This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (147)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Thrombolysis  • Neurology  • Cardiovascular System  • Arrhythmias  • Alert me on articles by topic  Social Bookmarking   What's this?

Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study

Annette Lemche Gulløv, MD; Birgitte Gade Koefoed, MD; Palle Petersen, MD, DMSc; Trine Sander Pedersen, MD; Ellen Damgaard Andersen, MD; John Godtfredsen, MD, DMSc; Gudrun Boysen, MD, DMSc

Arch Intern Med. 1998;158:1513-1521.

Background  Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation, many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients.

Methods  The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study was a randomized, controlled trial examining the following therapies: warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; and aspirin, 300 mg/d. These were compared with adjusted-dose warfarin therapy (international normalized ratio of prothrombin time [INR], 2.0-3.0). Stroke or a systemic thromboembolic event was the primary outcome event. Transient ischemic attack, acute myocardial infarction, and death were secondary events. Data were handled as survival data, and risk factors were identified using the Cox proportional hazards model. The trial was scheduled for 6 years from May 1, 1993, but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study, our trial was prematurely terminated on October 2, 1996.

Results  We included 677 patients (median age, 74 years). The cumulative primary event rate after 1 year was 5.8% in patients receiving minidose warfarin; 7.2%, warfarin plus aspirin; 3.6%, aspirin; and 2.8%, adjusted-dose warfarin (P=.67). After 3 years, no difference among the groups was seen. Major bleeding events were rare.

Conclusions  Although the difference was insignificant, adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment. The results do not justify a change in the current recommendation of adjusted-dose warfarin (INR, 2.0-3.0) for stroke prevention in atrial fibrillation.

From the Copenhagen General Practitioners Laboratory, (Drs Gulløv, Koefoed, Pedersen, and Andersen); the Division of Stroke, Medical Center, Hvidovre University Hospital (Dr Petersen); the Department of Cardiology, Herlev University Hospital (Dr Godtfredsen); and the Department of Neurology, Bispebjerg University Hospital (Dr Boysen), Copenhagen, Denmark.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

Choice of Antithrombotic Therapy for Stroke Prevention in Atrial Fibrillation: Warfarin, Aspirin, or Both?
Gregory W. Albers
Arch Intern Med. 1998;158(14):1487-1491.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Does the Combination of Warfarin and Aspirin Have a Place in Secondary Stroke Prevention?: No
Fisher
Stroke 2009;40:1944-1945.
FULL TEXT  

Effect of Age on Stroke Prevention Therapy in Patients With Atrial Fibrillation: The Atrial Fibrillation Investigators
van Walraven et al.
Stroke 2009;40:1410-1416.
ABSTRACT | FULL TEXT  

Warfarin for the prevention of systemic embolism in patients with non-valvular atrial fibrillation: a meta-analysis
Andersen et al.
Heart 2008;94:1607-1613.
ABSTRACT | FULL TEXT  

Anticoagulation Control and Prediction of Adverse Events in Patients With Atrial Fibrillation: A Systematic Review
Wan et al.
Circ Cardiovasc Qual Outcomes 2008;1:84-91.
ABSTRACT | FULL TEXT  

Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Ansell et al.
Chest 2008;133:160S-198S.
ABSTRACT | FULL TEXT  

Hemorrhagic Complications of Anticoagulant and Thrombolytic Treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Schulman et al.
Chest 2008;133:257S-298S.
ABSTRACT | FULL TEXT  

Antithrombotic Therapy in Atrial Fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Singer et al.
Chest 2008;133:546S-592S.
ABSTRACT | FULL TEXT  

Dual Antithrombotic Therapy Increases Severe Bleeding Events in Patients With Stroke and Cardiovascular Disease: A Prospective, Multicenter, Observational Study
Toyoda et al.
Stroke 2008;39:1740-1745.
ABSTRACT | FULL TEXT  

Use of Anticoagulation in Elderly Patients with Atrial Fibrillation Who Are at Risk for Falls
Garwood and Corbett
The Annals of Pharmacotherapy 2008;42:523-532.
ABSTRACT | FULL TEXT  

Outcome parameters for trials in atrial fibrillation: executive summary: Recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork (AFNET) and the European Heart Rhythm Association (EHRA)
Kirchhof et al.
Eur Heart J 2007;28:2803-2817.
ABSTRACT | FULL TEXT  

ASHP Therapeutic Position Statement on Antithrombotic Therapy in Chronic Atrial Fibrillation
Nutescu
Am J Health Syst Pharm 2007;64:2281-2291.
FULL TEXT  

Outcome parameters for trials in atrial fibrillation: Recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork and the European Heart Rhythm Association
Kirchhof et al.
Europace 2007;9:1006-1023.
ABSTRACT | FULL TEXT  

Adjusted-Dose Warfarin versus Aspirin for Preventing Stroke in Patients with Atrial Fibrillation
Hart et al.
ANN INTERN MED 2007;147:590-592.
FULL TEXT  

Meta-analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrial Fibrillation
Hart et al.
ANN INTERN MED 2007;146:857-867.
ABSTRACT | FULL TEXT  

Frequency of adverse events in patients with poor anticoagulation: a meta-analysis
Oake et al.
CMAJ 2007;176:1589-1594.
ABSTRACT | FULL TEXT  

Warfarin and Antiplatelet Combination Use Among Commercially Insured Patients Enrolled in an Anticoagulation Management Service
Johnson et al.
Chest 2007;131:1500-1507.
ABSTRACT | FULL TEXT  

The Influence of Patient Adherence on Anticoagulation Control With Warfarin: Results From the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study
Kimmel et al.
Arch Intern Med 2007;167:229-235.
ABSTRACT | FULL TEXT  

Newly Detected Atrial Fibrillation and Compliance With Antithrombotic Guidelines
Glazer et al.
Arch Intern Med 2007;167:246-252.
ABSTRACT | FULL TEXT  

Combined Aspirin-Oral Anticoagulant Therapy Compared With Oral Anticoagulant Therapy Alone Among Patients at Risk for Cardiovascular Disease: A Meta-analysis of Randomized Trials
Dentali et al.
Arch Intern Med 2007;167:117-124.
ABSTRACT | FULL TEXT  

Mixed comparison of stroke prevention treatments in individuals with nonrheumatic atrial fibrillation.
Cooper et al.
Arch Intern Med 2006;166:1269-1275.
ABSTRACT | FULL TEXT  

Effect of Study Setting on Anticoagulation Control: A Systematic Review and Metaregression
van Walraven et al.
Chest 2006;129:1155-1166.
ABSTRACT | FULL TEXT  

Percutaneous Left Atrial Appendage Transcatheter Occlusion (PLAATO System) to Prevent Stroke in High-Risk Patients With Non-Rheumatic Atrial Fibrillation: Results From the International Multi-Center Feasibility Trials
Ostermayer et al.
J Am Coll Cardiol 2005;46:9-14.
ABSTRACT | FULL TEXT  

Avoiding Central Nervous System Bleeding During Antithrombotic Therapy: Recent Data and Ideas
Hart et al.
Stroke 2005;36:1588-1593.
ABSTRACT | FULL TEXT  

Rate Control Is Preferable to Rhythm Control in the Majority of Patients With Atrial Fibrillation
Falk
Circulation 2005;111:3141-3150.
FULL TEXT  

Direct thrombin inhibitors: novel antithrombotics on the horizon in the thromboprophylactic management of atrial fibrillation
Katira et al.
Postgrad. Med. J. 2005;81:370-375.
ABSTRACT | FULL TEXT  

Current status of stroke prevention in patients with atrial fibrillation
Bath et al.
Eur Heart J Suppl 2005;7:C12-C18.
ABSTRACT | FULL TEXT  

Indication for antithrombotic therapy for atrial fibrillation: reconciling the guidelines with clinical practice
Emmerich et al.
Eur Heart J Suppl 2005;7:C28-C33.
ABSTRACT | FULL TEXT  

Costs and Effectiveness of Ximelagatran for Stroke Prophylaxis in Chronic Atrial Fibrillation
O'Brien and Gage
JAMA 2005;293:699-706.
ABSTRACT | FULL TEXT  

Warfarin Anticoagulation and Outcomes in Patients With Atrial Fibrillation: A Systematic Review and Metaanalysis
Reynolds et al.
Chest 2004;126:1938-1945.
ABSTRACT | FULL TEXT  

Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: A randomized multicenter study
Perez-Gomez et al.
J Am Coll Cardiol 2004;44:1557-1566.
ABSTRACT | FULL TEXT  

Selecting Patients With Atrial Fibrillation for Anticoagulation: Stroke Risk Stratification in Patients Taking Aspirin
Gage et al.
Circulation 2004;110:2287-2292.
ABSTRACT | FULL TEXT  

The Pharmacology and Management of the Vitamin K Antagonists: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Ansell et al.
Chest 2004;126:204S-233S.
ABSTRACT | FULL TEXT  

Hemorrhagic Complications of Anticoagulant Treatment: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Levine et al.
Chest 2004;126:287S-310S.
ABSTRACT | FULL TEXT  

Antithrombotic Therapy in Atrial Fibrillation: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Singer et al.
Chest 2004;126:429S-456S.
ABSTRACT | FULL TEXT  

Anticoagulation in the Elderly
Dowd
Journal of Pharmacy Practice 2004;17:94-102.
ABSTRACT  

Establishing an Optimal Therapeutic Range for Coumarins: Filling in the Gaps
O'Donnell and Hirsh
Arch Intern Med 2004;164:588-590.
FULL TEXT  

Management of Newly Detected Atrial Fibrillation: A Clinical Practice Guideline from the American Academy of Family Physicians and the American College of Physicians
Snow et al.
ANN INTERN MED 2003;139:1009-1017.
ABSTRACT | FULL TEXT  

Management of Atrial Fibrillation: Review of the Evidence for the Role of Pharmacologic Therapy, Electrical Cardioversion, and Echocardiography
McNamara et al.
ANN INTERN MED 2003;139:1018-1033.
ABSTRACT | FULL TEXT  

Anticoagulation in atrial fibrillation: what is certain and what is to come
Villani et al.
Eur Heart J Suppl 2003;5:H45-H50.
ABSTRACT  

American Heart Association/American College of Cardiology Foundation guide to warfarin therapy
Hirsh et al.
J Am Coll Cardiol 2003;41:1633-1652.
FULL TEXT  

A Clinical Prediction Rule to Identify Patients With Atrial Fibrillation and a Low Risk for Stroke While Taking Aspirin
van Walraven et al.
Arch Intern Med 2003;163:936-943.
ABSTRACT | FULL TEXT  

American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy
Hirsh et al.
Circulation 2003;107:1692-1711.
FULL TEXT  

Oral Anticoagulants vs Aspirin in Nonvalvular Atrial Fibrillation: An Individual Patient Meta-analysis
van Walraven et al.
JAMA 2002;288:2441-2448.
ABSTRACT | FULL TEXT  

Management of the Older Person With Atrial Fibrillation
Aronow
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2002;57:M352-363.
ABSTRACT | FULL TEXT  

Balancing the Risks of Stroke and Upper Gastrointestinal Tract Bleeding in Older Patients With Atrial Fibrillation
Man-Son-Hing and Laupacis
Arch Intern Med 2002;162:541-550.
ABSTRACT | FULL TEXT  

Warfarin Therapy for an Octogenarian Who Has Atrial Fibrillation
Gage et al.
ANN INTERN MED 2001;134:465-474.
ABSTRACT | FULL TEXT  

Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation
Taylor et al.
BMJ 2001;322:321-326.
ABSTRACT | FULL TEXT  

Hemorrhagic Complications of Anticoagulant Treatment
Levine et al.
Chest 2001;119 :108S-121S.
FULL TEXT  

Antithrombotic Therapy in Atrial Fibrillation
Albers et al.
Chest 2001;119 :194S-206S.
FULL TEXT  

Antithrombotic Therapy To Prevent Stroke in Patients with Atrial Fibrillation
Hart and Pearce
ANN INTERN MED 2000;132:841-842.
FULL TEXT  

Effects of Fixed Low-Dose Warfarin, Aspirin-Warfarin Combination Therapy, and Dose-Adjusted Warfarin on Thrombogenesis in Chronic Atrial Fibrillation
Li-Saw-Hee et al.
Stroke 2000;31:828-833.
ABSTRACT | FULL TEXT  

Aspirin
Awtry and Loscalzo
Circulation 2000;101:1206-1218.
FULL TEXT  

Warfarin Use among Ambulatory Patients with Nonvalvular Atrial Fibrillation: The AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study
Go et al.
ANN INTERN MED 1999;131:927-934.
ABSTRACT | FULL TEXT  

Atrial Fibrillation and Thromboembolism: A Decade of Progress in Stroke Prevention
Hart and Halperin
ANN INTERN MED 1999;131:688-695.
ABSTRACT | FULL TEXT  

Antithrombotic Therapy To Prevent Stroke in Patients with Atrial Fibrillation: A Meta-Analysis
Hart et al.
ANN INTERN MED 1999;131:492-501.
ABSTRACT | FULL TEXT  

State-of-the-Art Review: Warfarin Therapy: A Review of the Literature Since the Fifth American College of Chest Physicians' Consensus Conference on Antithrombotic Therapy
Lodwick
CLIN APPL THROMB HEMOST 1999;5:208-215.
 

Managing atrial fibrillation in elderly people
Lancaster et al.
BMJ 1999;319:452a-452.
FULL TEXT  

Bleeding During Warfarin and Aspirin Therapy in Patients With Atrial Fibrillation: The AFASAK 2 Study
Gullov et al.
Arch Intern Med 1999;159:1322-1328.
ABSTRACT | FULL TEXT  

Factors Associated With Ischemic Stroke During Aspirin Therapy in Atrial Fibrillation : Analysis of 2012 Participants in the SPAF I–III Clinical Trials
Hart et al.
Stroke 1999;30:1223-1229.
ABSTRACT | FULL TEXT  

Preventing Stroke in Patients With Atrial Fibrillation
Ezekowitz and Levine
JAMA 1999;281:1830-1835.
ABSTRACT | FULL TEXT  

Warfarin vs Aspirin and AFASAK 2
Bloom et al.
Arch Intern Med 1999;159:1010-1011.
FULL TEXT  

Choice of Antithrombotic Therapy for Stroke Prevention in Atrial Fibrillation: Warfarin, Aspirin, or Both?
Albers
Arch Intern Med 1998;158:1487-1491.
FULL TEXT