Thorax：肺癌患者可从辅助性抗凝治疗中获益

肺癌患者是发生静脉血栓栓塞（VTE）高危因素，高凝状态和VTE预示着临床预后差，与肺癌患者的死亡率增加相关。虽然已有研究表明对于没有抗凝指针的肺癌患者进行辅助性抗凝治疗可以使患者长期生存获益，但是单项研究的样本量有限且各个研究间缺乏一致性。针对这种情况，来自复旦大学附属中山医院的JingZhang等对这方面的研究予以整理并进行meta分析，该研究结果在线发表于2013年1月15日的《胸腔》（Thorax）杂志上。作者通过meta分析指出对于没有抗凝指针的肺癌患者尤其是小细胞肺癌（SCLC）患者进行辅助性抗凝治疗可以达到长期生存获益。

该研究通过文献检索入组9篇合格的随机对照试验（RCTs）文献，共2185例肺癌患者进行meta分析。根据组织学分型(NSCLC和SCLC)和分期从中共提炼出使用抗凝剂（肝素和维生素K拮抗剂）的肺癌患者13组用于进一步分析。研究者分别对患者6个月、1年、2年的生存率，血栓事件和出血事件进行了meta分析。

研究结果表明，使用抗凝剂较未使用抗凝剂的肺癌患者的1年（p=0.004）、2年（p=0.002）生存率增高，尤其对于SCLC，肝素抗凝，早期或局限期的患者更为明显。此外发现，使用抗凝剂的肺癌患者发生VET的风险明显下降，然而随之发生的出血风险也明显增加。

该研究发现，使用抗凝剂较未使用抗凝剂的肺癌患者有明显的生存获益，尤其对于SCLC、早期或局限期的患者更加明显。同时发现使用肝素抗凝是安全的，较维生素K拮抗剂并未明显增加大出血的风险。此前的研究报道，肺癌患者辅助性抗凝治疗使生存获益，对此该项研究予以确认。然而，对于NSCLC该项研究只有两项研究入组分析，所以不能充分的说明抗凝剂可以使这部分患者的生存获益。同时对于抗凝剂的选择、使用量、持续时间该项研究并未予以研究，有待进一步证实。
与肺癌相关的拓展阅读：

• JCO：肺癌的HER2靶向治疗方案应纳入HER2基因检查
• Radiother Oncol：FDG-PET可评估局部晚期非小细胞肺癌同步放化疗后放疗剂量和急性食管炎的关系
• AJRCCM：Th9细胞对肺癌细胞有重要免疫调节作用
• J Thorac Oncol：利用化疗和药物治疗延长对肺癌恶化的控制
• Diabetes Care：糖尿病患者使用二甲双胍与患肺癌风险无关
• BMJ：中国宣威县家庭使用烟煤与患上肺癌的风险相关联
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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.