Efficacy and safety of adjunctive anticoagulation in patients with lung cancer without indication for anticoagulants: a systematic review and meta-analysis

Background Patients with lung cancer are at high risk of venous thromboembolism (VTE), and VTE predicts a poor prognosis. Anticoagulation therefore might be beneficial for these patients. It is not clear whether anticoagulants could improve survival and other outcomes in patients with lung cancer with no indication for anticoagulation. Methods We searched the Web of Science, Medline, EMBASE and Cochrane databases for relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcomes were 1-year survival and incidence of VTE. Pooled risk ratios (RR) were calculated using control as a reference group and significance was determined by the Z test. Results Nine eligible studies with 2185 participants were included. Anticoagulation showed significant improvement in survival at 1 year (RR 1.18, 95% CI 1.06 to 1.32; p=0.004) and at 2 years (RR 1.27, 95% CI 1.04 to 1.56; p=0.02), but not at 6 months. Subgroup analysis showed a survival benefit for patients with small cell lung cancer (SCLC) and those with non-advanced/limited cancer. The incidence of VTE (RR=0.55, 95% CI 0.31 to 0.97; p=0.04) and thromboembolic events (RR=0.48, 95% CI 0.28 to 0.82; p=0.008) was reduced with anticoagulation. Both vitamin K antagonist (VKA) and subcutaneous heparin increased the risk of haemorrhage, but heparin did not increase the incidence of major bleeding. Conclusions Anticoagulation showed a survival benefit, especially for those with SCLC and prolonged life expectancy, and reduced the risk of VTE in lung cancer patients with no indication for anticoagulants. Subcutaneous heparin is superior to VKA because of a potentially smaller risk of major bleeding.