Association between statin use and plasma D-dimer levels

Amirhossein Sahebkar; Corina Serban; Dimitri P. Mikhailidis; Anetta Undas; Gregory Y. H. Lip; Paul Muntner; Vera Bittner; Kausik K. Ray; Gerald F. Watts; G. Kees Hovingh; Jacek Rysz; John J. P. Kastelein; Maciej Banach; Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group

doi:10.1160/TH14-11-0937

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 114(03): 546-557
DOI: 10.1160/TH14-11-0937

Coagulation and Fibrinolysis

Schattauer GmbH

Association between statin use and plasma D-dimer levels

A systematic review and meta-analysis of randomised controlled trials

Authors

Amirhossein Sahebkar^#

¹Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

²Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia
Corina Serban^#

³Department of Functional Sciences, Discipline of Pathophysiology, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania
Dimitri P. Mikhailidis

⁴Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK
Anetta Undas

⁵Institute of Cardiology, Jagiellonian University Medical College, and John Paul II Hospital, Krakow, Poland
Gregory Y. H. Lip

⁶University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
Paul Muntner

⁷Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
Vera Bittner

⁸Division of Cardiovascular Disease, Preventive Cardiology Section, University of Alabama at Birmingham, Birmingham, Alabama, USA
Kausik K. Ray

⁹Department of Primary Care and Public Health, School of Public Health, Imperial College London, UK
Gerald F. Watts

¹⁰Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia
G. Kees Hovingh

¹¹Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Jacek Rysz

¹²Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland
John J. P. Kastelein

¹¹Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Maciej Banach

¹²Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland

Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group

Abstract

Summary

D-dimers, specific breakdown fragments of cross-linked fibrin, are generally used as circulating markers of activated coagulation. Statins influence haemostatic factors, but their effect on plasma D-dimer levels is controversial. Therefore, the aim of this meta-analysis was to evaluate the association between statin therapy and plasma D-dimer levels. We searched PubMed, Web of Science, Cochrane Library, Scopus and EMBASE (up to September 25, 2014) to identify randomised controlled trials (RCTs) investigating the impact of statin therapy on plasma D-dimer levels. Two independent reviewers extracted data on study characteristics, methods and outcomes. Meta-analysis of data from nine RCTs with 1,165 participants showed a significant effect of statin therapy in reducing plasma D-dimer levels (standardised mean difference [SMD]: –0.988 µg/ml, 95 % confidence interval [CI]: –1.590 – –0.385, p=0.001). The effect size was robust in sensitivity analysis and omission of no single study significantly changed the overall estimated effect size. In the subgroup analysis, the effect of statins on plasma D-dimer levels was significant only in the subsets of studies with treatment duration ≥ 12 weeks (SMD: –0.761 µg/ml, 95 %CI: –1.163– –0.360; p< 0.001), and for lipophilic statins (atorvastatin and simvastatin) (SMD: –1.364 µg/ml, 95 % CI: –2.202– –0.526; p=0.001). Hydrophilic statins (pravastatin and rosuvastatin) did not significantly reduce plasma D-dimer levels (SMD: –0.237 µg/ml, 95 %CI: –1.140–0.665, p=0.606). This meta-analysis of RCTs suggests a decrease of plasma D-dimer levels after three months of statin therapy, and especially after treatment with lipophilic statins. Well-designed trials are required to validate these results.

Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.

Keywords

D-dimer - statin - coagulation - fibrinolysis

Full Text

References

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