Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Ville de Québec, Canada.
Service de Médecine Vasculaire et Thérapeutique, CHU de St-Etienne, Saint-Etienne, France.
PLoS One. 2019 Apr 1;14(4):e0214134. doi: 10.1371/journal.pone.0214134. eCollection 2019.
Extended treatment is preconized in a significant proportion of patients with unprovoked venous thromboembolism (VTE). However, limited direct/indirect comparisons are available to appropriately weight the benefit/risk ratio of the diverse treatments available. We aimed to compare the rate of symptomatic recurrent VTE and major bleeding (MB), the net clinical benefit (VTE+MB) and death on vitamin-K antagonist (VKA), direct oral anticoagulants (DOAC) and antiplatelet drugs for extended anticoagulation.
A systematic literature search through September 2018 identified randomized trials studying these pharmacologic therapies for extended anticoagulation following VTE. Treatment effects were calculated using network meta-analysis with frequentist fixed-effects model.
18 trials (18,221 patients) were included in the analysis. All treatments reduced the risk of recurrence compared to placebo/observation. Nonetheless, VKA (RR 0.22; 95%CI 0.13-0.39) and DOAC (RRs ranging from 0.25-0.32; 95%CI ranging from 0.13-0.52) were more effective than aspirin, whereas low-dose VKA was less effective than standard-dose VKA (RR 2.47; 95%CI 1.34-4.55). The efficacy of DOAC was globally comparable to standard-adjusted dose VKA. Low- (RR 3.13; 95%CI 1.37-7.16) and standard-dose (RR 3.23; 95%CI 1.16-8.99) VKA also increased the risk of MB, which was not the case for any DOAC. Low-dose VKA and low-dose DOAC had similar effects on MB compared to standard-doses. Although there was a trend for reduced MB and enhanced net clinical benefit for DOAC compared to VKA, this was not statistically significant. The specific anticoagulant therapies had no significant effects on deaths.
Standard-dose VKA and low/standard-dose DOAC share similar effects on VTE recurrence and MB, whereas aspirin and low-dose VKA were associated with lower benefit/risk ratio.
在很大一部分无诱因静脉血栓栓塞症（VTE）患者中，推荐进行延长治疗。然而，目前可获得的直接/间接比较有限，无法恰当地权衡各种可用治疗方法的获益/风险比。我们旨在比较维生素 K 拮抗剂（VKA）、直接口服抗凝剂（DOAC）和抗血小板药物用于延长抗凝治疗时，症状性复发性 VTE 和主要出血（MB）、净临床获益（VTE+MB）和死亡的发生率。
通过 2018 年 9 月的系统文献检索，确定了研究这些药物治疗 VTE 后延长抗凝的随机试验。使用具有固定效应模型的频率似然网络荟萃分析计算治疗效果。
纳入了 18 项试验（18221 名患者）进行分析。与安慰剂/观察相比，所有治疗均降低了复发风险。然而，VKA（RR0.22；95%CI0.13-0.39）和 DOAC（RR 分别为 0.25-0.32；95%CI 分别为 0.13-0.52）比阿司匹林更有效，而低剂量 VKA 不如标准剂量 VKA 有效（RR2.47；95%CI1.34-4.55）。DOAC 的疗效总体上与标准调整剂量 VKA 相当。低剂量（RR3.13；95%CI1.37-7.16）和标准剂量（RR3.23；95%CI1.16-8.99）VKA 也增加了 MB 的风险，但任何一种 DOAC 都不会增加 MB 风险。与标准剂量相比，低剂量 VKA 和低剂量 DOAC 对 MB 的影响相似。尽管与 VKA 相比，DOAC 有降低 MB 和提高净临床获益的趋势，但无统计学意义。特定的抗凝治疗对死亡没有显著影响。
标准剂量 VKA 和低/标准剂量 DOAC 对 VTE 复发和 MB 的影响相似，而阿司匹林和低剂量 VKA 的获益/风险比较低。
