Dept. of Clinical Pharmacology Hospital of Saint-Etienne, France.
Thromb Res. 2012 Dec;130(6):853-8. doi: 10.1016/j.thromres.2012.08.290. Epub 2012 Aug 28.
Due to its specific pharmacokinetic profile, tinzaparin, a low-molecular-weight heparin (LMWH), appears not to be associated with anti-factor Xa accumulation. Our meta-analysis aimed at determining whether long-term curative doses of tinzaparin is a valuable alternative to vitamin K antagonists (VKA) for the treatment of symptomatic venous thromboembolism (VTE), especially in patients with cancer who are at higher risk of recurrence and bleeding.
A systematic literature search identified randomized studies on long-term tinzaparin compared to VKA in patients with VTE. Outcome measures were VTE recurrence, major bleeding, deaths and net clinical benefit combining the three endpoints during the treatment period and at one year. Pooled relative risk was estimated using the logarithm of the relative risk (RR) method based on a fixed-effect model in the overall population and cancer population.
Five randomized controlled studies were eligible. No difference between groups in VTE recurrence was found in the overall population (RR=0.85 [0.55; 1.31]). In cancer patients, a non-significant 38% VTE risk reduction in favor of tinzaparin was observed on treatment (RR=0.62 [0.30; 1.31]). The difference was significant at the end of follow-up at one year (RR=0.40 [0.19; 0.82], p<0.01). The incidence of major bleeding in the tinzaparin group was not significantly different from the VKA group in the overall population and cancer patients.
Tinzaparin appears as a valuable option for long-term treatment of patients in whom VKA are contraindicated or difficult to monitor. Tinzaparin may have a more favorable benefit-risk ratio than VKA in patients with cancer and VTE.
由于其独特的药代动力学特征,丁扎肝素(一种低分子肝素)似乎不会导致抗因子 Xa 蓄积。我们的荟萃分析旨在确定长期治疗剂量的丁扎肝素是否是治疗有症状静脉血栓栓塞症(VTE)的维生素 K 拮抗剂(VKA)的一种有价值的替代方案,尤其是在癌症患者中,这些患者复发和出血的风险更高。
系统文献检索确定了关于长期丁扎肝素与 VKA 治疗 VTE 的随机研究。主要终点为治疗期间和 1 年时 VTE 复发、大出血、死亡和将三个终点结合起来的净临床获益。使用基于固定效应模型的相对风险对数法(RR)估计汇总相对风险,适用于总体人群和癌症人群。
符合条件的有 5 项随机对照研究。总体人群中,两组在 VTE 复发方面无差异(RR=0.85 [0.55; 1.31])。在癌症患者中,丁扎肝素组的 VTE 风险降低了 38%,但无统计学意义(RR=0.62 [0.30; 1.31])。在 1 年的随访结束时,差异有统计学意义(RR=0.40 [0.19; 0.82],p<0.01)。丁扎肝素组的大出血发生率与 VKA 组在总体人群和癌症患者中均无显著差异。
丁扎肝素似乎是 VKA 禁忌或难以监测的患者长期治疗的一种有价值的选择。对于癌症合并 VTE 的患者,丁扎肝素可能比 VKA 具有更有利的获益风险比。