Tinzaparin for Long-Term Treatment of Venous Thromboembolism in Patients With Cancer: A Systematic Review and Meta-Analysis

Patients with cancer are at increased risk of recurrent venous thromboembolism (VTE) and bleeding. Thus, long-term treatment with anticoagulants for secondary prevention is challenging. The objective of this review was to evaluate current evidence on the safety and efficacy of tinzaparin compared with other anticoagulants for long-term VTE treatment in patients with cancer. Based on a preregistered protocol, we identified randomized controlled trials (RCTs) comparing long-term tinzaparin (therapeutic dose: 175 IU/kg) versus other anticoagulants for at least 3 months after an acute episode of VTE that included adult patients with underlying malignancy. We extracted predefined, clinically relevant outcomes of patients with cancer and, using standard methodology, pooled available data and assessed risk of bias and quality of evidence for each study. Three open-label RCTs evaluating 1169 patients with cancer were included in the analysis. Tinzaparin was associated with a significantly lower risk of recurrent VTE at the end of treatment (relative risk [RR], [95% confidence interval] 0.67 [0.46-0.99]) and at longest follow-up (RR: 0.58 [0.39-0.88]) and showed a lower risk of clinically relevant non-major bleeding at the end of treatment (RR: 0.71 [0.51-1.00]). No significant between-treatment differences were found for all-cause mortality (RR: 1.09 [0.91-1.30]) or fatal and non-fatal major bleeding events (RR: 1.06 [0.56-1.99]). The overall quality of evidence was deemed moderate, mainly due to small sample size in 2 of the studies and limited number of events in the meta-analyses. In conclusion, both short- and long-term treatments with tinzaparin were found to be superior to vitamin K antagonists for avoiding recurrences of VTE.