Background: The long-term risk for major bleeding in patients receiving extended (beyond the initial 3 to 6 months) anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. Purpose: To determine the incidence of major bleeding during extended anticoagulation of up to 5 years among patients with a first unprovoked VTE, overall, and in clinically important subgroups. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021. Study Selection: Randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagulation for a minimum of 6 additional months after completing at least 3 months of initial anticoagulant treatment. Data Extraction: Two reviewers independently abstracted data and assessed study quality. Unpublished data required for analyses were obtained from authors of included studies. Data Synthesis: Among the 14 RCTs and 13 cohort studies included in the analysis, 9982 patients received a vitamin K antagonist (VKA) and 7220 received a direct oral anticoagulant (DOAC). The incidence of major bleeding per 100 person- years was 1.74 events (95% CI, 1.34 to 2.20 events) with VKAs and 1.12 events (CI, 0.72 to 1.62 events) with DOACs. The 5-year cumulative incidence of major bleeding with VKAs was 6.3% (CI, 3.6% to 10.0%). Among patients receiving either a VKA or a DOAC, the incidence of major bleeding was statistically significantly higher among those who were older than 65 years or had creatinine clearance less than 50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a hemoglobin level less than 100 g/L. The case-fatality rate of major bleeding was 8.3% (CI, 5.1% to 12.2%) with VKAs and 9.7% (CI, 3.2% to 19.2%) with DOACs. Limitation: Data were insufficient to estimate incidence of major bleeding beyond 1 year of extended anticoagulation with DOACs. Conclusion: In patients with a first unprovoked VTE, the long-term risks and consequences of anticoagulant-related major bleeding are considerable. This information will help inform patient prognosis and guide decision making about treatment duration for unprovoked VTE.

Long-term risk for major bleeding during extended oral anticoagulant therapy for first unprovoked venous thromboembolism: A systematic review and meta-analysis

Ageno W.
Membro del Collaboration Group
;
2021-01-01

Abstract

Background: The long-term risk for major bleeding in patients receiving extended (beyond the initial 3 to 6 months) anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. Purpose: To determine the incidence of major bleeding during extended anticoagulation of up to 5 years among patients with a first unprovoked VTE, overall, and in clinically important subgroups. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021. Study Selection: Randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagulation for a minimum of 6 additional months after completing at least 3 months of initial anticoagulant treatment. Data Extraction: Two reviewers independently abstracted data and assessed study quality. Unpublished data required for analyses were obtained from authors of included studies. Data Synthesis: Among the 14 RCTs and 13 cohort studies included in the analysis, 9982 patients received a vitamin K antagonist (VKA) and 7220 received a direct oral anticoagulant (DOAC). The incidence of major bleeding per 100 person- years was 1.74 events (95% CI, 1.34 to 2.20 events) with VKAs and 1.12 events (CI, 0.72 to 1.62 events) with DOACs. The 5-year cumulative incidence of major bleeding with VKAs was 6.3% (CI, 3.6% to 10.0%). Among patients receiving either a VKA or a DOAC, the incidence of major bleeding was statistically significantly higher among those who were older than 65 years or had creatinine clearance less than 50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a hemoglobin level less than 100 g/L. The case-fatality rate of major bleeding was 8.3% (CI, 5.1% to 12.2%) with VKAs and 9.7% (CI, 3.2% to 19.2%) with DOACs. Limitation: Data were insufficient to estimate incidence of major bleeding beyond 1 year of extended anticoagulation with DOACs. Conclusion: In patients with a first unprovoked VTE, the long-term risks and consequences of anticoagulant-related major bleeding are considerable. This information will help inform patient prognosis and guide decision making about treatment duration for unprovoked VTE.
2021
Administration, Oral; Age Factors; Aged; Anticoagulants; Hemorrhage; Humans; Middle Aged; Risk Factors; Venous Thromboembolism
Khan, F.; Tritschler, T.; Kimpton, M.; Wells, P. S.; Kearon, C.; Weitz, J. I.; Buller, H. R.; Raskob, G. E.; Ageno, W.; Couturaud, F.; Prandoni, P.; Palareti, G.; Legnani, C.; Kyrle, P. A.; Eichinger, S.; Eischer, L.; Becattini, C.; Agnelli, G.; Vedovati, M. C.; Geersing, G. -J.; Takada, T.; Cosmi, B.; Aujesky, D.; Marconi, L.; Palla, A.; Siragusa, S.; Bradbury, C. A.; Parpia, S.; Mallick, R.; Lensing, A. W. A.; Gebel, M.; Grosso, M. A.; Thavorn, K.; Hutton, B.; Le Gal, G.; Fergusson, D. A.; Rodger, M. A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2121804
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