Prevention of Stroke in Patients with Atrial Fibrillation: The Role of New Antiarrhythmic and Antithrombotic Drugs

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is associated with increased cardiovascular mortality and morbidity, including stroke. Results: Rate or rhythm control and prevention of thromboembolism with oral anticoagulants are the main management objectives for patients with AF. Until recently, rhythm control studies did not show prevention of cardiovascular complications. However, dronedarone, a novel antiarrhythmic drug, has been shown to decrease stroke risk by 34% (p = 0.027). In addition, the Randomized Evaluation of Long-Term Anticoagulant Therapy trial showed significant stroke reductions with the anticoagulant dabigatran 150 mg b.i.d. compared with adjusted-dose warfarin (the results for dabigatran 110 mg b.i.d. were similar to warfarin). Conclusions: Novel antithrombotic agents and antiarrhythmic agents with cardiovascular prophylactic properties may enhance the management of stroke risk in patients with AF.

[1]  S. Connolly,et al.  Effect of dronedarone on cardiovascular events in atrial fibrillation. , 2009, The New England journal of medicine.

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

[3]  Stephan Willems,et al.  Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFNET-EHRA consensus conference 'research perspectives in AF'. , 2009, European heart journal.

[4]  S. Connolly,et al.  Analysis of Stroke in ATHENA: A Placebo-Controlled, Double-Blind, Parallel-Arm Trial to Assess the Efficacy of Dronedarone 400 mg BID for the Prevention of Cardiovascular Hospitalization or Death From Any Cause in Patients With Atrial Fibrillation/Atrial Flutter , 2009, Circulation.

[5]  M. Ezekowitz,et al.  Reducing stroke rates in patients with atrial fibrillation: how low can we go? , 2009, Circulation.

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

[7]  D. Singer,et al.  Effect of Age on Stroke Prevention Therapy in Patients With Atrial Fibrillation: The Atrial Fibrillation Investigators , 2009, Stroke.

[8]  P. Rothwell,et al.  Costs of Stroke Using Patient-Level Data: A Critical Review of the Literature , 2009, Stroke.

[9]  K. Kelly,et al.  Atrial fibrillation detected by mobile cardiac outpatient telemetry in cryptogenic TIA or stroke , 2008, Neurology.

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

[11]  A. Camm,et al.  Defining endpoints in clinical trials on atrial fibrillation , 2008 .

[12]  A. Camm,et al.  Rhythm Control versus Rate Control for Atrial Fibrillation and Heart Failure , 2009 .

[13]  Gary A. Ford,et al.  Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. , 2008, Cerebrovascular diseases.

[14]  R. de Caterina,et al.  Risks and Benefits of Oral Anticoagulation Compared With Clopidogrel Plus Aspirin in Patients With Atrial Fibrillation According to Stroke Risk: The Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE-W) , 2008, Stroke.

[15]  A. Capucci,et al.  Should we abandon the common practice of withholding oral anticoagulation in paroxysmal atrial fibrillation? , 2008, European heart journal.

[16]  V. Fuster,et al.  Economic Costs Associated with Atrial Fibrillation , 2008 .

[17]  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.

[18]  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.

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

[20]  S. Lévy,et al.  Guideline-adherent antithrombotic treatment is associated with improved outcomes compared with undertreatment in high-risk patients with atrial fibrillation. The Euro Heart Survey on Atrial Fibrillation. , 2007, American heart journal.

[21]  R. Sacco,et al.  Risk of Myocardial Infarction or Vascular Death After First Ischemic Stroke: The Northern Manhattan Study , 2007, Stroke.

[22]  J. Seward,et al.  Mortality trends in patients diagnosed with first atrial fibrillation: a 21-year community-based study. , 2007, Journal of the American College of Cardiology.

[23]  S. Willich,et al.  The impact of atrial fibrillation on the cost of stroke: the berlin acute stroke study. , 2007, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[24]  K. Channer,et al.  A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). , 2007, Age and ageing.

[25]  Giancarlo Agnelli,et al.  Efficacy and Safety of Anticoagulant Treatment in Acute Cardioembolic Stroke: A Meta-Analysis of Randomized Controlled Trials , 2007, Stroke.

[26]  D. Sherman.  Stroke Prevention in Atrial Fibrillation: Pharmacological Rate Versus Rhythm Control , 2007, Stroke.

[27]  T. Olsen,et al.  Reduced Poststroke Mortality in Patients With Stroke and Atrial Fibrillation Treated With Anticoagulants: Results From a Danish Quality-Control Registry of 22 179 Patients With Ischemic Stroke , 2007, Stroke.

[28]  E. Aliot,et al.  Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation. , 2006, European heart journal.

[29]  Samuel Wann,et al.  [Guidelines for the management of patients with atrial fibrillation. Executive summary]. , 2006, Revista espanola de cardiologia.

[30]  J. García-Rafanell,et al.  Prevention of stroke in patients with ischemic stroke or transient ischemic attack. , 2006, Stroke.

[31]  G. Guyatt,et al.  Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study , 2006, The Lancet Neurology.

[32]  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.

[33]  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.

[34]  Irene Katzan,et al.  Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the , 2006, Stroke.

[35]  R. Sacco,et al.  Recurrent stroke and cardiac risks after first ischemic stroke , 2006, Neurology.

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

[37]  V. Chair,et al.  Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the , 2006, Circulation.

[38]  F. Lombardi,et al.  Antithrombotic treatment in real-life atrial fibrillation patients: A report from the Euro Heart Survey on Atrial Fibrillation , 2006 .

[39]  H. Diener.  Stroke prevention using the oral direct thrombin inhibitor ximelagatran inpatients with nonvalvular atrial fibrillation. Pooled analysis from the SPORTIF III ad V studies. , 2006 .

[40]  Massimo Santini,et al.  Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers. , 2005, Journal of the American College of Cardiology.

[41]  R. Becker,et al.  Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. , 2005, Journal of the American College of Cardiology.

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

[43]  D. Reda,et al.  Amiodarone versus sotalol for atrial fibrillation. , 2005, The New England journal of medicine.

[44]  Palle Petersen,et al.  Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. , 2005, JAMA.

[45]  T. Truelsen,et al.  Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (The Copenhagen City Heart Study). , 2004, The American journal of cardiology.

[46]  A. Torbicki,et al.  Rate control vs rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study. , 2004, Chest.

[47]  Theodor Landis,et al.  Usefulness of Ambulatory 7-Day ECG Monitoring for the Detection of Atrial Fibrillation and Flutter After Acute Stroke and Transient Ischemic Attack , 2004, Stroke.

[48]  C. Israel,et al.  Long-term risk of recurrent atrial fibrillation as documented by an implantable monitoring device: implications for optimal patient care. , 2004, Journal of the American College of Cardiology.

[49]  A. John Camm,et al.  Clinical Relevance of Silent Atrial Fibrillation: Prevalence, Prognosis, Quality of Life, and Management , 2000, Journal of Interventional Cardiac Electrophysiology.

[50]  R. Sacco,et al.  The Northern Manhattan Study , 2004 .

[51]  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.

[52]  Yuchiao Chang,et al.  Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. , 2003, The New England journal of medicine.

[53]  Ralph B D'Agostino,et al.  A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. , 2003, JAMA.

[54]  U. Tebbe,et al.  Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. , 2003, Journal of the American College of Cardiology.

[55]  H. Crijns,et al.  A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. , 2002, The New England journal of medicine.

[56]  H. Crijns,et al.  A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation , 2002 .

[57]  A L Waldo,et al.  A comparison of rate control and rhythm control in patients with atrial fibrillation. , 2002, The New England journal of medicine.

[58]  Simon Stewart,et al.  A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study. , 2002, The American journal of medicine.

[59]  H. Adams.  Emergent Use of Anticoagulation for Treatment of Patients With Ischemic Stroke , 2002, Stroke.

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

[61]  Steven Shea,et al.  Race-Ethnic Disparities in the Impact of Stroke Risk Factors: The Northern Manhattan Stroke Study , 2001, Stroke.

[62]  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.

[63]  M. Glanz,et al.  The Sharer , 2000, Annals of Internal Medicine.

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

[65]  W. J. Hamilton,et al.  Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial , 1996, The Lancet.

[66]  P. Kowey,et al.  Atrial fibrillation, anticoagulation, and stroke. , 1996, American Journal of Cardiology.

[67]  F A Mathewson,et al.  The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study. , 1995, The American journal of medicine.

[68]  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.

[69]  P. Wolf,et al.  Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. , 1991, Stroke.

[70]  J Nyboe,et al.  Stroke incidence and risk factors for stroke in Copenhagen, Denmark. , 1988, Stroke.

[71]  A. Keren,et al.  Effect of Chronic Atrial Fibrillation on Regional Cerebral Blood Flow , 1980, Stroke.

[72]  A. Belanger,et al.  The Framingham study. , 1976, British medical journal.