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D-dimer levels predict ischemic and hemorrhagic outcomes after acute myocardial infarction: a HORIZONS-AMI biomarker substudy

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Abstract

D-dimer is a product of cross linked fibrin degradation and is a measure of the amount of fibrin turnover. As such, D-dimer might be of utility in the prediction of both thrombotic and hemorrhagic events. Therefore, the aim of the present study was to evaluate whether elevated D-dimer levels on admission and at discharge could predict subsequent ischemic and hemorrhagic events in patients with acute myocardial infarction (AMI). D-dimer was measured on admission and at discharge in 461 out of a total of 3,602 patients in the HORIZONS-AMI trial, as part of the formal prespecified biomarker substudy. The predictive value for major adverse cardiovascular events (MACE) and non-CABG major bleeding after 3 year follow up was investigated by stratifying patients in groups of D-dimer level and comparing event rates using Kaplan–Meier and calculating hazard ratios using Cox proportional hazards models. D-dimer levels ≥ 0.71 μg/mL on admission were associated with an adjusted hazard ratio of 2.58 for MACE (p = 0.0014) and 4.61 for major bleeding (p = 0.0018). A discharge D-dimer level ≥ 1.26 μg/mL was associated with a higher risk for MACE by univariate analysis (HR 1.88, p = 0.037), but lost its significance after multivariate adjustment (HR 1.77, p = 0.070). High D-dimer levels on admission were associated with a higher risk of MACE and non-CABG major bleeding in STEMI patients undergoing pPCI.

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Abbreviations

PCI:

Percutaneous coronary intervention

AMI:

Acute myocardial infarction

CABG:

Coronary artery bypass grafting

UFH:

Unfractionated heparin

GPI:

Glycoprotein IIb/IIIa inhibitor

HORIZONS-AMI:

Harmonizing outcomes with revascularization and stents in acute myocardial infarction trial

TIMI:

Thrombolysis in myocardial infarction

MACE:

Major adverse cardiovascular events

PES:

Paclitaxel-eluting stent

BMS:

Bare metal stent

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Acknowledgments

The HORIZONS-AMI trial was supported by the Cardiovascular Research Foundation, with grant support from Boston Scientific and the Medicines Company.

Conflict of interest

The HORIZONS-AMI trial was supported by the Cardiovascular Research Foundation, with grant support from Boston Scientific and the Medicines Company. Dr. Stone has served as a consultant to the Medicines Company and Boston Scientific. Dr. Dangas and Dr. Mehran have received speaker grants from Sanofi Aventis, Bristol-Meiers Squibb, The Medicines Co, Eli Lilly, Daiichi Sankyo, and honoraria from Astra Zeneca, Johnson & Johnson, and Abbott Vascular. Dr. Witzenbichler has received lecture honoraria from Boston Scientific and The Medicines Company. Dr. Witkowski has received honoraria from Medtronic, Abbott Vascular and Eli Lilly. Dr. Guagliumi has served as a consultant to Boston Scientific and St. Jude Medical and is receiving grant support from Abbott Vascular, Medtronic, Boston Scientific and St. Jude Medical. The other authors report no conflicts.

Author information

Authors and Affiliations

  1. Cardiovascular Research Foundation, New York, NY, USA

    Bimmer E. Claessen, Gregg W. Stone, Roxana Mehran, Elias A. Sanidas, Vasiliki Chantziara, Ke Xu & George D. Dangas

  2. Columbia University Medical Center, New York, NY, USA

    Gregg W. Stone, Elias A. Sanidas & Vasiliki Chantziara

  3. Cardiovascular Institute, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1030, New York, NY, 10029, USA

    Roxana Mehran & George D. Dangas

  4. Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Wouter J. Kikkert, Bimmer E. Claessen, José P. S. Henriques & Jan G. P. Tijssen

  5. Ospedali Riuniti di Bergamo, Bergamo, Italy

    Giulio Guagliumi

  6. Charité Universitatsmedizin, Campus Benjamin Franklin, Berlin, Germany

    Bernhard Witzenbichler

  7. University of Ulm, Ulm, Germany

    Jochen Wöhrle

  8. LeBauer CV Research Foundation, Greensboro, NC, USA

    Bruce R. Brodie

  9. National Institute of Cardiology, Warsaw, Poland

    Adam Witkowski

  10. Szpital Jana Pawla II, Kraków, Poland

    Krzysztof Zmudka

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  1. Wouter J. Kikkert
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  2. Bimmer E. Claessen
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  3. Gregg W. Stone
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  4. Roxana Mehran
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  5. Bernhard Witzenbichler
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  6. Bruce R. Brodie
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  7. Jochen Wöhrle
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  8. Adam Witkowski
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  9. Giulio Guagliumi
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  10. Krzysztof Zmudka
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  11. José P. S. Henriques
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  12. Jan G. P. Tijssen
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  13. Elias A. Sanidas
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  14. Vasiliki Chantziara
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  15. Ke Xu
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  16. George D. Dangas
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Correspondence to George D. Dangas.

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Kikkert, W.J., Claessen, B.E., Stone, G.W. et al. D-dimer levels predict ischemic and hemorrhagic outcomes after acute myocardial infarction: a HORIZONS-AMI biomarker substudy. J Thromb Thrombolysis 37, 155–164 (2014). https://doi.org/10.1007/s11239-013-0953-5

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