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
Amirhossein Sahebkar#
1   Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
2   Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia
,
Corina Serban#
3   Department of Functional Sciences, Discipline of Pathophysiology, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania
,
Dimitri P. Mikhailidis
4   Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK
,
Anetta Undas
5   Institute of Cardiology, Jagiellonian University Medical College, and John Paul II Hospital, Krakow, Poland
,
Gregory Y. H. Lip
6   University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
,
Paul Muntner
7   Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
,
Vera Bittner
8   Division of Cardiovascular Disease, Preventive Cardiology Section, University of Alabama at Birmingham, Birmingham, Alabama, USA
,
Kausik K. Ray
9   Department of Primary Care and Public Health, School of Public Health, Imperial College London, UK
,
Gerald F. Watts
10   Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia
,
G. Kees Hovingh
11   Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
,
Jacek Rysz
12   Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland
,
John J. P. Kastelein
11   Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
,
Maciej Banach
12   Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland
,
Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group › Author Affiliations
Further Information

Publication History

Received: 15 November 2014

Accepted after major revision: 29 March 2015

Publication Date:
01 December 2017 (online)

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.

# Drs Sahebkar and Serban contributed equally to this meta-analysis.


 
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