Elsevier

Canadian Journal of Cardiology

Volume 27, Issue 1, January–February 2011, Pages 74-90
Canadian Journal of Cardiology

Society guideline
Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: Prevention of Stroke and Systemic Thromboembolism in Atrial Fibrillation and Flutter

https://doi.org/10.1016/j.cjca.2010.11.007Get rights and content

Abstract

The stroke rate in atrial fibrillation is 4.5% per year, with death or permanent disability in over half. The risk of stroke varies from under 1% to over 20% per year, related to the risk factors of congestive heart failure, hypertension, age, diabetes, and prior stroke or transient ischemic attack (TIA). Major bleeding with vitamin K antagonists varies from about 1% to over 12% per year and is related to a number of risk factors. The CHADS2 index and the HAS-BLED score are useful schemata for the prediction of stroke and bleeding risks.

Vitamin K antagonists reduce the risk of stroke by 64%, aspirin reduces it by 19%, and vitamin K antagonists reduce the risk of stroke by 39% when directly compared with aspirin. Dabigatran is superior to warfarin for stroke prevention and causes no increase in major bleeding. We recommend that all patients with atrial fibrillation or atrial flutter, whether paroxysmal, persistent, or permanent, should be stratified for the risk of stroke and for the risk of bleeding and that most should receive antithrombotic therapy. We make detailed recommendations as to the preferred agents in various types of patients and for the management of antithrombotic therapies in the common clinical settings of cardioversion, concomitant coronary artery disease, surgical or diagnostic procedures with a risk of major bleeding, and the occurrence of stroke or major bleeding. Alternatives to antithrombotic therapies are briefly discussed.

Résumé

L'incidence annuelle de l'accident vasculaire cérébral (AVC) attribuable à la fibrillation auriculaire (FA) est de 4.5 %, causant la mort ou l'invalidité permanente dans plus de la moitié des cas. Cette incidence varie de moins de 1 % à plus de 20 % par année en fonction des facteurs de risque: insuffisance cardiaque, hypertension, âge, diabète et antécédents d'AVC ou d'ischémie cérébrale transitoire. Le risque d'hémorragie majeure sous traitement avec les antagonistes de la vitamine K varie entre 1 % et 12 % par année et s'avère lié à beaucoup d'autres facteurs. L'index de CHADS2 et le score HAS-BLED sont utiles pour la prédiction du risque d'AVC ou d'hémorragie. Le risque d'AVC est réduit de 64% avec le traitement aux antagonistes de la vitamine K et de 19% avec l'aspirine. Comparativement à l'aspirine, les antagonistes de la vitamine K réduisent ce risque de 39%. Le Dabigatran est supérieur à la warfarine pour la prévention du risque d'AVC sans augmentation du risque de saignement majeur. Nous recommandons que le risque d'AVC et de saignement majeur soit déterminé chez tous les patients avec FA ou flutter auriculaire (paroxystique, persistant ou permanent) et que la plupart reçoivent un traitement antithrombotique. Nos recommandations font état des agents antithrombotiques à favoriser dans les contextes cliniques de cardioversion, maladie cardiaque athérosclérotique concomitante, procédures diagnostiques ou chirurgicales avec risque d'hémorragie majeure associée, et en cas d'AVC ou de saignement majeur. Les alternatives au traitement antithrombotique sont brièvement discutées.

Section snippets

Risk factors and risk estimation schemes

In the 5 landmark randomized clinical trials of oral anticoagulants (OACs) among patients with nonvalvular atrial fibrillation (AF),1, 2, 3, 4, 5, 6 most of whom had no previous stroke or TIA, control subjects had a mean 4.5% annual incidence of stroke (range, 3%-7%), over half of which resulted in death or permanent disability.7 The mean annual incidence of the composite of stroke or other systemic emboli was 5% (range, 3%-7.4%). These subjects had no contraindications to warfarin and no

Oral vitamin K antagonists and antiplatelet agents

An overview7 of the initial 5 randomized trials of oral vitamin K antagonists compared with no treatment found the incidence of ischemic stroke was reduced from 4.5% per year to 1.4% per year (relative risk reduction [RRR] 68%; 95% CI, 50%-79%; P < .001). The rate of major hemorrhage with vitamin K antagonists was 1.3% per year vs 1% per year in controls. The most recent meta-analysis of such trials26 included 1 additional trial (of secondary prevention of stroke) and calculated an RRR of 64%

Risk of Hemorrhage

The efficacy of any antithrombotic therapy for the prevention of ischemic stroke must be balanced against the risk of major hemorrhage, particularly cerebral hemorrhage, which is often fatal. In each of the initial randomized trials of antithrombotic therapies, the principal outcome was the composite of ischemic stroke or systemic embolus. Although hemorrhage and the subsets of intracranial and intracerebral hemorrhage were generally reported, the net benefit for major clinical outcomes was not

Elderly patients

Advanced age (>75 years) has been consistently noted as a risk factor for both ischemic stroke and major hemorrhage, particularly intracranial. Hylek et al53 reported a series of 472 patients aged ≥65 years (153 patients aged ≥80 years), with electrocardiogram-verified AF, newly started on warfarin at the study institution, and managed by the on-site anticoagulation clinic. Anticoagulation control was very good, with 56% of person-time within the INR range of 2.0 to 3.0, 29% below 2.0, 11%

Coronary Artery Disease

The clinician managing a patient with AF must often deal with concomitant coronary artery disease in the settings of primary prevention, stable coronary artery disease, an acute coronary syndrome (ACS), or percutaneous coronary intervention (PCI). There is good evidence for the use of aspirin for primary prevention,74, 75 for aspirin or clopidogrel for stable coronary artery disease,76 for aspirin supplemented by clopidogrel for up to 1 year following an ACS (with or without PCI77, 78, 79, 80,

Invasive Procedures

When a patient receiving an OAC or antiplatelet agent is to undergo a surgical or diagnostic procedure that has a risk of major bleeding, the risk of a thromboembolic event occurring while the antithrombotic agent is reduced or stopped must be weighed against the goal of a reduced risk of major bleeding.94, 95 We suggest that such patients be stratified as to their risk of stroke, which can range from <1% to >20% per year. If there is a very low to moderate risk of stroke (CHADS2 ≤ 2), the

Stroke Management in Patients With AF

Among AF patients experiencing a stroke, the high rate of recurrence suggested that there was some urgency in initiating anticoagulation after the occurrence of embolic stroke. The International Stroke Trial Collaborative Group randomized 18,451 patients with ischemic stroke within 24 hours of onset to subcutaneous unfractionated heparin (5000 IU twice a day or 12,500 IU twice a day), aspirin 300 mg per day, both, or neither and maintained for 14 days or until prior hospital discharge.24 CT

Hemorrhage on OAC Therapy

The major determinants of OAC-induced bleeding are the INR, patient characteristics, and the concomitant use of drugs that interfere with hemostasis. The acute management of hemorrhage in a patient receiving OAC requires a graded response according to published guidelines,103 beginning with the immediate measurement of the INR, stopping the OAC, and assessment of the severity of hemorrhage. If there is major bleeding, vitamin K may be given intravenously, and if the bleeding is life

Pharmacogenomics

Eventually, pharmacogenomic algorithms may allow more rapid and safe determinations of initial warfarin dosage, particularly among patients whose warfarin requirements are particularly low or high.104 For the present, routine genetic testing is not advised in the management of therapy with a vitamin K antagonist.

Rhythm control and stroke risk

An overview105 of the 5 trials that compared the strategies of rhythm vs rate control in AF found a mortality of 13.0% with rate control vs 14.6% with rhythm control (odds ratio 0.87, P = .09). The rates of ischemic stroke and major hemorrhage were similar. The AFFIRM trial58 is by far the largest, mandated anticoagulation (INR 2.0-3.0) in the rate-control group (85% maintained warfarin) and strongly encouraged in the rhythm-control group, while allowing cessation at the physician's discretion

Acknowledgements

The authors are grateful to Grant Stotts, MD, FRCPC, for advice and liaison with the Canadian Stroke Network and to Marie-Josee Martin and Jody McCombe for final transcription of the manuscript. Administrative and technical support was provided by the Canadian Cardiovascular Society.

References (109)

  • R. Pisters et al.

    A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey

    Chest

    (2010)
  • A.L. Waldo et al.

    Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation

    J Am Coll Cardiol

    (2005)
  • S.B. Rowan et al.

    Trends in anticoagulation for atrial fibrillation in the U.S.: an analysis of the national ambulatory medical care survey database

    J Am Coll Cardiol

    (2007)
  • J. Mant et al.

    Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomized controlled trial

    Lancet

    (2007)
  • D. Poli et al.

    Bleeding risk during oral anticoagulation in patients older than 80 years

    J Am Coll Cardiol

    (2009)
  • L.B. Mitchell

    Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: prevention and treatment of atrial fibrillation following cardiac surgery

    Can J Cardiol

    (2011)
  • C.J. Bjerkelund et al.

    The efficacy of anticoagulant therapy in preventing embolism related to DC electrical conversion of atrial fibrillation

    Am J Cardiol

    (1969)
  • M. Berger et al.

    Timing of thromboembolic events after electrical cardioversion of atrial fibrillation or flutter: a retrospective analysis

    Am J Cardiol

    (1998)
  • W.J. Manning et al.

    Transesophageal echocardiographically facilitated early cardioversion from atrial fibrillation using short-term anticoagulation: final results of a prospective 4.5 year study

    J Am Coll Cardiol

    (1995)
  • M.M. Gallagher et al.

    Embolic complications of direct current cardioversion of atrial arrhythmias: association with low intensity of anticoagulation at the time of cardioversion

    J Am Coll Cardiol

    (2002)
  • I.G. Stiell et al.

    Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: management of recent-onset atrial fibrillation and flutter in the emergency department

    Can J Cardiol

    (2011)
  • A. Elhendy et al.

    Thromboembolic complications after electrical cardioversion in patients with atrial flutter

    Am J Med

    (2001)
  • E. Moreyra et al.

    Limitations of transesophageal echocardiography in the risk assessment of patients before nonanticoagulated cardioversion from atrial fibrillation and flutter: an analysis of pooled trials

    Am Heart J

    (1995)
  • S.R. Mehta et al.

    Effects of pretreatment with clopidogrel and aspirin followed by long-tern therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study

    Lancet

    (2001)
  • R.C. Becker et al.

    The primary and secondary prevention of coronary artery disease

    Chest

    (2008)
  • R.C. Becker et al.

    The primary and secondary prevention of coronary artery disease

    Chest

    (2008)
  • J.D. Douketis et al.

    The perioperative management of antithrombotic therapy

    Chest

    (2008)
  • G.W. Albers et al.

    Antithrombotic and thrombolytic therapy for ischemic stroke

    Chest

    (2008)
  • The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation

    N Engl J Med

    (1990)
  • M.D. Ezekowitz et al.

    Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation

    N Engl J Med

    (1992)
  • P. Petersen et al.

    Letter to editor

    N Engl J Med

    (1990)
  • Stroke Prevention in Atrial Fibrillation study: final results

    Circulation

    (1991)
  • Risk factors for stroke and efficiency of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials

    Arch Intern Med

    (1994)
  • P.A. Wolf et al.

    Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham Study

    Neurology

    (1978)
  • Independent predictors of stroke in patients with atrial fibrillation: a systematic review

    Neurology

    (2007)
  • Prevention of thromboembolism in atrial fibrillation: I. Clinical features of patients at risk

    Ann Intern Med

    (1992)
  • Prevention of thromboembolism in atrial fibrillation: II. Echocardiographic features of patients at risk

    Ann Intern Med

    (1992)
  • V. Fuster et al.

    ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines

    Circulation

    (2006)
  • B.F. Gage et al.

    Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation

    JAMA

    (2001)
  • B.F. Gage et al.

    Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin

    Circulation

    (2004)
  • Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation

    Stroke

    (2008)
  • A.J. Camm et al.

    Guidelines for the management of atrial fibrillation

    Eur Heart J

    (2010)
  • P. Petersen et al.

    Embolic complications in paroxysmal atrial fibrillation

    Stroke

    (1986)
  • P.A. Wolf et al.

    Duration of atrial fibrillation and eminence of stroke: the Framingham Study

    Stroke

    (1983)
  • Secondary prevention in non-rheumatic atrial fibrillation after transient ischemic attack or minor stroke

    Lancet

    (1993)
  • R. Saxena et al.

    Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and atrial fibrillation in the International Stroke Trial

    Stroke

    (2001)
  • R.G. Hart et al.

    Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation

    Ann Intern Med

    (2007)
  • R.G. Hart et al.

    Adjusted-dose warfarin versus aspirin for preventing stroke in patients with atrial fibrillation

    Ann Intern Med

    (2007)
  • Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study

    Lancet

    (1994)
  • A.L. Gullov et al.

    Fixed minidose warfarin and aspirin alone and in combination vs. adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study

    Arch Intern Med

    (1998)
  • Cited by (264)

    • Reversal of anticoagulation in neurosurgical and neurocritical care settings

      2021, Essentials of Evidence-Based Practice of Neuroanesthesia and Neurocritical Care
    • The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation

      2020, Canadian Journal of Cardiology
      Citation Excerpt :

      Although this risk is comparable with that of planned cardioversion in patients with AF of > 48 hours who receive OAC, these reports were limited by selection bias; describing low-risk patients who presented in a stable state early in the 48-hour window, with a significant proportion receiving OAC.339 Moreover, despite the significant selection bias the rate of stroke/systemic embolism substantially exceeded the established threshold for OAC initiation (1.5% per year or 0.12% per 30 days).351 More recent data specifically focused on patients who underwent cardioversion for AF of < 48 hours in the absence of OAC provide a more disquieting viewpoint.352-359

    View all citing articles on Scopus

    The disclosure information of the authors and reviewers is available from the CCS on the following Web sites: www.ccs.ca and www.ccsguidelineprograms.ca.

    This statement was developed following a thorough consideration of medical literature and the best available evidence and clinical experience. It represents the consensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific recommendations. These recommendations are aimed to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowing optimal care to patients and families, and can be subject to change as scientific knowledge and technology advance and as practice patterns evolve. The statement is not intended to be a substitute for physicians using their individual judgment in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, diagnostic and treatment options available and available resources. Adherence to these recommendations will not necessarily produce successful outcomes in every case.

    e

    For a complete listing of committee members, see Gillis AM, Skanes AC. Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: Implementing GRADE and Achieving Consensus. Can J Cardiol 2011;27:27-30.

    View full text