2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Evidence that D-dimer levels predict subsequent thromboembolic and cardiovascular events in patients with atrial fibrillation during oral anticoagulant therapy. Morbidity and mortality in 229 elderly patients with nonrheumatic atrial fibrillation. A five-year follow-up. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Causes of Death and Influencing Factors in Patients With Atrial Fibrillation: A Competing-Risk Analysis From the Randomized Evaluation of Long-Term Anticoagulant Therapy Study Anticoagulant (Fluindione)-Aspirin Combination in Patients with High-Risk Atrial Fibrillation [Study of combined anticoagulant (fluindione)-aspirin therapy in patients with atrial fibrillation at high risk for thromboembolic complications. A randomized trial (FFAACS)]. Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study. Mending the rhythm does not improve prognosis in patients with persistent atrial fibrillation: a subanalysis of the RACE study. Management of Newly Detected Atrial Fibrillation: A Clinical Practice Guideline from the American Academy of Family Physicians and the American College of Physicians Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF): study protocol for a randomised controlled trial Early Risks of Death, Stroke/Systemic Embolism, and Major Bleeding in Patients With Newly Diagnosed Atrial Fibrillation: Results From the GARFIELD-AF Registry
ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American – Australian – African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association AND ROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific Heart Rhythm Society aPTT : activated partial thromboplastin time ARB : angiotensin-receptor blocker ARISTOTLE : Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation ATHENA : A placebo-controlled , double-blind , parallel arm Trial to assess the efficacy of dronedarone 400 mg b.i.d . for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ATRIA : AnTicoagulation and Risk factors In Atrial fibrillation AVERROES : Apixaban VErsus acetylsalicylic acid ( ASA ) to Reduce the Rate Of Embolic Stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment AVRO : A prospect i ve , r and omized , double-blind , Active-controlled , superiority study of Vernakalant vs. amiodarone in Recent Onset atrial fibrillation b.i.d : bis in die ( twice daily ) b.p.m . : beats per minute CABANA : Catheter ABlation vs . ANtiarrhythmic drug therapy for Atrial fibrillation CABG : coronary artery bypass graft CAP : Continued Access to Protect AF CHA2DS2-VASc : Congestive heart failure or left ventricular dysfunction Hypertension , Age ≥75 ( doubled ) , Diabetes , Stroke (doubled)-Vascular disease , Age 65–74 , Sex category ( female ) CHADS2 : Congestive heart failure , Hypertension , Age ≥75 , Diabetes , Stroke ( doubled ) CI : confidence interval CRAFT : Controlled R and omized Atrial Fibrillation Trial CrCl : creatinine clearance DAFNE : Dronedarone Atrial FibrillatioN study after Electrical cardioversion DIONYSOS : R and omized Double blind trIal to evaluate efficacy and safety of drOnedarone ( 400 mg b.i.d . ) vs . amiodaroNe ( 600 mg q.d . for 28 daYS , then 200 mg qd thereafter ) for at least 6 mOnths for the maintenance of Sinus rhythm in patients with atrial fibrillation EAST : Early treatment of Atrial fibrillation for Stroke prevention Trial EHRA : European Heart Rhythm Association ECG : electrocardiogram EMA : European Medicines Agency ERATO : Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation EURIDIS : EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm FAST : atrial Fibrillation catheter Ablation vs . Surgical ablation Treatment FDA : Food and Drug Administration Flec-SL : Flecainide Short-Long trial HAS-BLED : Hypertension , Abnormal renal/liver function , Stroke , Bleeding history or predisposition , Labile INR , Elderly , Drugs/alcohol concomitantly HF-PEF : heart failure with preserved ejection fraction HF-REF : heart failure with reduced ejection fraction HR : hazard ratio HRS : Heart Rhythm Society ICH : intracranial haemorrhage INR : international normalized ratio i.v . : intravenous J-RHYTHM : Japanese RHYTHM management trial for atrial fibrillation LAA : left atrial appendage LoE : level of evidence LVEF : left ventricular ejection fraction MANTRA-PAF : Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation NICE : National Institute for Health and Clinical Excellence NOAC : novel oral anticoagulant NSAID : non-steroidal anti-inflammatory drug NYHA : New York Heart Association OAC : oral anticoagulant or oral anticoagulation o.d . : omni die ( every day ) PALLAS : Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of st and ard therapy PCI : percutaneous coronary intervention PREVAIL : Prospect i ve R and omized EVAluation of the LAA closure device In patients with atrial fibrillation v s. Long-term warfarin therapy PROTECT AF : WATCHMAN LAA system for embolic PROTECTion in patients with Atrial Fibrillation PT : prothrombin time RAAFT : Radio frequency Ablation Atrial Fibrillation Trial RE-LY : R and omized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate ROCKET-AF : Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in atrial fibrillation RRR : relative risk reduction TE : thromboembolism TIA : transient ischaemic attack t.i.d . : ter in die ( three times daily ) TOE : transoesophageal echocardiogram TTR : time in therapeutic range VKA : vitamin K antagonist Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition , taking into account the impact on OBJECTIVES The aim of the present study was to evaluate whether elevated D-dimer levels can predict subsequent thromboembolic and cardiovascular events in patients with atrial fibrillation during oral anticoagulant therapy .  BACKGROUND Atrial fibrillation is associated with hemostatic abnormalities even during oral anticoagulant therapy . D-dimer levels reflect a pro-thrombogenic state and thus might serve as a marker of thromboembolic and cardiovascular events . METHODS This was a single-center , prospect i ve , observational study . Patients with atrial fibrillation ( 269 patients , age 74 + /- 9 years , 160 paroxysmal atrial fibrillation ) treated with warfarin ( target prothrombin time-international normalized ratio : 1.5 to 3.0 ) were included .  D-dimer levels were measured to assess the relationship of this parameter with subsequent thromboembolic and cardiovascular events . End points were thromboembolic events and combined cardiovascular events ( thromboembolic events , cerebral hemorrhage , myocardial infa rct ion , cardiovascular death ) . RESULTS D-dimer levels were elevated ( > or = 0.5 microg/ml ) in 63 ( 23 % ) patients . During an average follow-up period of 756 + /- 221 days , 10 ( 1.8%/year ) thromboembolic events ( 8 ischemic strokes , 1 transient ischemic attack , and 1 peripheral embolism ) and 27 ( 4.8%/year ) combined cardiovascular events ( 10 thromboembolisms , 9 deaths from heart failure , 3 sudden deaths , 2 myocardial infa rct ions , and 3 cerebral hemorrhages ) occurred . Patients with elevated D-dimer levels experienced higher thromboembolic and combined cardiovascular events . Cox proportional hazard model revealed that elevated D-dimer levels were associated with both thromboembolic ( p < 0.01 , hazard ratio : 15.8 ; 95 % confidence interval : 3.33 to 75.5 ) and combined cardiovascular ( p < 0.01 , hazard ratio : 7.64 ; 95 % confidence interval : 3.42 to 17.1 ) events . CONCLUSIONS D-dimer might be a useful marker of both thromboembolic and cardiovascular events in patients with atrial fibrillation during oral anticoagulant therapy BACKGROUND In the elderly the impact of atrial fibrillation on mortality and morbidity is substantial . Oral anticoagulant therapy reduces the risk of stroke by 70 % ; nevertheless , it remains largely underused . We evaluated , in a community prospect i ve study , the factors associated with embolic events and death and the feasibility of oral anticoagulant therapy managed by general practitioners . METHODS We enrolled at the Trieste Cardiovascular Center 229 patients aged > or = 65 years with non-rheumatic atrial fibrillation . At baseline , each patient underwent a transesophageal echocardiography and received instructions about oral anticoagulation . Patients were regularly followed by their general practitioner and finally evaluated at the Center . RESULTS At baseline , the mean age was 73 years , 14 % of patients were free of heart disease , 27 % had had a previous embolic event , and 33 % had an atrial thrombus . After a 5-year follow-up , 85 % of the patients had been admitted to hospital , 17 % had suffered an embolic event , and 35 % were dead . Diabetes and the presence of a low flow in the left atrial appendage were predictive of embolic events . Heart failure , spontaneous echocontrast and aortic plaques were predictive of death . Anticoagulant therapy increased from 14 to 34 % but the incidence of major bleeding did not change . The patients on anticoagulant therapy at follow-up constituted the group with the worst cardiovascular profile and embolic rate , but had a lower death rate ( 19 % ) compared with those on antiplatelet therapy ( 32 % ) and with those without antithrombotic therapy ( 67 % ) . The hospitalization rates were respectively 78 , 83 and 100 % . CONCLUSIONS In a group of elderly patients followed by their general practitioner with the support of a specialized cardiologic unit , oral anticoagulant therapy was well tolerated and associated with a significant decrease in mortality and hospitalization AIMS The impact of some risk factors for stroke and bleeding , and the value of stroke and bleeding risk scores , in atrial fibrillation ( AF ) , has been debated , as clinical trial cohorts have not adequately tested these . Our objective was to investigate risk factors for stroke and bleeding in AF , and application of the new CHA(2)DS(2)-VASc and HAS-BLED schemes for stroke and bleeding risk assessment s , respectively . METHODS AND RESULTS We used the Swedish Atrial Fibrillation cohort study , a nationwide cohort study of 182 678 subjects with a diagnosis of AF at any Swedish hospital between 1 July 2005 and 31 December 2008 , who were prospect ively followed for an average of 1.5 years ( 260 000 years at risk ) . With the use of the National Swedish Drug Registry , all patients who used an oral anticoagulant  anytime during follow-up were identified . Most of the analyses were made on a subset of 90 490 patients who never used anticoagulants .  Risk factors for stroke , the composite thromboembolism endpoint ( stroke , TIA , or systemic embolism ) , and bleeding , and the performance of published stroke and bleeding risk stratification schemes were investigated . On multivariable analysis , significant associations were found between the following ' new ' risk factors and thromboembolic events ; peripheral artery disease [ hazard ratio ( HR ) 1.22 ( 95 % CI 1.12 - 1.32 ) ] , ' vascular disease ' [ HR 1.14 ( 1.06 - 1.23 ) ] , prior myocardial infa rct ion [ HR 1.09 ( 1.03 - 1.15 ) ] , and female gender [ HR 1.17 ( 1.11 - 1.22 ) ] . Previous embolic events , intracranial haemorrhage ( ICH ) , hypertension , diabetes , and renal failure were other independent predictors of the composite thromboembolism endpoint , while thyroid disease ( or hyperthyroidism ) was not an independent stroke risk factor . C-statistics for the composite thromboembolic endpoint with the CHADS(2 ) and CHA(2)DS(2)-VASc schemes were 0.66 ( 0.65 - 0.66 ) and 0.67 ( 0.67 - 0.68 ) , respectively . On multivariable analysis , age , prior ischaemic stroke or thromboembolism , prior major bleeding events , and hypertension were significant predictors of ICH and major bleeding . Heart failure , diabetes , renal failure , liver disease , anaemia or platelet/coagulation defect , alcohol abuse , and cancer were other significant predictors for major bleeding , but not ICH . The ability for predicting ICH and major bleeding with both bleeding risk schemes ( HEMORR(2)HAGES , HAS-BLED ) were similar , with c-statistics of ~0.6 . CONCLUSION Several independent risk factors ( prior ICH , myocardial infa rct ion , vascular disease , and renal failure ) predict ischaemic stroke and /or the composite thromboembolism endpoint in AF , but thyroid disease ( or hyperthyroidism ) was not an independent risk factor for stroke . There is a better performance for CHA(2)DS(2)-VASc over CHADS(2 ) schemes for the composite thromboembolism endpoint . While both tested bleeding risk schemes have similar predictive value , the HAS-BLED score has the advantage of simplicity Background — Atrial fibrillation is associated with increased mortality , but the specific causes of death and their predictors have not been described among patients on effective anticoagulant therapy . Methods and Results — The R and omized Evaluation of Long-Term Anticoagulant Therapy ( RE-LY ) trial r and omized 18 113 patients ( age , 71.5±9 years ; male , 64 % ; CHADS2 score , 2.1±1 ) to receive dabigatran or warfarin .  Median follow-up was 2 years , and complete follow-up was achieved in 99.9 % of patients . All deaths were categorized by the investigators using prespecified definitions followed by central adjudication . Overall , 1371 deaths occurred ( annual mortality rate , 3.84 % ; 95 % confidence interval [ CI ] , 3.64–4.05 ) . Cardiac deaths ( sudden cardiac death and progressive heart failure ) accounted for 37.4 % of all deaths , whereas stroke- and hemorrhage-related deaths represented 9.8 % of the total mortality . An examination of the causes of death according to dabigatran or warfarin showed that dabigatran significantly reduced vascular ( embolism and hemorrhage-related ) mortality ( relative risk , 0.63 ; 95 % CI , 0.45–0.88 ; P=0.007 ) , whereas other causes of death were similar between treatments , including cardiac mortality ( relative risk , 0.96 ; 95 % CI , 0.80–1.15 ; P=0.638 ) . The two strongest independent predictors of cardiac death in this population were heart failure ( hazard ratio , 3.02 ; 95 % CI , 2.45–3.73 ; P<0.0001 ) , and prior myocardial infa rct ion ( hazard ratio , 2.05 ; 95 % CI , 1.61–2.62 ; P<0.0001 ) . Conclusions — The majority of deaths are not related to stroke in a contemporary anticoagulated atrial fibrillation population . These results emphasize the need to identify interventions beyond effective anticoagulation to further reduce mortality in atrial fibrillation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00262600 Background : A combination of low-dose aspirin with anticoagulants may provide better protection against thromboembolic events compared to anticoagulants alone in high-risk patients with atrial fibrillation . Objective : Evaluation of the preventive efficacy against nonfatal thromboembolic events and vascular deaths of the combination of the oral anticoagulant fluindione and aspirin ( 100 mg ) in patients with high-risk atrial fibrillation . Methods : A multicenter , placebo-controlled , double-blind , r and omized trial was conducted at 49 investigating centers in France . Atrial fibrillation patients with a previous thromboembolic event or older than 65 years and with either a history of hypertension , a recent episode of heart failure or decreased left ventricular function were included in the study . Patients were treated with fluindione plus placebo ( i.e. anticoagulant alone ) or fluindione plus aspirin ( i.e. combination therapy ) , with an international normalized ratio target of between 2 and 2.6 . The combined primary endpoint was stroke ( ischemic or hemorrhagic ) , myocardial infa rct ion , systemic arterial emboli or vascular death . The secondary endpoint was the incidence of hemorrhagic complications . Results : The 157 participants ( average age 74 years ; 52 % women ; 42 % with paroxysmal atrial fibrillation ) were followed for an average of 0.84 years . Three nonfatal thromboembolic events were observed ( 1 in the anticoagulation group , 2 in the combination group ) and 6 patients died ( 3 in the anticoagulation group , 3 in the combination group ) , none of them from a thromboembolic complication . However , 3 deaths were secondary to severe hemorrhagic complications ( 1 in the anticoagulation group , 2 in the combination group ) . Nonfatal hemorrhagic complications occurred more often in the combination group ( n = 10 , 13.1 % ) compared to the anticoagulation group ( n = 1 , 1.2 % ) ( p = 0.003 ) . Conclusion : The combination of aspirin with anticoagulant is associated with increased bleeding in elderly atrial fibrillation patients . The effect on thromboembolism and the overall balance of benefit to risk could not be accurately assessed in this study due to the limited number of ischemic events BACKGROUND A combination of low-dose aspirin ( A ) and anticoagulation ( AC ) may provide better protection against thromboembolic events compared with AC alone in high-risk patients with atrial fibrillation ( AF ) . METHODS We performed a multicentric placebo-controlled double blind-trial to test the preventive efficacy against thromboembolic events of the addition of aspirin ( A ) ( 100 mg ) or placebo ( P ) to anticoagulant treatment in patients with high-risk atrial fibrillation . A total of 157 patients were included , with atrial fibrillation and previous thromboembolic event or older than 65 years with either a history of hypertension , a recent episode of heart failure or a left ventricular dysfunction . All patients received fluindione ( F ) and P or F and A , with an INR target between 2 and 2.6 . The primary endpoint was a combined endpoint of stroke ( ischaemic or haemorrhagic ) , myocardial infa rct ion , systemic arterial emboli or vascular death . RESULTS The study had to be stopped prematurely owing to a too low recruitment rate . During follow-up ( 0.84 years ) 3 non-fatal thromboembolic events were recorded ( 1P , 2A ) and 6 patients died ( 3P , 3A ) , none of them from a thromboembolic complication . However , 3 deaths were secondary to severe haemorrhagic complications ( 1P , 2A ) . Non-fatal haemorrhagic complications occurred more often in group A ( n = 10 , 13.1 pour cent ) compared with group P ( n = 1 , 1.2 pour cent ) , p = 0.003 . CONCLUSION The FFAACS study was not able to show any therapeutic benefit from the addition of aspirin to anticoagulant in patients with high-risk AF . Such a combination increased the incidence rate of bleeding complications , which therefore greatly reduces its potential overall benefit BACKGROUND It is not clear if long-term antithrombotic treatment has a beneficial effect on the incidence of thromboembolism in chronic heart failure ( CHF ) . The HELAS study ( Heart failure Long-term Antithrombotic Study ) is a multicentre , r and omised , double-blind , placebo-controlled trial to evaluate antithrombotic treatment in patients with CHF . METHODS 197HF patients ( EF < 35 % ) were enrolled . Patients with Ischaemic Heart Disease were r and omised to receive either aspirin 325 mg or warfarin .  Patients with Dilated Cardiomyopathy ( DCM ) were r and omised to receive either warfarin or placebo . RESULTS Analysis of the data from 312 patient years showed an incidence of 2.2 embolic events per 100 patient years , with no significant difference between groups . The incidence of myocardial infa rct ion , hospitalisation , exacerbation of heart failure , death and haemorrhage were not different between the groups . No peripheral or pulmonary emboli were reported . Echocardiographic follow-up for 2years showed an overall increase in left ventricular ejection fraction from 28.2+/-6 to 30.3+/-7 p<0.05 , which was most obvious in patients with DCM taking warfarin ( EF 26.8+/-5.3 at baseline , 30.7+/-10 at 2 years , p<0.05 ) . CONCLUSIONS ( 1 ) Overall embolic events are rare in heart failure regardless of treatment . ( 2 ) Treatment does not seem to affect outcome AIMS To compare outcome of AF patients with effective rhythm control with patients treated with rate control .  METHODS AND RESULTS Out of the 266 AF patients r and omized to rhythm control in the RACE study , 49 patients turned to long-term sinus rhythm and were continuously treated with oral anticoagulation . The incidence of the primary endpoint in these patients was compared to that in 178 patients out of the initial 256 rate-control patients of RACE who were in AF and using oral anticoagulation continuously . Baseline characteristics of both groups were not different . After a mean follow-up of 2.3+/-0.6 years , the primary endpoint ( a composite of cardiovascular mortality , heart failure , thrombo-embolic complications ( TECs ) , bleeding , serious adverse effects of antiarrhythmic drugs and pacemaker implants ) was 22.4 % in the rhythm-control group vs. 15.2 % in the rate-control group . Multivariable regression analysis indicated coronary artery disease , heart failure , and digitalis as independent risk indicators of cardiovascular morbidity and mortality . Chronic sinus rhythm did not matter . CONCLUSION Among patients who remained on warfarin  , those who mostly were maintained in sinus rhythm under a rhythm-control strategy did not have a superior prognosis compared to those who remained in AF under a rate-control strategy Atrial fibrillation is the most common type of arrhythmia in adults . It is more common as patients age ; the prevalence is 1 % among those younger than age 60 years and increases to more than 8 % in those older than age 80 years . When data are adjusted for age , men are affected more often than women . Cardiac conditions associated with the development of atrial fibrillation are hypertension , rheumatic mitral valve disease , coronary artery disease , and congestive heart failure . Noncardiac causes include hyperthyroidism , hypoxic pulmonary conditions , surgery , and alcohol intoxication . Patients with atrial fibrillation may have symptoms of hemodynamic compromise , such as irregular palpitations and lightheadedness , or more vague symptoms , such as malaise , but may be asymptomatic . Patients with atrial fibrillation are at increased risk for thromboembolic disease . The purpose of this guideline is to make recommendations on the pharmacologic management of newly detected atrial fibrillation in primary care . The target patient population is adult patients with first-detected atrial fibrillation , defined as the presence of symptoms or electrocardiographic evidence of atrial fibrillation . The American College of Cardiology/American Heart Association has recommended using first-detected atrial fibrillation regardless of whether it is symptomatic or self-limited , recognizing that there can be uncertainty about the duration of the episode and about previous undetected episodes ( 1 ) . This guideline does not apply to patients with postoperative or postmyocardial infa rct ion atrial fibrillation , patients with class IV heart failure , patients already taking antiarrhythmic drugs , or patients with valvular disease . The target physician audience is internists and family physicians dedicated to primary care . This guideline is based on the accompanying background paper by McNamara and colleagues ( 2 ) and on the evidence report Management of New-Onset Atrial Fibrillation ( 3 ) , which was produced by the Johns Hopkins Evidence -based Practice Center under contract to the Agency for Healthcare Research and Quality ( AHRQ ) , Rockville , Maryl and . The American Academy of Family Physicians ( AAFP ) and the American College of Physicians ( ACP ) created this guideline in collaboration . The Joint AAFP/ACP Panel review ed the evidence and developed and grade d the recommendations ( Table 1 ) . The guideline was then approved by both organizations . The guideline makes recommendations in the following areas : rate control versus rhythm control , stroke prevention and anticoagulation , electrical cardioversion versus pharmacologic cardioversion , the role of transesophageal echocardiography in guiding therapy , and maintenance therapy . Table 1 . The Guyatt Approach to Grading Recommendations * Section 1 : Rate Control versus Rhythm Control One of the fundamental questions in the management of atrial fibrillation is whether to attempt cardioversion . The answer to this question depends on whether rate control or rhythm control provides more effective protection from thromboembolic events , improved mortality , better relief of symptoms , or improved quality of life . Another significant clinical question is whether certain population s , such as women , patients with hypertension or congestive heart failure , or young people with structurally healthy hearts , have better outcomes with one or the other strategy . Four studies have compared rate control with rhythm control . The study sample s have generally involved older patients ( > 65 years of age ) , and women and younger patients with healthy hearts and paroxysmal atrial fibrillation have not been well represented ( 5 ) . The Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) trial compared rhythm control versus rate control , and use of anticoagulation was recommended in both arms ( 6 ) . More than 4000 patients who were at least 65 years of age or who had at least 1 risk factor for stroke or death , such as hypertension , diabetes , previous stroke , or poor ventricular function , were followed for a mean of 3.5 years . Slightly more than one third of the patients were enrolled after their first episode of atrial fibrillation , and more than 90 % had had their qualifying episode within the previous 6 weeks . In more than two thirds of patients , the qualifying episode lasted at least 2 days . The average patient age was 70 years . Sixty-one percent of patients were men , and 89 % were white . Seventy-one percent of patients had hypertension , 38 % had coronary heart disease , 18 % had previously had failure of antiarrhythmic therapy , and 12 % had no apparent heart disease ( lone atrial fibrillation ) . Patients were r and omly assigned to rate or rhythm control , and their physicians chose the specific therapies ( pharmacologic first , then nonpharmacologic if needed ) . Anticoagulation was continued indefinitely in the rate-control group and was encouraged in the rhythm-control group but could be stopped at the physician 's discretion if sinus rhythm had been maintained for at least 4 , and preferably 12 , consecutive weeks with antiarrhythmic therapy . The prevalence of sinus rhythm in the rhythm-control group was 82 % , 73 % , and 63 % at 1 , 3 , and 5 years , respectively . The prevalence of sinus rhythm in the rate-control group was 34.6 % at 5 years . The primary end point in the AFFIRM trial , overall mortality , was not statistically significantly different between the groups . However , the rhythm-control strategy was associated with a higher risk for death than the rate-control strategy among older patients , those without congestive heart failure , and those with coronary disease .  Rates of stroke also did not differ between groups ; 70 % of all strokes occurred in patients who had stopped receiving anticoagulation or who had subtherapeutic international normalized ratios ( < 2.0 ) . More hospitalizations were reported in the rhythm-control group ( P < 0.001 ) . Another recent study , the RAte Control versus Electrical cardioversion for persistent atrial fibrillation ( RACE ) study , r and omly assigned patients to receive aggressive rhythm control or rate control ( 7 ) . This was a smaller study , involving 522 patients ( mean age , 68 years ) . Sixty-four percent of patients were men , 49 % had hypertension , and 27 % had coronary artery disease . All patients had persistent atrial fibrillation lasting less than 1 year and had had at least 1 previous electrical cardioversion ( a maximum of 2 previous cardioversions was permitted for study inclusion ) . The primary end point was a composite of cardiovascular mortality , heart failure , thromboembolic complications , bleeding , pacemaker implantation , and severe side effects of antiarrhythmic drugs . Again , no difference was seen between groups in the primary composite end point . As in the AFFIRM study , most of the strokes occurred in patients whose anticoagulation had been halted or patients whose international normalized ratio was subtherapeutic ( < 2.0 ) . In post hoc analysis , a benefit for rate control over rhythm control was seen in patients with hypertension and in women . Since this was a post hoc analysis , these results will need to be confirmed by further studies . Of note , despite an aggressive treatment protocol , at the end of follow-up only 39 % of the patients in the rhythm-control group were in sinus rhythm . The Pharmacological Intervention in Atrial Fibrillation ( PIAF ) trial r and omly assigned 252 patients 18 to 75 years of age with new-onset or permanent symptomatic atrial fibrillation ( mean duration of atrial fibrillation , approximately 4 months ) to rate control with diltiazem or aggressive conversion ( many times if necessary ) and maintenance therapy with amiodarone ( 8) . The primary end point of the study was improvement in symptoms related to atrial fibrillation . After 1 year of follow-up , relief of symptoms was similar in both groups , as were quality -of-life measures . Walking distance was improved in the rhythm-control group , but hospital admissions were more frequent in this group . Although final results are not yet available , preliminary reports of the Strategies of Treatment of Atrial Fibrillation ( STAF ) trial have been presented ( 9 ) . Patients were r and omly assigned to receive anticoagulation for 3 weeks before conversion and for 4 weeks after attempted conversion , with antiarrhythmic therapy to maintain sinus rhythm , or to long-term anticoagulation and rate control . ( Patients included in this study had at least 1 previous conversion attempt . ) After more than 1.5 years of follow-up , no difference was seen between the groups in rates of the primary end points of death , stroke , transient ischemic attacks , cardiopulmonary resuscitation , or thromboembolism . Of interest , only 40 % of patients in the rhythm-control group were still in sinus rhythm at 1 year , and all primary end points occurred in patients in atrial fibrillation , even in the rhythm-control group . This result has created speculation about whether fewer events would have occurred if anticoagulation had been continued indefinitely in the conversion group . It also suggests that despite aggressive rhythm management , a substantial number of patients can not maintain sinus rhythm . In general , the trial sample s were older and male and had risk factors for stroke , such as hypertension , congestive heart failure , and coronary disease . Certain subgroups of patients with atrial fibrillation , such as younger patients with healthy hearts or paroxysmal atrial fibrillation , were not well represented in the trials . Therefore , it is not certain whether these subgroups of patients may benefit from more aggressive rhythm control or rate control . Recommendation 1 : Rate control with chronic anticoagulation is the recommended strategy for the majority of patients with atrial fibrillation . Rhythm control has not been shown to be superior to rate control ( with chronic anticoagulation ) in reducing morbidity and mortality and may be inferior in some patient subgroups to rate control . Rhythm Background There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thromboembolic events in patients with non-valvular atrial fibrillation and a recent intracerebral haemorrhage during treatment with oral anticoagulation .  These patients are currently treated with oral anticoagulants , antiplatelet drugs , or no antithrombotic treatment , depending on personal and institutional preferences . Compared with warfarin , the direct oral anticoagulant apixaban reduces the risk of stroke or systemic embolism , intracranial haemorrhage , and case fatality in patients with atrial fibrillation . Compared with aspirin , apixaban reduces the risk of stroke or systemic embolism in patients with atrial fibrillation , and has a similar risk of intracerebral haemorrhage . Novel oral anticoagulants have not been evaluated in patients with atrial fibrillation and a recent intracerebral haemorrhage . To inform a phase III trial , the phase II Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation ( APACHE-AF ) trial aims to obtain estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage treated with apixaban and in those in whom oral anticoagulation is avoided . Methods / Design APACHE-AF is a phase II , multicentre , open-label , parallel-group , r and omised clinical trial with masked outcome assessment . One hundred adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention strategy will be enrolled in 14 hospitals in The Netherl and s . These patients will be r and omly assigned in a 1:1 ratio to either apixaban or to avoiding oral anticoagulation . Patients in the control group may be treated with antiplatelet drugs at the discretion of the treating physician . The primary outcome is the composite of vascular death or non-fatal stroke during follow-up . We aim to include 100 patients in 2.5 years . All patients will be followed-up for the duration of the study , but at least for 1 year . Recruitment commenced in September 2014 and is ongoing . This trial is funded by the Dutch Heart Foundation ( 2012 T077 ) and ZonMW (015008048).Trial registration NTR4526 ( 16 April 2014 ) Background : Atrial fibrillation is associated with increased risks of death , stroke/systemic embolism , and bleeding ( incurred by antithrombotic therapy ) , which may occur early after diagnosis . Methods : We assessed the risk of early events ( death , stroke/systemic embolism , and major bleeding ) over 12 months and their relation to the time after diagnosis of atrial fibrillation in 52 014 patients prospect ively enrolled in the GARFIELD-AF registry ( Global Anticoagulant Registry in the FIELD – Atrial Fibrillation ) between March 2010 and August 2016 . Results : Over 12 months , 2140 patients died ( mortality rate , 4.3 ; 95 % CI , 4.2–4.5 per 100 person-years ) , of whom 288 ( 13.5 % ) died in the first month ( 6.8 ; 95 % CI , 6.1–7.6 ) . Over 12 months , 657 patients had a stroke/systemic embolism ( 1.3 ; 95 % CI , 1.2–1.4 ) and 411 had a major bleeding ( 0.8 ; 95 % CI , 0.8–0.9 ) . During the first month , the rates ( per 100 person-years ) of stroke/systemic embolism and major bleed were 2.3 ( 95 % CI , 1.9–2.8 ) and 1.5 ( 95 % CI , 1.2–1.9 ) , respectively . The elevated 1-month mortality rate was mostly attributable to cardiovascular mortality ( 3.5 ; 95 % CI , 3.0–4.1 ) , in particular , heart failure , sudden death , and acute coronary syndromes ( 1.0 [ 95 % CI , 0.8–1.4 ] , 0.6 [ 95 % CI , 0.4–0.8 ] , and 0.5 [ 95 % CI , 0.3–0.8 ] , respectively ) . Age , heart failure , prior stroke , history of cirrhosis , vascular disease , moderate-to-severe kidney disease , diabetes mellitus , and living in North or Latin America were independent predictors of a higher risk of early death , whereas anticoagulation and living in Europe or Asia were independent predictors of a lower risk of early death . A predictive model developed for the 1-month risk of death had a C-statistic of 0.81 ( 95 % CI , 0.78–0.83 ) . Conclusions : The increased hazard of early events , in particular , cardiovascular mortality , in newly diagnosed atrial fibrillation points to the importance of comprehensive care for such patients and should alert clinicians to detect warning signs of possible early mortality . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT01090362
Based on the two major r and omised trials ( HELAS 2006 ; WASH 2004 ) , there is no convincing evidence that oral anticoagulant therapy modifies mortality or vascular events in patients with heart failure and sinus rhythm .
Although oral anticoagulation is indicated in certain groups of patients with heart failure ( for example those with atrial fibrillation ) , the available data does not support the routine use of anticoagulation in heart failure patients who remain in sinus rhythm
BACKGROUND Patients with chronic heart failure ( heart failure ) are at risk of thromboembolic events , including stroke , pulmonary embolism and peripheral arterial embolism , whilst coronary ischaemic events also contribute to the progression of heart failure .
Long-term oral anticoagulation is established in certain patient groups , including patients with heart failure and atrial fibrillation , but there is wide variation in the indications and use of oral anticoagulation in the broader heart failure population .
OBJECTIVES To determine whether long-term oral anticoagulation reduces total deaths , cardiovascular deaths and major thromboembolic events in patients with heart failure .