Prevention of stroke in patients with atrial fibrillation

As the population ages, the prevalence of atrial fibrillation (AF) continues to rise. The most feared complication of this common cardiac arrhythmia is cardioembolic stroke. Strokes related to AF are associated with greater morbidity and mortality than ischemic strokes of most other etiologies and impose a substantial economic burden on healthcare systems around the world. Until recently, warfarin was the sole anticoagulant proven effective for stroke prevention patients with AF at elevated risk, but its narrow therapeutic margin and variable dose response limited clinical utility. The emergence of new anticoagulants that offer equal or superior efficacy, greater safety and the convenience of fixed oral dosing may make warfarin the less preferred option. This review provides an update on recent advancements in antithrombotic therapy for stroke prevention in patients with AF.

[1]  H. White,et al.  Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation : stroke prevention in atrial fibrillation II study. Commentary , 1994 .

[2]  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.

[3]  S. Yusuf,et al.  Newly identified events in the RE-LY trial. , 2010, The New England journal of medicine.

[4]  M. Rich,et al.  Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). , 2006, American heart journal.

[5]  B. Gage,et al.  Use and Effectiveness of Warfarin in Medicare Beneficiaries With Atrial Fibrillation , 2006, Stroke.

[6]  Gregory Y H Lip,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. , 2010, Chest.

[7]  D. Singer,et al.  Gender Differences in the Risk of Ischemic Stroke and Peripheral Embolism in Atrial Fibrillation: The AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) Study , 2005, Circulation.

[8]  A. Clemens,et al.  Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin. , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[9]  G. Hankey,et al.  Dabigatran Etexilate: A New Oral Thrombin Inhibitor , 2011, Circulation.

[10]  G. Wells,et al.  A clinical prediction rule to identify patients with atrial fibrillation and a low risk for stroke while taking aspirin , 2003 .

[11]  S. Olsson,et al.  Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial , 2003, The Lancet.

[12]  S. Hohnloser Stroke prevention versus bleeding risk in atrial fibrillation: a clinical dilemma. , 2011, Journal of the American College of Cardiology.

[13]  D. Singer,et al.  Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. , 2001, JAMA.

[14]  E. Unger,et al.  Anticoagulant options--why the FDA approved a higher but not a lower dose of dabigatran. , 2011, The New England journal of medicine.

[15]  Kenneth A Ellenbogen,et al.  2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. , 2011, Circulation.

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

[17]  G. Lip,et al.  Identifying Patients at High Risk for Stroke Despite Anticoagulation: A Comparison of Contemporary Stroke Risk Stratification Schemes in an Anticoagulated Atrial Fibrillation Cohort , 2010, Stroke.

[18]  M. Pfeffer,et al.  Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial , 2006, The Lancet.

[19]  Deepak L. Bhatt,et al.  Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis. , 2008, American heart journal.

[20]  S. Yusuf,et al.  Dabigatran versus warfarin in patients with atrial fibrillation. , 2009, The New England journal of medicine.

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

[22]  Robby Nieuwlaat,et al.  Revised A novel user-friendly score (HAS-BLED) to assess one-year risk of major bleeding in atrial fibrillation patients: The Euro Heart Survey , 2012 .

[23]  E. Antman,et al.  Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation-Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF-TIMI 48). , 2010, American heart journal.

[24]  Kenneth A Ellenbogen,et al.  2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on Dabigatran): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. , 2011, Circulation.

[25]  P. Kamphuisen,et al.  Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate: A Randomized, Placebo-Controlled, Crossover Study in Healthy Subjects , 2011, Circulation.

[26]  Kenneth A Ellenbogen,et al.  2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on dabigatran). A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. , 2011, Heart rhythm.

[27]  R B D'Agostino,et al.  Stroke severity in atrial fibrillation. The Framingham Study. , 1996, Stroke.

[28]  A. Sheikh,et al.  Living and dying with severe chronic obstructive pulmonary disease: multi-perspective longitudinal qualitative study , 2011, BMJ : British Medical Journal.

[29]  S. Yusuf,et al.  Dabigatran and Warfarin in Vitamin K Antagonist–Naive and –Experienced Cohorts With Atrial Fibrillation , 2010, Circulation.

[30]  M. Böhm,et al.  Atrial fibrillation and heart rate independently correlate to microalbuminuria in hypertensive patients. , 2009, European heart journal.

[31]  Gregory Y H Lip,et al.  Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. , 2011, Journal of the American College of Cardiology.

[32]  D. Singer,et al.  A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. , 2011, Journal of the American College of Cardiology.

[33]  I. Pragst,et al.  Beriplex P/N reverses bleeding in an acute renal injury model after dabigatran overdose in rabbits , 2012 .

[34]  G. Breithardt,et al.  Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. , 2011, The New England journal of medicine.

[35]  A. Brett Ximelagatran vs. Warfarin for Atrial Fibrillation , 2003 .

[36]  Gregory Y H Lip,et al.  Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. , 2010, Chest.

[37]  Gregory Y H Lip,et al.  Improving stroke risk stratification in atrial fibrillation. , 2010, The American journal of medicine.

[38]  A. Banerjee,et al.  Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: A modelling analysis based on a nationwide cohort study , 2011, Thrombosis and Haemostasis.

[39]  S. Sacco,et al.  Contribution of Atrial Fibrillation to Incidence and Outcome of Ischemic Stroke: Results From a Population-Based Study , 2005, Stroke.

[40]  R. Hart,et al.  Avoiding Central Nervous System Bleeding During Antithrombotic Therapy: Recent Data and Ideas , 2005, Stroke.

[41]  D. Atar,et al.  Apixaban versus warfarin in patients with atrial fibrillation. , 2011, The New England journal of medicine.

[42]  H. Adams Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation. , 2007, Current neurology and neuroscience reports.

[43]  Salim Yusuf,et al.  Effect of clopidogrel added to aspirin in patients with atrial fibrillation. , 2009, The New England journal of medicine.

[44]  A Laupacis,et al.  Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. , 1995, Archives of internal medicine.

[45]  J. Tolstrup,et al.  Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study , 2011, BMJ : British Medical Journal.

[46]  R. Beyth,et al.  Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. , 1998, The American journal of medicine.