Dranitsaris George, Shane Lesley G, Woodruff Seth
1 Augmentium Pharma Consulting Inc., Toronto, Canada.
2 Pfizer Inc., New York, NY, USA.
J Oncol Pharm Pract. 2019 Jan;25(1):68-75. doi: 10.1177/1078155217727140. Epub 2017 Aug 31.
Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are receiving anticancer therapy, have an even higher risk of a recurrent event. Similarly, the risk of recurrent venous thromboembolism is higher than the risk of an initial event. To reduce the risk, extended duration of prophylaxis for up to six months with low-molecular-weight heparins such as dalteparin, enoxaparin, nadroparin, and tinzaparin is recommended by international guidelines. In this paper, the clinical and economic literature is reviewed to provide evidenced based recommendations based on clinical benefit and economic value.
A systematic review of major databases was conducted from January 1996 to October 2016 for randomized controlled trials evaluating the four distinct low-molecular-weight heparins against a vitamin K antagonists control group for the prevention of recurrent venous thromboembolism in patients with active cancer. This was then followed by the application of the National Institute of Health and Clinical Excellence guidance to assess the quality of all trials that met the inclusion criteria. Finally, the cost-effectiveness literature supporting the value proposition of each product was reviewed.
Six randomized trials met the inclusion criteria. There were one, two, and three trials that compared dalteparin, tinzaparin, and enoxaparin to a vitamin K antagonists control group. However, there were no trials for nadroparin in the setting of secondary venous thromboembolism prevention. In addition, only the dalteparin and one of the tinzaparin trials were of high quality and adequately powered. Of the two studies, only the dalteparin trial reported a statistically significant benefit in terms of venous thromboembolism absolute risk reduction when compared to a vitamin K antagonists control group (HR = 0.48; p = 0.002). In addition, there was robust pharmacoeconomic data from Canada, the Netherlands, France, and Austria supporting the cost-effectiveness of dalteparin for this indication. There were no such studies for any of the other agents.
The totality of high-quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer.
癌症患者发生静脉血栓栓塞的风险升高。重要的是，患有转移性疾病、肾功能不全或正在接受抗癌治疗的癌症患者发生复发性事件的风险更高。同样，复发性静脉血栓栓塞的风险高于初次事件的风险。为降低风险，国际指南建议使用低分子肝素（如达肝素、依诺肝素、那屈肝素和替扎肝素）进行长达6个月的延长预防。本文回顾了临床和经济学文献，以根据临床获益和经济价值提供循证建议。
对1996年1月至2016年10月的主要数据库进行系统综述，纳入评估四种不同低分子肝素与维生素K拮抗剂对照组相比预防活动性癌症患者复发性静脉血栓栓塞的随机对照试验。随后应用英国国家卫生与临床优化研究所的指南评估所有符合纳入标准的试验的质量。最后，回顾支持每种产品价值主张的成本效益文献。
六项随机试验符合纳入标准。分别有一项、两项和三项试验将达肝素、替扎肝素和依诺肝素与维生素K拮抗剂对照组进行比较。然而，在继发性静脉血栓栓塞预防方面没有那屈肝素的试验。此外，只有达肝素试验和一项替扎肝素试验质量高且样本量充足。在这两项研究中，只有达肝素试验报告与维生素K拮抗剂对照组相比，在静脉血栓栓塞绝对风险降低方面具有统计学显著获益（HR = 0.48；p = 0.002）。此外，来自加拿大、荷兰、法国和奥地利的有力药物经济学数据支持达肝素用于该适应症的成本效益。其他任何药物均无此类研究。
高质量临床和成本效益数据的总体情况支持在预防癌症患者复发性静脉血栓栓塞方面，使用达肝素优于其他低分子肝素。
