Copenhagen Atrial Fibrillation, Aspirin and Anticoagulation II (1997)


Prevention of VTE in chronic non-valvular AF

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To investigate the antithrombotic effects of a fixed minidose warfarin alone or in combination with ASA, of conventional dose-adjusted warfarin and of ASA alone in patients with chronic non-valvular AF

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Trial design

Randomized, controlled phase III study with parallel groups
Active treatment: warfarin fixed low dose 1.25 mg/d (n=167)
Control treatment: warfarin fixed low dose 1.25 mg/d + ASA 300 mg once daily (n=171) or ASA 300 mg once daily (n=169) or dose-adjusted warfarin to target INR 2.0–3.0 (n=170)

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Primary endpoint: stroke (ischemic or hemorrhagic) or a systemic thromboembolic event
Secondary endpoint: transient ischemic attack, acute myocardial infarction, and death

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Trial participants

677 patients (mean age 74 years), with chronic non-rheumatic AF, documented twice using electrocardiography (ECG), with an interval of at least 1 month

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Efficacy outcome: 39 primary thromboembolic events occurred in patients receiving treatment: 12 with minidose warfarin, 12 with warfarin plus ASA, 8 with ASA, and 7 with adjusted dose warfarin. The cumulative primary event rate after 1 year was 5.8% in patients receiving minidose warfarin, 7.2% with warfarin plus ASA, 3.6% with ASA alone, and 2.8% with adjusted-dose warfarin; differences between groups were not significant (p=0.67). After 3 years of treatment, there was no difference between the groups
Safety outcome: On treatment, 47 patients had a secondary adverse event: 12 with minidose warfarin, 8 with warfarin plus ASA, 13 with ASA, and 14 with dose-adjusted warfarin. The cumulative mortality after 3 years was 3.9% in patients receiving minidose warfarin, 5.9% with warfarin plus ASA, 13.4% with ASA alone, and 10.3% with dose-adjusted warfarin (p=0.27). The cumulative rate of any bleeding was significantly higher in patients receiving dose-adjusted warfarin than in other groups (p=0.003).

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Efficacy: There was no significant difference in the frequency of stroke, systemic thromboembolic events, myocardial infarction, TIA, or death between the groups. Although the difference was not significant, dose-adjusted warfarin seemed superior to minidose warfarin and to warfarin plus ASA after 1 year of treatment
Safety: Major bleeding events were rare in all groups. The higher rate of bleeding with dose-adjusted warfarin was ascribed only to a higher rate of minor bleeding

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Gulløv AL, Koefoed BG, Petersen P, Pedersen TS, Andersen ED, Godtfredsen J, Boysen G. 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;158:1513-1521

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Corresponding author

Anette Lemche Gulløv, MD, Glostrup Hospital, Departement of Rheuma­tology U, Glostrup Ringvej, DK-2600 Glostrup, Denmark, e-mail:

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