Long-Term Use of Different Doses of Low-Molecular-Weight Heparin Versus Vitamin K Antagonists in the Treatment of Venous Thromboembolism

Background: We evaluated whether the incidence of recurrent venous thromboembolic events (VTEs) during and after therapy differs for patients treated with full or reduced doses of low-molecular-weight heparin (LMWH) used long term compared with vitamin K antagonists (VKAs). Methods: We identified randomized studies of long-term treatment with LMWH or VKA by searching MEDLINE, EMBASE, BIOSIS, and PASCAL. Seventeen studies were included, with 4,002 patients. Results: In the assessment at 12 months of 1,957 patients without cancer, the recurrence rates of VTE in the LMWH/VKA groups were 8.3%/7.6% in the studies using full doses and 12.3%/12.1% in those using prophylactic doses. However, combined analysis after treatment to 1 year showed a nonsignificant (NS) trend to lower recurrent symptomatic VTE in favor of VKA (RR = 1.46, 95% CI 0.96-2.23). In 1,292 patients with cancer the recurrence rates of VTE in the LMWH/VKA groups were 6.5%/17.9% (p = 0.005) in the studies using full doses, 7.1%/13.4% (p = 0.002) in the studies using intermediate doses, and 14.3%/19.1% (p = NS) in the studies using prophylactic doses. Furthermore, the recurrences of VTE after discontinuation of treatment in the LMWH/VKA groups were 1.6%/9.5% (RR = 0.25, 95% CI 0.06-1.1) in 252 patients with full doses and 12%/7.4% (RR = 1.49, 95% CI 0.3-7.48) in 52 patients with prophylactic doses. In this population with cancer, the full-treatment LMWH regimen did not produce more major bleeding events than intermediate or prophylactic doses (5.1% vs. 6.3% or 8.1%, respectively). Conclusion: Full-dose LMWH for 3-6 months is as safe as intermediate and prophylactic doses for the long-term treatment of deep vein thrombosis. In patients with cancer it appears that there is an excess of VTE recurrence after treatment with prophylactic doses that does not occur with full therapeutic doses.