{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:03:27Z","timestamp":1781136207147,"version":"3.54.1"},"reference-count":17,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2000,4]]},"abstract":"<jats:p>\n            <jats:italic>Background and Purpose<\/jats:italic>\n            \u2014Recent 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).\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods<\/jats:italic>\n            \u2014Sixty-one patients with AF (44 men, mean\u00b1SD age 64\u00b119 years) who were not receiving any antithrombotic therapy were prospectively randomized into 1 of 3 treatment groups: warfarin (2 mg) (n=23; group 1), combination 1 mg warfarin plus 300 mg aspirin (n=21; group 2) or combination 2 mg warfarin plus 300 mg aspirin (n=17; 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.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Results<\/jats:italic>\n            \u2014When 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 (\n            <jats:italic>P<\/jats:italic>\n            =0.025), vWf (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0001), and fibrin D-dimer (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0001) 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 (\n            <jats:italic>P<\/jats:italic>\n            =0.024) 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 (\n            <jats:italic>P<\/jats:italic>\n            =0.023) and fibrin D-dimer (\n            <jats:italic>P<\/jats:italic>\n            =0.0067) levels. There were no significant changes in the levels of PAI-1 (\n            <jats:italic>P<\/jats:italic>\n            =0.198) or vWf (\n            <jats:italic>P<\/jats:italic>\n            =0.33).\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014The 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.\n          <\/jats:p>","DOI":"10.1161\/01.str.31.4.828","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T20:10:52Z","timestamp":1308341452000},"page":"828-833","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":76,"title":["Effects of Fixed Low-Dose Warfarin, Aspirin-Warfarin Combination Therapy, and Dose-Adjusted Warfarin on Thrombogenesis in Chronic Atrial Fibrillation"],"prefix":"10.1161","volume":"31","author":[{"given":"Foo Leong","family":"Li-Saw-Hee","sequence":"first","affiliation":[{"name":"From the Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, England."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Blann","sequence":"additional","affiliation":[{"name":"From the Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, England."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y. H.","family":"Lip","sequence":"additional","affiliation":[{"name":"From the Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, England."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1994.00420130036007"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-76-3-112-6-423"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90008-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)11475-1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","unstructured":"Lip GYH. Does atrial fibrillation confer a hypercoagulable state? Lancet. 1995; 346: 1313\u20131314.","DOI":"10.1016\/S0140-6736(95)92339-X"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.94.3.425"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.158.14.1513"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)03487-3"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","unstructured":"Vermeer F Langenberg M Hellemons BS Lodder J Schouten H van Ree JW Knottnerus JA. Primary prevention of arterial thrombo-embolism in non-rheumatic atrial fibrillation: results of the PATAF study. Eur Heart J. 1998;19(suppl):154. 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