Does low-molecular-weight heparin influence cancer-related mortality?

In a large multicenter prospective trial [1], in which 672 cancer patients were randomly assigned to receive LMWH or oral anticoagulant therapy (OAT) for 6 months, a statistically significant improvement in overall survival (death for any cause at 12 months) in favor of dalteparin over OAT was demonstrated in patients affected by non-metastatic disease (hazard ratio, 0.50; 95% CI, 0.27–0.95; P = 0.03) [2]. These authors used all-cause mortality rather than cancer-related mortality. For this reason, we performed a literature-based pooled analysis to summarize the results of the randomized trials concerning cancer-related death during anticoagulant therapy and follow-up in cancer patients receiving LWMH or OAT (Table 1). Event-based relative risk (RR) ratios with 95% CIs were derived. Combined-effect estimation was computed with both randomand fixed-effect models. A heterogeneity test was applied as well. Concerning cancer-related death, we selected eight studies [1, 3–9] to evaluate the incidence of cancer-related mortality during treatment and follow up in cancer patients by type of anticoagulant therapy. We considered only cancer patients, according to the data reported in a pooled-analysis of 1726 patients [10]. Our previously reported results [11] were based on data extracted from a prior meta-analysis [12]. No significant difference in cancer mortality was observed between the two treatment modalities: (RR 0.97; 95% CI 0.81–1.15; P = 0.75) (Figure 1). The test for heterogeneity was not significant (P = 0.97). Conversely, we selected seven studies [3–8, 13] that recruited patients with and without cancer in order to evaluate the incidence of overall mortality during treatment and follow up by type of anticoagulant therapy. No significant difference was registered: a total of 15 of 495 patients (3%) in the LMWHgroup died versus 12 of 607 patients (1.9%) in the OAT group, with a non-significant reduction of the risk of recurrent symptomatic VTE in favor OAT (RR 1.38; 95% CI 0.63–3.00; P = 0.41). The test for heterogeneity was not significant (P = 0.78). No difference was observed applying both the fixedand the random-effect model.

[1]  M. Mandalà,et al.  Low-molecular-weight heparin versus oral anticoagulant therapy for the long-term treatment of symptomatic venous thromboembolism: Is there any difference in cancer-related mortality? , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  M. Prins,et al.  Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  A. Iorio,et al.  Low‐molecular‐weight heparin for the long‐term treatment of symptomatic venous thromboembolism: meta‐analysis of the randomized comparisons with oral anticoagulants , 2003, Journal of thrombosis and haemostasis : JTH.

[4]  A. Iorio,et al.  Low-Molecular-Weight Heparin and Cancer Survival: Review of the Literature and Pooled Analysis of 1,726 Patients Treated for at Least Three Months , 2003, Pathophysiology of Haemostasis and Thrombosis.

[5]  M. Prins,et al.  Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. , 2003, The New England journal of medicine.

[6]  V. Kakkar,et al.  Low-molecular-weight heparin in the acute and long-term treatment of deep vein thrombosis , 2003, Thrombosis and Haemostasis.

[7]  Yves Gruel,et al.  Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. , 2002, Archives of internal medicine.

[8]  J. Ribera,et al.  Low Molecular Weight Heparin (Enoxaparin) Versus Oral Anticoagulant Therapy (Acenocoumarol) in the Long-Term Treatment of Deep Venous Thrombosis in the Elderly: a Randomized Trial , 2000, Thrombosis and Haemostasis.

[9]  S. Carrera,et al.  Venographic comparison of subcutaneous low-molecular weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis. , 1999, Journal of vascular surgery.

[10]  M. Pini,et al.  Low Molecular Weight Heparin versus Warfarin in the Prevention of Recurrences after Deep Vein Thrombosis , 1994, Thrombosis and Haemostasis.

[11]  A. Martínez,et al.  Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis. , 2001, Journal of vascular surgery.

[12]  S. Lopaciuk,et al.  Low Molecular Weight Heparin versus Acenocoumarol in the Secondary Prophylaxis of Deep Vein Thrombosis , 1999, Thrombosis and Haemostasis.