학술논문
Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Systematic Review and Meta-analysis.
Document Type
Academic Journal
Author
Khan F; University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada (F.K., K.T., B.H.).; Tritschler T; Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (T.T., D.A.).; Kimpton M; Ottawa Hospital Research Institute, University of Ottawa, and The Ottawa Hospital, Ottawa, Ontario, Canada (M.K., P.S.W., G.L.).; Wells PS; Ottawa Hospital Research Institute, University of Ottawa, and The Ottawa Hospital, Ottawa, Ontario, Canada (M.K., P.S.W., G.L.).; Kearon C; McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada (C.K., J.I.W.).; Weitz JI; McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada (C.K., J.I.W.).; Büller HR; Amsterdam University Medical Center, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands (H.R.B.).; Raskob GE; University of Oklahoma Health Sciences Center, Hudson College of Public Health, Oklahoma City, Oklahoma (G.E.R.).; Ageno W; University of Insubria, Varese, Italy (W.A.).; Couturaud F; Brest University Hospital, Brest, France (F.C.).; Prandoni P; Arianna Foundation on Anticoagulation, Bologna, Italy (P.P., G.P., C.L.).; Palareti G; Arianna Foundation on Anticoagulation, Bologna, Italy (P.P., G.P., C.L.).; Legnani C; Arianna Foundation on Anticoagulation, Bologna, Italy (P.P., G.P., C.L.).; Kyrle PA; Medical University of Vienna, Vienna, Austria (P.A.K., S.E., L.E.).; Eichinger S; Medical University of Vienna, Vienna, Austria (P.A.K., S.E., L.E.).; Eischer L; Medical University of Vienna, Vienna, Austria (P.A.K., S.E., L.E.).; Becattini C; University of Perugia, Perugia, Italy (C.B., G.A., M.C.V.).; Agnelli G; University of Perugia, Perugia, Italy (C.B., G.A., M.C.V.).; Vedovati MC; University of Perugia, Perugia, Italy (C.B., G.A., M.C.V.).; Geersing GJ; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands (G.G., T.T.).; Takada T; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands (G.G., T.T.).; Cosmi B; Sant'Orsola-Malpighi University Hospital, Bologna, Italy (B.C.).; Aujesky D; Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (T.T., D.A.).; Marconi L; University of Pisa, Pisa, Italy (L.M., A.P.).; Palla A; University of Pisa, Pisa, Italy (L.M., A.P.).; Siragusa S; University of Palermo, Palermo, Italy (S.S.).; Bradbury CA; University of Bristol, Bristol, United Kingdom (C.A.B.).; Parpia S; McMaster University, Hamilton, Ontario, Canada (S.P.).; Mallick R; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada (R.M.).; Lensing AWA; Bayer, Wuppertal, Germany (A.W.L., M.G.).; Gebel M; Bayer, Wuppertal, Germany (A.W.L., M.G.).; Grosso MA; Daiichi Sankyo, Basking Ridge, New Jersey (M.A.G.).; Thavorn K; University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada (F.K., K.T., B.H.).; Hutton B; University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada (F.K., K.T., B.H.).; Le Gal G; Ottawa Hospital Research Institute, University of Ottawa, and The Ottawa Hospital, Ottawa, Ontario, Canada (M.K., P.S.W., G.L.).; Fergusson DA; University of Ottawa, Ottawa Hospital Research Institute, and The Ottawa Hospital, Ottawa, Ontario, Canada (D.A.F.).; Rodger MA; Ottawa Hospital Research Institute, Ottawa, Ontario, and McGill University, Montreal, Quebec, Canada (M.A.R.).
Source
Publisher: American College of Physicians--American Society of Internal Medicine Country of Publication: United States NLM ID: 0372351 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1539-3704 (Electronic) Linking ISSN: 00034819 NLM ISO Abbreviation: Ann Intern Med Subsets: MEDLINE
Subject
Language
English
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.
Primary Funding Source: Canadian Institutes of Health Research. (PROSPERO: CRD42019128597).
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.
Primary Funding Source: Canadian Institutes of Health Research. (PROSPERO: CRD42019128597).