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Thromb Haemost 2016; 115(05): 921-930
DOI: 10.1055/s-0037-1615530
Coagulation and Fibrinolysis
Schattauer GmbH

D-dimer and factor VIIa in atrial fibrillation – prognostic values for cardiovascular events and effects of anticoagulation therapy

A RE-LY substudy
Agneta Siegbahn
1   Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
2   Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
,
Jonas Oldgren
2   Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
3   Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
,
Ulrika Andersson
2   Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
,
Michael D. Ezekowitz
4   Lankenau Institute for Medical Research and the Heart Center, Wynnewood, Pennsylvania, USA
,
Paul A. Reilly
5   Boehringer Ingelheim Pharmaceuticals, Ridgefield, Conneticut, USA
,
Stuart J. Connolly
6   Population Health Research Institute, Hamilton, Ontario, Canada
,
Salim Yusuf
6   Population Health Research Institute, Hamilton, Ontario, Canada
,
Lars Wallentin
2   Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
3   Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
,
John W. Eikelboom
6   Population Health Research Institute, Hamilton, Ontario, Canada
› Author Affiliations Financial Support: The RE-LY trial was funded by Boehringer Ingelheim Pharmaceuticals.
Further Information

Publication History

Received: 02 July 2015

Accepted after major revision: 03 January 2015

Publication Date:
29 December 2017 (online)

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Summary

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. Ontreatment 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.

Clinical Trial Registration: NCT00262600 (www.clinicaltrials.gov).

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Atrial fibrillation - anticoagulants - D-dimer - FVIIa - stroke

 

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