BACKGROUND The optimal duration of anticoagulation after a first unprovoked venous thromboembolism (VTE) remains controversial. Deciding to stop or continue anticoagulant therapy indefinitely after completing 3 to 6 months of initial treatment requires balancing the long-term risk of recurrent VTE if anticoagulation is stopped against the long-term risk of major bleeding if anticoagulation is continued. However, knowledge of the long-term risk for major bleeding events during extended anticoagulation in this patient population is limited. We plan to conduct a systematic review and meta-analysis to quantify the risk for major bleeding events during extended oral anticoagulation in patients with first unprovoked VTE. METHODS Electronic databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials will be systematically searched with the assistance of an information specialist (from inception to March 1, 2019) to identify randomized controlled trials and prospective cohort studies reporting major bleeding during extended oral anticoagulation in patients with first unprovoked VTE, who have completed at least 3 months of initial anticoagulant therapy. Study selection, risk of bias assessment, and data extraction will be performed independently by at least two investigators. The number of major bleeding events and person-years of follow-up will be used to calculate the rate (events per 100 person-years) with its 95% confidence interval for each study cohort, during clinically relevant time periods of extended anticoagulant therapy. Results will be pooled using random effect meta-analysis. DISCUSSION The planned systematic review and meta-analysis will provide reliable estimates of the risk for major bleeding events during extended anticoagulation. This information will help inform patient prognosis and assist clinicians with balancing the risks and benefits of treatment to guide management of unprovoked VTE. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019128597 .

中文翻译：

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首次无端静脉血栓栓塞患者长期口服抗凝期间发生大出血的风险：系统评价和荟萃分析方案。


背景首次无端静脉血栓栓塞（VTE）后的最佳抗凝持续时间仍存在争议。在完成 3 至 6 个月的初始治疗后决定无限期停止或继续抗凝治疗，需要平衡停止抗凝治疗时复发 VTE 的长期风险与继续抗凝治疗时发生大出血的长期风险。然而，对该患者群体长期抗凝治疗期间发生大出血事件的长期风险的了解有限。我们计划进行系统评价和荟萃分析，以量化首次无端静脉血栓栓塞患者长期口服抗凝治疗期间发生大出血事件的风险。方法 将在信息专家的协助下系统地检索包括 MEDLINE、EMBASE 和 Cochrane 对照试验中央注册库在内的电子数据库（从开始到 2019 年 3 月 1 日），以识别报告长期大出血的随机对照试验和前瞻性队列研究。首次无端静脉血栓栓塞患者已完成至少 3 个月的初始抗凝治疗的口服抗凝药物。研究选择、偏倚风险评估和数据提取将由至少两名研究人员独立进行。在延长抗凝治疗的临床相关时间段内，主要出血事件的数量和随访人年数将用于计算每个研究队列的比率（每 100 人年的事件数）及其 95% 置信区间。将使用随机效应荟萃分析汇总结果。讨论 计划中的系统评价和荟萃分析将为延长抗凝治疗期间发生大出血事件的风险提供可靠的估计。 这些信息将有助于告知患者预后，并帮助临床医生平衡治疗的风险和获益，以指导无端静脉血栓栓塞的治疗。系统审查注册 PROSPERO CRD42019128597 。