Division of General Internal Medicine, University Hospitals of Geneva, 4, rue Gabrielle Perret-Gentil, CH, Geneva, Switzerland.
Faculty of Medicine, University of Geneva, Geneva, Switzerland.
PLoS One. 2019 Mar 21;14(3):e0213940. doi: 10.1371/journal.pone.0213940. eCollection 2019.
Low-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily injections. We did a systematic review to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT.
We searched Pubmed, Embase and CENTRAL for randomised controlled trials comparing DOAC, VKA and LMWH in patients with CAT. Pairwise and network meta-analyses were computed for venous thromboembolism (VTE) recurrence and bleeding complications.
We identified 14 studies, including 4,661 patients. In pairwise comparison, DOAC were superior to LMWH to prevent VTE recurrence (HR 0.63; 95% CI 0.42-0.96) and LMWH was superior to VKA (HR 0.53; 95% CI 0.40-0.70). The rate of major bleeding was higher with DOAC compared to LMWH (HR 1.78; 95% CI 1.11-2.87). In the network meta-analysis, DOAC had a lower, but non-significant, rate of VTE recurrence compared to LMWH (HR 0.74; 95% CI 0.54-1.01). Both DOAC (HR 0.42; 95% CI 0.29-0.61) and LMWH (HR 0.57; 95% CI 0.44-0.75) were associated with lower rates of recurrence compared to VKA. No significant difference in major bleeding rate was observed in the network meta-analysis. Inconsistency was observed between pairwise and network meta-analysis comparisons for major bleeding.
DOAC are effective to prevent VTE recurrence in patients with CAT but are associated with an increased risk of bleeding compared to LMWH. The choice of anticoagulant should be personalised, taking into account the patient's bleeding risk, including cancer site, and patient's values and preferences.
低分子肝素(LMWH)通常被推荐用于治疗癌症相关血栓形成(CAT),但这种治疗需要每天进行繁琐的注射。我们进行了一项系统评价,以比较直接口服抗凝剂(DOAC)、维生素 K 拮抗剂(VKA)和 LMWH 在 CAT 患者中的疗效和安全性。
我们在 Pubmed、Embase 和 CENTRAL 中检索了比较 CAT 患者中 DOAC、VKA 和 LMWH 的随机对照试验。进行了成对和网络荟萃分析,以比较静脉血栓栓塞(VTE)复发和出血并发症。
我们确定了 14 项研究,包括 4661 名患者。在成对比较中,DOAC 优于 LMWH 预防 VTE 复发(HR 0.63;95%CI 0.42-0.96),而 LMWH 优于 VKA(HR 0.53;95%CI 0.40-0.70)。与 LMWH 相比,DOAC 导致大出血的发生率更高(HR 1.78;95%CI 1.11-2.87)。在网络荟萃分析中,DOAC 与 LMWH 相比,VTE 复发率较低,但无统计学意义(HR 0.74;95%CI 0.54-1.01)。与 VKA 相比,DOAC(HR 0.42;95%CI 0.29-0.61)和 LMWH(HR 0.57;95%CI 0.44-0.75)都与复发率降低相关。网络荟萃分析中未观察到大出血发生率的显著差异。在大出血方面,网络荟萃分析比较与成对比较之间存在不一致性。
DOAC 可有效预防 CAT 患者 VTE 复发,但与 LMWH 相比,出血风险增加。抗凝剂的选择应个体化,考虑患者的出血风险,包括癌症部位以及患者的价值观和偏好。