A revised systematic review and meta-analysis on the effect of statins on D-dimer levels

Eur J Clin Invest. 2019 Aug;49(8):e13130. doi: 10.1111/eci.13130. Epub 2019 Jun 3.

Abstract

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.

Keywords: D-dimer; fibrin fragment D; hydroxymethylglutaryl-CoA reductase inhibitors; meta-analysis; venous thromboembolism.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cholesterol, LDL / blood
  • Cohort Studies
  • Cross-Sectional Studies
  • Fibrin Fibrinogen Degradation Products / metabolism*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Meta-Analysis as Topic
  • Publication Bias
  • Venous Thromboembolism / diagnosis*

Substances

  • Cholesterol, LDL
  • Fibrin Fibrinogen Degradation Products
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • fibrin fragment D