近日，美国布列根和妇女医院Kueiyu Joshua Lin团队研究了持续与停止口服抗凝治疗不明原因静脉血栓栓塞症的患者预后。2025年11月12日，《英国医学杂志》发表了这一成果。

为了比较非诱发性静脉血栓栓塞（VTE）患者在初始治疗至少90天后继续或停止口服抗凝剂（OACs）对健康结果的影响，研究组进行了一项目标试验仿真。选择美国2009年1月1日至2025年2月28日的Optum临床数据集市（Optum CDM），以及2009年1月1日至2022年12月31日的医疗保险按服务收费索赔。参与者年龄≥18岁（Optum CDM）或≥65岁（Medicare）的静脉血栓栓塞患者在首次因静脉血栓栓塞入院后30天内启动OAC（华法林或直接OAC），且无可逆性诱发因素，且持续治疗≥90天。在继续治疗的患者和停止治疗的患者（即在30天内没有重新配药）之间进行倾向评分一对一匹配。

主要结局为静脉血栓栓塞复发住院（有效性）和大出血（安全性）。次要结局是净临床获益（静脉血栓栓塞复发和出血的综合结果）和死亡率。Cox比例风险模型估计了风险比，广义线性模型估计了每1000人年的风险差异。根据初始OAC治疗时间（90-179天、180-359天、360-719天、720-1079天或≥1080天）对分析进行分层。

研究队列包括30554对倾向评分匹配的患者继续或停止OAC治疗（平均年龄73.9岁，57.0%为女性）。初始抗凝≥90天后，与停止治疗的患者相比，继续治疗的患者静脉血栓栓塞复发率明显降低(校正风险比0.19,95%可信区间（CI） 0.13 ~ 0.29；每1000人年调整率差异（25.50,95% CI为39.38 ~ 11.63），大出血率较高（1.75,1.52 ~ 2.02;4.78,1.95 ~ 7.61），死亡率较低（0.74,0.69 ~ 0.79;14.31,22.02 ~ 6.59），临床净获益较高（0.39,0.36 ~ 0.42;21.01,32.31 ~ 9.71）。更大的净临床效益在OAC类型和初始OAC治疗时间上是一致的。

研究结果表明，基于美国两大具有全国代表性的常规诊疗数据库研究显示，在完成初始抗凝治疗（≥90天）后，持续使用口服抗凝药与中断治疗相比，可降低静脉血栓栓塞复发风险，但会增加大出血风险，并呈现净临床获益。该结论在静脉血栓栓塞后持续使用口服抗凝药至少三年的患者群体中依然成立。

附：英文原文

Title: Continued versus discontinued oral anticoagulant treatment for unprovoked venous thromboembolism: target trial emulation

Author: Kueiyu Joshua Lin, Dae Hyun Kim, Daniel E Singer, Yichi Zhang, Alexander Cervone, Anna R Kehoe, Katsiaryna Bykov

Issue&Volume: 2025/11/12

Abstract:

Objective To compare the effect on health outcomes of continuing or discontinuing oral anticoagulants (OACs) among patients with unprovoked venous thromboembolism (VTE) after initial treatment for at least 90 days.

Design Target trial emulation.

Setting Optum Clinformatics Data Mart (Optum CDM) from 1 January 2009 to 28 Februray 2025, and Medicare fee-for-service claims from 1 January 2009 to 31 December 2022, United States.

Participants Adults with VTE aged ≥18 years (Optum CDM) or ≥65 years (Medicare) initiating OACs (warfarin or direct OACs) within 30 days after a first hospital admission with VTE without reversible provoking factors and who continued treatment for ≥90 days. Propensity score one-to-one matching was performed between patients who continued and those who discontinued treatment (ie, absence of a refilled prescription within 30 days).

Main outcome measures The primary outcomes were hospital admission for recurrent VTE (effectiveness) and major bleeding (safety). Secondary outcomes were net clinical benefit (a composite of recurrent VTE and bleeding) and mortality. Cox proportional hazards models estimated hazard ratios and generalized linear models estimated rate differences per 1000 person years. Analyses were stratified by length of initial OAC treatment (90-179, 180-359, 360-719, 720-1079, or ≥1080 days).

Results The study cohort included 30554 propensity score matched pairs who had continued or discontinued an OAC (mean age 73.9 years, 57.0% women). After initial anticoagulation of ≥90 days, compared with those who discontinued treatment, those who continued treatment had markedly lower rates of recurrent VTE (adjusted hazard ratio 0.19, 95% confidence interval (CI) 0.13 to 0.29; adjusted rate difference per 1000 person years 25.50, 95% CI 39.38 to 11.63), higher rates of major bleeding (1.75, 1.52 to 2.02; 4.78, 1.95 to 7.61), lower mortality rates (0.74, 0.69 to 0.79; 14.31, 22.02 to 6.59), and greater net clinical benefit (0.39, 0.36 to 0.42; 21.01, 32.31 to 9.71). The greater net clinical benefit was consistent across OAC types and length of initial OAC treatment.

Conclusion Based on two US nationally representative routine care databases, continuing versus discontinuing OAC after initial anticoagulation of ≥90 days was associated with lower risk of recurrent VTE, higher risk of major bleeding, and a net clinical benefit. This observation persisted among those using OACs for at least three years after VTE.

DOI: 10.1136/bmj-2025-084380

Source: https://www.bmj.com/content/391/bmj-2025-084380