Adjuvant therapy with heparin in patients with lung cancer without indication for anticoagulants: A systematic review of the literature with meta-analysis

Background: The effect of heparin in improving cancer survival has gained increasing attention over the past decades. Several clinical trials have evaluated the role of heparin on survival outcome and its safety profile in lung cancer patients. Thus, we performed a systematic review and meta-analysis from the results of randomized controlled trials (RCTs) to assess the efficacy and safety of heparin in patients with lung cancer without indication for anticoagulants. Methods: We searched PubMed, Embase, and The Cochrane Central Register of Controlled Trials databases for relevant studies. The inclusion criteria used were patients with lung cancer without a concurrent diagnosis of venous thromboembolism (VTE) and were treated with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). The outcomes included survival outcome, VTE, bleeding, major bleeding, and thrombocytopenia. The results were presented as hazard ratio (HR) and relative risk (RR), and the STATA 12.0 package was used for comprehensive quantitative analysis. Results: A total of 6 studies with 753 cases and 640 controls were included for the final analysis. The meta-analysis showed significant differences in survival with an HR of 0.71 (95% confidence interval [CI] 0.60u0.84), particularly in limited-stage small cell lung cancer (SCLC) with an HR of 0.57 (95% CI 0.43u0.77), and also in VTE (RR 0.46; 95% CI 0.27u0.80) when heparin was compared with placebo or no anticoagulant. There were no significant differences in risks for bleeding (RR 1.53; 95% CI 0.96u2.45), major bleeding (RR 1.43; 95% CI 0.59u3.45), and thrombocytopenia (RR 0.86; 95% CI 0.66u1.12). Conclusion: Administration of heparin (mainly LMWH) as primary thromboprophylaxis for lung cancer patients without indication for anticoagulants was associated with a significant survival benefit, particularly in limited-stage SCLC.