Fatal recurrent VTE after anticoagulant treatment for unprovoked VTE: a systematic review

Current guidelines recommend long-term anticoagulant therapy in patients with unprovoked venous thromboembolism (VTE). The risk of fatal recurrent VTE after treatment discontinuation (versus that of fatal bleeding during anticoagulation) is of particular relevance in the decision to continue or stop anticoagulation after the first 3 months. Our primary aim was to provide a point-estimate of the yearly rate of fatal recurrent VTE and VTE case-fatality rate in patients with unprovoked VTE after anticoagulation cessation. Data were extracted from both randomised controlled trials and observational studies published before May 1, 2017. The pooled fatality rates were calculated using a random-effects model. 18 studies with low-to-moderate bias were included in the primary analysis, totalling 6758 patients with a median (range) follow-up duration of 2.2 (1-5) years. After anticoagulation cessation, the weighted pooled rate of VTE recurrence was 6.3 (95% CI 5.4-7.3) per 100 patient-years and the weighted pooled rate of fatal recurrent VTE was 0.17 (95% CI 0.047-0.33) per 100 patient-years, for a case-fatality rate of 2.6% (95% CI 0.86-5.0). These numbers are a solid benchmark for comparison to the risks associated with long-term anticoagulation treatment for the decision on the optimal duration of treatment of patients with unprovoked VTE.