META-ANALYSIS OF LONG-TERM RISK OF FATAL PULMONARY EMBOLISM AFTER DISCONTINUING ANTICOAGULANT THERAPY FOR FIRST UNPROVOKED VENOUS THROMBOEMBOLISM

Abstract

Venous thromboembolism (VTE), manifesting itself as deep vein thrombosis and/or pulmonary embolism (PE) is a leading cause of cardiovascular death. The optimal duration of anticoagulant therapy in patients with a first unprovoked VTE is controversial, due to closely balanced risks of mortality from recurrent VTE if anticoagulation is discontinued, and mortality form major bleeding if anticoagulation is continued. As such, when deciding whether to discontinue anticoagulation after completing initial course of treatment, the subsequent risk of fatal PE is an important prognostic consideration. This risk however, is unclear, hindering decision making. We performed a systematic review and meta-analysis of randomized clinical trials and prospective observational studies to establish precise and reliable estimates of the absolute, long-term risk of fatal PE at standardized time intervals of 1, 2, 5, and 10 years after discontinuing anticoagulant therapy, as well the case-fatality rate of recurrent VTE in patients with a first episode of unprovoked VTE, who had completed at least three months of initial anticoagulation. Absolute rate of fatal PE was calculated for each study from the total number of fatal PE events and the corresponding patient-years of follow-up. Case-fatality rate was defined as the proportion of overall recurrent VTE events that were fatal. Study results were pooled using random-effects meta-analyses. Of 896 identified records, data was available and/or obtained from authors of 15 eligible studies involving 6,627 patients. The weighted, pooled absolute rate of fatal PE (per 100 patient-years) after stopping anticoagulation was 0.4 events (95% CI, 0.2-0.7) in the first year; 0.3 events (95% CI, 0.2-0.6) in the second year; and average 0.1 events/year (95% CI, 0.0-0.3) in the subsequent eight years off treatment (i.e. between year 2 and 10) [Table 1], resulting in a cumulative 10-year risk of 1.5% after discontinuing anticoagulant therapy. Based on a total of 1,035 recurrent VTE and 48 fatal PE events, the weighted, pooled case-fatality rate for recurrent VTE after stopping anticoagulation was 4.0% (95% CI, 2.1%-6.3%) [Figure 1]. Unselected patients with a first episode unprovoked VTE have a low long-term risk (<1% per year) of fatal PE after stopping anticoagulation. This information, together with the case-fatality rate of recurrent VTE helps inform patient prognosis, and may assist clinicians when considering the risks of mortality from recurrent VTE and major bleeding to decide whether to stop or continue anticoagulant therapy for unprovoked VTE.View Large Image Figure ViewerDownload Hi-res image Download (PPT)