Stroke and thromboembolism in atrial fibrillation: A systematic review of stroke risk factors, risk stratification schema and cost effectiveness data

The risk of stroke in atrial fibrillation (AF) needs to be assessed in each patient to determine the clinical and cost-effectiveness of thromboprophylaxis, with the aim of appropriate use of antithrombotic therapy. To achieve this, stroke risk factors in AF populations need to be identified and stroke risk stratification models have been devised on the basis of these risk factors. In this article, we firstly provide a systematic review of studies examining the attributable stroke risk of various clinical, demographic and echocardiographic patient characteristics in AF populations. Secondly, we performed a systematic review of published stroke risk stratification models, in terms of the results of the review of stroke risk factors and their ability to accurately discriminate between different levels of stroke risk. Thirdly, we review the health economic evidence relating to the cost-effectiveness of anticoagulation and antiplatelet therapy as thromboprophylaxis in AF patients. The studies included in the systematic review of stroke risk factors identified history of stroke or TIA, increasing age, hypertension and structural heart disease (left-ventricular dysfunction or hypertrophy) to be good predictors of stroke risk in AF patients. The evidence regarding diabetes mellitus, gender and other patient characteristics was less consistent. Three stroke risk stratification models were identified that were able to discriminate between different categories of stroke risk to at least 95% accuracy. Few models had addressed the cumulative nature of risk factors where a combination of risk factors would confer a greater risk than either factor alone. In patients at high risk of stroke, anticoagulation is cost effective, but not for those with a low risk of stroke. With the evidence available for stroke risk factors and the various alternative stroke risk stratification models, a review of these models in terms of the evidence on which they are devised and their performance in representative AF populations is important. The appropriate administration of thromboprophylaxis in AF patients would need to balance the risks and benefits of antithrombotic therapy with its cost-effectiveness.

[1]  V. Fuster,et al.  ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation , 2001 .

[2]  Predictors of Thromboembolism in Atrial Fibrillation: I. Clinical Features of Patients at Risk , 1992, Annals of Internal Medicine.

[3]  U. Ikeda,et al.  Mitral regurgitation reduces the risk of stroke in patients with nonrheumatic atrial fibrillation. , 1998, American heart journal.

[4]  G. Lowe,et al.  ABC of Atrial Fibrillation: ANTITHROMBOTIC TREATMENT FOR ATRIAL FIBRILLATION , 1996, BMJ.

[5]  Echocardiographic predictors of stroke in patients with atrial fibrillation: a prospective study of 1066 patients from 3 clinical trials. , 1998, Archives of internal medicine.

[6]  B. Gage,et al.  Selecting Patients With Atrial Fibrillation for Anticoagulation: Stroke Risk Stratification in Patients Taking Aspirin , 2004, Circulation.

[7]  A R Feinstein,et al.  Risk for systemic embolization of atrial fibrillation without mitral stenosis. , 1990, The American journal of cardiology.

[8]  J. Finsterer,et al.  Mortality and rate of stroke or embolism in atrial fibrillation during long‐term follow‐up in the embolism in left atrial thrombi (ELAT) study , 2004, Clinical cardiology.

[9]  M. Rich,et al.  Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. , 2001, JAMA.

[10]  Daniel Levy,et al.  Arrhythmias: abstractA risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community. The Framingham Heart Study☆ , 2003 .

[11]  Predictors of Thromboembolism in Atrial Fibrillation: II. Echocardiographic Features of Patients at Risk , 1992, Annals of Internal Medicine.

[12]  R. Cheung Patients with nonvalvular atrial fibrillation at low risk of stroke during treatment with aspirin: Stroke Prevention in Atrial Fibrillation III Study. The SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators. , 1998, JAMA.

[13]  Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. , 1994, Archives of internal medicine.

[14]  A. Laupacis,et al.  A clinical prediction rule to identify patients with atrial fibrillation and a low risk for stroke while taking aspirin. , 2003, Archives of internal medicine.

[15]  D. Singer,et al.  Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. , 2004, Chest.

[16]  J. Halperin,et al.  Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. , 2000, Journal of the American College of Cardiology.

[17]  D. Macaulay,et al.  Atrial fibrillation in general practice: how useful is echocardiography in selection of suitable patients for anticoagulation? , 1999, The British journal of general practice : the journal of the Royal College of General Practitioners.

[18]  S. Pauker,et al.  Making decisions about antithrombotic therapy in heart disease: decision analytic and cost-effectiveness issues. , 1995, Chest.

[19]  L. Pearce Risk factors for thromboembolism during aspirin therapy in patients with atrial fibrillation: The stroke prevention in atrial fibrillation study. , 1995, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[20]  V. Fuster,et al.  ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary 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 and Policy Conference , 2001, Circulation.

[21]  J. Senges,et al.  Risk of thromboembolic events in patients with atrial flutter. , 1998, The American journal of cardiology.

[22]  R. D. Murray,et al.  Role of transesophageal echocardiography-guided cardioversion of patients with atrial fibrillation. , 2001, Journal of the American College of Cardiology.

[23]  Steven J Edwards,et al.  Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular atrial fibrillation: a systematic review and meta-analysis. , 2006, Thrombosis research.

[24]  M. Aguilar,et al.  Meta-analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrial Fibrillation , 2007, Annals of Internal Medicine.

[25]  Silvia G Priori,et al.  ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: 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 (Writing Commit , 2006, Journal of the American College of Cardiology.

[26]  李永军,et al.  Atrial Fibrillation , 1999 .

[27]  D. Levy,et al.  Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. , 1998, Circulation.

[28]  C. Lau,et al.  Transient atrial fibrillation complicating acute inferior myocardial infarction: implications for future risk of ischemic stroke. , 2007, Chest.

[29]  A. Mcguire,et al.  Cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation in the primary prevention of ischemic stroke. , 1998, Stroke.

[30]  H. Inoue,et al.  Risk factors for thromboembolism in patients with paroxysmal atrial fibrillation. , 2000, The American journal of cardiology.

[31]  S. Ryu,et al.  Carotid Artery Stenosis in Ischemic Stroke Patients with Nonvalvular Atrial Fibrillation , 2002, Cerebrovascular Diseases.

[32]  D. Singer,et al.  Risk factors for stroke in patients with nonrheumatic atrial fibrillation: a case-control study. , 1991, The American journal of medicine.

[33]  R. Thomson,et al.  Decision analysis and guidelines for anticoagulant therapy to prevent stroke in patients with atrial fibrillation , 2000, The Lancet.

[34]  N. Desbiens Deciding on Anticoagulating the Oldest Old with Atrial Fibrillation: Insights from Cost‐Effectiveness Analysis , 2002, Journal of the American Geriatrics Society.

[35]  J. Kastrup,et al.  Risk factors for thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. , 1990 .

[36]  W. Aronow,et al.  Risk factors for thromboembolic stroke in elderly patients with chronic atrial fibrillation. , 1989, The American journal of cardiology.

[37]  B. Norrving,et al.  Cost effectiveness of primary stroke prevention in atrial fibrillation: Swedish national perspective. , 1992, BMJ.

[38]  Susan Regan,et al.  Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation , 2007, Circulation.

[39]  A. Algra,et al.  Predictors of major vascular events in patients with a transient ischemic attack or minor ischemic stroke and with nonrheumatic atrial fibrillation. European Atrial Fibrillation Trial (EAFT) Study Group. , 1995, Stroke.

[40]  G. Lip,et al.  Antithrombotic therapy for atrial fibrillation , 2002, BMJ : British Medical Journal.

[41]  Yuchiao Chang,et al.  Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? , 2003, JAMA.

[42]  D K Owens,et al.  Cost-effectiveness of warfarin and aspirin for prophylaxis of stroke in patients with nonvalvular atrial fibrillation. , 1995, JAMA.

[43]  W. Aronow,et al.  Risk factors for new thromboembolic stroke in patients > or = 62 years of age with chronic atrial fibrillation. , 1998, The American journal of cardiology.

[44]  R McBride,et al.  Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. , 1999, Stroke.

[45]  G. Lip,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 randomised controlled trial , 2007, The Lancet.

[46]  T. Iwasaka,et al.  Mild mitral regurgitation was associated with increased prevalence of thromboembolic events in patients with nonrheumatic atrial fibrillation. , 2000, International journal of cardiology.

[47]  J. Halperin,et al.  Assessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation. , 2000, The American journal of medicine.

[48]  G. Lip,et al.  Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review. , 2007, QJM : monthly journal of the Association of Physicians.

[49]  Samuel Wann,et al.  ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-executive summary: 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 (Writing Committ , 2006, European heart journal.

[50]  G. Lip,et al.  Additive Role of Plasma von Willebrand Factor Levels to Clinical Factors for Risk Stratification of Patients With Atrial Fibrillation , 2006, Stroke.

[51]  Robert Safford,et al.  Asymptomatic atrial fibrillation: demographic features and prognostic information from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. , 2005, American heart journal.

[52]  Kamakshi Lakshminarayan,et al.  Atrial Fibrillation and Stroke in the General Medicare Population: A 10-Year Perspective (1992 to 2002) , 2006, Stroke.