distinct from atrial fibrillation ( AF ) . OBJECTIVE The purpose of this study was to examine the clinical correlates of flutter and its associated outcomes to distinguish them from those associated with AF in the Framingham Heart Study . METHODS We review ed  and adjudicated electrocardiograms ( ECGs ) previously classified as flutter or AF/flutter and another 100 ECGs r and omly selected from AF cases . We examined the clinical correlates of flutter by matching up to 5 AF and 5 referents to each flutter case using a nested case referent design . We determined the 10-year outcomes associated with flutter with Cox models . RESULTS During mean follow-up of 33.0 ± 12.2 years , 112 participants ( mean age 72 ± 10 years , 30 % women ) developed flutter . In multivariable analyses , smoking ( odds ratio [ OR ] 2.84 , 95 % confidence interval [ CI ] 1.54 - 5.23 ) , increased PR interval ( OR 1.28 per SD , 95 % CI 1.03 - 1.60 ) , myocardial infa rct ion ( OR 2.25 , 95 % CI 1.05 - 4.80 ) and heart failure ( OR 5.22 , 95 % CI 1.26 - 21.64 ) were associated with incident flutter . In age- and sex-adjusted models , flutter ( vs referents ) was associated with 10-year increased risk of AF ( hazard ratio [ HR ] 5.01 , 95 % CI 3.14 - 7.99 ) , myocardial infa rct ion ( HR 3.05 , 95 % CI 1.42 - 6.59 ) , heart failure ( HR 4.14 , 95 % CI 1.90 - 8.99 ) , stroke ( HR 2.17 , 95 % CI 1.13 - 4.17 ) , and mortality ( HR 2.00 , 95 % CI 1.44 - 2.79 ) . CONCLUSION We identified the clinical correlates associated with flutter and observed that flutter was associated with multiple adverse outcomes 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 OBJECTIVE Recommendations for optimal first-shock energies with biphasic waveforms are conflicting . We evaluated prospect ively the relation between type and duration of atrial tachyarrhythmias and the probability of successful cardioversion with a specific biphasic shock waveform to develop recommendations for the initial energy setting aim ing at the lowest total cumulative energy with 2 or less consecutive shocks . METHODS We analyzed 453 consecutive patients undergoing their first transthoracic electrical cardioversion , including 358 attempts for atrial fibrillation ( AF ) and 95 attempts for atrial flutter ( AFL ) or atrial tachycardia ( AT ) . A step-up protocol with a truncated exponential biphasic waveform starting at 50 J was used . Total cumulative energies were estimated under the assumption of a 2-tiered escalating shock protocol with different initial energy setting s and a " rescue shock " of 250 J for AFL/AT or 360 J for AF . The initial energy setting leading to the lowest total cumulative energy was regarded as the optimal first-shock level . RESULTS Cardioversion was successful in 448 patients ( cumulative efficacy , 99 % ) . In patients with AFL/AT , the lowest total cumulative energy was attained with an initial energy setting of 50 J. In patients with AF , lowest values were achieved with an initial energy of 100 J for arrhythmia duration s of 2 days or less and an initial energy of 150 J for arrhythmia duration s of more than 2 days . CONCLUSION We recommend an initial energy setting of 50 J in patients with AFL/AT , of 100 J in patients with AF 2 days or less , and of 150 J with AF more than 2 days Background Clinical evidence continues to exp and and is increasingly difficult to overview . We aim ed at conceptualizing a visual assessment tool , i.e. , a matrix for overviewing studies and their data in order to assess the clinical evidence at a glance . Methods A four-step matrix was constructed using the three dimensions of systematic error , r and om error , and design error . Matrix step I ranks the identified studies according to the dimensions of systematic errors and r and om errors . Matrix step II orders the studies according to the design errors . Matrix step III assesses the three dimensions of errors in studies . Matrix step IV assesses the size and direction of the intervention effect . Results The application of this four-step matrix is illustrated with two examples : peri-operative beta-blockade initialized in relation to surgery versus placebo for major non-cardiac surgery , and antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation .  When clinical evidence is deemed both internally and externally valid , the size of the intervention effect is to be assessed . Conclusion The error matrix provides an overview of the validity of the available evidence at a glance , and may assist in deciding which interventions to use in clinical practice 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 BACKGROUND Among patients undergoing mitral-valve surgery , 30 to 50 % present with atrial fibrillation , which is associated with reduced survival and increased risk of stroke .  Surgical ablation of atrial fibrillation has been widely adopted , but evidence regarding its safety and effectiveness is limited . METHODS We r and omly assigned 260 patients with persistent or long-st and ing persistent atrial fibrillation who required mitral-valve surgery  to undergo either surgical ablation ( ablation group ) or no ablation ( control group ) during the mitral-valve operation . Patients in the ablation group underwent further r and omization to pulmonary-vein isolation or a biatrial maze procedure . All patients underwent closure of the left atrial appendage . The primary end point was freedom from atrial fibrillation at both 6 months and 12 months ( as assessed by means of 3-day Holter monitoring ) . RESULTS More patients in the ablation group than in the control group were free from atrial fibrillation at both 6 and 12 months ( 63.2 % vs. 29.4 % , P<0.001 ) . There was no significant difference in the rate of freedom from atrial fibrillation between patients who underwent pulmonary-vein isolation and those who underwent the biatrial maze procedure ( 61.0 % and 66.0 % , respectively ; P=0.60 ) . One-year mortality was 6.8 % in the ablation group and 8.7 % in the control group ( hazard ratio with ablation , 0.76 ; 95 % confidence interval , 0.32 to 1.84 ; P=0.55 ) . Ablation was associated with more implantations of a permanent pacemaker than was no ablation ( 21.5 vs. 8.1 per 100 patient-years , P=0.01 ) . There were no significant between-group differences in major cardiac or cerebrovascular adverse events , overall serious adverse events , or hospital readmissions . CONCLUSIONS The addition of atrial fibrillation ablation to mitral-valve surgery significantly increased the rate of freedom from atrial fibrillation at 1 year among patients with persistent or long-st and ing persistent atrial fibrillation , but the risk of implantation of a permanent pacemaker was also increased . ( Funded by the National Institutes of Health and the Canadian Institutes of Health Research ; Clinical Trials.gov number , NCT00903370 . ) AIMS Digoxin is recommended for long-term rate control in paroxysmal , persistent , and permanent atrial fibrillation ( AF ) . While some analyses suggest an association of digoxin with a higher mortality in AF , the intrinsic nature of this association has not been examined in propensity-matched cohorts , which is the objective of the current study . METHODS AND RESULTS In Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) , 4060 patients with paroxysmal and persistent AF were r and omized to rate ( n = 2027 ) vs. rhythm ( n = 2033 ) control strategies . Of these , 1377 received digoxin as initial therapy and 1329 received no digoxin at baseline . Propensity scores for digoxin use were estimated for each of these 2706 patients and used to assemble a cohort of 878 pairs of patients receiving and not receiving digoxin , who were balanced on 59 baseline characteristics . Matched patients had a mean age of 70 years , 40 % were women , and 11 % non-white . During the 3.4 years of the mean follow-up , all-cause mortality occurred in 14 and 13 % of matched patients receiving and not receiving digoxin , respectively [ hazard ratio ( HR ) associated with digoxin use : 1.06 ; 95 % confidence interval ( CI ) : 0.83 - 1.37 ; P = 0.640 ] . Among matched patients , digoxin had no association with all-cause hospitalization ( HR : 0.96 ; 95 % CI : 0.85 - 1.09 ; P = 0.510 ) or incident non-fatal cardiac arrhythmias ( HR : 0.90 ; 95 % CI : 0.37 - 2.23 ; P = 0.827 ) . Digoxin had no multivariable-adjusted or propensity score-adjusted associations with these outcomes in the pre-match cohort . CONCLUSIONS In patients with paroxysmal and persistent AF , we found no evidence of increased mortality or hospitalization in those taking digoxin as baseline initial therapy BACKGROUND Clinical studies have shown that biphasic shocks are more effective than monophasic shocks for ventricular defibrillation . The purpose of this study was to compare the efficacy of a rectilinear biphasic waveform with a st and ard damped sine wave monophasic waveform for the transthoracic cardioversion of atrial fibrillation . METHODS AND RESULTS In this prospect i ve , r and omized , multicenter trial , patients undergoing transthoracic cardioversion of atrial fibrillation were r and omized to receive either damped sine wave monophasic or rectilinear biphasic shocks .  Patients r and omized to the monophasic protocol ( n=77 ) received sequential shocks of 100 , 200 , 300 , and 360 J. Patients r and omized to the biphasic protocol ( n=88 ) received sequential shocks of 70 , 120 , 150 , and 170 J. First-shock efficacy with the 70-J biphasic waveform ( 60 of 88 patients , 68 % ) was significantly greater than that with the 100-J monophasic waveform ( 16 of 77 patients , 21 % , P<0.0001 ) , and it was achieved with 50 % less delivered current ( 11+/-1 versus 22+/-4 A , P<0.0001 ) . Similarly , the cumulative efficacy with the biphasic waveform ( 83 of 88 patients , 94 % ) was significantly greater than that with the monophasic waveform ( 61 of 77 patients , 79 % ; P=0.005 ) . The following 3 variables were independently associated with successful cardioversion : use of a biphasic waveform ( relative risk , 4.2 ; 95 % confidence intervals , 1.3 to 13.9 ; P=0.02 ) , transthoracic impedance ( relative risk , 0.64 per 10-Omega increase in impedance ; 95 % confidence intervals , 0.46 to 0.90 ; P=0.005 ) , and duration of atrial fibrillation ( relative risk , 0.97 per 30 days of atrial fibrillation ; 95 % confidence intervals , 0.96 to 0.99 ; P=0.02 ) . CONCLUSIONS For transthoracic cardioversion of atrial fibrillation , rectilinear biphasic shocks have greater efficacy ( and require less energy ) than damped sine wave monophasic shocks OBJECTIVES This study compared a biphasic waveform with a conventional monophasic waveform for cardioversion of atrial fibrillation ( AF ) . BACKGROUND Biphasic shock waveforms have been demonstrated to be superior to monophasic shocks for termination of ventricular fibrillation , but data regarding biphasic shocks for conversion of AF are still emerging . METHODS In an international , multicenter , r and omized , double-blind clinical trial , we compared the effectiveness of damped sine wave monophasic versus impedance-compensated truncated exponential biphasic shocks for the cardioversion of AF . Patients received up to five shocks , as necessary for conversion : 100 J , 150 J , 200 J , a fourth shock at maximum output for the initial waveform ( 200 J biphasic , 360 J monophasic ) and a final cross-over shock at maximum output of the alternate waveform . RESULTS Analysis included 107 monophasic and 96 biphasic patients . The success rate was higher for biphasic than for monophasic shocks at each of the three shared energy levels ( 100 J : 60 % vs. 22 % , p < 0.0001 ; 150 J : 77 % vs. 44 % , p < 0.0001 ; 200 J : 90 % vs. 53 % , p < 0.0001 ) . Through four shocks , at a maximum of 200 J , biphasic performance was similar to monophasic performance at 360 J ( 91 % vs. 85 % , p = 0.29 ) . Biphasic patients required fewer shocks ( 1.7 + /- 1.0 vs. 2.8 + /- 1.2 , p < 0.0001 ) and lower total energy delivered ( 217 + /- 176 J vs. 548 + /- 331 J , p < 0.0001 ) . The biphasic shock waveform was also associated with a lower frequency of dermal injury ( 17 % vs. 41 % , p < 0.0001 ) . CONCLUSIONS For the cardioversion of AF , a biphasic shock waveform has greater efficacy , requires fewer shocks and lower delivered energy , and results in less dermal injury than a monophasic shock waveform Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . The present study was undertaken to reassess prospect ively the immediate and long-term results of direct-current electrical cardioversion in chronic atrial fibrillation or atrial flutter , and to determine factors predicting clinical outcome of the arrhythmia after direct-current cardioversion .  Two-hundred forty-six patients underwent direct-current electrical cardioversion  and were followed during a mean of 260 days . Multivariate analysis was used to identify factors predicting short- and long-term arrhythmia outcome . Cardioversion was achieved in 70 % of patients with atrial fibrillation and in 96 % of patients with atrial flutter . Stepwise logistic regression analysis revealed that arrhythmia duration ( p less than 0.001 ) , type of arrhythmia ( fibrillation vs flutter , p less than 0.02 ) and age ( p less than 0.05 ) independently influenced conversion rate . On an actuarial basis , 42 and 36 % of patients remained in sinus rhythm during 1 and 2 years , respectively . Multivariate regression analysis revealed that the type of arrhythmia ( p = 0.0008 ) , low precardioversion functional class ( p = 0.002 ) and the presence of nonrheumatic mitral valve disease ( p = 0.03 ) independently increased the length of the arrhythmia-free episode . Rheumatic heart disease shortened this period ( p = 0.03 ) . In conclusion , patients having a high probability of conversion together with a prolonged post-shock arrhythmia-free episode can be identified . This may improve the cost-benefit ratio of cardioversion Background : Digoxin is widely used for rate control of atrial fibrillation . However , recent studies have reported conflicting results on the association of digoxin with mortality when used in patients with atrial fibrillation . Moreover , the relationship of digoxin use to mortality in hypertensive patients with atrial fibrillation has not been examined . Methods and results : All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline ( n = 134 ) or who developed atrial fibrillation during follow-up ( n = 803 ) , r and omly assigned to losartan or atenolol-based treatment , in post-hoc analysis of a sub study of the Losartan  Intervention For Endpoint Reduction in hypertension ( LIFE ) trial . During 4.7 ± 1.1 years of mean follow-up , 167 patients died ( 17.8 % ) and 372 ( 39.7 % ) were treated with digoxin . In univariate Cox analyses , in-treatment digoxin use , entered as a time-varying covariate , was associated with a 61 % higher risk of dying ( hazard ratio 1.61 , 95 % confidence interval 1.18–2.19 , P = 0.003 ) . After adjusting for other univariate predictors of death in this population , including age , diabetes , history of ischemic heart disease , stroke , or heart failure , baseline Cornell product , QRS duration , heart rate , serum glucose , creatinine and high-density lipoprotein cholesterol , and a propensity score for digoxin use entered as st and ard covariates , and for in-treatment heart rate , pulse pressure , and Sokolow – Lyon voltage treated as time-varying covariates , digoxin use was no longer a significant predictor of mortality ( hazard ratio 1.04 , 95 % confidence interval 0.73–1.48 , P = 0.839 ) . Conclusion : In hypertensive patients with ECG left ventricular hypertrophy with existing or new atrial fibrillation , digoxin use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors associated with the propensity to use digoxin in this population . These findings suggest that factors other than digoxin use may account for the increased mortality found with digoxin use in some studies . Clinical Trials Registration : http:// clinical Previous studies on digoxin use in patients with atrial fibrillation ( AF ) and the risk of all-cause mortality  found conflicting results . We conducted a population -based , retrospective , cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF , in Quebec province , Canada , from 1998 to 2012 . The AF cohort was grouped into patients with and without heart failure ( HF ) and into  digoxin and no-digoxin users according to the first prescription filled for digoxin within 30 days after AF hospital discharge . We derived propensity score-matched digoxin and no-digoxin treatment groups for the groups of patients with and without HF , respectively , and conducted multivariable Cox proportional hazards regression analyses to determine association between digoxin use and all-cause mortality . The AF propensity score-matched cohorts of patients with and without HF were well balanced on baseline characteristics . In the propensity score-matched HF group , digoxin use was associated with a 14 % greater risk of all-cause mortality ( adjusted hazard ratio 1.14 , 95 % confidence interval 1.10 to 1.17 ) . In the propensity score-matched no-HF group , digoxin use was associated with a 17 % greater risk of all-cause mortality ( adjusted hazard ratio 1.17 , 95 % confidence interval 1.14 to 1.19 ) . In conclusion , our retrospective analyses found that digoxin use was associated with a greater risk for all-cause mortality in patients aged ≥65 years with AF regardless of concomitant HF . Large , multicenter , r and omized controlled trials or prospect i ve cohort studies are required to clarify this issue BACKGROUND Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation . However , many patients are not suitable c and i date s for or are unwilling to receive vitamin K antagonist therapy , and these patients have a high risk of stroke . Apixaban , a novel factor Xa inhibitor , may be an alternative treatment for such patients . METHODS In a double-blind study , we r and omly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive  apixaban ( at a dose of 5 mg twice daily ) or aspirin ( 81 to 324 mg per day ) , to determine whether apixaban was superior . The mean follow up period was 1.1 years . The primary outcome was the occurrence of stroke or systemic embolism . RESULTS Before enrollment , 40 % of the patients had used a vitamin K antagonist .  The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban . There were 51 primary outcome events ( 1.6 % per year ) among patients assigned to apixaban and 113 ( 3.7 % per year ) among those assigned to aspirin ( hazard ratio with apixaban , 0.45 ; 95 % confidence interval [ CI ] , 0.32 to 0.62 ; P<0.001 ) . The rates of death were 3.5 % per year in the apixaban group and 4.4 % per year in the aspirin group ( hazard ratio , 0.79 ; 95 % CI , 0.62 to 1.02 ; P=0.07 ) . There were 44 cases of major bleeding ( 1.4 % per year ) in the apixaban group and 39 ( 1.2 % per year ) in the aspirin group ( hazard ratio with apixaban , 1.13 ; 95 % CI , 0.74 to 1.75 ; P=0.57 ) ; there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin . The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin ( 12.6 % per year vs. 15.9 % per year , P<0.001 ) . The treatment effects were consistent among important subgroups . CONCLUSIONS In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable , apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding or intracranial hemorrhage . ( Funded by Bristol-Myers Squibb and Pfizer ; Clinical Trials.gov number , NCT00496769 . ) The occurrence of ventricular premature depolarizations in survivors of myocardial infa rct ion is a risk factor for subsequent sudden death , but whether antiarrhythmic therapy reduces the risk is not known . The Cardiac Arrhythmia Suppression Trial ( CAST ) is evaluating the effect of antiarrhythmic therapy ( encainide , flecainide , or moricizine ) in patients with asymptomatic or mildly symptomatic ventricular arrhythmia ( six or more ventricular premature beats per hour ) after myocardial infa rct ion . As of March 30 , 1989 , 2309 patients had been recruited for the initial drug-titration phase of the study : 1727 ( 75 percent ) had initial suppression of their arrhythmia ( as assessed by Holter recording ) through the use of one of the three study drugs and had been r and omly assigned to receive active drug or placebo . During an average of 10 months of follow-up , the patients treated with active drug had a higher rate of death from arrhythmia than the patients assigned to placebo . Encainide and flecainide accounted for the excess of deaths from arrhythmia and nonfatal cardiac arrests ( 33 of 730 patients taking encainide or flecainide [ 4.5 percent ] ; 9 of 725 taking placebo [ 1.2 percent ] ; relative risk , 3.6 ; 95 percent confidence interval , 1.7 to 8.5 ) . They also accounted for the higher total mortality ( 56 of 730 [ 7.7 percent ] and 22 of 725 [ 3.0 percent ] , respectively ; relative risk , 2.5 ; 95 percent confidence interval , 1.6 to 4.5 ) . Because of these results , the part of the trial involving encainide and flecainide has been discontinued . We conclude that neither encainide nor flecainide should be used in the treatment of patients with asymptomatic or minimally symptomatic ventricular arrhythmia after myocardial infa rct ion , even though these drugs may be effective initially in suppressing ventricular arrhythmia . Whether these results apply to other patients who might be c and i date s for antiarrhythmic therapy is unknown OBJECTIVES We sought to evaluate approaches used to control rate , the effectiveness of rate control , and switches from one drug class to another in the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study . BACKGROUND The AFFIRM study showed that atrial fibrillation ( AF ) can be treated effectively with rate control and anticoagulation , but drug efficacy to control rate remains uncertain . METHODS Patients ( n = 2,027 ) r and omized to rate control in the AFFIRM study were given rate-controlling drugs by their treating physicians . St and ardized rate-control efficacy criteria developed a priori included resting heart rate and 6-min walk tests and /or ambulatory electrocardiographic results . RESULTS Average follow-up was 3.5 + /- 1.3 years . Initial treatment included a beta-adrenergic blocker ( beta-blocker ) alone in 24 % , a calcium channel blocker alone in 17 % , digoxin alone in 16 % , a beta-blocker and digoxin in 14 % , or a calcium channel blocker and digoxin in 14 % of patients . Overall rate control was achieved in 70 % of patients given beta-blockers as the first drug ( with or without digoxin ) , 54 % with calcium channel blockers ( with or without digoxin ) , and 58 % with digoxin alone . Adequate overall rate control was achieved in 58 % of patients with the first drug or combination . Multivariate analysis revealed an association between first drug class and several clinical variables . There were more changes to beta-blockers than to the other two-drug classes ( p < 0.0001 ) . CONCLUSIONS Rate control in AF is possible in the majority of patients with AF . Beta-blockers were the most effective drugs . To achieve the goal of adequate rate control in all patients , frequent medication changes and drug combinations were needed
target: Discussion The results of this systematic review have the potential to benefit thous and s of patients worldwide as well as healthcare systems and healthcare economy .
background: Background Atrial fibrillation is the most common arrhythmia of the heart with a prevalence of approximately 2 % in the western world .
  Atrial flutter , another arrhythmia , occurs less often with an incidence of approximately 200,000 new patients per year in the USA .
  Patients with atrial fibrillation and atrial flutter have an increased risk of death and morbidities .
  The management of atrial fibrillation and atrial flutter is often based on interventions aim ing at either a rhythm control strategy or a rate control strategy .
  The evidence on the comparable effects of these strategies is unclear .
  This protocol for a systematic review aims at identifying the best overall treatment strategy for atrial fibrillation and atrial flutter .