title: D-dimer and factor VIIa in atrial fibrillation - prognostic values for cardiovascular events and effects of anticoagulation therapy. A RE-LY substudy.
abstract: Coagulation markers may improve monitoring the risk of stroke and bleeding in patients with atrial fibrillation (AF) during anticoagulant treatment. We examined baseline levels of D-dimer and their association with stroke, cardiovascular death and major bleeding in 6,202 AF patients randomised to dabigatran or warfarin in the RE-LY trial. The effects of treatment on serial levels of D-dimer and coagulation factor (F) VIIa in 2,567 patients were also analysed. Baseline D-dimer levels were related to the rate of stroke/systemic embolism (SEE) with 0.64 % in the lowest quartile (Q1, as reference) (D-dimer < 298 µg/l), 1.38 % Q2 (D-dimer 298-473 µg/l), 1.71 % Q3 (D-dimer 474-822 µg/l) and 2.00 % in Q4 (D-dimer > 822 µg/l) (p=0.0007). Similar associations were shown for cardiovascular death and major bleeding. Addition of baseline D-dimer to established clinical risk factors improved prediction of stroke/SEE, cardiovascular death and major bleeding (C-index increased from 0.66 to 0.68, 0.71 to 0.73 and 0.66 to 0.67, respectively). Dabigatran provided a greater reduction of D-dimer levels than warfarin regardless of baseline anticoagulant treatment. On-treatment levels of FVIIa were markedly reduced by warfarin (median 12.1-13.8 mU/ml) but significantly higher with dabigatran (median 39.4-49.0 mU/ml) at all-time points. Dabigatran is associated with greater reduction in D-dimer without the pronounced reduction of FVIIa seen with warfarin. These different effects on the coagulation system might explain the better efficacy and less intracranial bleeding observed with dabigatran compared with warfarin.
authors.affiliation: Prof. Agneta Siegbahn, Department of Medical Sciences, Clinical Chemistry, University Hospital, 751 85 Uppsala, Sweden, Tel.: +46 18 611 42 51, Fax: +46 18 55 25 62, E-mail: Agneta.Siegbahn@medsci.uu.se.
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.forename: Jonas
authors.initials: J
authors.lastname: Oldgren
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ezekowitz
authors.forename: Paul A
authors.initials: PA
authors.lastname: Reilly
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D000069604:Dabigatran / Q000627:therapeutic use; D004617:Embolism / Q000097:blood / Q000517:prevention & control; D015942:Factor VIIa / Q000378:metabolism*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D014859:Warfarin; D015942:Factor VIIa; D000069604:Dabigatran
keywords: Atrial fibrillation; D-dimer; FVIIa; anticoagulants; stroke