Relation between the time to achieve the lower limit of the APTT therapeutic range and recurrent venous thromboembolism during heparin treatment for deep vein thrombosis

BACKGROUND: Randomized trials have demonstrated the importance of achieving adequate heparinization early in the course of therapy. Recently, some authors reported a pooled analysis of selected studies in the literature that suggested that there is no convincing evidence that the risk of recurrent venous thromboembolism is critically dependent on achieving a therapeutic activated partial thromboplastin time result at 24 to 48 hours. METHODS: We provide the analyses of patient groups entered into our series of 3 consecutive double-blind randomized trials evaluating initial heparin therapy for proximal deep venous thrombosis. RESULTS: Logistic regression analysis of the patient groups receiving the less intense initial intravenous heparin dose of 30,000 U/24 h demonstrated that subtherapy for 24 hours predicted the onset of venous thromboembolic events. Failure to achieve a therapeutic activated partial thromboplastin time by 24 hours was associated with a 23.3% frequency of venous thromboembolism vs 4% to 6% for those whose activated partial thromboplastin time exceeded the therapeutic threshold by 24 hours (P=.02). Time-to-event analysis shows the increased frequency of recurrent venous thromboembolic events during the period of study in patients who were subtherapeutic for 24 hours compared with those who were therapeutic (P=.001). CONCLUSIONS: Our findings reaffirm the clinical importance of rapidly achieving therapeutic levels of heparin. Patients who failed to achieve the therapeutic threshold by 24 hours were at an increased risk of subsequent recurrent venous thromboembolism. These findings are independently supported by the results of a randomized trial comparing different intensities of initial heparin treatment by continuous infusion.