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A revised systematic review and meta-analysis on the effect of statins on D-dimer levels
Suzanne Schol-Gelok1, Francesca Morelli1, Lidia R Arends2
1Department of Hospital Pharmacy and Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Insights
Statins, a class of cholesterol-lowering drugs, are associated with reduced D-dimer levels, a marker for blood clots. This meta-analysis confirms a small but consistent effect, independent of statin type or duration.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Hematology
Background:
- D-dimers play a key role in diagnosing venous thromboembolism.
- Statins possess antithrombotic properties beyond LDL-cholesterol reduction.
- Previous studies may have overestimated the effect of statins on D-dimer levels.
Purpose of the Study:
- To systematically review and meta-analyze the association between statin use and D-dimer levels.
- To re-evaluate the influence of statins on D-dimer, addressing methodological limitations of prior research.
Main Methods:
- Comprehensive electronic literature search across multiple databases (EMBASE, Medline Epub, Cochrane, Web of Science, Google Scholar).
- Inclusion of randomized controlled trials, cohort studies, and cross-sectional studies.
- Independent data extraction and quality assessment by two reviewers.
Main Results:
- Meta-analysis of 18,052 participants revealed significantly lower D-dimer levels in statin users compared to controls (SMD: -0.165).
- Sensitivity analyses confirmed the robustness of the findings.
- No significant modification of the effect based on treatment duration or statin type (lipophilic/hydrophilic).
Conclusions:
- Statin use is associated with a reduction in D-dimer levels.
- This association is independent of treatment duration and statin type.
- The observed effect is statistically significant but clinically small, requiring cautious interpretation.
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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