A systematic review and meta-analysis for the association between duration of anticoagulation therapy and the risk of venous thromboembolism in patients with lower limb superficial venous thrombosis

Abstract

Objective: The aim of this study was to determine the association between the duration of systemic anticoagulation therapy (ACT) and the risk of further venous thromboembolism (VTE) in patients with superficial venous thrombosis (SVT).

Methods: A systematic review and meta-analysis were performed using searches of Medline and Cochrane Library databases in September 2023. Papers that provided VTE incidence within mid-term follow-up of ≥45 days in patients who received any ACT were included. Patients were categorized into subgroups according to the course of treatment: (1) no ACT (0 days); (2) ACT of ≤14 days; (3) ACT of 15 to 30 days; (4) ACT of 31 to 45 days; and (5) ACT of >45 days. Reported events were transformed to events per 100 patient-years, and a random-effects model was used to calculate pooled rates for proportions. The primary outcome (VTE) was a combination of SVT progression or recurrence with the occurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE). Secondary outcomes included major and clinically relevant non-major or minor bleeding.

Results: Twenty-four studies (10 randomized controlled trials and 14 cohort studies) combining outcomes in 12,341 patients were included in the quantitative synthesis. Minimum VTE and SVT recurrence or progression rates were observed with the ACT duration of 31 to 45 days of 16.2 (95% confidence interval [CI], 10.4-23.3) and 8.2 (95% CI, 3.1-15.8) events per 100 patient-years, respectively. Minimum DVT and PE rates observed with the treatment duration of 15 to 30 days were 5.5 (95% CI, 2.8-9.1) and 0.9 (95% CI, 0.5-1.3) events per 100 patient-years, respectively. Short-term treatment of ≤14 days was associated with the highest rates of VTE of 59.7 (95% CI, 37.7-86.4), DVT of 13.7 (95% CI, 9.6-18.4), and PE of 3.1 (95% CI, 1.4-5.6) events per 100 patient-years. Major bleeding rates were unrelated to the duration of ACT and did not exceed 0.5 events per 100 patient-years. The highest rate of clinically relevant non-major or minor bleeding was observed with ACT duration of 31 to 45 days of 14.2 (95% CI, 5.5-26.8) events per 100 patient-years. The most common risk factors for VTE included male sex, cancer, personal history of DVT, PE, or SVT, and thrombosis of non-varicose veins.

Conclusions: Prolonged systemic anticoagulation is associated with the tendency to decrease VTE rates in patients with lower limb SVT.

Keywords: Anticoagulation; Superficial vein thrombosis; Treatment; Venous thromboembolism.

Fig

The pooled event rates of primary and secondary outcomes. Data are presented as per 100 patient-years. Boxes indicate polled event rates and whisker–lower and upper 95% confidence interval (CI). The vertical dashed line corresponds to the polled event rate in the group of no anticoagulation (0 days). CRNM, Clinically relevant non-major; DVT, deep vein thrombosis; PE, pulmonary embolism; SVT, superficial venous thrombosis; VTE, venous thromboembolism.

Supplementary Fig 1 (online only)

Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram.

Supplementary Fig 2 (online only)

The results of bias (RoB) risk assessment of randomized clinical trials with RoB 2 Tool. VTE, Venous thromboembolism.