Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism

作者：Faizan Khan, Tobias Tritschler, Miriam Kimpton, Philip S. Wells, Clive Kearon, Jeffrey I. Weitz, Harry R. Büller, Gary E. Raskob, Walter Ageno, Françis Couturaud, Paolo Prandoni, Gualtiero Palareti, Cristina Legnani, Paul A. Kyrle, Sabine Eichinger, Lisbeth Eischer, Cecilia Becattini, Giancarlo Agnelli, Maria Cristina Vedovati, Geert‐Jan Geersing, Toshihiko Takada, Benilde Cosmi, Drahomir Aujesky, Letizia Marconi, Antonio Palla, Sergio Siragusa, Charlotte Bradbury, Sameer Parpia, Ranjeeta Mallick, Anthonie W.A. Lensing, Martin Gebel, Michael Grosso, Kednapa Thavorn, Brian Hutton, Grégoire Le Gal, Dean Fergusson, Marc Rodger, MAJESTIC Collaborators, Faizan Khan, Tobias Tritschler, Miriam Kimpton, Philip S. Wells, Clive Kearon, Jeffrey I. Weitz, Harry R. Büller, Gary E. Raskob, Walter Ageno, Francis Couturaud, Paolo Prandoni, Gualtiero Palareti, Cristina Legnani, Paul A. Kyrle, Sabine Eichinger, Lisbeth Eischer, Cecilia Becattini, Giancarlo Agnelli, Maria Cristina Vedovati, Geert-Jan Geersing, Toshihiko Takada, Benilde Cosmi, Drahomir Aujesky, Letizia Marconi, Antonio Palla, Sergio Siragusa, Charlotte A. Bradbury, Sameer Parpia, Ranjeeta Mallick, Anthonie W.A. Lensing, Martin Gebel, Michael A. Grosso, Kednapa Thavorn, Brian Hutton, Gregoire Le Gal, Dean A. Fergusson, Marc A. Rodger · 发表于：Annals of Internal Medicine · 年份：2021 · DOI：10.7326/m21-1094 · 被引用次数：141 · 研究领域：Venous Thromboembolism Diagnosis and Management、Atrial Fibrillation Management and Outcomes、Blood Coagulation and Thrombosis Mechanisms

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...