Background: D-dimers are generated during endogenous fibrinolysis of a blood clot and have a central role in diagnostic algorithms to rule out venous thromboembolism. HMG-CoA reductase inhibitors, more commonly called statins, are known to have effects independent of LDL-cholesterol lowering, including antithrombotic properties. An effect of statins on D-dimer levels has been reported in a prior systematic review and meta-analysis, but methodological shortcomings might have led to an overestimated effect. To re-evaluate the association between statins and D-dimer levels, we systematically reviewed all published articles on the influence of statins on D-dimer levels and conducted a novel meta-analysis (PROSPERO registration number CRD42017058932). Materials and methods: We electronically searched EMBASE, Medline Epub, Cochrane, Web of Science and Google Scholar (100 top relevance) (date of last search: 5 October 2017). We included randomized controlled trials, cohort studies and cross-sectional studies. Two reviewers independently screened all articles retrieved and extracted data on study and patient characteristics, study quality and D-dimer levels. Results: Study-level meta-analysis involving 18,052 study participants showed lower D-dimer levels in those receiving statin treatment than controls (SMD: −0.165, 95% CI −0.234; −0.096, P = <0.001). Sensitivity analyses and additional analyses on treatment duration (<12 weeks vs ≥12 weeks) and type of statin (lipophilic or hydrophilic) did not modify this overall result. Conclusion: This meta-analysis suggests an association between use of statins and reduction of D-dimer levels, independent of treatment duration and type of statin used. This effect is small but robust, and should be interpreted with caution.

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Keywords D-dimer, fibrin fragment D, hydroxymethylglutaryl-CoA reductase inhibitors, meta-analysis, venous thromboembolism
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Journal European Journal of Clinical Investigation
Schol-Gelok, S, Morelli, F. (Francesca), Arends, L.R, Boersma, H, Kruip, M.J.H.A, Versmissen, J, & van Gelder, T. (2019). A revised systematic review and meta-analysis on the effect of statins on D-dimer levels. European Journal of Clinical Investigation (Vol. 49). doi:10.1111/eci.13130