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.
Keywords
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© 2005 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
