School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
BMJ. 2019 Jul 24;366:l4363. doi: 10.1136/bmj.l4363.
To determine the rate of a first recurrent venous thromboembolism (VTE) event after discontinuation of anticoagulant treatment in patients with a first episode of unprovoked VTE, and the cumulative incidence for recurrent VTE up to 10 years.
Systematic review and meta-analysis.
Medline, Embase, and the Cochrane Central Register of Controlled Trials (from inception to 15 March 2019).
Randomised controlled trials and prospective cohort studies reporting symptomatic recurrent VTE after discontinuation of anticoagulant treatment in patients with a first unprovoked VTE event who had completed at least three months of treatment.
Two investigators independently screened studies, extracted data, and appraised risk of bias. Data clarifications were sought from authors of eligible studies. Recurrent VTE events and person years of follow-up after discontinuation of anticoagulant treatment were used to calculate rates for individual studies, and data were pooled using random effects meta-analysis. Sex and site of initial VTE were investigated as potential sources of between study heterogeneity.
18 studies involving 7515 patients were included in the analysis. The pooled rate of recurrent VTE per 100 person years after discontinuation of anticoagulant treatment was 10.3 events (95% confidence interval 8.6 to 12.1) in the first year, 6.3 (5.1 to 7.7) in the second year, 3.8 events/year (95% confidence interval 3.2 to 4.5) in years 3-5, and 3.1 events/year (1.7 to 4.9) in years 6-10. The cumulative incidence for recurrent VTE was 16% (95% confidence interval 13% to 19%) at 2 years, 25% (21% to 29%) at 5 years, and 36% (28% to 45%) at 10 years. The pooled rate of recurrent VTE per 100 person years in the first year was 11.9 events (9.6 to 14.4) for men and 8.9 events (6.8 to 11.3) for women, with a cumulative incidence for recurrent VTE of 41% (28% to 56%) and 29% (20% to 38%), respectively, at 10 years. Compared to patients with isolated pulmonary embolism, the rate of recurrent VTE was higher in patients with proximal deep vein thrombosis (rate ratio 1.4, 95% confidence interval 1.1 to 1.7) and in patients with pulmonary embolism plus deep vein thrombosis (1.5, 1.1 to 1.9). In patients with distal deep vein thrombosis, the pooled rate of recurrent VTE per 100 person years was 1.9 events (95% confidence interval 0.5 to 4.3) in the first year after anticoagulation had stopped. The case fatality rate for recurrent VTE was 4% (95% confidence interval 2% to 6%).
In patients with a first episode of unprovoked VTE who completed at least three months of anticoagulant treatment, the risk of recurrent VTE was 10% in the first year after treatment, 16% at two years, 25% at five years, and 36% at 10 years, with 4% of recurrent VTE events resulting in death. These estimates should inform clinical practice guidelines, enhance confidence in counselling patients of their prognosis, and help guide decision making about long term management of unprovoked VTE.
PROSPERO CRD42017056309.
确定首次无诱因静脉血栓栓塞（VTE）发作后停止抗凝治疗的患者首次复发性静脉血栓栓塞（VTE）事件的发生率，以及 10 年内复发性 VTE 的累积发生率。
系统评价和荟萃分析。
Medline、Embase 和 Cochrane 对照试验中心注册库（从成立到 2019 年 3 月 15 日）。
报告首次无诱因 VTE 发作后停止抗凝治疗的患者中，至少完成 3 个月治疗后出现有症状复发性 VTE 的随机对照试验和前瞻性队列研究。
两名研究者独立筛选研究、提取数据并评估偏倚风险。从合格研究的作者处寻求数据澄清。使用随机效应荟萃分析，根据个体研究的复发性 VTE 事件和停止抗凝治疗后的随访人年计算发生率。性别和初始 VTE 的部位被视为研究间异质性的潜在来源。
纳入了 18 项研究，共 7515 例患者。停止抗凝治疗后第一年的复发性 VTE 每 100 人年的发生率为 10.3 例（95%置信区间 8.6 至 12.1），第二年为 6.3 例（5.1 至 7.7），第三至第五年为 3.8 例/年（95%置信区间 3.2 至 4.5），第六至第十年为 3.1 例/年（1.7 至 4.9）。复发性 VTE 的累积发生率为 2 年时 16%（95%置信区间 13%至 19%），5 年时 25%（21%至 29%），10 年时 36%（28%至 45%）。第一年的复发性 VTE 每 100 人年发生率为男性 11.9 例（9.6 至 14.4），女性 8.9 例（6.8 至 11.3），分别在 10 年时达到 41%（28%至 56%）和 29%（20%至 38%）的累积发生率。与单纯肺栓塞患者相比，近端深静脉血栓形成患者的复发性 VTE 发生率较高（比率比 1.4，95%置信区间 1.1 至 1.7），肺栓塞合并深静脉血栓形成患者的复发性 VTE 发生率较高（1.5，1.1 至 1.9）。在远端深静脉血栓形成患者中，停止抗凝治疗后第一年的复发性 VTE 每 100 人年发生率为 1.9 例（95%置信区间 0.5 至 4.3）。复发性 VTE 的病死率为 4%（95%置信区间 2%至 6%）。
在完成至少 3 个月抗凝治疗的首次无诱因 VTE 发作患者中，治疗后第一年复发性 VTE 的风险为 10%，第二年为 16%，第五年为 25%，第十年为 36%，其中 4%的复发性 VTE 事件导致死亡。这些估计值应能为临床实践指南提供信息，增强对患者预后的信心，并有助于指导无诱因 VTE 的长期管理决策。
PROSPERO CRD42017056309。
