THE IMPORTANCE OF INITIAL HEPARIN TREATMENT ON LONG-TERM CLINICAL OUTCOMES OF ANTITHROMBOTIC THERAPY - THE EMERGING THEME OF DELAYED RECURRENCE

Background: Recent clinical trials of venous thromboembolism treatment suggest inadequate initial heparin therapy predisposes patients to la te recurrence of thromboembolism. However, a recent review article was unable to demonstrate a relationship between initial heparin therapy and late recurrence. Objective: To evaluate the relationship between i nitial heparin treatment and long-term clinical outcome in 3 consecuti ve, randomized, double-blind trials that used similar study designs an d patient populations and objective documentation of recurrent venous thromboembolism. Methods: The trials were performed sequentially and c ompared the use of continuous intravenous with subcutaneous heparin, c ontinuous intravenous heparin for 10 or 5 days, and continuous intrave nous heparin with once-daily subcutaneous low-molecular-weight heparin . All patients were followed up for 3 months to assess the a priori hy pothesis that inadequate initial heparin therapy could lead to recurre nt venous thromboembolism during long-term therapy with warfarin sodiu m. Results: The following were the observed rates of recurrent venous thromboembolism: continuous intravenous heparin, 3 (5.2%) of 58 patien ts vs subcutaneous heparin, 11 (19.3%) of 57 patients; continuous intr avenous heparin for 10 days, 7 (7.0%) of 100 patients or for 5 days, 7 (7.1%) of 99 patients; and continuous intravenous heparin, 15 (6.9%) of 219 patients vs low-molecular-weight heparin, 6 (2.8%) of 213 patie nts. Pooled analysis of the patients treated with continuous intraveno us heparin showed that of the total 32 patients with recurrent venous thromboembolism, in 6 patients thromboembolism occurred early (<10 day s) and in 26 patients thromboembolism occurred late. Of these patients , the majority (20/32 [62.5%]) had therapeutic prothrombin time or int ernational normalized ratio values before or at the time of the recurr ent thromboembolic event. Conclusion: Our findings demonstrate that th e initial heparin treatment affects the long-term outcome. This conclu sion applies when these data are analyzed for each individual study by treatment group, observed difference in outcome, and pooled analysis.