Surrogate endpoints for the assessment of efficacy in venous thromboembolism treatment trials

For the assessment of the efficacy of anticoagulant therapy In patients wit h symptomatic venous thrombosis, the incidence of symptomatic venous thromb oembolic complications is the outcome measure of choice. However, the low i ncidence of such complications necessitates the inclusion of a prohibitivel y large number of patients in randomized trials evaluating anticoagulant re gimens. Therefore, alternative efficacy outcome measures are desirable. Thi s paper discusses the validity of the following alternative tests: venograp hy and compression ultrasound for deep vein thrombosis: and pulmonary angio graphy and perfusion lung scanning for pulmonary embolism. It is concluded that a combination of one of the deep vein thrombosis tests and perfusion l ung scanning is the optimal approach. A thrombotic burden assessment, using repeat venography and perfusion lung scanning, has been performed at the e nd of treatment (day 10) with low-molecular-weight heparin and unfractionat ed heparin in 170 patients with symptomatic proximal deep vein thrombosis. An improved thrombotic burden was associated with a low number of subsequen t symptomatic venous thromboembolic complications (4%), whereas this figure gradually increased for patients with an unchanged (10%) and deteriorated (29%) outcome (p < 0.005). It is concluded that the thrombotic burden asses sment has potential to replace symptomatic outcomes, especially in dose-fin ding studies.