What is the problem and what is known about it so far?

Although some patients who develop blood clots called venous thromboembolisms may have clear risk factors, some of these events are considered unprovoked, with no clear reason why the clot formed. In these cases, guidelines recommend treating with anticoagulation for at least 3 months. Decisions about longer courses need to consider the potential risk for more clots compared with the risk for a major bleeding event from the anticoagulation. The risk for further venous thromboembolisms after stopping anticoagulation is 10% at 1 year and 36% at 10 years; 4% of these recurrent venous thromboembolisms result in death, and the overall risk for death at 10 years due to recurrent thromboembolism is 1.4%.

Why did the researchers do this particular study?

To make informed decisions about the risks of continuing anticoagulation compared with the known risks of stopping anticoagulation, researchers did a systematic review and meta-analysis to determine the risk for major bleeding during extended anticoagulation lasting up to 5 years, with special attention to particular demographic and clinical factors.

Who was studied?

Twenty-seven studies contributed information from 17,202 patients who had an unprovoked or weakly provoked venous thromboembolism and had completed at least 3 months of initial anticoagulant therapy.

How was the study done?

Researchers searched 3 databases through July 2021. After finding 28 studies that met the requirements to address the question, researchers asked the authors of the original studies for more detailed information for their analyses. They received the needed information for 27 studies. Using this information, they did statistical analyses to calculate the incidence of major bleeding for 2 types of anticoagulant therapies. They also analyzed if there were differences in bleeding based on age, sex, site of clot, kidney function, history of bleeding, use of other therapies, level of anemia, or study design.

What did the researchers find?

For every 1000 people who use vitamin K antagonists, such as warfarin, for a year, 17 people will have a major bleeding event. For every 1000 people who use direct oral anticoagulants, such as rivaroxaban, 11 will have a major bleeding event. People who are older than 65 years, have kidney disease, have a history of bleeding, are using antiplatelet therapy, or have anemia are more likely to experience bleeding. The risk for death from major bleeding with continued anticoagulation after 10 years would be more than 2.4%.

What were the limitations of the study?

Many studies, particularly for direct oral anticoagulants, followed patients for only 1 year, so estimates for longer-term use are assumed to be similar to those in the first year. The overall number of studies was small for some of the estimates, which may be subject to change with more research.

What are the implications of the study?

Major bleeding risk is higher with vitamin K antagonists; in older people; in people using antiplatelet therapy; and in people with kidney disease, a history of bleeding, or anemia. Estimated bleeding risks with different drugs can inform decisions about extended anticoagulation after a first unprovoked venous thromboembolism.

中文翻译：

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患者总结：静脉血栓栓塞延长抗凝治疗期间的出血风险

问题是什么，到目前为止已知的情况是什么？

尽管一些发生称为静脉血栓栓塞的血栓的患者可能有明确的危险因素，但其中一些事件被认为是无端的，没有明确的血栓形成原因。在这些情况下，指南建议抗凝治疗至少 3 个月。关于更长疗程的决定需要考虑与抗凝治疗引起的大出血事件的风险相比更多凝块的潜在风险。停止抗凝治疗后发生进一步静脉血栓栓塞的风险在 1 年时为 10%，在 10 年时为 36%；这些复发性静脉血栓栓塞中有 4% 导致死亡，10 年内因复发性血栓栓塞导致死亡的总体风险为 1.4%。

研究人员为什么要进行这项特别的研究？

为了对继续抗凝的风险与停止抗凝的已知风险相比做出明智的决定，研究人员进行了系统回顾和荟萃分析，以确定持续长达 5 年的延长抗凝期间发生大出血的风险，并特别注意特定的人群和临床因素。

谁被研究了？

27 项研究提供了来自 17,202 名无诱因或微诱因静脉血栓栓塞患者的信息，这些患者已完成至少 3 个月的初始抗凝治疗。

研究是如何进行的？

研究人员在 2021 年 7 月之前搜索了 3 个数据库。在找到 28 项符合解决问题要求的研究后，研究人员要求原始研究的作者提供更详细的信息以进行分析。他们收到了 27 项研究所需的信息。使用这些信息，他们进行了统计分析以计算两种抗凝治疗的大出血发生率。他们还根据年龄、性别、凝块部位、肾功能、出血史、其他疗法的使用、贫血程度或研究设计分析了出血是否存在差异。

研究人员发现了什么？

每1000人使用华法林等维生素K拮抗剂一年，就有17人发生大出血事件。每 1000 名使用利伐沙班等直接口服抗凝剂的人中，就有 11 人发生大出血事件。65 岁以上、患有肾脏疾病、有出血史、正在使用抗血小板治疗或患有贫血症的人更有可能出现出血。10 年后继续抗凝治疗的大出血死亡风险将超过 2.4%。

研究的局限性是什么？

许多研究，特别是针对直接口服抗凝剂的研究，仅对患者进行了 1 年的随访，因此假设对长期使用的估计与第一年相似。某些估计的研究总数很小，这可能会随着更多的研究而改变。

研究的意义是什么？

维生素 K 拮抗剂的主要出血风险更高；在老年人中；在使用抗血小板治疗的人中；以及患有肾脏疾病、出血史或贫血的人。不同药物的估计出血风险可以为首次无端静脉血栓栓塞后延长抗凝的决定提供信息。