1-49-02 Fixed low-dose warfarin alone or combined with aspirin and aspirin alone versus adjusted-dose warfarin for stroke prevention in atrial fibrillation. Second copenhagen atrial fibrillation, aspirin and anticoagulation study (AFASAK 2)

Gulløv, Annette Lemche; Koefoed, Birgitte Gade; Petersen, P.; Pedersen, Trine Sander; Boysen, Gudrun; Godtfredsen, John; Andersen, E

doi:10.1016/s0022-510x(97)85159-3

Cited by 11 publications

(22 citation statements)

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“…[7][8][9][10] This is not surprising because various studies (including the present study) of similar regimens of low-dose warfarin, aspirin, or combination aspirin/low-dose warfarin have not shown any significant effect on the elevated indices of thrombogenesis in patients with AF. For example, fixed ultralow-dose warfarin (1 mg) did not significantly reduce thrombogenesis or platelet activation in AF, 6 which is in keeping with subsequent results from the AFASAK 2 study.…”

Section: Discussionmentioning

confidence: 66%

“…For example, fixed ultralow-dose warfarin (1 mg) did not significantly reduce thrombogenesis or platelet activation in AF, 6 which is in keeping with subsequent results from the AFASAK 2 study. 7 The latter group also reported that after 3 months of therapy with fixed-dose warfarin (1.25 mg), the level of INR increased significantly from baseline in patients receiving warfarin in any dose but only dose-adjusted warfarin (INR 2.0 to 3.0) had a marked effect on F1ϩ2 levels, another index of thrombogenesis. 17 However, therapy with fixed minidose warfarin, combined minidose warfarin-aspirin, and aspirin alone did not significantly alter F1ϩ2 levels.…”

Section: Discussionmentioning

confidence: 92%

“…This was in keeping with the subsequent publication of the results from the second Copenhagen Atrial Fibrillation Aspirin and Anticoagulant Therapy Study (AFASAK 2) clinical trial. 7 We had hypothesized that the introduction of fixed lowdose warfarin regimens (2 mg) alone or in combination with aspirin (300 mg) could normalize hemostatic markers, namely plasma fibrin D-dimer (an index of thrombogenesis), plasminogen activator inhibitor-1 (PAI-1, an index of fibrinolysis), fibrinogen, and von Willebrand factor (vWf, an index of endothelial dysfunction), in a manner comparable to adjusted-dose warfarin (target INR 2.0 to 3.0). The present study was initiated before the premature termination of the third Stroke Prevention in Atrial Fibrillation Trial (SPAF III), the Minidose Warfarin (MIWAF) trial, the Primary Prevention of Arterial Thrombo-embolism in Non-rheumatic Atrial Fibrillation (PATAF) trial, and the Copenhagen AFASAK 2 trial of the effect of fixed aspirin-warfarin combination, conventional-dose warfarin, and aspirin regimens in patients with AF.…”

Section: R Ecent Clinical Trials Have Firmly Established That Adjustementioning

confidence: 99%

“…The present study was initiated before the premature termination of the third Stroke Prevention in Atrial Fibrillation Trial (SPAF III), the Minidose Warfarin (MIWAF) trial, the Primary Prevention of Arterial Thrombo-embolism in Non-rheumatic Atrial Fibrillation (PATAF) trial, and the Copenhagen AFASAK 2 trial of the effect of fixed aspirin-warfarin combination, conventional-dose warfarin, and aspirin regimens in patients with AF. [7][8][9][10] …”

Section: R Ecent Clinical Trials Have Firmly Established That Adjustementioning

confidence: 99%

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Effects of Fixed Low-Dose Warfarin, Aspirin-Warfarin Combination Therapy, and Dose-Adjusted Warfarin on Thrombogenesis in Chronic Atrial Fibrillation

Li‐Saw‐Hee

Blann

Lip

2000

Stroke

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Background and Purpose-Recent clinical trials have established that adjusted-dose warfarin (international normalized ratio [INR] 2.0 to 3.0) is highly effective in the reduction of ischemic stroke in patients with nonvalvular atrial fibrillation (AF). We hypothesized that the introduction of fixed low-dose warfarin alone or in combination with aspirin (300 mg) could normalize hemostatic markers, namely plasma fibrin D-dimer (an index of thrombogenesis), plasminogen activator inhibitor-1 (PAI-1, an index of fibrinolysis), fibrinogen, and von Willebrand factor (vWf, an index of endothelial dysfunction), in a manner comparable to adjusted-dose warfarin (target INR 2.0 to 3.0). Methods-Sixty-one patients with AF (44 men, meanϮSD age 64Ϯ19 years) who were not receiving any antithrombotic therapy were prospectively randomized into 1 of 3 treatment groups: warfarin (2 mg) (nϭ23; group 1), combination 1 mg warfarin plus 300 mg aspirin (nϭ21; group 2) or combination 2 mg warfarin plus 300 mg aspirin (nϭ17; group 3). Subjects from all 3 AF groups were matched for sex, age, and blood pressure. Blood samples were taken for sequential measurements for changes in plasma fibrin D-dimer, PAI-1, fibrinogen, and vWf before and at 2 and 8 weeks after randomization (phase 1). All patients were subsequently offered adjusted-dose warfarin therapy (phase 2), and an additional blood sample was taken 6 weeks later. Results-When pretreatment results were compared with those from 60 age-and sex-matched healthy control subjects in sinus rhythm, there were significant elevations in levels of fibrinogen (Pϭ0.025), vWf (PϽ0.0001), and fibrin D-dimer (PϽ0.0001) in patients with AF compared with control subjects. There were no significant changes in the levels of various indices measured after 2 and 8 weeks of therapy in all 3 groups, except for an increase in PAI-1 level (Pϭ0.024) in group 3. After 6 weeks of therapy with dose-adjusted warfarin (INR 2.0 to 3.0), there was a significant decrease in plasma fibrinogen (Pϭ0.023) and fibrin D-dimer (Pϭ0.0067) levels. There were no significant changes in the levels of PAI-1 (Pϭ0.198) or vWf (Pϭ0.33). Conclusions-The present results confirmed that high levels of vWf, fibrinogen, and fibrin D-dimer levels were present in patients with AF compared with control subjects. Moreover, the introduction of 300 mg aspirin plus low-dose warfarin (1 mg/d), low-dose warfarin alone (2 mg/d), or 300 mg aspirin plus low-dose warfarin (2 mg/d) did not significantly reduce any of the hemostatic markers studied (except PAI-1 levels), whereas conventional full-dose warfarin (INR 2.0 to 3.0) significantly reduced levels of fibrin D-dimer and fibrinogen. These results are in keeping with the disappointing ineffectiveness of low-intensity warfarin therapy, aspirin-warfarin combination, and ultralow-dose warfarin therapy in the recent prematurely terminated clinical trials and the established benefits of conventional adjusted-dose anticoagulation therapy. (Stroke. 2000;31:828-833.)

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 92%

Section: R Ecent Clinical Trials Have Firmly Established That Adjustementioning

confidence: 99%

Section: R Ecent Clinical Trials Have Firmly Established That Adjustementioning

confidence: 99%

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Effects of Fixed Low-Dose Warfarin, Aspirin-Warfarin Combination Therapy, and Dose-Adjusted Warfarin on Thrombogenesis in Chronic Atrial Fibrillation

Li‐Saw‐Hee

Blann

Lip

2000

Stroke

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“…[47][48][49] In the AFASAK II trial, the INR was not prolonged beyond the normal range by low-dose warfarin, and it is not included. 50 †One intracranial bleed per patient was counted. ‡INRs estimated from prothrombin times or thrombotest values.…”

Section: Anticoagulation Intensity and Central Nervous System Bleedingmentioning

confidence: 99%

Avoiding Central Nervous System Bleeding During Antithrombotic Therapy

Hart

Tonarelli

Pearce

2005

Stroke

329

212

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Background-Approximately 7000 intracerebral hemorrhages (ICHs) annually in the US are caused by use of antithrombotic therapies. We review the incidence, risk factors, and predictors of ICH in patients receiving long-term anticoagulation or antiplatelet therapy. Summary of Review-ICH rates range from 0.3% to 0.6% per year during oral anticoagulation in recent reports. Major risk factors are advanced patient age, elevated blood pressure, intensity of anticoagulation, and previous cerebral ischemia. Combining antiplatelet agents with anticoagulation and the combined use of aspirin plus clopidogrel appear to increase ICH risk. Modest blood pressure-lowering halves the frequency of ICH during antiplatelet therapy. Conclusion-ICH is an uncommon, but often fatal, complication of antithrombotic therapy that particularly afflicts patients with previous stroke. Recent data support that keeping international normalized ratio Յ3.0, control of hypertension, and avoiding the combination of aspirin with warfarin reduce its frequency. (Stroke. 2005;36:1588-1593.)

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Establishing an Optimal Therapeutic Range for Coumarins

O’Donnell¹,

Hirsh²

2004

Arch Intern Med

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1-49-02 Fixed low-dose warfarin alone or combined with aspirin and aspirin alone versus adjusted-dose warfarin for stroke prevention in atrial fibrillation. Second copenhagen atrial fibrillation, aspirin and anticoagulation study (AFASAK 2)

Cited by 11 publications

References 0 publications

Effects of Fixed Low-Dose Warfarin, Aspirin-Warfarin Combination Therapy, and Dose-Adjusted Warfarin on Thrombogenesis in Chronic Atrial Fibrillation

Effects of Fixed Low-Dose Warfarin, Aspirin-Warfarin Combination Therapy, and Dose-Adjusted Warfarin on Thrombogenesis in Chronic Atrial Fibrillation

Avoiding Central Nervous System Bleeding During Antithrombotic Therapy

Establishing an Optimal Therapeutic Range for Coumarins

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