Antiarrhythmics After Ablation of Atrial Fibrillation (5A Study) 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. Quality of Life in the Antiarrhythmics Versus Implantable Defibrillators Trial: Impact of Therapy and Influence of Adverse Symptoms and Defibrillator Shocks Causes of death in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. Cost-Effectiveness of the Implantable Cardioverter-Defibrillator Versus Antiarrhythmic Drugs in Survivors of Serious Ventricular Tachyarrhythmias: Results of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Economic Analysis Substudy Costs of treating cardiovascular events in Germany: a systematic literature review Radiofrequency Catheter Ablation and Antiarrhythmic Drug Therapy: A Prospective, Randomized, 4-Year Follow-Up Trial: The APAF Study Relationships Between Sinus Rhythm, Treatment, and Survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study Atrial fibrillation: the rate versus rhythm management controversy. Relation of plasma total homocysteine to cardiovascular mortality in a French population. Radiofrequency catheter ablation maintains its efficacy better than antiarrhythmic medication in patients with paroxysmal atrial fibrillation: On-treatment analysis of the randomized controlled MANTRA-PAF trial. Cost-Effectiveness of Radiofrequency Catheter Ablation Compared With Antiarrhythmic Drug Therapy for Paroxysmal Atrial Fibrillation Extensive antiarrhythmic drugs after catheter ablation of persistent atrial fi brillation A Systematic Assessment of Cardiovascular Outcomes in the Saxagliptin Drug Development Program for Type 2 Diabetes Dietetic guidelines: diet in secondary prevention of cardiovascular disease. Improvements in Symptoms and Quality of Life in Patients With Paroxysmal Atrial Fibrillation Treated With Radiofrequency Catheter Ablation Versus Antiarrhythmic Drugs Prognostic effects of rosuvastatin in patients with co-existing chronic obstructive pulmonary disease and chronic heart failure: A sub-analysis of GISSI-HF trial. Causes of death and rehospitalization in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction: results from Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) program. Renal sympathetic denervation versus antiarrhythmic drugs for drug-resistant hypertension and symptomatic atrial fibrillation (RSDforAF) trial: study protocol for a randomized controlled trial Prevalence and prognostic importance of precipitating factors leading to heart failure hospitalization: recurrent hospitalizations and mortality Usefulness of ablation of complex fractionated atrial electrograms using nifekalant in persistent atrial fibrillation. A randomized clinical trial of early invasive intervention for atrial fibrillation (EARLY-AF) - methods and rationale. Contemporary management of patients undergoing atrial fibrillation ablation: in-hospital and 1-year follow-up findings from the ESC-EHRA atrial fibrillation ablation long-term registry Cardiovascular risk in relation to body mass index and use of evidence-based preventive medications in patients with or at risk of atherothrombosis. Depression predicts mortality and hospitalization in heart failure: A six-years follow-up study. Financial Conflicts of Interest and Conclusions About Neuraminidase Inhibitors for Influenza Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme.
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 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 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 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 —The implantable cardioverter-defibrillator ( ICD ) is an effective but expensive device . We used prospect ively collected data from a large r and omized clinical trial of secondary prevention of life-threatening ventricular arrhythmias to determine the cost-effectiveness of the ICD compared with antiarrhythmic drug ( AAD ) therapy , largely with amiodarone . Methods and Results —Charges for initial and repeat hospitalizations , emergency room , and day surgery stays and the costs of antiarrhythmic drugs  were collected on 1008 patients . Detailed records of all other medical encounters and expenses were collected on a subgroup of 237 patients . Regression models were then created to attribute these expenses to the rest of the patients . Charges were converted to 1997 costs using st and ard methods . Costs and life years were discounted at 3 % per year . Three-year survival data from the Antiarrhythmics Versus Implantable Defibrillators trail were used to calculate the base-case cost-effectiveness ( C/E ) ratio . Six-year , twenty-year , and lifetime C/E ratios were also estimated . At 3 years , total costs were $ 71 421 for a patient taking AADs and $ 85 522 for a patient using an ICD , and the ICD provided a 0.21-year survival benefit over AAD treatment . The base-case C/E ratio was thus $ 66 677 per year of life saved by the ICD compared with AAD therapy ( 95 % CI , $ 30 761 to $ 154 768 ) . Six- and 20-year C/E ratios remained stable between $ 68 000 and $ 80 000 per year of life saved . Conclusions —The ICD is moderately cost-effective for secondary prevention of life-threatening ventricular arrhythmias , as judged from prospect ively collected data in a r and omized clinical trial Objective This study aims to systematic ally evaluate available evidence regarding direct medical costs of treating cardiovascular ( CV ) events in Germany after 2003 on an individual patient basis and from a payer perspective . The CV events of interest were myocardial infa rct ion ( MI ) , unstable angina , heart failure ( HF ) , stroke , and peripheral artery disease ( PAD ) . Method A systematic literature search was performed in the following data bases according to Preferred Reporting Items for Systematic Review s and Meta- Analysis ( PRISMA ) guidelines - Medline , Embase , Centre for Review s and Dissemination , TIBORDER , and German dissertation data base from January 2003 to October 2013 . Both observational studies and r and omized clinical trials were considered for the review . All values stated in € are inflation adjusted to 2014 € unless stated otherwise . Result This review included 13 articles . For newly occurred MI patients , the average hospitalization costs during the acute phase were reported to be between € 6790 and € 8918 per admission . In the first year after a MI event , direct medical costs were € 13,838–14,792 per patient . Direct medical costs of chronic HF patients were found to be between € 3417 and 5576 per patient per year . Treatment costs increase with disease progression . The average treatment costs  for hospitalized PAD in the acute phase were reported to be € 4963 per admission , € 2535 per patient during month 1–6 after the initial hospitalization , € 1601 in month 7–12 , and € 1390 in month 13–18 . For stroke of all types , total direct medical costs in the 1st year after an event were reported to be € 13,273 per patient . Total direct medical costs during the 1st year after an ischemic stroke event were € 17,399–21,954 per patient , € 6260 in month 13–18 , and € 6496 per year in the subsequent 4 years . Conclusion MI , unstable angina , HF , stroke and PAD have a high financial impact on the German health care system . Treatment costs of these diseases are mostly incurred during the acute phase of events and tend to decrease over time . Hospitalization and rehabilitation costs were two major cost drivers . Medication costs was one of the smallest cost component reported Background — Information on comparative outcome between radiofrequency catheter ablation ( RFA ) and antiarrhythmic drugs ( AADs ) > 1 year after r and omization is important for clinical decision-making . Methods and Results — A total of 198 patients ( age , 56±10 years ) with paroxysmal atrial fibrillation were r and omly assigned to RFA ( 99 patients ) or to AADs ( 99 patients ) . We evaluated efficacy of RFA or AADs in a comparable 48-month follow-up period according to intention-to-treat analysis . Cardiac rhythm was assessed with daily transtelephonic transmissions . Quality of life was also analyzed . At 4 years , among the 99 patients first assigned to RFA , the procedure was repeated because of recurrent atrial fibrillation/atrial tachycardia in 27 patients ( 27.3 % ) . Among the 99 patients r and omly assigned to AADs , 87 ( 87.9 % ) crossed over to undergo RFA and 4 years after r and om assignment only 12 ( 12.1 % ) were in sinus rhythm with AAD alone without ablation . Despite the high level of crossovers , at 4 years the intention-to-treat analysis showed that 72.7 % of patients in the ablation arm and 56.5 % of those initially r and omly assigned to AADs were free of recurrent atrial fibrillation/atrial tachycardia ( P=0.017 ) . During the follow-up , 19.2 % of AAD patients progressed to persistent atrial fibrillation before switching to RFA . RFA significantly improved quality of life ( P<0.001 ) , whereas before crossing over to RFA , patients receiving AADs showed poorer quality of life . Except for new left atrial tachycardia , there were no serious complications caused by RFA . Conclusions — With follow-up extended to 4 years after r and omly assigned , ablation remains superior to antiarrhythmic drug in these patients with paroxysmal atrial fibrillation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00340314 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 The fundamental management strategy for atrial fibrillation ( AF ) is still debated . There is no doubt that those patients at risk of thromboembolic events should be offered anticoagulant therapy . However , it is uncertain whether rhythm control ( restoration and maintenance of sinus rhythm ) or rate control ( adjustment to a physiological ventricular rate while allowing AF to continue ) is the preferred primary treatment option for the reduction of symptoms and major cardiovascular ( CV ) outcomes associated with AF . Several well conducted trials comparing the two strategies led to the conclusion that there was little to choose between them . However , guidelines leaned towards recommending rate control as the initial strategy , and reserved rhythm control for those who remained symptomatic . Recently this status quo is being increasingly challenged by the clear demonstration that left atrial catheter ablation is effective at suppressing AF resistant to traditional antiarrhythmic drugs , such as those that failed to demonstrate any superiority when compared with rate control . Also , recently introduced antiarrhythmic therapy may have superior efficacy with regard to reducing unexpected CV hospitalization , CV mortality and stroke . In addition , there is a growing perception that atrial remodelling should be best prevented by early rhythm control rather than delaying until rate control has proven unsatisfactory . For these reasons the results of large r and omised clinical trials , which recruit patients soon after the presentation of AF and compare ' aggressive ' modern rhythm control against the guideline approach of primary rate control , are eagerly awaited . In the meantime the pendulum of clinical opinion has begun to swing towards a rhythm control strategy Although there is considerable epidemiologic evidence for a relation between plasma homocysteine ( HCY ) and cardiovascular ( CV ) disease , the role of HCY as a causal CV risk factor remains controversial , mainly because of the intercorrelation between HCY and other CV risk factors . The goal of the present nested case-control prospect i ve study is to determine the multiadjusted relation between HCY and CV mortality in a large and low CV risk population after a mean follow-up of 14 years . In 1980 and 1981 , plasma was saved from 5,000 patients who underwent a systematic health checkup , including clinical and biologic examinations .  In 1999 ,  HCY concentration was measured in 110 subjects who died of CV disease ( cases ) and in 154 r and omly matched survivors ( control subjects ) . Statistical analysis was adjusted for CV risk factors . Based on Cox analyses , 3 factors emerged as independent predictors of CV mortality : C-reactive protein , systolic blood pressure , and HCY . The adjusted hazard ratio for CV mortality was 1.22 ( 95 % confidence interval 1.04 to 1.41 ) per 1 SD ( 3.9 micromol/L ) increment of HCY . Thus , HCY is an independent risk predictor for CV mortality . Because of extensive adjustment procedures , the present study provides additional epidemiologic evidence for a causal relation between HCY and CV disease BACKGROUND The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation ( MANTRA-PAF ) is a r and omized trial comparing radiofrequency catheter ablation ( RFA ) to antiarrhythmic drugs ( AADs ) as first-line treatment of paroxysmal atrial fibrillation ( PAF ) . In order to eliminate the clouding effect of crossover we performed an on-treatment analysis of the data . METHODS AND RESULTS Patients ( n=294 ) were divided into three groups : those receiving only the assigned therapy ( RFA and AAD groups ) and those receiving both therapies ( crossover group ) . The primary end points were AF burden in 7-day Holter recordings at 3 , 6 , 12 , 18 , and 24 months and cumulative AF burden in all recordings . At 24 months , AF burden was significantly lower in the RFA ( n=110 ) than in the AAD ( n=92 ) and the crossover ( n=84 ) groups ( 90th percentile 1 % vs. 10 % vs. 16 % , P=0.007 ) , and more patients were free from any AF ( 89 % vs. 73 % vs. 74 % , P=0.006 ) . In the RFA , AAD and the crossover groups 63 % , 59 % and 21 % ( P<0.001 ) of the patients had no AF episodes in any Holter recording , respectively . Quality of life improved significantly in all groups . There were no differences in serious adverse events between the RFA , AAD and crossover groups ( 19 % vs. 8 % vs. 23 % ) ( P=0.10 ) . CONCLUSIONS In the treatment of antiarrhythmic therapy naïve patients with PAF long-term efficacy of RFA was superior to AAD therapy . Thus , it is reasonable to offer RFA as first-line treatment for highly symptomatic patients who accept the risks of the procedure and are aware of frequent need for reablation(s ) Background —Radiofrequency catheter ablation ( RFA ) has emerged as an important treatment strategy for atrial fibrillation ( AF ) . The potential cost-effectiveness of RFA for AF , relative to antiarrhythmic drug ( AAD ) therapy , has not been fully explored from a US perspective . Methods and Results —We constructed a Markov disease simulation model for a hypothetical cohort of patients with drug-refractory paroxysmal AF , treated either with RFA with/without AAD or AAD alone .  Costs and quality -adjusted life-years were projected over 5 years . Model inputs were drawn from published clinical trial and registry data , from new registry and trial data analysis , and from data prospect ively collected from patients with AF treated with RFA at our institution . We assumed no benefit from ablation on stroke , heart failure or death , but did estimate changes in quality -adjusted life expectancy using data from several AF cohorts . In the base case scenario , cumulative costs with the RFA and AAD strategies were $ 26 584 and $ 19 898 , respectively . Over 5 years , quality -adjusted life expectancy was 3.51 quality -adjusted life-years with RFA versus 3.38 for the AAD group . The incremental cost-effectiveness ratio for RFA versus AAD was thus $ 51 431 per quality -adjusted life-year . Model results were most sensitive to time horizon , the relative utility weights of successful ablation versus unsuccessful drug therapy , and to the cost of an ablation procedure . Conclusions —RFA with/without AAD for symptomatic , drug-refractory paroxysmal AF appears to be reasonably cost-effective compared with AAD therapy alone from the perspective of the US health care system , based on improved quality of life and avoidance of future health care costs Objective Whether early rhythm suppression with extensive antiarrhythmic drugs ( AADs ) in persistent atrial fi brillation ( AF ) after catheter ablation decreases arrhythmia recurrence is unknown . We now report the 12-month follow-up data in this prospect i ve and r and omized study . Methods and results 123 consecutive patients with persistent AF undergoing catheter ablation were r and omly divided into an extensive AADs therapy group ( group 1 : 62 patients using both class Ic and III AADs ) or one AAD therapy group ( group 2 : 61 patients using class Ic or III AADs alone ) for the initial 2 months after ablation . Recurrence of atrial tachyarrhythmias ( ATa ) was valuated at both 2 months and 12 months following ablation . During the fi rst 2 months after ablation , less ATa were found in group 1 compared with group 2 ( 17/62 versus 29/61 , P= 0.021 ) . However , there was no diff erence with regard to ATa at 12 months between the groups ( 21/62 versus 22/61 , P= 0.799 ) . ATa at 2 months and left atrial diameter ( LAD ) were the statistically signifi ca nt predictors of ATa during 12-month follow-up . Conclusions While use of extensive AADs within the initial 2 months after persistent AF ablation decreases early ATa , it does not prevent late ATa . Moreover , LAD as well as early ATa is a strong predictor of ATa at 12 months Abstract Objective : The objective was to assess the relative risk ( RR ) for cardiovascular ( CV ) events across all 8 r and omized phase 2/3 trials evaluating saxagliptin in patients with type 2 diabetes mellitus . Methods : Cardiovascular events ( death , myocardial infa rct ion [ MI ] , stroke , revascularization procedures , and cardiac ischemia ) were reported by investigators through st and ard adverse event reporting procedures and were systematic ally identified . Post hoc blinded adjudication of all deaths , MIs , and strokes was performed using prespecified endpoint definitions by an independent clinical events committee ( CEC ) . Results : A total of 4607 r and omized and treated patients ( n = 3356 treated with saxagliptin [ 2.5–100 mg/d ] ; n = 1251 , comparator [ n = 656 , placebo ; n = 328 , metformin ; n = 267 , uptitrated glyburide ] ) were included . The median ages were 54 years ( saxagliptin ) and 55 years ( comparator ) ( interquartile range , 47–61 each ) ; 51 % were female , 73 % were white , 52 % were hypertensive , 44 % had hypercholesterolemia , 39 % had a smoking history , 20 % had a first-degree family member with premature coronary heart disease , and 12 % had prior CV disease . Cardiovascular events were experienced by 61 patients ( 38 [ 1.1 % ] , saxagliptin ; 23 [ 1.8 % ] , comparator ) , and CV death/MI/stroke events were reported by investigators in 41 patients : 23 ( 0.7 % ) , saxagliptin ; 18 ( 1.4 % ) , comparator ( relative risk , 95 % confidence interval [ CI ] , 0.44 [ 0.24–0.82 ] ) . The CEC review ed 147 patients with potential CV events and identified a total of 40 patients with CV death/MI/stroke : 22 ( 0.7 % ) , saxagliptin ; 18 ( 1.4 % ) , comparator ( RR , 0.43 [ 0.23–0.80 ] ) . Component proportions for CV death , MI , and stroke were ( saxagliptin vs comparator ) : 7 ( 0.2 % ) vs 10 ( 0.8 % ) , 8 ( 0.2 % ) vs 8 ( 0.6 % ) , and 11 ( 0.3 % ) vs 5 ( 0.4 % ) , respectively . Conclusion : No increased risk of CV death/MI/stroke was observed in patients r and omly assigned saxagliptin across a broad drug development program . Although this systematic overview has inherent and important limitations , the data support a potential reduction in CV events with saxagliptin . The hypothesis of CV protection with saxagliptin will be tested prospect ively in a large r and omized clinical outcome trial evaluating saxagliptin compared with st and ard of care in patients with type 2 diabetes at increased risk for CV events AIM To produce dietetic guidelines summarizing the systematic review evidence on dietary advice for secondary prevention of cardiovascular disease . METHODS The Cochrane Library , MEDLINE and EMBASE were comprehensively search ed for systematic review s on aspects of diet and heart health . Review s were included if they search ed systematic ally for r and omised controlled trials relating to diet and secondary prevention of cardiovascular disease . Two members of the UK Heart Health and Thoracic Dietitians Group critically appraised each review . The quality and results of each review were discussed and summarized in a whole group meeting . The guidelines were trialled in seven dietetic departments and modified where necessary . RESULTS Providing evidence -based dietary information ( including increasing omega-3 fat plus fruit and vegetable intake ) to all people after myocardial infa rct ion will save more lives than concentrating dietary advice on those in need of weight loss or lipid lowering . The practice of prioritizing dietetic time to those with raised lipids is out of date since the advent of statin therapy . CONCLUSION There is good systematic review evidence that dietary advice to those with cardiovascular disease can reduce mortality and morbidity as well as modify risk factors .  Dietary advice that does this most effectively should be prioritized Background —In patients with paroxysmal atrial fibrillation ( AF ) , catheter ablation maintains sinus rhythm more effectively than antiarrhythmic drugs ( AADs ) , but its effect on symptoms and quality of life ( QOL ) has not been fully characterized . Methods and Results —We evaluated symptoms and QOL in a multicenter , r and omized trial comparing catheter ablation with AADs as second-line treatment for patients with paroxysmal AF . The Short Form (SF)-36 health survey and the AF Symptom Checklist were administered at baseline and 3 , 6 , and 9 months after a blanking or dose-titration period . The primary between-group comparisons were conducted at 3 months because of permitted crossover from AAD to ablation beyond this time . Additional analyses based on subsequent follow-up were performed , including the construction of mixed linear regression models to assess the impact of multiple factors on follow-up QOL scores . At baseline in both the ablation ( n=103 ) and the AAD ( n=56 ) groups , 7 of 8 SF-36 scales were well below population norms , as were the physical ( PCS ) and mental ( MCS ) summary scores . At 3 months , the same 7 SF-36 scales were significantly ( P<0.01 ) higher in the ablation than in the AAD group , as were the PCS ( 52.0±7.8 versus 47.1±10.6 ; P<0.01 ) and MCS ( 52.4±8.1 versus 46.6±9.8 ; P<0.01 ) scores , whereas symptom frequency ( 9.3±9.2 versus 19.0±12.6 ; P<0.001 ) and symptom severity ( 7.7±7.2 versus 16.2±10.0 ; P<0.001 ) were significantly reduced . In multivariable analysis , ablation and recurrent arrhythmias most strongly correlated with QOL changes over time . Conclusions —For second-line therapy of paroxysmal AF , ablation is superior to AAD treatment at improving symptoms and QOL . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00116428 OBJECTIVES Rising evidence s showed a possible protective role of statins in chronic obstructive pulmonary disease ( COPD ) . We aim ed to evaluate in a post-hoc analysis of the GISSI-HF trial the prognostic effect of the use of rosuvastatin in patients with co-existing COPD and HF , assuming that the anti-inflammatory properties of these drugs may imply a potential beneficial effect in these associated chronic inflammatory conditions . METHODS We analyzed patients with chronic HF and history of COPD deriving from the GISSI-HF study . Of all 4574 patients eligible to statin , 1060 ambulatory patients with HF and concomitant COPD were enrolled and r and omly assigned to rosuvastatin 10 mg daily ( 538 patients ) or placebo ( 522 patients ) . The primary end-point was to compare all cause death rate in patients r and omized to rosuvastatin or placebo . Further , we assessed the effects of rosuvastatin ( 10 mg daily ) on cardiovascular ( CV ) death , non-CV death and hospital admissions . Median follow-up was 3.9 years with an interquartile range ( IQR ) of 3.0 - 4.4 . RESULTS During the follow-up 438 ( 41.3 % ) patients died , 304 ( 28.6 % ) for CV death and 687 ( 64.8 % ) had at least one hospitalization . The two patient groups had similar outcome , irrespective of r and omization , in terms of all-cause mortality ( log-rank test p = 0.30 ) CV , non CV-death ( p = 0.88 and 0.09 respectively ) and all-cause hospitalization ( p = 0.82 ) . Cox regression analysis did not show a favorable association between the use of statin and the examined end-points both on unadjusted and adjusted models . CONCLUSIONS Statin use is not associated with a beneficial effects on all cause , CV , non CV mortality and hospitalization in patients with coexistent chronic HF and history of COPD . Clinical Trials.gov Identifier : NCT00336336 BACKGROUND The postdischarge rehospitalization and death rates are high in patients with acute heart failure ( HF ) syndromes despite optimization of st and ard therapy for chronic HF . To the best of our knowledge , there has been no systematic analysis of the causes of death and rehospitalization in this patient population . METHODS This was a prespecified analysis of adjudicated cause-specific all-cause mortality and  cardiovascular ( CV ) hospitalization in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan ( EVEREST ) trial , a r and omized , double-blind , placebo-controlled study in patients hospitalized with worsening HF and left ventricular ejection fraction < or = 40 % comparing tolvaptan  , an oral vasopressin receptor antagonist to placebo , in addition to st and ard care . RESULTS Of the 4,133 r and omized , there were 5,239 rehospitalizations  and 1,080  deaths during a median of 9.9 months . Of all deaths , 41.0 % were due to HF , 26.0 % due to sudden cardiac death ( SCD ) , 2.6 % due to acute myocardial infa rct ion ( MI ) , 2.2 % due to stroke , and 13.2 % due to non-CV causes . Of all hospitalizations , 39.2 % were non-CV , whereas 46.3 % were for HF , and a minority of hospitalizations was due to stroke , MI , arrhythmia , or other CV causes . CONCLUSIONS Despite close follow-up and evidence -based therapy within a clinical trial , rehospitalization and death remain high . Although most deaths were from HF , one quarter of patients had SCD . In addition , there were almost as many non-CV hospitalizations as HF hospitalizations . Knowledge of the causes of death and rehospitalization may be essential for proper management and early initiation of therapy Background Recently , catheter-based renal sympathetic denervation ( RSD ) has been verified to be safely used to substantially reduce the levels of blood pressure , left ventricular hypertrophy , sleep apnea severity and norepinephrine spillover , and improve glucose tolerance . All these pathological changes are recognized as independent risk factors for the development and recurrence of atrial fibrillation ( AF ) . A r and omized , single-blind , parallel-control , multicenter clinical trial is being conducted to compare RSD with antiarrhythmic drugs ( AAD ) in patients with drug-resistant hypertension and symptomatic AF ( RSDforAF trial ) . Methods / design Patients with drug-resistant hypertension and symptomatic AF will be r and omized to RSD and the drug treatment groups . Patients will be followed for 12 months until study closure . Up to 200 patients may be enrolled in six medical centers in China . The primary objective is to study the effects of RSD on AF burden and blood pressure in patients with hypertension and symptomatic AF . Discussion RSDforAF trial will test the hypothesis that RSD is superior to AAD in reducing AF burden and blood pressure in patients with drug-resistant hypertension and symptomatic AF.Trial registration Clinical Trials.gov , AIMS Hospitalizations for heart failure ( HF ) are common and are associated with significant morbidity , mortality and cost . However , precipitating factors leading to HF hospitalization and their importance with respect to subsequent outcomes are not well understood . METHODS AND RESULTS The symptoms and signs present at admission and investigator-identified factors thought to have contributed to the first adjudicated HF hospitalization in the C and esartan in Heart Failure : Assessment of Reduction in Mortality and Morbidity ( CHARM ) programme were prospect ively collected and stratified by ejection fraction ( EF ) . Potential precipitants were collected using a specifically design ed case report form and categorized according to the presence of cardiovascular ( CV ) , non-CV and unknown factors . Associations between these factors and subsequent rehospitalization and mortality rates were examined . Of 1668 patients who experienced HF hospitalization , 1152 had reduced EF ( ≤40 % , HFrEF ) and 516 had preserved EF ( HFpEF ) . Overall , 54 % had CV , 32 % had non-CV and 14 % had unknown factors thought to have precipitated HF , with similar proportions in the HFrEF and HFpEF groups . The most common precipitants were arrhythmia ( 15 % ) , other non-CV factors ( 11 % ) and respiratory infection ( 10 % ) . Subsequent CV readmission rates were highest in those whose initial HF hospitalization was precipitated by CV factors . However , mortality rates were similar among patients with any of the three categories of precipitating factors . Results were similar in HFrEF and HFpEF . CONCLUSIONS Among chronic HF patients hospitalized for decompensation , the investigator-reported precipitating factor was not associated with the subsequent mortality rate , but was associated with type of readmission : readmissions for CV reasons were more likely when the index precipitant was CV BACKGROUND Additional ablation of complex fractionated atrial electrograms ( CFAE ) after pulmonary vein isolation ( PVI ) has been shown to improve the success of ablation of persistent atrial fibrillation ( AF ) . However , extensive ablation is often necessary to eliminate all CFAE or to terminate AF . We assessed the usefulness of the administration of an antiarrhythmic drug ( AAD ) before CFAE ablation . METHODS AND RESULTS One-hundred and ten patients with persistent AF first underwent PVI , roof and floor linear ablation ( box isolation ) . One hundred patients who remained in AF after box isolation were then r and omized to either receive ( AAD group , n=50 ) or not receive ( no-AAD group , n=50 ) intravenous nifekalant ( 0.3mg/kg ) followed by a CFAE ablation . In the AAD group , nifekalant terminated AF in 19 ( 38 % ) patients and ablation of localized CFAE was performed in 31 patients who remained in AF after nifekalant , and terminated AF in 11 ( 35 % ) patients . In the no-AAD group , ablation of CFAE terminated AF in 13 ( 26 % ) patients . The AAD group had a significantly lesser number of radio frequency applications at CFAE sites ( 18 ± 12 versus 36 ± 10 , p<0.0001 ) and shorter procedure time ( 162 ± 34 versus 197 ± 29 min , p<0.0001 ) compared with the no-AAD group . However , there was no significant difference in success rate at 12 months after a single ablation procedure between the two groups ( AAD group , 74 % versus no-AAD group , 76 % ) . CONCLUSIONS An approach to ablation using nifekalant may be useful in localizing areas of CFAE , reducing the number of applications at CFAE sites and procedure time . Ablation of only CFAE localized with nifekalant may be sufficient for clinical outcome BACKGROUND The ideal management of patients with newly diagnosed symptomatic atrial fibrillation ( AF ) remains unknown . Current practice guidelines recommend a trial of antiarrhythmic drugs ( AAD ) prior to considering an invasive ablation procedure . However , earlier ablation offers an opportunity to halt the progressive patho-anatomical changes associated with AF , as well as impart other important clinical benefits . OBJECTIVE The aim of this study is to determine the optimal initial management strategy for patients with newly diagnosed , symptomatic atrial fibrillation . METHODS / DESIGN The EARLY-AF study ( Clinical Trials.govNCT02825979 ) is a prospect i ve , open label , multicenter , r and omized trial with a blinded assessment of outcomes . A total of 298 patients will be r and omized in a 1:1 fashion to first-line AAD therapy , or first-line cryoballoon-based pulmonary vein isolation .  Patients with symptomatic treatment naïve AF will be included . Arrhythmia outcomes will be assessed by implantable cardiac monitor ( ICM ) . The primary outcome is time to first recurrence of AF , atrial flutter , or atrial tachycardia ( AF/AFL/AT ) between days 91 and 365 following AAD initiation or AF ablation . Secondary outcomes include arrhythmia burden , quality of life , and healthcare utilization . DISCUSSION The EARLY-AF study is a r and omized trial design ed to evaluate the optimal first management approach for patients with AF . We hypothesize that catheter ablation will be superior to drug therapy in prevention of AF recurrence Aims The ESC-EHRA Atrial Fibrillation Ablation Long-Term registry is a prospect i ve , multinational study that aims at providing an accurate picture of contemporary real-world ablation for atrial fibrillation ( AFib ) and its outcome . Methods and results A total of 104 centres in 27 European countries participated and were asked to enrol 20–50 consecutive patients scheduled for first and re-do AFib ablation .  Pre-procedural , procedural and 1-year follow-up data were captured on a web-based electronic case record form . Overall , 3630 patients were included , of which 3593 underwent an AFib ablation ( 98.9 % ) . Median age was 59 years and 32.4 % patients had lone atrial fibrillation .  Pulmonary vein isolation was attempted in 98.8 % of patients and achieved in 95–97 % . AFib-related symptoms were present in 97 % . In-hospital complications occurred in 7.8 % and one patient died due to an atrioesophageal fistula . One-year follow-up was performed in 3180 ( 88.6 % ) at a median of 12.4 months ( 11.9–13.4 ) after ablation : 52.8 % by clinical visit , 44.2 % by telephone contact and 3.0 % by contact with the general practitioner . At 12-months , the success rate with or without antiarrhythmic drugs ( AADs ) was 73.6 % . A significant portion ( 46 % ) was still on AADs . Late complications included 14 additional deaths ( 4 cardiac , 4 vascular , 6 other causes ) and 333 ( 10.7 % ) other complications . Conclusion AFib ablation in clinical practice is mostly performed in symptomatic , relatively young and otherwise healthy patients . Overall success rate is satisfactory , but complication rate remains considerable and a significant portion of patients remain on AADs . Monitoring after ablation shows wide variations . Antithrombotic treatment after ablation shows insufficient guideline -adherence AIM Explore the relation between body mass index ( BMI ) and cardiovascular disease , and the influence of optimal medical therapy ( OMT ) on this relationship . METHODS AND RESULTS Patients from the REACH cohort , an international , prospect i ve cohort of patients with or at high risk of atherosclerosis with documentation of potential confounders , including treatments and risk factors , were followed up to 4 years ( n = 54 285 ) . Patients were categorized according to baseline BMI ( ranging from underweight to Grade III obesity ) . Optimal medical therapy was defined as the use of the four cardioprotective medication classes ( statins , ACE inhibitors/angiotensin II receptor blockers , β-blockers , and antiplatelet agents ) . The main outcomes were all-cause mortality , cardiovascular ( CV ) mortality , and CV events . In primary and secondary prevention , a reverse J-shaped curve best described the relationship between BMI categories and the incidence of the various outcomes . In secondary prevention , the highest adjusted risks were observed for underweight patients ( 1.97 , P < 0.01 , and 1.29 , P = 0.03 , for CV mortality and CV events ) and the lowest HRs were observed , respectively , in Grade II and Grade III obese patients ( 0.73 , P < 0.01 and 0.80 , P < 0.01 ) . The proportion of patients on OMT increased with BMI from 10.1 to 36 % ( P < 0.001 ) . The apparent CV protection conferred by obesity persisted in patients receiving OMT . CONCLUSION An obesity paradox was observed in both primary and secondary CV prevention patients . The intensity of use of evidence -based preventive medications does not account for the paradoxical CV protection associated with obesity . At extremes of BMI , further interventions beyond OMT may be needed to reduce CV risk BACKGROUND The aim of this study is to evaluate the prevalence of  depressive symptoms ( DS ) and its relation on hospitalization for cardiovascular ( CV ) causes and all-cause mortality risk among out patients with HF . METHODS A prospect i ve study was conducted on 130 adult out patients with HF . The  Beck Depression Inventory Scale-second edition ( BDI-II ) was used to screen for DS .  All-cause mortality and hospitalization for CV causes were registered over 6 years . Logistic regression and multinomial logistic regression analysis were used to evaluate the independent prognostic value of DS on mortality and hospitalization for CV causes after adjustment for clinical risk factors . RESULTS During a mean follow-up of 6 years , 44 % of patients were classified as having DS . Sixty-two participants died for all causes , representing 61 % of those with DS and 37 % of those without ( p=0.006 ) ; Forty-nine participants ( 38 % ) were hospitalized for CV causes , representing 49 % of those with DS and 29 % of those without ( p=0.027 ) . Logistic regression analysis indicated that DS predicted all-cause mortality ( OR : 2.905 ; 95 % CI:1.228 - 6.870 ; p=0.006 ) and multinomial logistic regression indicated that DS were predictive of hospitalization for CV causes ( OR : 3.169 ; 95 % CI : 1.230 - 8.164 ; p=0.027 ) . These associations were independent of conventional risk factors . LIMITATIONS Only outpatient sample ; measure of  DS  only at baseline ; cause of death was not known . CONCLUSION This study , first held in a portuguese population , showed that DS are independent predictors of death and hospitalization for CV causes  among HF patients and its impact persists over 6 years Industry funding and author financial conflicts of interest may influence the production and synthesis of scientific evidence ( 1 ) . Associations with the pharmaceutical company developing and marketing a drug have been found to influence the design of trials ( 2 ) , the conduct of trials ( 3 ) , and the reporting of trial results ( 47 ) . Furthermore , financial ties and industry funding seem to result in greater rates of favorable conclusions in clinical trials examining new drugs ( 812 ) . Fewer studies have considered the potential influence of financial conflicts of interest on the synthesis of clinical evidence in systematic review s ( 13 , 14 ) . Neuraminidase inhibitors , which are used in the prophylaxis and treatment of seasonal and p and emic influenza , have been the subject of ongoing uncertainty about their specific clinical benefits ( 15 , 16 ) . This is the result of not only the continuing emergence of strains with unknown drug responses but also the increasing awareness in the medical community that , until recently , its knowledge of the safety and efficacy of these drugs has been incomplete ( 17 ) . Despite the abundance of clinical trials and publications on neuraminidase inhibitors , the details of many key trials had not been disclosed ( 18 , 19 ) . As a result , systematic review ers analyzing and synthesizing evidence on the effectiveness of these agents have faced incomplete information , unresolved discrepancies in the data , and a high risk of publication and reporting biases among the primary clinical trials ( 20 , 21 ) . This prompted extensive efforts to access complete records of all published and unpublished clinical trials from manufacturers , culminating in the publication of several review s on the basis of comprehensive clinical study reports and potentially changing the way systematic review s will be undertaken in the future ( 2227 ) . Review s of neuraminidase inhibitors exhibit wide variation in their conclusions , ranging from strong endorsements of the use of these agents in the prophylaxis and treatment of influenza ( 28 , 29 ) to more conservative assessment s question ing the evidence on the drugs ' safety and efficacy ( 15 , 30 ) . The reasons for this discordance in review conclusions are likely multifactorial and may be related in part to the manner in which evidence is accessed , synthesized , and presented ( 23 , 27 ) , both in terms of the numerical results and the authors ' emphasis and interpretation ( 31 , 32 ) . Our aim was to determine whether there is an association between financial conflicts of interest and the favorable presentation of evidence in systematic review s on the use of neuraminidase inhibitors for the prophylaxis and treatment of influenza . Methods Data Sources Systematic review s were identified in PubMed , PubMed In Process , EMBASE , and the Cochrane Data base of Systematic Review s. Search es were done using the keywords influenza , neuraminidase inhibitors , oseltamivir , zanamivir , peramivir , and laninamivir . Articles were retrieved if the search terms appeared in the title or abstract or were included as data base-specific keywords . In PubMed and EMBASE , search es were also constrained to review publication types . We limited our search to English- language articles published since 1 January 2005 . These articles were manually review ed to identify those that focused on the use of neuraminidase inhibitors for influenza prophylaxis or treatment ( such as excluded articles primarily about drug development or other manufacturing processes ) . We selected all review s that used a systematic search protocol , which we defined as the inclusion and reporting of an explicit search strategy , including reasons for subsequent exclusion of articles . The final search es were done on 26 May 2014 . Cochrane review s are periodically up date d to incorporate new evidence , and the results and conclusions are resynthesized as indicated . The authors of these review s are typically different , and there may be differences in the methods as well as the results and language of the review . These up date d review s were included separately . Other Cochrane review s are occasionally rewritten by a subset of the authors for publication in medical journals as abridged versions to increase dissemination . These reports have separate peer review s and are prepared on the basis of a selection of the complete results . We considered these review s separately as well but also did a sensitivity analysis in which they were combined with the original Cochrane review s. Data Extraction Financial conflicts of interest were identified for all authors of the review s and included affiliations with or funding from the pharmaceutical company manufacturing any of the neuraminidase inhibitors under review . We defined financial conflicts of interest as employment , the funding of grants paid to an author or an author 's research group , and the funding of medical writers for the systematic review . These financial conflicts of interest were identified using information about affiliations or funding listed in the systematic review s , as well as in any other articles published by one of the authors during the 3 years before the publication of the index systematic review . In addition , we search ed authors ' personal and institutional Web sites ; lists of disclosures from GlaxoSmithKline ( Research Triangle Park , North Carolina ) and Roche Pharmaceuticals ( Basel , Switzerl and ) ; and performed Web search es combining the names of the authors , drugs , and pharmaceutical companies to identify any additional information about financial relationships . Details of the specific financial conflicts of interest identified for each author are listed in Appendix Table 1 . Appendix Table 1 . Financial Conflicts of Interest Among Authors of the Systematic Review s For each systematic review , we recorded whether prophylaxis or treatment was assessed , the forms of evidence to be included ( such as r and omized , controlled trials and observational studies ) , the specific clinical outcomes assessed , the population s examined , and whether meta-analyses were done . We also examined whether the review s included information about the validity or quality of the primary literature . In particular , we recorded whether there were statements addressing nonpublication of primary studies or publication bias , including tests done by the review ers to assess for bias in meta-analyses ( such as the Egger or Begg test [ 33 , 34 ] ) , difficulty in accessing comprehensive study data , and the prevalence or role of industry in conducting and funding the primary studies . Data Analysis Two investigators were provided with redacted copies of each review that did not include the review s ' authors , their affiliations , or information on financial conflicts of interest . These versions also did not contain the journal name , journal formatting , or the article 's acknowledgments or references . The investigators independently evaluated the review s and classified the prophylaxis and treatment assessment s as favorable or not favorable toward the use of neuraminidase inhibitors . They were instructed to do this grading on the basis of the entirety of the review text without restriction to conclusions or recommendations made in any specific section of the review , thus allowing them to take into account the emphasis and interpretation of the authors throughout the review . The agreement between the investigators was strong at 86 % ( Cohen , 0.72 ; P < 0.001 ) . Disagreements were resolved by a third investigator using the same redacted copies . Descriptive analyses were done to examine the associations between financial conflicts of interest and the grading of the systematic review s. A sensitivity analysis excluding the summary review s was done to further examine this association . We also assessed the association between financial conflicts of interest and the inclusion of statements addressing the validity or quality of the primary evidence . Role of the Funding Source This study was funded by the Australian National Health and Medical Research Council . The funding source had no role in the design and conduct of the study , analysis of the results , or the decision to su bmi t the manuscript for publication . Results We identified 827 published articles across the 4 data bases using the specified search criteria , with 26 systematic review s included in the final cohort ( Figure ) . Thirteen review s examined prophylaxis and 24 examined treatment of influenza , accounting for 37 distinct assessment s ( Appendix Table 2 ) . In terms of review methods , 7 were Cochrane systematic review s and 19 conducted and reported a meta- analysis ( 73 % ) . The evidence inclusion criteria were limited to r and omized , controlled trials for 14 of the systematic review s ( 54 % ) , and 5 included evidence from clinical study reports or patient-level data . The main population s examined were healthy adults ( 18 of 26 systematic review s ) , children ( 13 of 26 ) , and hospitalized patients ( 6 of 24 ) . The outcome measures for prophylaxis assessment s included influenza-like illness and laboratory-confirmed influenza . For the treatment assessment s , the outcomes were illness duration , influenza-related complications , hospitalization , and mortality , mostly in combination . Five review s were up date s of previous Cochrane review s , and 3 were summary review s based on Cochrane review s. Figure . Summary of evidence search and selection . Eligible systematic review s included those with outcomes related to the prophylaxis or treatment of influenza . Appendix Table 2 . Characteristics of Systematic Review s Examining Prophylaxis and Treatment Outcomes for Neuraminidase Inhibitors Association Between Financial Conflicts of Interest and Favorable Assessment s Seven of the 26 systematic review s ( 27 % ) , corresponding to 8 of the 37 assessment s ( 22 % ) , were associated with a financial conflict of interest ( Appendix Table 1 ) . We identified financial conflicts of interest in publications other than the index systematic review in 2 cases , and no additional AIMS To determine whether the risk of adverse cardiovascular ( CV ) outcomes associated with diabetes differs in patients with low and preserved ejection fraction ( EF ) heart failure ( HF ) . METHODS AND RESULTS We analysed outcomes in the C and esartan in Heart failure- Assessment of Reduction in Mortality and morbidity ( CHARM ) programme which r and omized 7599 patients with symptomatic HF and a broad range of EF . The prevalence of diabetes was 28.3 % in patients with preserved EF ( > 40 % ) and 28.5 % in those with low EF ( < or=40 % ) . Diabetes was associated with a greater relative risk of CV death or HF hospitalization in patients with preserved EF [ hazard ratio ( HR ) 2.0 ( 1.70 - 2.36 ) ] than in patients with low EF [ HR 1.60 ( 1.44 - 1.77 ) ; interaction test P = 0.0009 ] . For all-cause mortality , the risk conferred by diabetes was similar in both low and preserved EF groups . The effect of c and esartan in reducing CV morbidity and mortality outcomes was not modified by having diabetes at baseline ( P = 0.09 test for interaction ) . CONCLUSION Diabetes was an independent predictor of CV morbidity and mortality in patients with HF , regardless of EF . The relative risk of CV death or HF hospitalization conferred by diabetes was significantly greater in patients with preserved when compared with those with low EF HF
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 .