Review
Quantitative assessment of thrombus burden predicts the outcome of treatment for venous thrombosis: A systematic review

https://doi.org/10.1016/j.amjmed.2005.01.025Get rights and content

Abstract

Purpose

Clot-burden change in patients receiving anticoagulant therapy, by predicting subsequent recurrent venous thromboembolism, may provide a clinically relevant surrogate endpoint of prognostic importance. The validity of this objective measure is yet to be established.

Methods

A PubMed search was performed to retrieve articles published up to December 2003. We identified 11 randomized trials reported from 1990 to 2003 that met our study identification and selection criteria. Anticoagulant therapy subsequently approved by regulatory affairs was assessed by clot-burden change and the validated outcome measure, long-term venous thromboembolism. Two additional randomized trials, partly meeting the inclusion criteria, were included in the sensitivity analysis.

Results

Individual studies suggested a predictive relationship between clot-burden change and likelihood of recurrent venous thromboembolism irrespective of the particular anticoagulant. The summary treatment effects strongly favored the therapy under evaluation and were in harmony for improved clot-burden (relative risk 0.82; 95% CI, 0.76–0.88; P <0.001) and for recurrent venous thromboembolism (relative risk 0.56; 95% CI, 0.42–0.76; P <0.001). The aggregate data show a striking predictive correlation for clot-burden change and subsequent recurrent venous thromboembolism using meta-regression analysis; (correlation = 0.81, P = 0.005) validating quantitative clot-burden assessment.

Conclusion

Clot-burden change predicts long-term outcome, providing clinically relevant, patient-specific prognostic findings that may guide duration of anticoagulant therapy as well as provide a valid surrogate endpoint for clinical trials of innovative antithrombotic therapy, allowing more efficient trials exposing far fewer patients to the hazards of ineffective therapy than is required for outcome studies. Noninvasive assessment (duplex ultrasonography) of clot-burden change is currently being deployed for use in clinical trials.

Section snippets

Methods

To ensure high methodologic quality, our systematic review adhered to 10 validated criteria for methodological rigor,11, 12 and 5 additional criteria were used to evaluate the scientific basis of treatment recommendations.12 We also adhered to the QUOROM (Quality of Reporting of Meta-analyses) guidelines13 for the reporting of meta-analyses of randomized trials. Systematic methods were used to identify articles for inclusion in the analysis, describe variations in study design and execution,

Study identification and selection

Our research strategies identified 740 potentially relevant studies. We excluded 678 studies: 527 studies did not include patients receiving venous thromboembolism therapy, 96 were reviews, 28 were nonrandomized, 22 were previously reported, and 5 were meta-analyses, systematic reviews or surveys. Of the remaining 62 original articles, 21 studies assessed change in clot-burden in randomized trials evaluating innovative therapy (subcutaneous low-molecular-weight heparin, which is now widely

Discussion

Our findings show a striking predictive correlation between change in clot-burden using quantitative assessment and subsequent long-term clinical outcome. A predictive relationship is suggested by the individual study population findings (Figure 1A, B, and C), irrespective of whether the treatment regimen was that under evaluation or usual care. The aggregate data show a striking predictive correlation for clot-burden change and subsequent recurrent venous thromboembolism using meta-regression

Acknowledgment

The authors thank Avneet Brar, Jeanne Sheldon, BA, and Charlene Wrona for their assistance with the manuscript.

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