Causes of death in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. Risk of proarrhythmic events in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: a multivariate analysis. Quality of Life in the Antiarrhythmics Versus Implantable Defibrillators Trial: Impact of Therapy and Influence of Adverse Symptoms and Defibrillator Shocks Are lipid-lowering drugs also antiarrhythmic drugs? An analysis of the Antiarrhythmics versus Implantable Defibrillators (AVID) trial. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. Antiarrhythmics After Ablation of Atrial Fibrillation (5A Study) Effect of Implantable Defibrillators on Arrhythmic Events and Mortality in the Multicenter Unsustained Tachycardia Trial Evaluation of outpatient initiation of antiarrhythmic drug therapy in patients reverting to sinus rhythm after an episode of atrial fibrillation. The Midlands Trial of Empirical Amiodarone versus Electrophysiology-guided Interventions and Implantable Cardioverter-defibrillators (MAVERIC): a multi-centre prospective randomised clinical trial on the secondary prevention of sudden cardiac death. The MUSTT Study: Evaluating Testing and Treatment Relationships Between Sinus Rhythm, Treatment, and Survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study Designation and distribution of events in the Multicenter UnSustained Tachycardia Trial (MUSTT). Effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias: Basel Antiarrhythmic Study of Infarct Survival (BASIS) A randomized comparison of amiodarone and class IC antiarrhythmic drugs to treat atrial fibrillation in patients paced for sinus node disease: the Prevention Investigation and Treatment: A Group for Observation and Research on Atrial arrhythmias (PITAGORA) trial. The systematic coronary risk evaluation (SCORE) for the prevention of cardiovascular diseases. Does evidence exist for its effectiveness? A systematic review Psychosocial predictors of mortality in the Cardiac Arrhythmia Suppression Trial-1 (CAST-1).
OBJECTIVES This study analyzed the causes of death in the  Antiarrhythmics Versus Implantable Defibrillators ( AVID ) Trial . BACKGROUND Both implantable cardioverter-defibrillators ( ICDs ) and antiarrhythmic drugs ( AADs ) are used as mainstays of treatment for life-threatening ventricular arrhythmias in patients who have survived either ventricular fibrillation or sustained ventricular tachycardia with hemodynamic compromise and serious symptoms . The AVID Trial compared the effectiveness of these two therapies . Survival was better with the ICD . Assessment of the cause of death should help to determine the mechanism of improvement in survival with the ICD . METHODS Of 1,016 patients enrolled in the AVID Trial , 202 patients died . The mode of death was determined by the unblinded Principal Investigator and independently by an Events Committee , which review ed material s meticulously blinded with respect to treatment . Deaths were classified as cardiac or noncardiac . Cardiac deaths were further classified as arrhythmic or nonarrhythmic , and causes of noncardiac death were identified . RESULTS Deaths were more frequent in patients treated with an AAD ( n = 122 ) , compared with patients treated with the ICD ( n = 80 ) , unadjusted p < 0.001 , p = 0.012 adjusted for sequential monitoring . In AVID , 157 deaths were cardiac , and 79 were arrhythmic . The major effect of the ICD was to prevent arrhythmic death ( AAD = 55 , ICD = 24 , nominal unadjusted p < 0.001 ) . Nonarrhythmic cardiac deaths were equal ( AAD = 39 , ICD = 39 ) . Patients treated with an AAD had a slightly greater incidence of noncardiac deaths ( 28 vs. 17 , p = 0.053 ) , primarily due to pulmonary and renal causes . CONCLUSIONS The ICD is more effective than an AAD in reducing arrhythmic cardiac death , while nonarrhythmic cardiac death is unchanged . Of note , apparent arrhythmic death still seems to constitute 38 % of all cardiac deaths despite treatment with an ICD . However , the ICD remains superior to an AAD in prolonging survival after life-threatening arrhythmias BACKGROUND AND OBJECTIVES The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined . This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study , a r and omized clinical trial comparing warfarin , aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation . METHODS Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents . The relative risk of cardiac mortality , including arrhythmic death , in patients receiving antiarrhythmic drug therapy  was determined and adjusted for other cardiac risk factors . RESULTS In patients receiving antiarrhythmic drug therapy , cardiac mortality was increased 2.5-fold ( p = 0.006 , 95 % confidence interval [ CI ] 1.3 to 4.9 ) and arrhythmic death was increased 2.6-fold ( p = 0.02 , 95 % CI 1.2 to 5.6 ) . Among patients with a history of congestive heart failure , those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 ( p less than 0.001 , 95 % CI 1.9 to 11.6 ) compared with that of patients not so treated ; the relative risk of arrhythmic death in the treated group was 3.7 ( p = 0.01 , 95 % CI 1.3 to 10.4 ) . Patients without a history of congestive heart failure had no increased risk of cardiac mortality ( relative risk 0.70 , 95 % CI 0.2 to 3.1 ) during antiarrhythmic drug therapy . After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death , patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death . However , in patients with a history of heart failure who received antiarrhythmic drug therapy , the relative risk of cardiac death was 3.3 ( p = 0.05 , 95 % CI 0.99 to 11.1 ) and that of arrhythmic death was 5.8 ( p = 0.009 , 95 % CI 1.5 to 21.7 ) compared with the risk in patients not taking antiarrhythmic medications . CONCLUSIONS Although antiarrhythmic drug therapy was not r and omly determined in this trial , the data suggest that in patients with atrial fibrillation and a history of congestive heart failure , the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm OBJECTIVES This study examined the risk of proarrhythmic events in patients receiving antiarrhythmic drugs for treatment of atrial fibrillation ( AF ) according to present-day safety guidelines . BACKGROUND Advances in underst and ing the proarrhythmic risk of antiarrhythmic drugs has led to development of safety guidelines for these agents . Such guidelines were used in the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study . METHODS This study was an analysis of the risk of arrhythmic events ( arrhythmic death , resuscitated cardiac arrest , sustained ventricular tachycardia ( VT ) , and torsade de pointes VT ) in the antiarrhythmic drug arm of the AFFIRM study . Each time an antiarrhythmic drug was begun , it was counted as an exposure to that drug and the risk of an arrhythmic event was calculated . RESULTS A total of 2,033 patients received 3,030 exposures to antiarrhythmic drugs . Ninety-six arrhythmic events occurred by six years . Patients with a left ventricular ejection fraction < 40 % had more arrhythmic events . Twelve documented cases of torsade de pointes VT were noted . The incidence of torsade de pointes was 0.6 % at five years ( 95 % confidence interval 0.32 to 1.07 ) . CONCLUSIONS The overall risk of adverse arrhythmic events upon exposure to antiarrhythmic drugs in the AFFIRM study was reasonably low . Strict criteria for the safe use of antiarrhythmic drugs were successful in minimizing proarrhythmic events Background —Implantable cardioverter defibrillator ( ICD ) use reduces mortality in patients with serious ventricular arrhythmias compared with antiarrhythmic drug ( AAD ) use . However , the relative impact of these therapies on self-perceived quality of life ( QoL ) is unknown . Methods and Results —Three self-administered instruments were used to measure generic and disease-specific QoL in  Antiarrhythmics  Versus  Implantable Defibrillators  trial participants . Generalized linear models were used to assess the relationships between self-perceived QoL and treatment ( AAD versus ICD ) and adverse symptoms and ICD shocks . To minimize the impact of missing data , only patients surviving 1 year were included in the primary analyses . Baseline characteristics among QoL participants ( n=905 ) and non participants ( n=111 ) were similar , but participants who survived 1 year ( n=800 ) were healthier at baseline than nonsurvivors ( n=105 ) . Of the 800 patients in the primary analysis , characteristics of those r and omized to AAD ( n=384 ) versus ICD ( n=416 ) were similar . Overall , ICD and AAD use were associated with similar alterations in QoL. The development of sporadic shocks and adverse symptoms were each associated with reduced physical functioning and mental well-being and increased concerns among ICD recipients , whereas development of adverse symptoms was associated with reduced physical functioning and increased concerns among AAD recipients . Conclusions —ICD and AAD therapy are associated with similar alterations in self-perceived QoL over 1-year follow-up . Adverse symptoms were associated with reduced self-perceived QoL in both groups , and sporadic shocks were associated with reduced QoL in ICD recipients OBJECTIVES This study sought to evaluate the antiarrhythmic effects of lipid-lowering drug therapy as assessed by ventricular tachyarrhythmia ( ventricular tachycardia [VT]/ventricular fibrillation [ VF ] ) recurrences recorded by an implantable cardioverter defibrillator ( ICD ) in patients with atherosclerotic heart disease ( ASHD ) . BACKGROUND R and omized trials of lipid-lowering drugs suggest reduction of sudden death ( SD ) in patients with ASHD . Because SD is usually secondary to VT/VF , this observation suggests that lipid-lowering therapy has antiarrhythmic effects . METHODS The probability of VT/VF recurrence in patients with ASHD treated with an ICD in the Antiarrhythmics Versus Implantable Defibrillators ( AVID ) trial who did not receive lipid-lowering drug therapy ( n = 279 ) was compared with that in patients who received early and consistent lipid-lowering therapy ( n = 83 ) . In addition , all-cause mortality and cardiac mortality of all patients in the AVID trial with ASHD who did not receive lipid-lowering therapy ( n = 564 ) were compared with that of those who received early and consistent lipid-lowering therapy  ( n = 149 ) . RESULTS Using multivariate analyses , lipid-lowering therapy was associated with a reduction in the relative hazard for VT/VF recurrence of 0.40 ( 95 % confidence interval [ CI ] 0.15 to 0.58 ) ( adjusted p = 0.003 ) in the ICD subgroup . Lipid-lowering therapy was also associated with a reduction in the relative hazard for all-cause mortality of 0.36 ( 95 % CI 0.15 to 0.68 ) ( adjusted p = 0.03 ) and a reduction in the relative hazard for cardiac mortality of 0.39 ( 95 % CI 0.16 to 0.78 ) ( adjusted p = 0.04 ) in the larger study population . CONCLUSIONS In patients with ASHD who have received an ICD , lipid-lowering therapy is associated with reduction in the probability of VT/VF recurrence , suggesting that part of the benefit of lipid-lowering therapy may be due to an antiarrhythmic effect BACKGROUND Empirical antiarrhythmic therapy has not reduced mortality among patients with coronary artery disease and asymptomatic ventricular arrhythmias . Previous studies have suggested that antiarrhythmic therapy guided by electrophysiologic testing might reduce the risk of sudden death . METHODS We conducted a r and omized , controlled trial to test the hypothesis that electrophysiologically guided antiarrhythmic therapy would reduce the risk of sudden death among patients with coronary artery disease , a left ventricular ejection fraction of 40 percent or less , and asymptomatic , unsustained ventricular tachycardia . Patients in whom sustained ventricular tachyarrhythmias were induced by programmed stimulation were r and omly assigned to receive either antiarrhythmic therapy , including drugs and implantable defibrillators , as indicated by the results of electrophysiologic testing , or no antiarrhythmic therapy . Angiotensin-converting-enzyme inhibitors and beta-adrenergic-blocking agents were administered if the patients could tolerate them . RESULTS A total of 704 patients with inducible , sustained ventricular tachyarrhythmias were r and omly assigned to treatment groups . Five-year Kaplan-Meier estimates of the incidence of the primary end point of cardiac arrest or death from arrhythmia were 25 percent among those receiving electrophysiologically guided therapy and 32 percent among the patients assigned to no antiarrhythmic therapy ( relative risk , 0.73 ; 95 percent confidence interval , 0.53 to 0.99 ) , representing a reduction in risk of 27 percent ) . The five-year estimates of overall mortality were 42 percent and 48 percent , respectively ( relative risk , 0.80 ; 95 percent confidence interval , 0.64 to 1.01 ) . The risk of cardiac arrest or death from arrhythmia among the patients who received treatment with defibrillators was significantly lower than that among the patients discharged without receiving defibrillator treatment ( relative risk , 0.24 ; 95 percent confidence interval , 0.13 to 0.45 ; P<0.001 ) . Neither the rate of cardiac arrest or death from arrhythmia nor the overall mortality rate was lower among the patients assigned to electrophysiologically guided therapy and treated with antiarrhythmic drugs than among the patients assigned to no antiarrhythmic therapy . CONCLUSIONS Electrophysiologically guided antiarrhythmic therapy with implantable defibrillators , but not with antiarrhythmic drugs , reduces the risk of sudden death in high-risk patients with coronary disease Background — Atrial arrhythmias are common early after atrial fibrillation ( AF ) ablation . We hypothesized that empirical antiarrhythmic drug ( AAD ) therapy for 6 weeks after AF ablation would reduce the occurrence of atrial arrhythmias . Methods and Results — We r and omized consecutive patients with paroxysmal AF undergoing ablation to empirical antiarrhythmic therapy ( AAD group ) or no antiarrhythmic therapy ( no-AAD group ) for the first 6 weeks after ablation . In the no-AAD group , only atrioventricular nodal blocking agents were prescribed . All patients wore a transtelephonic monitor for 4 weeks after discharge and were reevaluated at 6 weeks . The primary end point of the study was a composite of ( 1 ) atrial arrhythmias lasting more than 24 hours ; ( 2 ) atrial arrhythmias associated with severe symptoms requiring hospital admission , cardioversion , or initiation/change of antiarrhythmic drug therapy ; and ( 3 ) intolerance to antiarrhythmic agent requiring drug cessation .  Of 110 enrolled patients ( age 55±9 years , 71 % male ) , 53 were r and omized to AAD and 57 to no-AAD . There was no difference in baseline characteristics between groups . During the 6 weeks after ablation , fewer patients reached the primary end point in the AAD compared with the no-AAD group ( 19 % versus 42 % ; P=0.005 ) . There remained fewer events in the AAD group ( 13 % versus 28 % ; P=0.05 ) when only end points of AF > 24 hours , arrhythmia-related hospitalization , or electrical cardioversion were compared . Conclusions — AAD treatment during the first 6 weeks after AF ablation is well tolerated and reduces the incidence of clinical ly significant atrial arrhythmias and need for cardioversion/hospitalization for arrhythmia management Background —The Multicenter Unsustained Tachycardia Trial ( MUSTT ) was design ed to evaluate an antiarrhythmic treatment strategy , including drugs and implantable defibrillators ( ICDs ) , guided by electrophysiological ( EP ) testing . We performed several statistical analyses to assess the contribution of defibrillators to the observed treatment benefit . Methods and Results —First , the effects of defibrillators were indirectly examined by comparing the r and omized treatment arms ( EP-guided therapy versus no antiarrhythmic therapy ) within subgroups that varied according to ICD usage . Use of ICDs increased during the trial ; hence , the r and omized treatments were compared according to date of enrollment . There were also site-specific differences in ICD use ; hence , the r and omized arms were compared within groups of sites defined by level of ICD use . There was a distinct “ dose response ” in relation to ICD use . Where ICD use was high , EP-guided therapy produced significant reductions in arrhythmic death or cardiac arrest ( P < 0.004 ) . Where ICD use was low , there was no benefit of EP-guided therapy . Finally , outcomes of EP-guided therapy patients who received an ICD were directly compared with outcomes of other patients using the Cox proportional hazards model with receipt of an ICD as a time-dependent covariate . Adjusted for other prognostic factors , patients who received an ICD had risk reductions of > 70 % in arrhythmic death or cardiac arrest and > 50 % in total mortality ( P < 0.001 for both end points ) . Conclusions —The benefit of EP-guided antiarrhythmic therapy observed in MUSTT was due to improved outcomes among patients who received an ICD but not among patients who received antiarrhythmic drugs The safety of a method of outpatient antiarrhythmic drug loading utilizing a continuous loop event recorder was evaluated . The findings suggest that the st and ard 2-day hospital admission for drug loading is not necessary in all patients and a method of outpatient loading may be equally safe AIMS MAVERIC was a r and omised clinical trial design ed to test the possibility of prospect ively identifying patients who would benefit most from the implantable cardioverter-defibrillator ( ICD ) by electrophysiology ( EP ) study in the context of secondary prevention of sudden cardiac death ( SCD ) through comparing EP-guided interventions ( anti-arrhythmic drugs , coronary revascularization , and ICD ) against empirical amiodarone therapy . METHODS Two hundred and fourteen survivors of sustained ventricular tachycardia ( VT ) , ventricular fibrillation ( VF ) or SCD were r and omized to either treatment strategy , pre-stratified for haemodynamic status at index event , and followed up for a median of 5 years . RESULTS Of the 106 amiodarone arm patients , 89 ( 84 % ) received the drug and 5 ( 5 % ) received an ICD after crossing over . Of the 108 EP  arm patients , 31 ( 29 % ) received an ICD , 46 ( 43 % ) received  anti-arrhythmic drugs only ( mainly amiodarone or sotalol ) and 18 ( 17 % ) received coronary revascularization but no ICD . No significant differences in survival or arrhythmia recurrence existed between the two treatment arms after 6 years . However , ICD recipients had a lower mortality than non-ICD recipients , regardless of allocated treatment ( hazard ratio=0.54 , p=0.0391 ) . CONCLUSIONS Prospect i ve selection of patients to receive the ICD by EP study did not improve survival compared with empirical amiodarone therapy among survivors of VT , VF or SCD , whereas ICD implantation improved survival regardless of allocated treatment . On this basis , routine EP study has no role in the management of such patients , who should be offered empirical ICD therapy according to the results of other secondary prevention ICD trials The multicenter unsustained tachycardia trial ( MUSTT ) tested the value of electrophysiologically guided antiarrhythmic drug therapy against no therapy in high risk coronary artery disease with poor left ventricular function ( LV-EF ≤ 40 % ) and nonsustained ventricular tachycardia . Risk assessment was performed by testing inducibility of a sustained ventricular tachycardia . The primary endpoint of the study was sudden arrhythmic death or cardiac arrest . Significant information on risk stratification was gathered by the follow-up of patients that were noninducible . Although MUSTT was not a specific ICD trial for primary prevention of SCD the results of the trial revealed that only with ICD back-up — a significant reduction of arrhythmic death or cardiac arrest can be achieved . EP-guided antiarrhythmic drug treatment had a lower incidence of SCD/CA compared to no treatment ( 12 % versus 25 % , p = 0.043 , hazard ratio 0.73 after 24 months and 18 % versus 32 % after 60 months ) . A subgroup analysis showed that the benefit of antiarrhythmic treatment was only due to ICD implantation . No difference was found between those inducible pts treated exclusively with antiarrhythmic drugs  and those who were r and omized to no drug treatment . Patients who were not inducible did significantly better than pts who were inducible wether or not treated with antiarrhythmic drugs . MUSTT results strengthen the data of the MADIT study . They confirm the inducibility testing as the most accurate risk stratifier . MUSST demonstrated the poor value of serial EP drug testing as well as the risk of “ st and alone ” antiarrhythmic drug  treatment Background —The AFFIRM Study showed that treatment of patients with atrial fibrillation and a high risk for stroke or death with a rhythm-control strategy offered no survival advantage over a rate-control strategy in an intention-to-treat analysis . This article reports an “ on-treatment ” analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time . Methods and Results —Modeling techniques were used to determine the relationships among survival , baseline clinical variables , and time-dependent variables . The following baseline variables were significantly associated with an increased risk of death : increasing age , coronary artery disease , congestive heart failure , diabetes , stroke or transient ischemic attack , smoking , left ventricular dysfunction , and mitral regurgitation . Among the time-dependent variables , the presence of sinus rhythm ( SR ) was associated with a lower risk of death , as was warfarin use . Antiarrhythmic drugs ( AADs ) were associated with increased mortality only after adjustment for the presence of SR . Consistent with the original intention-to-treat analysis , AADs were no longer associated with mortality when SR was removed from the model . Conclusions —Warfarin use improves survival . SR is either an important determinant of survival or a marker for other factors associated with survival that were not recorded , determined , or included in the survival model . Currently available AADs are not associated with improved survival , which suggests that any beneficial antiarrhythmic effects of AADs are offset by their adverse effects . If an effective method for maintaining SR with fewer adverse effects were available , it might be beneficial Patients with coronary artery disease , depressed left ventricular ejection fraction , and nonsustained ventricular tachycardia ( VT ) have a high mortality rate due to arrhythmic ( arrhythmic death/cardiac arrest ) and other cardiac causes . The Multicenter UnSustained Tachycardia Trial ( MUSTT ) investigated whether electrophysiologic study ( EPS ) was helpful in choosing drug or defibrillator therapy in patients induced into sustained VT . The events committee attempted to categorize follow-up events in patients in MUSTT and to present a detailed breakdown of events . A derivative of the Hinkle-Thaler classification was used , incorporating lessons from other multicenter studies . The committee was blinded to results of EPS and implantable cardioverter-defibrillator ( ICD ) or other antiarrhythmic therapy status of patients . The primary end point was cardiac arrest or death from arrhythmia . Secondary end points were death from all causes , cardiac causes , and spontaneous sustained VT . Classifications were death and cardiac arrest . Each was similarly divided as arrhythmic with 14 subcategories , e.g. , unwitnessed or related to EPS and nonarrhythmic with 10 subcategories , e.g. , ischemia . Terminal VF in progressive heart failure was considered nonarrhythmic . Events were review ed by 2 members . Disagreements were resolved by the 2 members or , if needed , by the full committee . Of the 2,202 patients in MUSTT , there were 902 deaths . Sustained VT  requiring cardioversion occurred in 182 patients . An additional 94 patients had resuscitated cardiac arrests .  Events occurred in 1,027 patients , and all were review ed . The 3 leading events were deaths that were classed as sudden/unwitnessed ( 23 % of 902 ) , due to progressive heart failure ( 22 % ) , or due to noncardiovascular causes ( 18 % ) . Arrhythmic deaths or cardiac arrests were highest in inducible patients r and omized to no antiarrhythmic therapy ; next were inducible patients receiving an ICD ; and lowest were in patients who were noninducible . In conclusion , the classification system provided a detailed breakdown of events in consistent categories , showing utility for event analysis and interpretation and development of therapeutic strategies . The classifications assigned by the committee were used in all MUSTT outcomes reports , thus affecting all reported outcomes and overall interpretations of the MUSTT In view of the high risk of sudden cardiac death and the prognostic importance of complex ventricular ectopic activity , the effects of prophylactic antiarrhythmic treatment were investigated prospect ively in patients with persisting asymptomatic complex arrhythmias after myocardial infa rct ion . End points were total mortality and arrhythmic events ( sudden death , sustained ventricular tachycardia and ventricular fibrillation ) . Of 1,220 consecutively screened survivors of myocardial infa rct ion , 312 had Lown class 3 or 4b arrhythmia on 24 h electrocardiographic recordings before hospital discharge and consented to the study . They were r and omized to individualized antiarrhythmic treatment ( Group 1 , n = 100 ) , treatment with low dose amiodarone , 200 mg/day ( Group 2 , n = 98 ) or no antiarrhythmic therapy ( Group 3 [ control group ] , n = 114 ) . During the 1 year follow-up period , 10 patients in Group 1 died , as did 5 in Group 2 and 15 in Group 3 . On the basis of an intention to treat analysis , the probability of survival of patients given amiodarone was significantly greater than that of control patients ( p less than 0.05 ) . In addition , arrhythmic events were significantly reduced by amiodarone ( p less than 0.01 ) . These effects were less marked and not significant for individually treated patients ( Group 1 ) . These findings suggest that low dose amiodarone decreases mortality in the 1st year after myocardial infa rct ion in patients at high risk of sudden death BACKGROUND Rhythm control is an important goal in the treatment of recurrent atrial tachyarrhythmias ( AT ) . The PITAGORA study was a r and omized trial in patients paced for sinus node disease ( SND ) , design ed to test the noninferiority of class IC antiarrhythmic drugs ( AADs ) to amiodarone in terms of a primary end point composed of death , permanent AT , cardiovascular hospitalization , atrial cardioversion , or AAD change . METHODS R and omization was stratified to assign 2 patients to  amiodarone  and 2 patients to class  IC AADs : propafenone or flecainide .  One hundred seventy-six patients ( 46 % men , 72 + /- 8 years ) were enrolled . Device diagnostics continuously monitored AT recurrences and duration . RESULTS In a mean follow-up of 20 + /- 9 months , the primary end point occurred in 23 ( 30.7 % ) of 75 class IC patients and in 28 ( 40.0 % ) of 70 amiodarone patients . The absolute difference in the end point incidence ( -9.3 % ; 95 % CI between 3.7 % and -22.3 % ) confirmed the noninferiority of class IC to amiodarone ( P = .007 ) . Kaplan-Meier 1-year freedom from AT episodes > 10 minutes , 1 day , and 7 days was 40 % , 73 % , and 91 % for amiodarone and 28 % , 78 % , and 86 % for class IC AADs ( P = nonsignificant ) . CONCLUSIONS In patients paced for SND and suffering from AT , class IC AADs proved not to be inferior to amiodarone in terms of the primary composite end point described or end points which were differently composed of mortality , efficacy , or AAD side effects . The AADs studied also showed similar results in terms of symptoms , quality of life , and freedom from AT recurrences Objectives : The SCORE model predicts the ten-year risk of cardiovascular mortality but it is still unknown whether applying the SCORE in clinical practice subsequently improves cardiovascular disease ( CVD ) outcomes . The objective of this study is to assess the effect of total cardiovascular risk estimation using the SCORE in preventing serious cardiovascular events in European adults without prior CVD . Methods and results : Data sources : eight bibliographical data bases ( 2003 – August 2015 ) , other internet sources and reference lists of articles were checked . This was supplemented by contact with the board members of the European Society of Cardiology ( ESC ) and the authors of the SCORE model . Study eligibility criteria : all prospect i ve studies in any language investigating the effect of using the SCORE on the clinical outcome ( CVD death , major events and adverse outcomes ) in an adult population were examined . Two review ers assessed the studies independently ( titles , abstract s , full texts ) . After removal of duplicates , 5,256 records were screened and 14 full text papers considered . No eligible studies were identified . An extensive literature search revealed no r and omized control trial or other prospect i ve study comparing significant clinical outcomes between groups that used the SCORE and those who did not . Conclusions : The effect of using the SCORE ( with or without subsequent intervention ) on CVD death , all-cause mortality , major CVD events like myocardial infa rct ion and stroke , as well as adverse outcomes , is still unknown . A cluster r and omised controlled trial is warranted to evaluate the use of the SCORE on important outcomes Psychosocial variables predict the recurrence of clinical events in symptomatic patients , controlling for measures of disease severity . The Cardiac Arrhythmia Suppression Trial-1 , a pharmacologic test of the arrhythmia suppression and mortality hypothesis among postmyocardial infa rct ion patients , allowed a prospect i ve test of the relationship of distress , perceived support , social interaction , life stress , and other variables , to mortality , adjusting statistically for ejection fraction , arrhythmia rates , and other known risk factors for coronary heart disease . Results indicated that the treatment medications , encainide and flecainide , were powerful predictors of mortality . Although the psychosocial variables were significant as univariate predictors , these variables were not significant as predictors in a multivariate model that included drug treatment . When the data analysis was restricted to patients r and omized to placebo  , thereby eliminating the antiarrhythmic drug effect , the level of perceived social support was a significant multivariate predictor of mortality , adjusting for measures of disease severity . The adjusted hazards ratio for a 1-point decrease in the perceived support score is equal to 1.46 , based on the multivariate model
Assessment of the comparative effectiveness of individual AADs on CV hospitalization and mortality end points is not possible with the current evidence
AIM To assess , through a systematic review , evidence for the effects of antiarrhythmic drugs ( AADs ) on  cardiovascular ( CV ) hospitalization and mortality .