Long-Term Risk of Major Bleeding after Discontinuing Anticoagulation for Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis

Abstract

Background: The long-term risk of major bleeding after discontinuing anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. Objectives: To determine the incidence of major bleeding up to 5 years after discontinuing anticoagulation for a first unprovoked VTE. Methods: We searched MEDLINE, EMBASE, and Cochrane CENTRAL (from inception to January 2021) to identify relevant randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE who had completed ≥3 months of initial treatment. Unpublished data on major bleeding events and person-years were obtained from authors of included studies to calculate study-level incidence rates. Random-effects meta-analysis was used to pool results across studies. Results: Of 1123 records identified by the search, 20 studies (17 RCTs) and 8740 patients were included in the analysis. During 13 011 person-years of follow-up after discontinuing anticoagulation, the pooled incidence of major bleeding (n=41) and fatal bleeding (n=7) per 100 person-years was 0.35 (95% confidence interval [CI], 0.20-0.54) and 0.09 (95% CI, 0.05-0.15). The 5-year cumulative incidence of major bleeding was of 1.0% (95% CI, 0.4%-2.4%). The case-fatality rate of major bleeding after discontinuing anticoagulation was 19.9% (95% CI, 10.6%-31.1%). Conclusions: Patients with a first unprovoked VTE have a non-trivial risk of major bleeding once anticoagulants are discontinued. Estimates from this study can help clinicians counsel patients about the incremental risk of major bleeding with extended anticoagulation to guide decision making about treatment duration for unprovoked VTE.

Protocol for a modelling study to assess the clinical and cost-effectiveness of indefinite anticoagulant therapy for first unprovoked venous thromboembolism

“…The annual rate of major bleeding after stopping anticoagulant therapy will be defined as 0.4% per year based on a recent a systematic review and meta-analysis of 8740 patients with a first unprovoked VTE that had completed at least 3 months of initial anticoagulant treatment. 25 The annual rate of major bleeding during extended anticoagulant therapy will be defined as 1.1% per year based on a recent systematic review and meta-analysis of 7220 patients with a first unprovoked VTE that had completed at least 3 months of initial anticoagulant treatment and received extended anticoagulation of up to 1 year with a DOAC. 26 Based on input from clinical experts, for the base case, patients assigned to the ‘indefinite anticoagulation’ arm that experience a major bleeding event at any point will temporarily interrupt anticoagulation (for 2 weeks), 4 and then restart treatment.…”

Anticoagulation for Thromboprophylaxis in Patients with Intracerebral Hemorrhage: Less Room for Skepticism

“…The major guidelines that focus on the management of VTE risk or on the clinical management of patients with ICH generally provide weak recommendation with an overall low quality of evidence. [4][5][6][7][8][9] This is despite the intense interest into understanding the risk factors for bleeding (especially in high-risk patient groups, [10][11][12] the long-term risks of bleeding after discontinuing anticoagulation therapy, 13 and improved efforts at bleeding risk stratification and balancing the riskbenefits of reintroducing anticoagulation after a major bleeding event). 14,15 In this issue of Thrombosis and Haemostasis, Chi and colleagues present a systematic review of the association between pharmacological thromboprophylaxis with LMWH or UFH and the risk of VTE in patients with ICH.…”