Clinical research study
Long-term Low-Molecular-Weight Heparin versus Usual Care in Proximal-Vein Thrombosis Patients with Cancer

https://doi.org/10.1016/j.amjmed.2006.02.022Get rights and content

Abstract

Purpose

A substantial clinical need exists for an alternative to vitamin K antagonists for treating deep-vein thrombosis in cancer patients who are at high risk of both recurrent venous thromboembolism and bleeding. Low-molecular-weight heparin, body-weight adjusted, avoids anticoagulant monitoring and has been shown to be more effective than vitamin-K-antagonist therapy.

Subjects and Methods

Subjects were patients with cancer and acute symptomatic proximal-vein thrombosis. We performed a multi-centre randomized, open-label clinical trial using objective outcome measures comparing long-term therapeutic tinzaparin subcutaneously once daily with usual-care long-term vitamin-K-antagonist therapy for 3 months. Outcomes were assessed at 3 and 12 months.

Results

Of 200 patients, 100 received tinzaparin and 100 received usual care. At 12 months, the usual-care group had an excess of recurrent venous thromboembolism; 16 of 100 (16%) versus 7 of 100 (7%) receiving low-molecular-weight heparin (P = .044; risk ratio = .44; absolute difference −9.0; 95% confidence interval [CI], −21.7 to −0.7). Bleeding, largely minor, occurred in 27 patients (27%) receiving tinzaparin and 24 patients (24%) receiving usual care (absolute difference −3.0; 95% CI, −9.1 to 15.1). In patients without additional risk factors for bleeding at the time of randomization, major bleeding occurred in 0 of 51 patients (0%) receiving tinzaparin and 1 of 48 patients (2.1%) receiving usual care. Mortality at 1 year was high, reflecting the severity of the cancers; 47% in each group died.

Conclusion

Our findings confirm the limited but benchmark data in the literature that long-term low-molecular-weight heparin is more effective than vitamin-K-antagonist therapy for preventing recurrent venous thromboembolism in patients with cancer and proximal venous thrombosis.

Section snippets

Study Design

We used a multicenter, open-label randomized design and compared long-term subcutaneous low-molecular-weight heparin against usual-care initial intravenous heparin and long-term oral warfarin sodium for a therapy duration of 3 months in cancer patients with proximal-vein thrombosis. An evaluation of patients with cancer and proximal deep-vein thrombosis was planned prospectively as cancer patients were randomized separately within the Main-LITE population of patients. Patients with cancer and

Study Population

Two hundred patients were recruited and randomized to tinzaparin (100 patients) or usual-care anticoagulants (100 patients). Figure 1 shows the patient flow for the eligible patients and for those randomized to the treatment groups. The tinzaparin and usual-care groups were comparable at entry (Table 2). The study began in 1994 at 23 centers across Canada (Table 3). Due to difficulties with occasional patient follow-up, which were overcome, successful patient follow-up was completed in July

Discussion

Long-term therapeutic dose low-molecular-weight heparin, when compared with usual-care vitamin-K-antagonist therapy for cancer patients with acute proximal-vein thrombosis, offered improved efficacy against recurrent venous thromboembolism. The outcome measures were assessed during study therapy and at 1 year, because there is evidence that the impact of study therapy on outcome persists after therapy is discontinued.16, 40 Our results are consistent with those of a benchmark trial evaluating

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