title: Association between statin use and plasma D-dimer levels. A systematic review and meta-analysis of randomised controlled trials.
abstract: 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.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.forename: Corina
authors.initials: C
authors.lastname: Serban
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.forename: Paul
authors.initials: P
authors.lastname: Muntner
authors.forename: Vera
authors.initials: V
authors.lastname: Bittner
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.forename: Jacek
authors.initials: J
authors.lastname: Rysz
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: Prof. Maciej Banach, MD, PhD, FNLA, FAHA, FESC; FASA, Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113; 90-549 Lodz, Poland, Tel.: +48 42 639 37 71, Fax: +48 42 639 37 71, E-mail: maciejbanach@aol.co.uk.
authors.forename: Maciej
authors.initials: M
authors.lastname: Banach
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C036309:fibrin fragment D
keywords: D-dimer; coagulation; fibrinolysis; statin