Effects on mortality of extended versus short-term anticoagulation in venous thromboembolism: a systematic review and meta-analysis of randomized trials

Background: Venous thromboembolism (VTE) is a common disease, particularly in older age. In 30% of cases the VTE is unprovoked, with a risk of recurrence and therefore of mortality that is higher in these patients. The duration of anticoagulation is still a matter of debate: standard or short-term (3-6 months) versus extended (no end date). Objectives: To analyze the potential benefit of prolonged anticoagulation on overall mortality, according to type and duration of treatments. Methods: PubMed, EMBASE, and Cochrane were searched to identify randomized controlled trials. They had to be designed to compare 2 anticoagulation strategies in patients with unprovoked VTE: short versus extended. No date restrictions were applied the search was last updated on September 30, 2023. Results: Sixteen articles were included in the meta-analysis. Four studies evaluated full dose of direct oral anticoagulants (DOACs), one of them also considered the half dose of DOACs. One study used idraparinux and the others used vitamin K antagonists. The overall risk of bias in individual studies was considered low using the Rob 2 tool. Overall deaths occurred in 88 patients (1.51%) in the extended treatment group and 99 patients (1.88%) in the short-term group. Extended anticoagulation therapy does not significantly reduce total mortality (relative risk [RR]: 0.81 [95% CI: 0.61-1.08]). Subgroup analysis showed a significant reduction of deaths in the extended treatment group with DOACs (RR: 0.49 [95% CI: 0.28-0.86]), but the absolute risk of death was low (<1% in the short-term DOACs subgroup). Conclusion: Extended anticoagulation has no benefit on overall mortality compared with short-term treatment. However, subgroup analysis shows a benefit of DOACs that reduces overall mortality, contrary to vitamin K antagonists..