Probing oral anticoagulation in patients with atrial high rate episodes: Rationale and design of the Non–vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH–AFNET 6) trial Anticoagulant and/or Antiplatelet Treatment in Patients with Atrial Fibrillation after Percutaneous Coronary Intervention [Study of combined anticoagulant (fluindione)-aspirin therapy in patients with atrial fibrillation at high risk for thromboembolic complications. A randomized trial (FFAACS)]. Morbidity and mortality in 229 elderly patients with nonrheumatic atrial fibrillation. A five-year follow-up. The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. Efficacy and safety of percutaneous left atrial appendage closure to prevent thromboembolic events in atrial fibrillation patients with high stroke and bleeding risk Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: NICE guidance Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients With Chronic Heart Failure: The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial Clinical Relevance of Anticoagulation and Dual Antiplatelet Therapy to the Outcomes of Patients With Atrial Fibrillation and Recent Percutaneous Coronary Intervention With Stent Antithrombotic therapy is associated with better survival in patients with severe heart failure and left ventricular systolic dysfunction (EPICAL study). Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Low-Intensity Oral Anticoagulant Plus Low-Dose Aspirin During the First Six Months Versus Standard-Intensity Oral Anticoagulant Therapy After Mechanical Heart Valve Replacement: A Pilot Study of Low-Intensity Warfarin and Aspirin in Cardiac Prostheses (LIWACAP) Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation. Adverse outcomes and predictors of underuse of antithrombotic therapy in medicare beneficiaries with chronic atrial fibrillation.
Background Oral anticoagulation prevents ischemic strokes in patients with atrial fibrillation ( AF ) . Early detection of AF and subsequent initiation of oral anticoagulation help to prevent strokes in AF patients . Implanted cardiac pacemakers and defibrillators allow seamless detection of atrial high rate episodes ( AHRE ) , but the best antithrombotic therapy in patients with AHRE is not known . Rationale Stroke risk is higher in pacemaker patients with AHRE than in those without , but the available data also show that stroke risk in patients with AHRE is lower than in patients with AF . Furthermore , only a minority of patients with AHRE will develop AF , many strokes occur without a temporal relation to AHRE , and AHRE can reflect other arrhythmias than AF or artifacts . An adequately powered controlled trial of oral anticoagulation in patients with AHRE is needed . Design The Non – vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes ( NOAH – AFNET 6 ) trial tests whether oral anticoagulation with edoxaban is superior to prevent the primary efficacy outcome of stroke or cardiovascular death compared with aspirin or no antithrombotic therapy based on evidence ‐based indications . The primary safety outcome will be major bleeding . NOAH – AFNET 6 will r and omize 3,400 patients with AHRE , but without documented AF , aged ≥65 years with at least 1 other stroke risk factor , to oral anticoagulation therapy ( edoxaban ) or no anticoagulation . All patients will be followed until the end of this investigator‐driven , prospect i ve , parallel‐group , r and omized , event‐driven , double‐blind , multicenter phase IIIb trial . Patients will be censored when they develop AF and offered open‐label anticoagulation . The sponsor is the Atrial Fibrillation NETwork ( AFNET ) . The trial is supported by the DZHK ( German Centre for Cardiovascular Research ) , the BMBF ( German Ministry of Education and Research ) , and Daiichi Sankyo Europe . Conclusion NOAH – AFNET 6 will provide robust information on the effect of oral anticoagulation in patients with atrial high rate episodes detected by implanted devices . Graphical abstract Figure . No Caption available Background : Atrial fibrillation ( AF ) is the most common cardiac arrhythmia sustained and frequently occurs in patients with coronary heart disease . Thus , a large number of patients requiring percutaneous coronary intervention ( PCI  ) also suffer from AF . An anticoagulant regimen has not been st and ardized for patients with AF after coronary stent implantation . Patients and Methods : The authors investigated data from 159 patients with AF who underwent PCI in their department . Baseline variables and incidence of a combined endpoint ( stroke , myocardial infa rct ion , cardiovascular death , severe bleeding ) were compared in patients receiving clopidogrel and acetylsalicylic acid ( ASA ; group 1 ) versus patients receiving the combination of clopidogrel and ASA with low-molecular-weight heparin ( LMWH ; group 2 ) versus patients receiving the combination of clopidogrel and ASA with oral anticoagulation ( OAC ; group 3 )  at discharge . Results : Patients discharged with triple therapy including OAC seemed to be at higher risk : patients in group 3 had decreased left ventricular ejection fraction and increased inflammatory state as measured by plasma fibrinogen and C-reactive protein . Moreover , previous OAC treatment and strokes were found more often in this subgroup of patients . In a median follow-up of 1.4 years , two severe bleeding events ( both in group 1 ) , four myocardial infa rct ions ( all in group 1 ) , 13 strokes ( nine in group 1 , four in group 2 ) , and nine cardiovascular deaths ( three in group 1 , five in group 2 , one in group 3 ) occurred . Conclusion : In this analysis , no treatment regimen seemed to be clearly superior . It underlines the importance of prospect i ve , r and omized trials to investigate the optimal antithrombotic/antiplatelet treatment for patients with AF after PCI.ZusammenfassungHintergrund : Vorhofflimmern ( VHF ) ist die häufigste Herzrhythmusstörung und wichtige Komorbidität bei Patienten mit koronarer Herzkrankheit . Welche antithrombotische/antithrombozytäre Therapiestrategie bei Patienten mit Vorhofflimmern nach perkutaner Koronarintervention ( PCI ) verfolgt werden sollte , ist aktuell nicht eindeutig zu beantworten . Patienten und Method ik : Die Autoren identifizierten retrospektiv 159 Patienten mit VHF , die in ihrer Abteilung in den Jahren 1999–2004 eine PCI erhalten hatten . Die Grunderkrankungen und die Inzidenz eines kombinierten Endpunkts ( Schlaganfall , Myokardinfarkt , kardiovaskulär bedingter Tod , schwere Blutung ) wurden bei Patienten verglichen , die Clopidogrel und Acetylsalicylsäure ( ASS ; Gruppe 1 ) , Clopidogrel und ASS in Kombination mit niedermolekularem Heparin ( Gruppe 2 ) sowie Clopidogrel und ASS und zusätzlich orale Antikoagulation erhalten hatten ( Gruppe 3).Ergebnisse : Die Grunderkrankungen der Patienten in den drei Gruppen waren nicht signifikant unterschiedlich . In einem medianen Beobachtungszeitraum von 1,4 Jahren konnten zwei schwere Blutungen ( in Gruppe 1 ) , vier Myokardinfarkte ( in Gruppe 1 ) , 13 Schlaganfälle ( neun in Gruppe 1 , vier in Gruppe 2 ) und neun kardiovaskulär bedingte Todesfälle ( drei in Gruppe 1 , fünf in Gruppe 2 , einer in Gruppe 3 ) nachgewiesen werden . Schlussfolgerung : In dieser Untersuchung erwies sich keine Therapiestrategie einer and eren gegenüber als eindeutig überlegen . Die erhobenen Date n zeigen , wie wichtig es ist , prospektive , r and omisierte Studien bezüglich der antithrombotischen/antithrombozytären Therapie durchzuführen , um Patienten mit AF nach PCI optimal beh and eln zu können 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 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 BACKGROUND Heart failure is commonly associated with vascular disease and a high rate of athero-thrombotic events , but the risks and benefits of antithrombotic therapy are unknown . METHODS The current study was an open-label , r and omized , controlled trial comparing no antithrombotic therapy , aspirin ( 300 mg/day ) , and warfarin ( target international normalized ratio 2.5 ) in patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy . The primary objective was to demonstrate the feasibility and inform the design of a larger outcome study . The primary clinical outcome was death , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS Two hundred seventy-nine patients were r and omized and 627 patient-years exposure were accumulated over a mean follow-up time of 27 + /- 1 months . Twenty-six ( 26 % ) , 29 ( 32 % ) , and 23 ( 26 % ) patients r and omized to no antithrombotic treatment , aspirin , and warfarin , respectively , reached the primary outcome ( ns ) . There were trends to a worse outcome among those r and omized to aspirin for a number of secondary outcomes . Significantly ( P = .044 ) more patients r and omized to aspirin were hospitalized for cardiovascular reasons , especially worsening heart failure . CONCLUSIONS The Warfarin/Aspirin Study in Heart failure ( WASH ) provides no evidence that aspirin is effective or safe in patients with heart failure . The benefits of warfarin for patients with heart failure in sinus rhythm have not been established . Antithrombotic therapy in patients with heart failure is not evidence based but commonly contributes to polypharmacy BACKGROUND Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation . However , recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits of sinus rhythm . We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation . METHODS We r and omly assigned 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aim ed at rate control or rhythm control . Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication . Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs . The end point was a composite of death from cardiovascular causes , heart failure , thromboembolic complications , bleeding , implantation of a pacemaker , and severe adverse effects of drugs . RESULTS After a mean ( + /-SD ) of 2.3+/-0.6 years , 39 percent of the 266 patients in the rhythm-control group had sinus rhythm , as compared with 10 percent of the 256 patients in the rate-control group . The primary end point occurred in 44 patients ( 17.2 percent ) in the rate-control group and in 60 ( 22.6 percent ) in the rhythm-control group . The 90 percent ( two-sided ) upper boundary of the absolute difference in the primary end point was 0.4 percent ( the prespecified criterion for noninferiority was 10 percent or less ) . The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups . CONCLUSIONS Rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion Aims The r and omized PROTECT AF trial demonstrated non-inferiority of left atrial appendage ( LAA ) closure to oral anticoagulation with warfarin . Current guidelines give a class IIb recommendation for LAA closure . We evaluated the efficacy and safety of LAA closure in a consecutive series of non-valvular atrial fibrillation patients with contraindications to long-term oral anticoagulation or at high bleeding risk . Methods and results 101 consecutive non-valvular atrial fibrillation patients ( age 74.7 ± 7.5 years ) at high risk for stroke ( CHA2DS2-VASc Score 4.4 ± 1.6 ) and high bleeding risk ( HAS-BLED Score 4.2 ± 1.3 ) received LAA closure with either the Watchman closure device ( n = 38 ) or the Amplatzer cardiac plug ( n = 63 ) . Dual antiplatelet therapy with aspirin and clopidogrel was recommended for 3–6 months after device implantation , followed by long-term antiplatelet therapy with aspirin . No anticoagulation was given after device implantation . Mean follow-up was 400 days . One patient ( 1 % ) experienced a transient ischemic attack , and two patients ( 2 % ) suffered from ischemic stroke . While on recommended antiplatelet therapy , bleeding occurred in 12/101 patients ( 12 % ) . Bleeding was significantly reduced with 3 compared with 6 months dual antiplatelet therapy ( 3.0 vs. 16.2 % , p < 0.05 ) while ischemic or thrombotic events were similar . Conclusion Left atrial appendage closure in patients with non-valvular atrial fibrillation and high risk for stroke and bleeding events effectively prevented stroke and reduced cerebral ischemic events compared to expected stroke rate according to CHA2DS2-VASc Score . Dual antiplatelet therapy for 3 months reduced the rate of bleeding events compared to 6 months therapy with no increase of thrombotic events Atrial fibrillation ( AF ) is the commonest sustained cardiac arrhythmia , whose importance has been realised given its strong association with stroke and systemic embolism that can be significantly reduced by oral anticoagulation . Until recently , the only oral anticoagulant ( OAC ) available was the vitamin K antagonist ( VKA ) class of drugs — for example , warfarin . Indeed , warfarin provides highly effective prophylaxis against thromboembolism as shown by extensive evidence from r and omised controlled trials , but its effectiveness is dependent upon good anticoagulation control ( as reflected by its high length of time in the therapeutic range).1 The risk of stroke in AF is not homogeneous , and depends upon the presence or absence of several risk factors . These risk factors have been used to formulate stroke risk stratification schemes , so that the focus has been to identify ‘ high-risk ’ patients who could be targeted for this ‘ inconvenient ’ drug , warfarin . The numerous practical limitations which affect a clinician 's willingness to prescribe warfarin , and a patient 's willingness to comply with it ( box 1 ) , have result ed in large numbers of high-risk patients either unprotected against stroke or suboptimally protected with antiplatelet therapy2—despite evidence that aspirin is less effective for stroke prevention and is not without its own bleeding risk , especially in the elderly.3 Box 1 # # # Limitations of warfarin The limitations of warfarin have driven efforts to establish new OACs which can circumvent the shortcomings of the VKAs . The new OACs fall into two classes : the oral direct thrombin inhibitors ( eg , dabigatran ) and the oral factor Xa inhibitors ( eg . rivaroxaban , apixaban).4 The National Institute for Health Background — Chronic heart failure remains a major cause of mortality and morbidity . The role of antithrombotic therapy in patients with chronic heart failure has long been debated . The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm . Methods and Results — This prospect i ve , r and omized clinical trial of open-label warfarin ( target international normalized ratio of 2.5 to 3.0 ) and double-blind treatment with either aspirin ( 162 mg once daily ) or clopidogrel ( 75 mg once daily ) had a 30-month enrollment period and a minimum of 12 months of treatment . We enrolled 1587 men and women ≥18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of ≤35 % . The primary outcome was the time to first occurrence of death , nonfatal myocardial infa rct ion , or nonfatal stroke . For the primary composite end point , the hazard ratios were as follows : for warfarin versus aspirin , 0.98 ( 95 % CI , 0.86 to 1.12 ; P=0.77 ) ; for clopidogrel versus aspirin , 1.08 ( 95 % CI , 0.83 to 1.40 ; P=0.57 ) ; and for warfarin versus clopidogrel , 0.89 ( 95 % CI , 0.68 to 1.16 ; P=0.39 ) . Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel  . Hospitalization for worsening heart failure occurred in 116 ( 22.2 % ) , 97 ( 18.5 % ) , and 89 ( 16.5 % ) patients treated with aspirin , clopidogrel , and warfarin , respectively ( P=0.02 for warfarin versus aspirin ) . Conclusion — The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin Background Chronic atrial fibrillation ( AF ) , coexisting with a history of recent coronary angioplasty with stent ( PCI-S ) , represents an encoded indication for oral anticoagulation ( OAC ) with warfarin plus dual antiplatelet therapy ( DAPT ) . Methods Using a retrospective cohort study , we determined the respective impacts on cardiovascular outcomes of three different pharmacologic regimens , i.e. , triple therapy ( TT ) with warfarin + clopidogrel and aspirin , dual therapy ( DT ) with warfarin + clopidogrel or aspirin , and DAPT with clopidogrel + aspirin . Outcomes of interest were all-cause mortality , ischemic cardiac events , ischemic cerebral events , and bleeding events . The inclusion criterion was the coexistence of an indication for OAC ( e.g. , chronic AF ) with an indication for DAPT due to recent PCI-S. Results Among the 98 patients enrolled , 48 ( 49 % ) , 31 ( 31.6 % ) , and 19 ( 19.4 % ) patients were prescribed TT , DT , and DAPT , respectively . Throughout a mean follow-up of 378 ± 15.7 days , there were no significant differences between the three regimens for all abovementioned outcomes . In particular , the total frequency of major bleeding was similar in the three groups : five cases ( 10.4 % ) in TT , one case ( 3.22 % ) in DT and no case in DAPT groups ( Chi-square test , P = 0.1987 ) . Conclusions TT , DT and DAPT displayed similar efficacy and safety . Although the superiority of OAC vs. DAPT for stroke prevention in AF patients has been demonstrated by previous r and omized trials , a smaller frequency of high thromboembolic risks ’ features in DAPT group of the present study may have prevented the observation of a higher incidence of ischemic stroke in this group BACKGROUND In patients with congestive heart failure ( CHF ) , clinical trials have demonstrated the benefit of a number of drugs on morbidity and mortality . Nevertheless so far , there is no published controlled study of long-term antithrombotic therapy in patients with CHF . The aim of this work was to identify the relationship between cardiovascular drug use , especially antithrombotic therapy , and survival of CHF patients in current clinical practice , using an observational , population -based data base . METHODS The EPICAL study ( Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine ) has identified prospect ively all patients with severe CHF in the community of Lorraine . Inclusion criteria were age 20 - 80 years in 1994 , at least one hospitalisation for cardiac decompensation , NYHA III/IV HF , ventricular ejection fraction < or = 30 % or cardiothoracic index > or = 60 % and arterial hypotension or peripheral and /or pulmonary oedema . A total of 417 consecutive patients surviving at hospital discharge were included in the data base . The average follow-up period was 5 years . Univariate Cox models were used to test the relationship of baseline biological and clinical factors to survival .  Cardiovascular drug prescriptions were tested in a multivariate Cox model adjusted by other known predictive factors . RESULTS Duration of disease > 1 year , renal failure , serum sodium > or = 138 mmol/l , old age , serious comorbidity , previous decompensation , high doses of furosemide and vasodilators use were independently associated with poor prognosis at 1 and 5 years . Oral anticoagulants , aspirin , lipid lowering drugs and beta-blockers use were associated with better survival . There was no interaction between aspirin and angiotensin converting enzyme inhibitor use on survival . CONCLUSION Antithrombotic therapy was associated with a better long-term survival in our study population of severe CHF . These results together with other previously published circumstantial evidence urge for a prospect i ve , controlled and r and omised trial specifically design ed to evaluate optimal oral anticoagulants and aspirin in patients with congestive heart failure The risk for ischemic stroke in patients with atrial fibrillation is related to underlying structural heart disease [ 1 - 3 ] . Although most strokes are believed to arise from embolism of left atrial thrombi [ 4 , 5 ] , other mechanisms may contribute . Transesophageal echocardiography ( TEE ) provides a unique diagnostic window for evaluating the left atrium , left atrial appendage , and thoracic aorta , but the manner in which specific TEE findings in patients with atrial fibrillation correlate with thromboembolic risk and response to therapy has not been fully established [ 6 - 13 ] . We performed TEE in patients with nonvalvular atrial fibrillation who were at high intrinsic risk for thromboembolism and were participating in the Stroke Prevention in Atrial Fibrillation ( SPAF-III ) study , a r and omized clinical trial . In that study , adjusted-dose warfarin ( target international normalized ratio [ INR ] , 2 to 3 ) was compared with combination therapy consisting of low-intensity warfarin ( INR , 1.2 to 1.5 ) plus aspirin , 325 mg/d . The trial was stopped after an interim analysis indicated that the efficacy of adjusted-dose warfarin therapy was superior to that of combination therapy . Low anticoagulation intensity in the combination therapy group yielded high stroke rates that were similar to those expected during treatment with aspirin alone [ 14 , 15 ] . In the current analysis , we 1 ) correlate TEE observations among patients with atrial fibrillation at high risk for thromboembolism with rate of subsequent stroke and 2 ) compare treatment responses . Methods Patients Patients were recruited from the SPAF-III multicenter trial , which was design ed to compare two antithrombotic medication regimens for prevention of ischemic stroke and systemic embolism ( primary events ) . The study , whose design is described else-where in detail [ 14 ] , involved patients with nonvalvular atrial fibrillation who were stratified for risk on the basis of clinical and transthoracic echocardiographic criteria derived from previous analyses [ 15 ] . Women older than 75 years of age and patients of any age and either sex with systolic hypertension ( systolic blood pressure > 160 mm Hg ) , previous thromboembolism , or impaired left ventricular function ( M-mode echocardiographic fractional shortening of 0.25 or recent clinical congestive heart failure ) were r and omly assigned to receive adjusted-dose warfarin ( target INR , 2.0 to 3.0 ) or a combination of low-intensity warfarin ( 0.5 to 3.0 mg/d ; dose was initially adjusted to cause deviation of the INR to 1.2 to 1.5 and was then fixed ) and aspirin . Seventy-three percent of the patients were receiving warfarin at various dose intensities before trial entry ; these patients were equally distributed between assigned treatment groups . Antithrombotic treatment was assigned before performance of TEE and was not influenced by TEE findings . Patients were followed monthly by telephone and in clinic every 3 months , and a st and ard question naire on stroke symptoms was administered annually . All patients whose responses to the question naire suggested the occurrence of stroke were referred for clinical examination by a local affiliated neurologist who was blinded to treatment , and all events were adjudicated by a blinded event verification committee [ 14 ] . This project was design ed to supplement the SPAF-III clinical trial on the basis of the hypothesis that spontaneous echocardiographic contrast detected by TEE identifies patients at high risk for thromboembolism for whom adjusted-dose warfarin  would prove superior to  combination therapy . All participants in the parent study were encouraged , but not required , to provide separate , written informed consent for TEE after r and om assignment to antithrombotic treatment . This was done to prevent the results of TEE from influencing recruitment of patients into the trial or from altering treatment . The intended sample size of 412 TEE examinations was selected to detect an absolute difference in event rates of 3.9 % per year ( based on projected event rates of 5.4 % per year in patients with spontaneous echocardiographic contrast and 1.5 % per year in patients without contrast ) over a mean observation period of 2.5 years . Secondary objectives were to correlate clinical thromboembolic events with function of the left atrial appendage , thrombus of the left atrium and left atrial appendage , and atherosclerotic lesions in the thoracic aorta imaged by TEE . Transesophageal Echocardiography Transesophageal echocardiography was performed within 3 months of enrollment with patients under light sedation and topical anesthesia , according to specific protocol s for acquisition and interpretation [ 16 ] . Commercially available ultrasonography equipment incorporated biplane or multiplane transducers with at least 48 crystals operating at a st and ard frequency of 5 MHz with gray-scale imaging . Signal processing , log compression , and persistence values were established for each manufacturer . Images were interpreted locally , and data were entered into st and ardized forms by echocardiographers who were blinded to antithrombotic treatment assignment but not to patient demographic or clinical features . Original videotaped recordings were collected in a central echocardiographic registry for validation and quality control . To assure generalizability of the results to laboratories used in clinical practice , the analyses reported here are based on image interpretation at the local laboratories . The following features were specifically assessed : left atrial appendage size , peak ante grade ( emptying ) velocity of blood flow in the left atrial appendage , spontaneous echocardiographic contrast in the left atrium or left atrial appendage , thrombus of the left atrium or left atrial appendage , and atherosclerotic disease of the thoracic aorta . Spontaneous echocardiographic contrast was defined as a pattern of slowly swirling intracavitary echodensities imaged with gain setting s adjusted to distinguish background noise . Contrast was classified as faint when visualized intermittently during the cardiac cycle or when enhanced gain setting s were required for detection and was classified as dense when continuously present at st and ard gain . Aortic plaque was classified by location and as either simple or complex according to mobility , ulceration , pedunculation , or thickness greater than 4 mm [ 16 ] . We postulated that reduced emptying velocity from the left atrial appendage , which reflects stasis , would be associated with dense spontaneous echocardiographic contrast and thrombus formation , whereas complex aortic plaque would be a consequence of atherosclerotic vascular abnormality . We also postulated that these findings would predispose patients to ischemic stroke through separate pathogenic mechanisms . Statistical Analysis The analyses reported here were limited to variables accessible only by TEE and were hypothesized a priori to have potential predictive relations to clinical thromboembolism . Baseline comparisons between groups were done by using the chi-square test for categorical data and the Student t-test for continuous variables . The Cox proportional-hazards regression model was used to estimate the univariate relative risk associated with TEE characteristics . The primary analysis compared rates of cerebral ischemic events and systemic embolism among patients who had dense spontaneous echocardiographic contrast detected in the left atrium or left atrial appendage with rates in patients who did not have dense contrast ; the log-rank statistic was used to compare the times to events between these groups . Secondary analyses , conducted similarly , compared event rates in groups that were identified by left atrial appendage size , flow velocity , thrombus , and aortic plaque . For these comparisons , the area of the left atrial appendage was dichotomized at the upper quartile ; flow velocity was dichotomized at the lower quartile . When interaction was seen between treatment and TEE characteristics , analysis of the relation of TEE findings to events was confined to the combination therapy group and treatment effect was described separately ; when no interaction was seen , the analysis was stratified by therapy . The relative reduction in event rate associated with adjusted-dose warfarin therapy was computed as the difference between unity and the rate ratio determined by a Poisson regression model [ 17 ] . A Cox proportional-hazards regression model was fit to confirm the independence of TEE characteristics identified as univariate thromboembolic risk factors . Confidence intervals for event rates were calculated by using a Poisson regression model ; tests of significance were two-sided and were not adjusted for multiple comparisons . All analyses were done according to the intention-to-treat principle . Results Of 1044 high-risk patients with atrial fibrillation enrolled in the r and omized trial , 382 ( 37 % ) volunteered for TEE ( range , 10 % to 80 % of SPAF-III participants recruited at 18 clinical centers offering TEE ) . Salient features of these 382 patients were similar to those of the 662 participants who did not undergo transesophageal imaging ( Table 1 ) . The mean patient age was 71 years , 36 % of patients had clinical ischemic heart disease , and almost half had a history of congestive heart failure . Balanced proportions of patients were assigned to therapy with adjusted-dose warfarin ( n = 190 ) or fixed-dose warfarin and aspirin ( n = 192 ) . Time from r and om assignment of treatment to TEE was similar in the two groups ( mean , 23 days ) . The trial was stopped after a mean observation period of 1.1 years because an interim analysis indicated the lack of efficacy of the combination regimen [ 18 ] . Up to that point , 23 primary events ( all of which were ischemic strokes ) occurred in the subset of participants who had undergone TEE ( event rate , 3.1 % per year in patients assigned to adjusted-dose warfarin compared with 7.8 % per year in those assigned to combination therapy ; P = 0.04 ) . The objective of this study was to evaluate the safety and efficacy of low-intensity warfarin treatment plus aspirin during the first 6 months after surgery in patients undergoing heart valve substitution with mechanical prostheses .  Vitamin K antagonists ( VKA ) are able to reduce but not eliminate thrombosis and systemic embolism in patients with mechanical heart valves . The intensity of treatment and additional use of aspirin in these patients is still controversial . Consecutive patients undergoing aortic or mitral valve replacement ( or a combination of the two ) with mechanical prostheses were invited to participate in the study . After stratifying for site of prosthesis , patients were r and omized to receive low intensity VKA treatment ( target INR 2.5 ) plus aspirin ( 100 mg/day ) for the first six months ( Group A ) or st and ard-intensity ( INR target 3.7 ) VKA treatment ( Group B ) . Mean follow-up was 1.5 years . Principal outcome events were systemic embolism , major bleeding , and vascular death . A total of 94 patients in Group A and 104 in Group B were r and omized and followed up for 144 and 163 patient years , respectively . There were 5 ( 5 % ) events in Group A ( 4 major bleeding events and 1 vascular death ) and 4 ( 4 % ) in group B ( 2 major bleeding events and 2 ischemic stroke ) . All the events except 1 occurred within the first 6 months after surgery . Cumulative incidence of primary outcome events was 5.8 % ( 95 % CI 0.9 to 10.7 ) in Group A and 4.3 % ( 95 % CI 0,2 to 8.4 ) in Group B ( p=0.6 ) . Low-intensity treatment plus aspirin during the first six months after surgery appears to be as effective and safe as moderate-high-intensity anticoagulation OBJECTIVES This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis . BACKGROUND Warfarin was more effective than aspirin in preventing stroke in these patients ; combined therapy with low anticoagulant intensity was ineffective . Mitral stenosis patients were not investigated . METHODS We performed a multicenter r and omized trial in 1,209 patients at risk . The intermediate-risk group included patients with risk factors or age > 60 years : 242 received the cyclooxygenase inhibitor triflusal  , 237 received  acenocumarol , and 235 received a combination of both .  The high-risk group included patients with prior embolism or mitral stenosis : 259 received anticoagulants and 236 received the combined therapy . Median follow-up was 2.76 years . Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism . RESULTS Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- ( hazard ratio [ HR ] 0.33 [ 95 % confidence interval (CI)0.12 to 0.91 ] ; p = 0.02 ) and the high-risk group ( HR 0.51 [ 95 % CI 0.27 to 0.96 ] ; p = 0.03 ) . Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group . Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy . CONCLUSIONS The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients Abstract Objective : To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice . Design : R and omised controlled trial . Participants : 729 patients aged ≥60 years with atrial fibrillation , recruited in general practice , who had no established indication for coumarin . Mean age was 75 years and mean follow up 2.7 years . Setting : Primary care in the Netherl and s. Interventions : Patients eligible for st and ard intensity coumarin ( international normalised ratio 2.5 - 3.5 ) were r and omly assigned to st and ard anticoagulation , very low intensity coumarin ( international normalised ratio 1.1 - 1.6 ) , or aspirin ( 150 mg/day ) ( stratum 1 ) . Patients ineligible for st and ard anticoagulation were r and omly assigned to low anticoagulation or aspirin ( stratum 2 ) . Main outcome measures : Stroke , systemic embolism , major haemorrhage , and vascular death . Results : 108 primary events occurred ( annual event rate 5.5 % ) , including 13 major haemorrhages ( 0.7 % a year ) . The hazard ratio was 0.91 ( 0.61 to 1.36 ) for low anticoagulation versus aspirin and 0.78 ( 0.34 to 1.81 ) for st and ard anticoagulation versus aspirin . Non-vascular death was less common in the low anticoagulation group than in the aspirin group ( 0.41 , 0.20 to 0.82 ) . There was no significant difference between the treatment groups in bleeding incidence . High systolic and low diastolic blood pressure and age were independent prognostic factors . Conclusion : In a general practice population ( without established indications for coumarin ) neither low nor st and ard intensity anticoagulation is better than aspirin in preventing primary outcome events . Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice . Key messages Studies have shown that patients with non-rheumatic atrial fibrillation may benefit from anticoagulation This study in a general practice population found no benefit of st and ard or low dose anticoagulation on risk of stroke , systemic embolism , major haemorrhage , or vascular death when compared with aspirin Hypertension and age were prognostic factors for event occurrence Aspirin is the treatment of choice for preventing thromboembolism in primary care patients at low OBJECTIVES Optimal antithrombotic/anticoagulation therapy in patients on chronic oral anticoagulation ( OAC ) undergoing drug-eluting stent ( DES ) implantation is unknown . We investigated the efficacy and safety of two regimens of antithrombotic/anticoagulation therapy in patients who present for DES implantation whilst on OAC . METHODS We included a series of 515 patients on OAC who underwent DES implantation between 2002 and 2007 . Based on predefined clinical and echocardiographic criteria , 306 patients continued OAC ( triple therapy )  and 209 patients discontinued OAC ( dual therapy ) for the time they received antiplatelet therapy with clopidogrel and aspirin [ stent-related antithrombotic treatment ( SRAT ) ] . The primary end point was a composite of death , myocardial infa rct ion , stent thrombosis or stroke . RESULTS During SRAT the primary endpoint was observed in 13 patients in the group with triple therapy versus 15 patients in the group with dual therapy [ Kaplan-Meier estimates 4.2 % and 7.2 % , odds ratio ( OR ) = 0.61 , 95 % confidence interval ( CI ) 0.29 - 1.28 ; P = 0.19 ] . At 2 years of follow-up , the primary endpoint was observed in 35 patients in the group with triple therapy versus 36 patients in the group with dual therapy ( Kaplan-Meier estimates 14.1 % and 18.0 % , OR = 0.76 , 95 % CI : 0.48 - 1.21 ; P = 0.25 ) . Two-year incidence of major bleeding was 1.4 % ( n = 4 , triple therapy ) versus 3.1 % ( n = 6 , dual therapy ) ( P = 0.34 ) . CONCLUSIONS In patients on chronic OAC undergoing DES implantation , clinical and echocardiographic criteria help to define postprocedural antithrombotic/anticoagulation therapy . Based on these criteria , both a double antiplatelet therapy ( clopidogrel plus aspirin ) and a triple therapy ( OAC plus clopidogrel plus aspirin ) are associated with favourable safety and efficacy BACKGROUND AND PURPOSE Antithrombotic therapy can prevent strokes and transient ischemic attacks ( TIAs ) in carefully selected patients who have chronic nonvalvular atrial fibrillation ( NVAF ) . Our objectives were 3-fold : to document the use of warfarin and aspirin therapy in Missouri Medicare beneficiaries with chronic NVAF ; to identify factors associated with warfarin and aspirin underuse ; and to determine the association between prescription of warfarin and aspirin at hospital discharge and adverse outcomes in this elderly , frail population . METHODS We linked chart review s from all Missouri hospitals to Medicare cl aims data from 1993 to 1996 . From chart review s , we documented Medicare beneficiaries ' demographic factors , comorbid conditions , and antithrombotic therapy prescribed at the time of hospital discharge . From Medicare cl aims , we determined the date of outcomes -death from any cause or hospitalization for an ischemic event ( a stroke , a TIA , or a myocardial infa rct ion ) . RESULTS Only 328 ( 55 % ) of the 597 Medicare beneficiaries were prescribed antithrombotic therapy at hospital discharge : 34 % received warfarin and 21 % received aspirin . Advanced age , female gender , and rural residency predicted underuse of antithrombotic therapy . After controlling for these factors , as well as stroke risk factors and contraindications to anticoagulation , the prescription of warfarin was associated with a 24 % relative risk reduction ( RRR ) in adverse outcomes ( P=0.003 ) . Prescription of aspirin was associated with a nonsignificant 5 % RRR in these events ( P=0.56 ) . CONCLUSIONS The underuse of antithrombotic therapy in Medicare beneficiaries who have NVAF is associated with measurable adverse outcomes . The benefit of warfarin therapy may extend to frail , elderly patients , a group that was excluded from r and omized controlled trials . The role of antiplatelet therapy in this population deserves further study because many of these patients have relative contraindications to warfarin
At present , there are no data on the role of oral anticoagulation versus antiplatelet agents in heart failure with preserved ejection fraction with sinus rhythm .
Also , there were no data from RCTs on the utility of non-vitamin K antagonist oral anticoagulants compared to antiplatelet agents in heart failure with sinus rhythm
BACKGROUND Morbidity in patients with chronic heart failure is high , and this predisposes them to thrombotic complications , including stroke and thromboembolism , which in turn contribute to high mortality .
Oral anticoagulants ( e.g. warfarin ) and antiplatelet agents ( e.g. aspirin ) are the principle oral antithrombotic agents .
Many heart failure patients with sinus rhythm take aspirin because coronary artery disease is the leading cause of heart failure .
Oral anticoagulants have become a st and ard in the management of heart failure with atrial fibrillation .
However , a question remains regarding the appropriateness of oral anticoagulants in heart failure with sinus rhythm .
This up date of a review previously published in 2012 aims to address this question .
OBJECTIVES To assess the effects of oral anticoagulant therapy versus antiplatelet agents for all-cause mortality , non-fatal cardiovascular events and risk of major bleeding in adults with heart failure ( either with reduced or preserved ejection fraction ) who are in sinus rhythm .