Fixed-dose, body weight-independent subcutaneous LMW heparin versus adjusted dose unfractionated intravenous heparin in the initial treatment of proximal venous thrombosis

Background. Body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjuste d intravenous unfractionated heparin (UFH) for the treatment of patients wi th venous thromboembolism. However, body weight-adjusted dosage of low-mole cular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rat ionalize initial treatment for venous thromboembolism. Methods. Patients wi th proven proximal deep-vein thrombosis were randomly assigned to fixed dos e subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients ) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antago nists were started between day 3 and 7 and continued for up to 6 months. Th e primary outcome measure was a 30 percent or greater improvement in the Ma rder Score, as revealed by repeated venography on day 12 (end of the initia l treatment). The secondary composite outcome measure included death, recur rent venous thromboembolism and major bleeding and was assessed at day 12 a nd after 6 months by a blinded adjunction committee. Results. The Marder sc ore improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite out come was obse rved in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 1 4 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months the se figures were 6.8% and 12. 8%, respectively (risk reduction 0.53, confide nce interval 0.31-0.90, 2p = 0.02). Conclusion. Fixed dose subcutaneous LMW H certoparin is at least as efficacious as UFH in resolving proximal vein t hrombosis. With respect to the composite outcome of death, recurrent venous thromboembolism and major bleeding LMWH treatment performed significantly better both during initial therapy and at a six-month follow-up.