Quantitative assessment of thrombus burden predicts the outcome of treatment for venous thrombosis: a systematic review.
OBJECTIVE
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.


CONCLUSIONS
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.
Hull
Russell D
RD
Thrombosis Research Unit, 601 South Tower, Foothills Hospital, 1403 29th Street NW, Calgary, Alberta, Canada T2N 2T9. jeanne.sheldon@calgaryhealthregion.ca
Marder
Victor J
VJ
Mah
Andrew F
AF
Biel
Rita K
RK
Brant
Rollin F
RF
D000925:Anticoagulants / Q000627:therapeutic use*; D006801:Humans; D011237:Predictive Value of Tests; D012008:Recurrence; D012044:Regression Analysis; D012306:Risk; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000473:pathology*
D000925:Anticoagulants